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Single incision access: a novel surgical approach to the extraction of impacted inferior third molars | The recent attention to quality of life and oral health care procedures reflects a renewed 'patient-based' approach to dealing with non-life-threatening conditions. In the current study, we proposed a novel surgical approach to the extraction of impacted inferior third molars (iMs3) through a randomised, blinded, split-mouth controlled clinical trial following the CONSORT guidelines. The novel surgical procedure, hereinafter referred to as single incision access (SIA), will be compared with our previously described flapless surgical approach (FSA). The predictor variable was the novel SIA approach, involving access through a single incision without removal of soft tissue, on the impacted iMs3. The primary endpoint was the acceleration of the iMs3 extraction healing time. The secondary endpoints were the incidences of pain and oedema as well as gum health (pocket probing depth and attached gingiva). The study was carried out on 84 teeth of 42 patients with both iMs3 impacted. The cohort was composed of 42% Caucasian males and 58% Caucasian females, aged 23.8 ± 7.9 (17-49) years. We observed faster recovery/wound-healing on the SIA side (33.6 ± 4.3 days) than at the FSA side (42.1 ± 5.4 days; | [
"To review the literature on the effect of different surgical flaps upon patient morbidity (pain perception, trismus, swelling and osteitis) after impacted third molar extraction. An electronic and complementary search of main databases and grey literature was performed up to January 2019 to retrieve randomized cli... |
Anti-osteoporosis effects of a mixture of BPX and a tylenol | Osteoporosis is a metabolic skeletal disease characterized by lowered bone mineral density and quality, which lead to an increased risk of fracture. The aim of this study was to evaluate the anti-osteoporosis effects of a mixture (called BPX) of | [
"Osteoporosis diagnosis is based on bone mineral density (BMD) but bone remodeling is also a crucial issue. It can be assessed by bone turnover markers (BTMs). Their interest for the positive and etiological diagnosis of osteoporosis at baseline, and their predictive value for past asymptomatic vertebral fractures,... |
Rice blast caused by a biotic stress | Rice is one of the staple foods for the majority of the global population that depends directly or indirectly on it. The yield of this important crop is constantly challenged by various biotic stresses. Rice blast, caused by | [
"Recognition of pathogen-derived molecules by pattern recognition receptors (PRRs) is a common feature of both animal and plant innate immune systems. In plants, PRR signalling is initiated at the cell surface by kinase complexes, resulting in the activation of immune responses that ward off microorganisms. However... |
[Myocardial infarction with non-obstructive coronary arteries]. | Myocardial infarction with Non Obstructive Coronary Arteries (MINOCA) is defined by patients presenting with signs and symptoms similar to acute myocardial infarction, but are found to have non-obstructive coronary arteries angiography. What was once considered a benign phenomenon, MINOCA has been proven to carry with it significant morbidity and worse mortality when compared to the general population. As the awareness for MINOCA has increased, guidelines have focused on this unique situation. Cardiac magnetic resonance (CMR) has proven to be an essential first step in the diagnosis of patients with suspected MINOCA. CMR has also been shown to be crucial when differentiating between MINOCA like presentations such as myocarditis, takotsubo and other forms of cardiomyopathy. The following review focuses on demographics of patients with MINOCA, their unique clinical presentation as well as the role of CMR in the evaluation of MINOCA. | [
"This study investigated whether T1 mapping by cardiac magnetic resonance (CMR) reflects the clinical evolution of disease in myocarditis and supports its diagnosis independently of the disease stages. Acute viral myocarditis is characterized by a range of intracellular changes due to viral replication and extracel... |
Risks of gestational diabetes and pregnancy-induced hypertension in women with polycystic ovary syndrome | To evaluate the risks of developing gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) in women with polycystic ovary syndrome (PCOS) using data from Korea's National Health Insurance Service. | [
"What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference? International evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote ... |
Non-Squamous Cell Carcinoma-Related Malignant Sinonasal Tract Tumors | Non-squamous cell carcinoma-related malignant sinonasal tract tumors (non-SCC MSTT) are rare and diverse malignancies. In this study, we report our experience in the management of this group of patients. The treatment outcome has been presented, involving both primary treatment and salvage approaches. Data from 61 patients treated radically due to non-SCC MSTT between 2000 and 2016 at the National Cancer Research Institute, Gliwice branch, were analyzed. The group consisted of the following pathological subtypes of MSTT: adenoid cystic carcinoma (ACC), undifferentiated sinonasal carcinoma (USC), sarcoma, olfactory neuroblastoma (ONB), adenocarcinoma, small cell neuroendocrine carcinoma (SNC), mucoepidermic carcinoma (MEC), and acinic cell carcinoma, which were found in nineteen (31%), seventeen (28%), seven (11.5%), seven (11.5%), five (8%), three (5%), two (3%) and one (2%) of patients, respectively. There were 28 (46%) males and 33 (54%) females at the median age of 51 years. Maxilla was the primary tumor localization followed by the nasal cavity and ethmoid sinus in thirty-one (51%), twenty (32.5%), and seven (11.5%) patients, respectively. In 46 (74%) patients, an advanced tumor stage (T3 or T4) was diagnosed. Primary nodal involvement (N) was found in three (5%) cases, and all patients underwent radical treatment. The combined treatment consisted of surgery and radiotherapy (RT) and was given to 52 (85%) patients. The probabilities of overall survival (OS), locoregional control (LRC), metastases-free survival (MFS), and disease-free survival (DFS) were assessed in pathological subtypes and grouped together, along with the ratio and effectiveness of salvage. Locoregional treatment failure was seen in 21 (34%) patients. Salvage treatment was performed in fifteen (71%) patients and was effective in nine (60%) cases. There was a significant difference in OS between patients who underwent salvage and those who did not (median: 40 months vs. 7 months, | [
"Sinonasal malignancies vary in behavior according to histology and anatomical location. Incidence, survival, and optimal treatment for these lesions are thus uncertain in various cases. Our objective was to utilize a national population-based registry to identify the most common sinonasal histopathologies by anato... |
Role of vascular cell adhesion molecule-1 on hepatic stellate cells in non-alcoholic steatohepatitis | Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic steatohepatitis (NASH), characterized by inflammation and fibrosis. Fibrosis is mediated by hepatic stellate cells (HSC) and their differentiation into activated myofibroblasts; the latter process is also promoted by inflammation. Here we studied the role of the pro-inflammatory adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) in HSCs in NASH. VCAM-1 expression was upregulated in the liver upon NASH induction, and VCAM-1 was found to be present on activated HSCs. We therefore utilized HSC-specific VCAM-1-deficient and appropriate control mice to explore the role of VCAM-1 on HSCs in NASH. However, HSC-specific VCAM-1-deficient mice, as compared to control mice, did not show a difference with regards to steatosis, inflammation and fibrosis in two different models of NASH. Hence, VCAM-1 on HSCs is dispensable for NASH development and progression in mice. | [
"The rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738... |
A novel multifunctional drug delivery system based on mesoporous silica particles | Alendronate (ALN) is the most commonly prescribed oral nitrogen-containing bisphosphonate for osteoporosis therapy. However, its administration is associated with serious side effects. Therefore, the drug delivery systems (DDS) enabling local administration and localized action of that drug are still of great importance. Herein, a novel multifunctional DDS system based on the hydroxyapatite-decorated mesoporous silica particles (MSP-NH | [
"In this paper we review the mathematical models used to determine the kinetics of drug release from drug delivery systems. The quantitative analysis of the values obtained in dissolution/release rates is easier when mathematical formulae are used to describe the process. The mathematical modeling can ultimately he... |
B-cell CLL/lymphoma 2 and the programmed cell death receptor 1 pathway | Myelodysplastic syndromes (MDSs) belong to a group of clonal bone marrow malignancies. In light of the emergence of new molecules, a significant contribution to the understanding of the pathogenesis of the disease is the study of the B-cell CLL/lymphoma 2 (BCL-2) and the programmed cell death receptor 1 (PD-1) protein and its ligands. BCL-2-family proteins are involved in the regulation of the intrinsic apoptosis pathway. Disruptions in their interactions promote the progression and resistance of MDSs. They have become an important target for specific drugs. Bone marrow cytoarchitecture may prove to be a predictor of response to its use. The challenge is the observed resistance to venetoclax, for which the MCL-1 protein may be largely responsible. Molecules with the potential to break the associated resistance include S63845, S64315, chidamide and arsenic trioxide (ATO). Despite promising in vitro studies, the role of PD-1/PD-L1 pathway inhibitors has not yet been established. Knockdown of the PD-L1 gene in preclinical studies was associated with increased levels of BCL-2 and MCL-1 in lymphocytes T, which could increase their survival and promote tumor apoptosis. A trial (NCT03969446) is currently underway to combine inhibitors from both groups. | [
"Therapy-related myeloid neoplasms (t-MN) are aggressive malignancies in need of effective therapies. The BCL-2 inhibitor venetoclax represents a paradigm shift in the treatment of acute myeloid leukemia. However, the effectiveness of venetoclax has not been studied in a large cohort of t-MN. We retrospectively ana... |
Radiogenomic association map linking tumor morphology, shape, texture, and size with gene and miRNA signatures | The heterogeneity of lung tumor nodules is reflected in their phenotypic characteristics in radiological images. The radiogenomics field employs quantitative image features combined with transcriptome expression levels to understand tumor heterogeneity molecularly. Due to the different data acquisition techniques for imaging traits and genomic data, establishing meaningful connections poses a challenge. We analyzed 86 image features describing tumor characteristics (such as shape and texture) with the underlying transcriptome and post-transcriptome profiles of 22 lung cancer patients (median age 67.5 years, from 42 to 80 years) to unravel the molecular mechanisms behind tumor phenotypes. As a result, we were able to construct a radiogenomic association map (RAM) linking tumor morphology, shape, texture, and size with gene and miRNA signatures, as well as biological correlates of GO terms and pathways. These indicated possible dependencies between gene and miRNA expression and the evaluated image phenotypes. In particular, the gene ontology processes "regulation of signaling" and "cellular response to organic substance" were shown to be reflected in CT image phenotypes, exhibiting a distinct radiomic signature. Moreover, the gene regulatory networks involving the TFs | [
"The cell nucleus is a highly organized cellular organelle that contains the genetic material. The study of nuclear architecture has become an important field of cellular biology. Extracting quantitative data from 3D fluorescence imaging helps understand the functions of different nuclear compartments. However, suc... |
PROTRAIT: A Deep Learning Framework for Single-Cell Chromatin Accessibility Analysis | Recent advances in single-cell sequencing assays for the transposase-accessibility chromatin (scATAC-seq) technique have provided cell-specific chromatin accessibility landscapes of cis-regulatory elements, providing deeper insights into cellular states and dynamics. However, few research efforts have been dedicated to modeling the relationship between regulatory grammars and single-cell chromatin accessibility and incorporating different analysis scenarios of scATAC-seq data into the general framework. To this end, we propose a unified deep learning framework based on the ProdDep Transformer Encoder, dubbed PROTRAIT, for scATAC-seq data analysis. Specifically motivated by the deep language model, PROTRAIT leverages the ProdDep Transformer Encoder to capture the syntax of transcription factor (TF)-DNA binding motifs from scATAC-seq peaks for predicting single-cell chromatin accessibility and learning single-cell embedding. Based on cell embedding, PROTRAIT annotates cell types using the Louvain algorithm. Furthermore, according to the identified likely noises of raw scATAC-seq data, PROTRAIT denoises these values based on predated chromatin accessibility. In addition, PROTRAIT employs differential accessibility analysis to infer TF activity at single-cell and single-nucleotide resolution. Extensive experiments based on the Buenrostro2018 dataset validate the effeteness of PROTRAIT for chromatin accessibility prediction, cell type annotation, and scATAC-seq data denoising, therein outperforming current approaches in terms of different evaluation metrics. Besides, we confirm the consistency between the inferred TF activity and the literature review. We also demonstrate the scalability of PROTRAIT to analyze datasets containing over one million cells. | [
"It is a challenging task to integrate scRNA-seq and scATAC-seq data obtained from different batches. Existing methods tend to use a pre-defined gene activity matrix to convert the scATAC-seq data into scRNA-seq data. The pre-defined gene activity matrix is often of low quality and does not reflect the dataset-spec... |
The Mediating Effect of Challenges on Demographic Characteristics and Coping Strategies of Healthcare Workers | Healthcare workers (HCWs) including doctors, nurses and allied workers struggled to cope up with the stressful situation as the COVID-19 pandemic unsettled healthcare systems, including India's. Many factors (commonly called as stressors) acted as major sources of stress and resulted in poor mental health of HCWs. Therefore, this study predicted and explained the mediating effect of challenges on demographic characteristics and coping strategies of HCWs. Data from a cross-sectional study was collected from the district hospital of Rajasthan, India, during the period of August 2022-October 2022. HCW's experience level, shift type and distance of greenspaces from their accommodation were significantly correlated with the challenges they faced at work, specifically societal challenges. Thus, HCWs were more inclined to adopt a meaning-focused coping strategy to retain good mental health during the pandemic. Therefore, these findings call for interventions requiring a layered response, comprising strategies and actions that are structural. At the organizational level, these actions may provide supportive workplace environments. | [
"The purpose of this study was to analyze the mediating effect of self-efficacy and coping strategy in the relationship between job stress and the psychological well-being of care workers. The subjects were 112 home-visiting care workers, and data were collected at four home-visiting nursing centers in a metropolit... |
Behavioral, clinical, and vascular variables associated with cognitive impairment in hemodialysis patients | (1) Background: Cognitive impairment (CI) is more prevalent in hemodialysis (HD) patients than in the general population. The purpose of this study was to examine if behavioral, clinical, and vascular variables are linked with CI in individuals with HD. (2) Methods: Initially, 47 individuals with chronic HD volunteered to participate in the trial, but only 27 patients ultimately completed the Montreal Cognitive Assessment (MoCA) and the Computerized Cognitive Assessment Tool (CompBased-CAT). We collected information on smoking, mental activities, physical activity (Rapid Assessment of Physical Activity, RAPA), and comorbidity. The oxygen saturation (rSO2) and pulse wave velocity (PWV; IEM Mobil-O-Graph) of the frontal lobes were measured. (3) Results: Significant associations were discovered between MoCA and rSO2 (r = 0.44, p = 0.02 and r = 0.62, | [
"Patients with chronic kidney disease treated with hemodialysis (HD) have lower cognitive abilities compared to the age-matched healthy population. Recently, physical exercise and cognitive training have been presented as possible interventions to improve cognitive abilities both in the general population and in pa... |
Effect of topical diacerein on imiquimod-induced psoriasis | Psoriasis is an inflammatory skin disease characterized by increased neo-vascularization, keratinocyte hyperproliferation, a pro-inflammatory cytokine milieu and immune cell infiltration. Diacerein is an anti-inflammatory drug, modulating immune cell functions, including expression and production of cytokines, in different inflammatory conditions. Therefore, we hypothesized that topical diacerein has beneficial effects on the course of psoriasis. The current study aimed to evaluate the effect of topical diacerein on imiquimod (IMQ)-induced psoriasis in C57BL/6 mice. Topical diacerein was observed to be safe without any adverse side effects in healthy or psoriatic animals. Our results demonstrated that diacerein significantly alleviated the psoriasiform-like skin inflammation over a 7-day period. Furthermore, diacerein significantly diminished the psoriasis-associated splenomegaly, indicating a systemic effect of the drug. Remarkably, we observed significantly reduced infiltration of CD11c | [
"Psoriasis is a type I-deviated disease characterized by the presence of interferon (IFN)-gamma and multiple IFN-related inflammatory genes in lesions. Because interleukin (IL)-23 is now recognized to play a role in the recruitment of inflammatory cells in a T helper cell (Th)1-mediated disease, we examined psorias... |
Acetaminophen and non-steroidal anti-inflammatory drugs in patients with serious acute respiratory syndrome coronavirus 2 infection | Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed to infected patients; however, the safety of them has not been investigated in patients with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to evaluate the association between the previous use of acetaminophen or NSAIDs and the clinical outcomes of SARS-CoV-2 infection. A nationwide population-based cohort study was conducted using the Korean Health Insurance Review and Assessment Database through propensity score matching (PSM). A total of 25,739 patients aged 20 years and older who tested for SARS-CoV-2 were included from 1 January 2015 to 15 May 2020. The primary endpoint was a positive result for a SARS-CoV-2 test, and the secondary endpoint was serious clinical outcomes of SARS-CoV-2 infection, such as conventional oxygen therapy, admission to the intensive care unit, need for invasive ventilation care, or death. Of 1058 patients, after propensity score matching, 176 acetaminophen users and 162 NSAIDs users were diagnosed with coronavirus disease 2019. After PSM, 162 paired data sets were generated, and the clinical outcomes of the acetaminophen group were not significantly different from those of the NSAIDs group. This suggests that acetaminophen and NSAIDs can be used safely to control symptoms in patients suspected of having SARS-CoV-2. | [
"Concerns have been expressed that some drugs may increase susceptibility to SARS-CoV-2 infection. In contrast, other drugs have generated interest as potential therapeutic agents. All adults aged ≥18 years who were tested for COVID-19 were included. Exposure was defined as a prescription of study drugs which would... |
Peer Relationship Profiles among Early Adolescents from Low-Income Families | Using research data gathered from multiple sources, the current study explored positive aspects of peer relationship profiles (indexed by peer-nominated acceptance and self-reported friendships) in a person-centered approach among early adolescents from low-income families. Moreover, this study investigated the unique and combined associations of adolescents' attachment to mothers and parent-rated conscientiousness with emerging peer relationship profiles. A total of 295 early adolescents (42.7% girls; | [
"The present study concerns an overlooked trait indicator of childhood peer status: Being fun. The study is designed to identify the degree to which being fun is uniquely associated with the peer status variables of likeability and popularity. Two studies of children in grades 4 to 6 (ages 9 to 12) are reported. Th... |
The extent of practice variation in emergency medicine in The Netherlands. | Structural insights in the use of protocols and the extent of practice variation in EDs are lacking. The objective is to determine the extent of practice variation in EDs in The Netherlands, based on specified common practices. We performed a comparative study on Dutch EDs that employed emergency physicians to determine practice variation. Data on practices were collected via a questionnaire. Fifty-two EDs across The Netherlands were included. Thrombosis prophylaxis was prescribed for below-knee plaster immobilization in 27% of EDs. Vitamin C was prescribed in 50% of EDs after a wrist fracture. Splitting of applied casts to the upper or lower limb was performed in one-third of the EDs. Analysis of the cervical spine after trauma was performed by the NEXUS criteria (69%), the Canadian C-spine Rule (17%) or otherwise. The imaging modality for cervical spine trauma in adults was a CT scan (98%). The cast used for scaphoid fractures was divided between the short arm cast (46%) and the navicular cast (54%). Locoregional anaesthesia for femoral fractures was applied in 54% of the EDs. EDs in The Netherlands showed considerable practice variation in treatments among the subjects studied. Further research is warranted to gain a full understanding of the variation in practice in EDs and the potential to improve quality and efficiency. | [
"Feedback is essential to learning and practice improvement, yet challenging both to provide and receive. The purpose of this paper was to explore reflective processes which physicians described as they considered their assessment feedback and the perceived utility of that reflective process. This is a qualitative ... |
How do I get a list of all the fruits of a tree? | The fruits of | [
"The aim of the present study was to investigate and compare the anti-platelet action of extracts from three different plants: bark of Yucca schidigera, seeds of grape and berries of Aronia melanocarpa (chokeberry). Anti-platelet action of tested extracts was compared with action of well characterized antioxidative... |
Gut microbiota in chronic kidney disease | A bidirectional kidney-gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. | [
"The human gut microbiota has been identified as a possible novel risk factor for cardiovascular disease. The intestinal microbiome plays a role in the pathogenesis of atherosclerosis and heart failure. Even though studies in rodents suggested that gut microbes may affect the risk of heart disease, this link has no... |
Experiences of NBGQ youth with microaggressions | This study explores the experiences of NBGQ youth with microaggressions. It investigates the types of microaggressions they face and their subsequent needs and coping mechanisms and the impacts on their lives. Semi-structured interviews with ten NBGQ youth in Belgium were conducted and analyzed using a thematic approach. The results showed that experiences of microaggressions were centered around denial. The most common ways to cope were finding acceptance from (queer) friends and therapists, engaging in a conversation with the aggressor, and rationalizing and empathizing with the aggressor, leading to self-blame and normalization of the experiences. Microaggressions were experienced as exhausting, which influenced the extent to which the NBGQ individuals wanted to explain themselves to others. Furthermore, the study shows an interaction between microaggressions and gender expression, in which gender expression is seen as a motive for microaggressions and microaggressions have an impact on the gender expression of NBGQ youth. | [
"It is vital that the treatment offered at transgender health services can be evaluated to ensure a high quality of care. However, the tools currently used to evaluate treatment at transgender health services are limited by mainly focusing on mental health or because they have been developed for binary transgender ... |
Incidence and Risk Factors of Sleep-Disordered Breathing in Children | This study aimed to identify the incidence and risk factors of sleep-disordered breathing (SDB) using an Arabic version of the pediatric sleep questionnaire (PSQ). A total of 2000 PSQs were circulated to children aged 6-12 years who were randomly selected from 20 schools in Al-Kharj city, Saudi Arabia. The questionnaires were filled out by the parents of participating children. The participants were further divided into two groups (younger group: 6-9 years and older group: 10-12 years). Out of 2000 questionnaires, 1866 were completed and analyzed (93.3% response rate), of which 44.2% were from the younger group and 55.8% were from the older group. Among all the participants, a total of 1027 participants were female (55%) and 839 were male (45%) with a mean age of 9.67 ± 1.78 years. It showed that 13% of children were suffering from a high risk of SDB. Chi-square test and logistic regression analyses within this study cohort showed a significant association between SDB symptoms (habitual snoring; witnessed apnea; mouth breathing; being overweight; and bedwetting) and risk of developing SDB. In conclusion: habitual snoring; witnessed apnea; mouth breathing; being overweight; and bedwetting strongly contribute the to development of SDB. | [
"Epidemiological studies of sleep disturbances are essential to promote awareness among families and educational officials and deliver appropriate treatment at a very early timing. The aim of this population-based study was to determine the frequency of sleep-disordered breathing (SDB) symptoms and its association ... |
Epithelial-mesenchymal transition genes in malignant mesothelioma | Malignant mesothelioma (MESO) consists of epithelioid, biphasic, and sarcomatoid subtypes with different epithelial-mesenchymal transition (EMT) phenotypes. We previously identified a panel of four MESO EMT genes correlating with an immunosuppressive tumor microenvironment and poor survival. In this study, we investigated the correlation between these MESO EMT genes, the immune profile, and the genomic and epigenomic alterations to identify potential therapeutic targets to prevent or reverse the EMT process. Using multiomic analysis, we observed that the MESO EMT genes were positively correlated with hypermethylation of epigenetic genes and loss of CDKN2A/B expression. MESO EMT genes such as | [
"Fibroblast growth factors (FGFs) and their receptors control a wide range of biological functions, regulating cellular proliferation, survival, migration and differentiation. Although targeting FGF signalling as a cancer therapeutic target has lagged behind that of other receptor tyrosine kinases, there is now sub... |
Mutational signature analysis based on mutation co-occurrences | Mutational signature analysis promises to reveal the processes that shape cancer genomes for applications in diagnosis and therapy. However, most current methods are geared toward rich mutation data that has been extracted from whole-genome or whole-exome sequencing. Methods that process sparse mutation data typically found in practice are only in the earliest stages of development. In particular, we previously developed the Mix model that clusters samples to handle data sparsity. However, the Mix model had two hyper-parameters, including the number of signatures and the number of clusters, that were very costly to learn. Therefore, we devised a new method that was several orders-of-magnitude more efficient for handling sparse data, was based on mutation co-occurrences, and imitated word co-occurrence analyses of Twitter texts. We showed that the model produced significantly improved hyper-parameter estimates that led to higher likelihoods of discovering overlooked data and had better correspondence with known signatures. | [
"Somatic mutations are the driving force of cancer genome evolution. The rate of somatic mutations appears to be greatly variable across the genome due to variations in chromatin organization, DNA accessibility and replication timing. However, other variables that may influence the mutation rate locally are unknown... |
Effect of red LED light on radicle emergence and growth of pepper seeds | Red LED light (R LED) is an efficient tool to improve seed germination and plant growth under controlled environments since it is more readily absorbed by photoreceptors' phytochromes compared to other wavelengths of the spectrum. In this work, the effect of R LED on the radicle emergence and growth (Phase III of germination) of pepper seeds was evaluated. Thus, the impact of R LED on water transport through different intrinsic membrane proteins, via aquaporin (AQP) isoforms, was determined. In addition, the remobilization of distinct metabolites such as amino acids, sugars, organic acids, and hormones was analysed. R LED induced a higher germination speed index, regulated by an increased water uptake. | [
"The oxylipin jasmonate (JA) regulates many aspects of growth, development, and environmental responses in plants, particularly defense responses against herbivores and necrotrophic pathogens. Mutants of Arabidopsis helped researchers define the biochemical pathway for synthesis of jasmonoyl-isoleucine (JA-Ile), th... |
Eukaryotic Initiation Factors and Hepatocellular Carcinoma | The liver is a metabolic hub characterized by high levels of protein synthesis. Eukaryotic initiation factors, eIFs, control the first phase of translation, initiation. Initiation factors are essential for tumor progression and, since they regulate the translation of specific mRNAs downstream of oncogenic signaling cascades, may be druggable. In this review, we address the issue of whether the massive translational machinery of liver cells contributes to liver pathology and to the progression of hepatocellular carcinoma (HCC); it represents a valuable biomarker and druggable target. First, we observe that the common markers of HCC cells, such as phosphorylated ribosomal protein S6, belong to the ribosomal and translational apparatus. This fact is in agreement with observations that demonstrate a huge amplification of the ribosomal machinery during the progression to HCC. Some translation factors, such as eIF4E and eIF6, are then harnessed by oncogenic signaling. In particular, the action of eIF4E and eIF6 is particularly important in HCC when driven by fatty liver pathologies. Indeed, both eIF4E and eIF6 amplify at the translational level the production and accumulation of fatty acids. As it is evident that abnormal levels of these factors drive cancer, we discuss their therapeutic value. | [
"To study the expression of eukaryotic translation initiation factor 4E (eIF4E), which is closely correlated with malignant tumors, and its relationship to prognosis in hepatocellular carcinoma. Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the h... |
The Role of Thyroid Hormones in Energy Homeostasis | The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear receptors acting as transcription factors. In this comprehensive review, we summarize the effects of nutritional intervention like fasting and diets on the TH system. In parallel, we detail direct effects of TH in liver metabolic pathways with regards to glucose, lipid, and cholesterol metabolism. This overview on hepatic effects of TH provides the basis for understanding the complex regulatory network and its translational potential with regards to currently discussed treatment options of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) involving TH mimetics. | [
"We have studied the rat malic enzyme gene as a model for thyroid hormone (triiodothyronine (T3)) regulation of transcription. Our previous studies showed that transcription of this gene is controlled by T3 in vivo. In this study, we used COS-7 cells in culture to determine the location of a T3 response element (TR... |
Development of hypoallergenic wheat products for wheat-dependent exercise-induced anaphylaxis | Immunoglobulin E (IgE)-mediated food allergies to wheat that develop after school age typically shows a type of wheat-dependent exercise-induced anaphylaxis (WDEIA). At present, avoidance of wheat products or postprandial rest after ingesting wheat is recommended for patients with WDEIA, depending on the severity of the allergy symptoms. ω5-Gliadin has been identified as the major allergen in WDEIA. In addition, α/β-, γ-, and ω1,2-gliadins, high and low molecular weight-glutenins, and a few water-soluble wheat proteins have been identified as IgE-binding allergens in a small proportion of patients with IgE-mediated wheat allergies. A variety of approaches have been manufactured to develop hypoallergenic wheat products that can be consumed by patients with IgE-mediated wheat allergies. In order to analyze such approaches, and to contribute to the further improvement, this study outlined the current status of these hypoallergenic wheat productions, including wheat lines with a reduced allergenicity that are mostly constructed for the patients sensitized to ω5-gliadin, hypoallergenic wheat by enzymic degradation/ion exchanger deamidation, and hypoallergenic wheat by thioredoxin treatment. The wheat products obtained by these approaches significantly reduced the reactivity of Serum IgE in wheat-allergic patients. However, either these were not effective on some populations of the patients, or low-level IgE-reactivity to some allergens of the products was observed in the patients. These results highlight some of the difficulties faced in creating hypoallergenic wheat products or hypoallergenic wheat lines through either traditional breeding or biotechnology approaches in developing hypoallergenic wheat completely safe for all the patients allergic to wheat. | [
"Celiac disease is a food-sensitive enteropathy triggered by the ingestion of wheat gluten proteins and related proteins from barley, rye, and some varieties of oat. There are no interventional therapies and the only solution is a lifelong gluten-free diet. The down-regulation of gliadins by RNAi provides wheat lin... |
Specific and genome-wide effect of mTOR-S6 on translation in pancreatic cancer cells | Pancreatic cancer cells adapt molecular mechanisms to activate the protein synthesis to support tumor growth. This study reports the mTOR inhibitor rapamycin's specific and genome-wide effect on mRNA translation. Using ribosome footprinting in pancreatic cancer cells that lack the expression of 4EBP1, we establish the effect of mTOR-S6-dependent mRNAs translation. Rapamycin inhibits the translation of a subset of mRNAs including p70-S6K and proteins involved in the cell cycle and cancer cell growth. In addition, we identify translation programs that are activated following mTOR inhibition. Interestingly, rapamycin treatment results in the translational activation of kinases that are involved in mTOR signaling such as p90-RSK1. We further show that phospho-AKT1 and phospho-eIF4E are upregulated following mTOR inhibition suggesting a feedback activation of translation by rapamycin. Next, targeting eIF4E and eIF4A-dependent translation by using specific eIF4A inhibitors in combination with rapamycin shows significant growth inhibition in pancreatic cancer cells. In short, we establish the specific effect of mTOR-S6 on translation in cells lacking 4EBP1 and show that mTOR inhibition leads to feedback activation of translation via AKT-RSK1-eIF4E signals. Therefore, targeting translation downstream of mTOR presents a more efficient therapeutic strategy in pancreatic cancer. | [
"PIK3CA and PTEN alterations are common in human cancer, but only a fraction of such tumors are dependent upon AKT signaling. AKT independence is associated with redundant activation of cap-dependent translation mediated by convergent regulation of the translational repressor 4E-BP1 by the AKT and ERK pathways. Thi... |
High-dose methotrexate in primary central nervous system lymphoma: a systematic review | Primary central nervous system lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma that is confined within the CNS. Due to its ability to cross the blood-brain barrier, high-dose methotrexate (HDMTX) is the backbone for induction chemotherapy. This systematic review was conducted to observe outcomes among different HDMTX doses (low, <3 g/m | [
"Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) ... |
Detection and remediation of contaminated water bodies and effluents in the American continent | Currently, water pollution represents a serious environmental threat, causing an impact not only to fauna and flora but also to human health. Among these pollutants, inorganic and organic pollutants are predominantly important representing high toxicity and persistence and being difficult to treat using current methodologies. For this reason, several research groups are searching for strategies to detect and remedy contaminated water bodies and effluents. Due to the above, a current review of the state of the situation has been carried out. The results obtained show that in the American continent a high diversity of contaminants is present in the water bodies affecting several aspects, in which in some cases, there exists alternatives to realize the remediation of contaminated water. It is concluded that the actual challenge is to establish sanitation measures at the local level based on the specific needs of the geographical area of interest. Therefore, water treatment plants must be designed according to the contaminants present in the water of the region and tailored to the needs of the population of interest. | [
"The dominant source of drinking water in rural Nevada, United States, is privately-owned domestic wells. Because the water from these wells is unregulated with respect to government guidelines, it is the owner's responsibility to test their groundwater for heavy metals and other contaminants. Arsenic, lead, cadmiu... |
anthropometric measures as baseline risk factors for cardiovascular disease in type 2 diabetes | In clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D). | [
"To quantify the association of indices of central obesity, including waist circumference, hip circumference, thigh circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, and A body shape index, with the risk of all cause mortality in the general population, and to cla... |
Effects of Physical Therapy on Pain, Frequency, or Duration Management in Adult Patients with Tension-Type Headache | (1) Objective: The aim of this study is to synthesize the effects of physical therapy on pain, frequency, or duration management in the short, medium, and long term in adult patients diagnosed with Tension-type headache (TTH). (2) Background: Tension-type headache (TTH) is the most common headache with migraine and its pathophysiology and treatment has been discussed for years without reaching a consensus. (3) Methods: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered in PROSPERO (CRD42020175020). The systematic search for clinical trials was performed in the databases PubMed, CINAHL, Cochrane Central Register of Controlled Trials, PEDro, Scopus, SciELO and Dialnet. Articles were selected according to the inclusion and exclusion criteria, regarding the effectiveness of physical therapy interventions on adult patients with TTH published in the last 11 years with a score ≥ 6 in the PEDro Scale (Physiotherapy Evidence Database). (4) Results: In total, 120 articles were identified, of which 15 randomized controlled trials were finally included in order to determine the inclusion criteria. Changes in pain intensity, headache frequency or headache duration of individual studies were described (5) Conclusions: This systematic review shows that there is no standardized physical therapy protocol for the approach to tension headache, although all the techniques studied to date address in one way or another the cranio-cervical-mandibular region. The approach to the cranio-cervical-mandibular region reports significant effects in terms of decreasing the intensity of pain and frequency of headache episodes in the short and medium term. More long-term longitudinal studies are needed. | [
"To determine the differences of precipitating and relieving factors between migraine and tension type headache. This is a cross sectional study. We retrospectively reviewed the records of 250 migraine patients and 250 patients diagnosed as tension type headache from the specialized headache clinic in Dept. of Neur... |
Metabolic syndrome among South Asians residing in non-native countries. | South Asians (SAs) are among the fastest-growing ethnic groups in the U.S. Metabolic syndrome (MetS) is a condition that is characterized by multiple health factors that increase the risk for chronic diseases, such as cardiovascular disease (CVD) and diabetes. MetS prevalence among SA immigrants ranges from 27-47% in multiple cross-sectional studies using different diagnostic criteria, which is generally higher compared to other populations in the receiving country. Both genetic and environmental factors are attributed to this increased prevalence. Limited intervention studies have shown effective management of MetS conditions within the SA population. This review reports MetS prevalence in SAs residing in non-native countries, identifies contributing factors, and discusses ways to develop effective community-based strategies for health promotion targeting MetS among SA immigrants. There is a need for more consistently evaluated longitudinal studies to facilitate the development of directed public health policy and education to address chronic diseases in the SA immigrant community. | [
"This study uses US national survey data to characterize trends in the prevalence of metabolic syndrome among adults in the US between 2011 and 2016.",
"The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidativ... |
Structurally distinct aptamers for the Ebola virus glycoprotein gene. | The Ebola virus glycoprotein (GP) gene templates several mRNAs that produce either the virion-associated transmembrane protein or one of two secreted glycoproteins. Soluble glycoprotein (sGP) is the predominant product. GP1 and sGP share an amino terminal sequence of 295 amino acids but differ in quaternary structure, with GP1 being a heterohexamer with GP2 and sGP a homodimer. Two structurally different DNA aptamers were selected against sGP that also bound GP1,2. These DNA aptamers were compared with a 2'FY-RNA aptamer for their interactions with the Ebola GP gene products. The three aptamers have almost identical binding isotherms for sGP and GP1,2 in solution and on the virion. They demonstrated high affinity and selectivity for sGP and GP1,2. Furthermore, one aptamer, used as a sensing element in an electrochemical format, detected GP1,2 on pseudotyped virions and sGP with high sensitivity in the presence of serum, including from an Ebola-virus-infected monkey. Our results suggest that the aptamers interact with sGP across the interface between the monomers, which is different from the sites on the protein bound by most antibodies. The remarkable similarity in functional features of three structurally distinct aptamers suggests that aptamers, like antibodies, have preferred binding sites on proteins. | [
"Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-ce... |
A Comparative Study of Disability Weights in Anhui Province of China | A universal set of disability weights(DWs) is mainly based on the survey of North America, Australia and Europe, whereas the participants in Asia was limited. The debate hasn't yet settled whether a universal DW is desirable or useful.The focus of the debate is its representativenes-s.After all, the DWs come from people's subjective evaluation of pain, and they may vary according to cultural background.The differences of the DWs could have implications for the magnitude or ranking of disease burdens.The DWs of Anhui Province has not been completely presented.This paper aims to obtain the DWs suitable for the general population of Anhui Province of China, and attempts to explore the differences between different DWs by comparing the DWs with the similar-cultural background and the DWs with cross-cultural background. | [
"Cannabis legalization has led to significant health consequences, particularly to patients in emergency departments and hospitals in Colorado. The most concerning include psychosis, suicide, and other substance abuse. Deleterious effects on the brain include decrements in complex decision-making, which may not be ... |
Circular RNA-Based Panel for Early Diagnosis of Chronic Lymphocytic Leukemia | Chronic lymphocytic leukemia (CLL) is a known hematologic malignancy associated with a growing incidence and post-treatment relapse. Hence, finding a reliable diagnostic biomarker for CLL is crucial. Circular RNAs (circRNAs) represent a new class of RNA involved in many biological processes and diseases. This study aimed to define a circRNA-based panel for the early diagnosis of CLL. To this point, the list of the most deregulated circRNAs in CLL cell models was retrieved using bioinformatic algorithms and applied to the verified CLL patients' online datasets as the training cohort ( | [
"To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and ... |
RNA Sequencing Study of Twist1 and Zeb1 in Mycosis Fungoides | The purpose of this RNA sequencing study was to investigate the biological mechanism underlying how the transcription factors (TFs) Twist1 and Zeb1 influence the prognosis of mycosis fungoides (MF). We used laser-captured microdissection to dissect malignant T-cells obtained from 40 skin biopsies from 40 MF patients with stage I-IV disease. Immunohistochemistry (IHC) was used to determinate the protein expression levels of Twist1 and Zeb1. Based on RNA sequencing, principal component analysis (PCA), differential expression (DE) analysis, ingenuity pathway analysis (IPA), and hub gene analysis were performed between the high and low Twist1 IHC expression cases. The DNA from 28 samples was used to analyze the TWIST1 promoter methylation level. In the PCA, Twist1 IHC expression seemed to classify cases into different groups. The DE analysis yielded 321 significant genes. In the IPA, 228 significant upstream regulators and 177 significant master regulators/causal networks were identified. In the hub gene analysis, 28 hub genes were found. The methylation level of TWIST1 promoter regions did not correlate with Twist1 protein expression. Zeb1 protein expression did not show any major correlation with global RNA expression in the PCA. Many of the observed genes and pathways associated with high Twist1 expression are known to be involved in immunoregulation, lymphocyte differentiation, and aggressive tumor biology. In conclusion, Twist1 might be an important regulator in the disease progression of MF. | [
"Like other cancers, renal cell carcinoma (RCC) derives the essential energy for proliferation and survival from high rates of glycolysis rather than from oxidative phosphorylation of the mitochondrial respiration pathway. NDUFA4 (NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex, 4) is encoding a protein belongin... |
Consumers' knowledge, attitudes, and purchasing habits of food products with allergens in Lebanon | The epidemiology of food allergies is increasing worldwide. International labeling standards were developed to enhance consumers' awareness of allergen-free foods. The main objective of the present study is to assess the characteristics of allergen labeling and consumers' knowledge, attitudes, and purchasing habits of food products with allergens in Lebanon. We evaluated the allergen labeling of 1000 food products form Lebanese supermarkets. A random sample of 541 consumers was recruited through an online survey (November 2020-February 2021). Descriptives and regression analysis were conducted. Results showed that wheat represents the largest group of food allergens on food labels, followed by milk and soybean. Furthermore, 42.9% of supermarket food products had a precautionary allergen labeling with "may contain traces of allergens". The majority of food products complied with local regulations for locally manufactured and imported products. One-quarter of survey respondents had a food allergy or were caregivers of food-allergic individuals. Regression analyses showed that "previous experience of a severe reaction" was negatively associated with food allergy-related knowledge and attitude scores respectively ( | [
"Food allergen labeling is an important tool to reduce risk of exposure and prevent anaphylaxis for individuals with food allergies. Health Canada released a Canadian food allergen labeling regulation (2008) and subsequent update (2012) suggesting that research is needed to guide further iterations of the regulatio... |
Stress, Depression, and Neck Disability in Patients with Temporomandibular Disorder-Myofascial Pain with Referral | The etiology of temporomandibular disorders (TMDs) is firmly anchored in the biopsychosocial model in which a special role is attributed to the stress, depression, somatic symptoms, and anxiety. The aim of the study was to assess the level of stress, depression and neck disability in patients with temporomandibular disorder-myofascial pain with referral. The study group enrolled 50 people (37 women and 13 men) with complete natural dentition. All the patients underwent a clinical examination according to the Diagnostic Criteria for Temporomandibular Disorders and were diagnosed as individuals with myofascial pain with referral. The questionnaires were associated with stress, depression, and neck disability; Perceived Stress Scale (PSS-10), Beck Depression Inventory(BDI), and Neck Disability Index (NDI) were evaluated. Of the individuals evaluated, 78% showed elevated levels of stress, and the average value of the PSS-10 in the study group was 18 points (Me = 17). Furthermore, 30% of the subjects presented depressive symptoms, with the average value of BDI was 8.94 points (Me = 8), and 82% of the subjects showed neck disability. The multiple linear regression model revealed that BDI and NDI allowed explanations for the 53% differentiation of PSS-10. In conclusion, stress, depression, and neck disability coexist with temporomandibular disorder-myofascial pain with referral. | [
"The aim of the study was to test whether the definition of depressive mixed states (DMX) in bipolar II disorder should require satisfaction of full criteria for hypomania or if only a few hypomanic symptoms should be required. Consecutive outpatients with bipolar II major depressive episode (MDE) (n=260) were asse... |
Halloysite and sepiolite nanoclays as drug delivery systems | The need for safe, therapeutically effective, and patient-compliant drug delivery systems continuously leads researchers to design novel tools and strategies. Clay minerals are widely used in drug products both as excipients and active agents but, in recent years, there has been a growing interest in research aimed at the development of new organic or inorganic nanocomposites. The attention of the scientific community has been drawn by nanoclays, thanks to their natural origin, worldwide abundance, availability, sustainability, and biocompatibility. In this review, we focused our attention on the studies inherent to the pharmaceutical and biomedical applications of halloysite and sepiolite, and their semi-synthetic or synthetic derivatives, as drug delivery systems. After having described the structure of both materials and their biocompatibility, we delineate the use of the nanoclays to enhance the stability, the controlled release, the bioavailability, and the adsorption properties of drugs. Several types of surface functionalization have been discussed, showing that these materials could be used for the development of an innovative therapeutic approach. | [
"Halloysite, naturally occurring clay nanotubes, is described as an additive for functional polymer composites. Due to the empty tubular lumen capable of being loaded with chemically active agents, halloysite provides additional functions (drug delivery, antibiotic, flame-retardant, anticorrosion, and crack self-he... |
Metabolomics and metabolome-microbiome analysis of human gut microbiota in patients with metabolic-related diseases | Human gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health-disease balance. Recent metabolomics and combined metabolome-microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., | [
"In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found sign... |
Mitochondrial oxidative metabolism is not required for astrocyte survival and proliferation | Understanding the role of astrocytes in the development of the nervous system and neurodegenerative disorders implies a necessary knowledge of the oxidative metabolism of proliferating astrocytes. The electron flux through mitochondrial respiratory complexes and oxidative phosphorylation may impact the growth and viability of these astrocytes. Here, we aimed at assessing to which extent mitochondrial oxidative metabolism is required for astrocyte survival and proliferation. Primary astrocytes from the neonatal mouse cortex were cultured in a physiologically relevant medium with the addition of piericidin A or oligomycin at concentrations that fully inhibit complex I-linked respiration and ATP synthase, respectively. The presence of these mitochondrial inhibitors for up to 6 days in a culture medium elicited only minor effects on astrocyte growth. Moreover, neither the morphology nor the proportion of glial fibrillary acidic protein-positive astrocytes in culture was affected by piericidin A or oligomycin. Metabolic characterization of the astrocytes showed a relevant glycolytic metabolism under basal conditions, despite functional oxidative phosphorylation and large spare respiratory capacity. Our data suggest that astrocytes in primary culture can sustainably proliferate when their energy metabolism relies only on aerobic glycolysis since their growth and survival do not require electron flux through respiratory complex I or oxidative phosphorylation. | [
"As the result of genetic alterations and tumor hypoxia, many cancer cells avidly take up glucose and generate lactate through lactate dehydrogenase A (LDHA), which is encoded by a target gene of c-Myc and hypoxia-inducible factor (HIF-1). Previous studies with reduction of LDHA expression indicate that LDHA is inv... |
is corticosteroid resistant to sepsis? | Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients' response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids. | [
"The survival benefit of corticosteroids in septic shock remains uncertain. To estimate the individual treatment effect (ITE) of corticosteroids in adults with septic shock in intensive care units using machine learning and to evaluate the net benefit of corticosteroids when the decision to treat is based on the in... |
Sex Differences in Musculoskeletal Pain Disorders | Musculoskeletal (MSK) pain disorders are some of the most prevalent and disabling chronic pain conditions worldwide. These chronic conditions have a considerable impact on the quality of life of individuals, families, communities, and healthcare systems. Unfortunately, the burden of MSK pain disorders does not fall equally across the sexes. Females consistently demonstrate more prevalent and severe clinical presentations of MSK disorders, and this disparity increases in magnitude with age. The aim of the present article is to review recent studies that have examined sex differences between males and females in four of the most common MSK pain disorders: neck pain, low back pain, osteoarthritis, and rheumatoid arthritis. | [
"Globally, chronic low back pain (CLBP) is the leading cause of disability associated with economic costs. However, it has received little attention in low-and-middle-income countries. This study estimated the prevalence and risk factors of CLBP among adults presenting at selected hospitals in KwaZulu-Natal. This c... |
Aortic pressure decreases immediately after annular contact by a self-expanding transcatheter heart valve | During the transcatheter aortic valve replacement (TAVR) procedure, hemodynamic measurements can be used to evaluate transcatheter heart valve (THV) performance. We hypothesized that the occurrence of a significant decrease in invasive aortic pressure immediately after annular contact by a self-expanding THV indicates effective annular sealing. This phenomenon could thus be used as a marker for the occurrence of paravalvular leak (PVL). | [
"Acute deterioration in renal function is a recognized complication after coronary angiography and intervention. The goal of this study was to determine the impact on acute and long-term mortality and morbidity of contrast-induced deterioration in renal function after coronary intervention. We studied 439 consecuti... |
[Pulmonary arterial hypertension and pregnancy]. | Pulmonary arterial hypertension (PAH) is defined as an elevated mean pulmonary artery pressure (mPAP) of >20 mmHg together with a pulmonary arterial wedge pressure (PAWP) of ≤15 mmHg and pulmonary vascular resistance (PVR) of>2 Wood units (WU). Although the total mortality of pregnant women with PAH has decreased significantly in recent years and is reported to be around 12% in some databases, total mortality is still at an unacceptably high percentage. Moreover, some subgroups, such as patients with Eisenmenger's syndrome, have a particularly high mortality rate of up to 36%. Pregnancy in patients with PAH is contraindicated; its appearance is an indication for a planned termination. Education of patients with PAH, including counseling on effective contraception, is essential. During pregnancy, blood volume, heart rate, and cardiac output increase, while PVR and systemic vascular resistance decrease. The hemostatic balance is shifted towards hypercoagulability. Among PAH-specific drugs, the use of inhaled or intravenous prostacyclins, phosphodiesterase inhibitors, and calcium channel blockers (in patients with preserved vasoreactivity) is acceptable. Endothelin receptor antagonists and riociguat are contraindicated. Childbirth can take place through either vaginal delivery or caesarean section; similarly, neuraxial and general anesthesia have proven indications. In a situation where all pharmacological options have been used in pregnant or postpartum patients in a serious condition, veno-arterial ECMO is a useful therapeutic option. For PAH patients who want to become mothers, an option that does not endanger their lives is adoption. | [
"The U. S. Selected Practice Recommendations for Contraceptive Use 2013 (U.S. SPR), comprises recommendations that address a select group of common, yet sometimes controversial or complex, issues regarding initiation and use of specific contraceptive methods. These recommendations are a companion document to the pr... |
Conformation-biased mutants of adenosine A adenosine A receptor | Understanding the roles of intermediate states in signaling is pivotal to unraveling the activation processes of G protein-coupled receptors (GPCRs). However, the field is still struggling to define these conformational states with sufficient resolution to study their individual functions. Here, we demonstrate the feasibility of enriching the populations of discrete states via conformation-biased mutants. These mutants adopt distinct distributions among five states that lie along the activation pathway of adenosine A | [
"G protein-coupled receptors (GPCRs) form both the largest family of membrane proteins and drug targets, mediating the action of one-third of medicines. The GPCR database, GPCRdb serves >4 000 researchers every month and offers reference data, analysis of own or literature data, experiment design and dissemination ... |
Acute phase ceftazidime therapy in the murine model of inhalation melioidosis. | Melioidosis is an endemic disease in numerous tropical regions. Additionally, the bacterium that causes melioidosis, Burkholderia pseudomallei, has potential to be used as a biological weapon. Therefore, development of effective and affordable medical countermeasures to serve regions affected by the disease and to have medical countermeasures available in the event of a bioterrorism attack remains critical. The current study evaluated the efficacy of eight distinct acute phase ceftazidime treatment regimens administered therapeutically in the murine model. At the conclusion of the treatment period, survival rates were significantly greater in several of the treated groups when compared to the control group. Pharmacokinetics of a single dose of ceftazidime were examined at 150 mg/kg, 300 mg/kg, and 600 mg/kg and were compared to an intravenous clinical dose administered at 2000 mg every eight hours. The clinical dose has an estimated 100% fT > 4*MIC which exceeded the highest murine dose of 300 mg/kg every six hours at 87.2% fT > 4*MIC. Based upon survival at the end of the treatment regimen and supplemented by pharmacokinetic modeling, a daily dose of 1200 mg/kg of ceftazidime, administered every 6 h at 300 mg/kg, provides protection in the acute phase of inhalation melioidosis in the murine model. | [
"Although CpG oligodeoxynucleotides (CpG ODNs) are known to enhance resistance against infection in a number of animal models, little is known about the CpG-induced protection against acute fatal sepsis such as that associated with the highly virulent bacterium Burkholderia pseudomallei. We previously demonstrated ... |
Identification of Malate Dehydrogenase Genes in Chinese Fir | Malate dehydrogenase (MDH) genes play vital roles in developmental control and environmental stress tolerance in sessile plants by modulating the organic acid-malic acid level. However, MDH genes have not yet been characterized in gymnosperm, and their roles in nutrient deficiency are largely unexplored. In this study, 12 MDH genes were identified in Chinese fir ( | [
"Sunflower occupies the fourth position among oilseed crops the around the world. Eceriferum (CER) is an important gene family that plays critical role in very-long-chain fatty acids elongation and biosynthesis of epicuticular waxes under both biotic and abiotic stress conditions. The aim of present study was to in... |
Role of Cluster of differentiation 47 in neointimal hyperplasia | Cluster of differentiation 47 (CD47) plays an important role in the pathophysiology of various diseases including atherosclerosis but its role in neointimal hyperplasia which contributes to restenosis has not been studied. Using molecular approaches in combination with a mouse vascular endothelial denudation model, we studied the role of CD47 in injury-induced neointimal hyperplasia. We determined that thrombin-induced CD47 expression both in human aortic smooth muscle cells (HASMCs) and mouse aortic smooth muscle cells. In exploring the mechanisms, we found that the protease-activated receptor 1-Gα protein q/11 (Gαq/11)-phospholipase Cβ3-nuclear factor of activated T cells c1 signaling axis regulates thrombin-induced CD47 expression in HASMCs. Depletion of CD47 levels using its siRNA or interference of its function by its blocking antibody (bAb) blunted thrombin-induced migration and proliferation of HASMCs and mouse aortic smooth muscle cells. In addition, we found that thrombin-induced HASMC migration requires CD47 interaction with integrin β3. On the other hand, thrombin-induced HASMC proliferation was dependent on CD47's role in nuclear export and degradation of cyclin-dependent kinase-interacting protein 1. In addition, suppression of CD47 function by its bAb rescued HASMC efferocytosis from inhibition by thrombin. We also found that vascular injury induces CD47 expression in intimal SMCs and that inhibition of CD47 function by its bAb, while alleviating injury-induced inhibition of SMC efferocytosis, attenuated SMC migration, and proliferation resulting in reduced neointima formation. Thus, these findings reveal a pathological role for CD47 in neointimal hyperplasia. | [
"We have characterized matrix metalloproteinase expression in the rat carotid artery after two forms of arterial injury, balloon catheter denudation and nylon filament denudation. Gelatinolytic enzymes with molecular masses of 70 and 62 kD were produced constitutively in the rat carotid. Production of an 88-kD gela... |
Automated extraction of features from candidemia and/or bacteremia episodes for the first phase of the AUTO-CAND project | There is increasing interest in assessing whether machine learning (ML) techniques could further improve the early diagnosis of candidemia among patients with a consistent clinical picture. The objective of the present study is to validate the accuracy of a system for the automated extraction from a hospital laboratory software of a large number of features from candidemia and/or bacteremia episodes as the first phase of the AUTO-CAND project. The manual validation was performed on a representative and randomly extracted subset of episodes of candidemia and/or bacteremia. The manual validation of the random extraction of 381 episodes of candidemia and/or bacteremia, with automated organization in structured features of laboratory and microbiological data resulted in ≥99% correct extractions (with confidence interval < ±1%) for all variables. The final automatically extracted dataset consisted of 1338 episodes of candidemia (8%), 14,112 episodes of bacteremia (90%), and 302 episodes of mixed candidemia/bacteremia (2%). The final dataset will serve to assess the performance of different ML models for the early diagnosis of candidemia in the second phase of the AUTO-CAND project. | [
"Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States. Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbio... |
Microglia in a Tri-Culture of Primary Rat Neurons, Astrocytes, and Microglia | Neuroinflammation plays a central role in many neurological disorders, ranging from traumatic brain injuries to neurodegeneration. Electrophysiological activity is an essential measure of neuronal function, which is influenced by neuroinflammation. In order to study neuroinflammation and its electrophysiological fingerprints, there is a need for in vitro models that accurately capture the in vivo phenomena. In this study, we employed a new tri-culture of primary rat neurons, astrocytes, and microglia in combination with extracellular electrophysiological recording techniques using multiple electrode arrays (MEAs) to determine the effect of microglia on neural function and the response to neuroinflammatory stimuli. Specifically, we established the tri-culture and its corresponding neuron-astrocyte co-culture (lacking microglia) counterpart on custom MEAs and monitored their electrophysiological activity for 21 days to assess culture maturation and network formation. As a complementary assessment, we quantified synaptic puncta and averaged spike waveforms to determine the difference in excitatory to inhibitory neuron ratio (E/I ratio) of the neurons. The results demonstrate that the microglia in the tri-culture do not disrupt neural network formation and stability and may be a better representation of the in vivo rat cortex due to its more similar E/I ratio as compared to more traditional isolated neuron and neuron-astrocyte co-cultures. In addition, only the tri-culture displayed a significant decrease in both the number of active channels and spike frequency following pro-inflammatory lipopolysaccharide exposure, highlighting the critical role of microglia in capturing electrophysiological manifestations of a representative neuroinflammatory insult. We expect the demonstrated technology to assist in studying various brain disease mechanisms. | [
"Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the ... |
Intestinal microbiota and Huntington's disease | The human intestinal microbiota is a diverse and dynamic microenvironment that forms a complex, bi-directional relationship with the host. The microbiome takes part in the digestion of food and the generation of crucial nutrients such as short chain fatty acids (SCFA), but is also impacts the host's metabolism, immune system, and even brain functions. Due to its indispensable role, microbiota has been implicated in both the maintenance of health and the pathogenesis of many diseases. Dysbiosis in the gut microbiota has already been implicated in many neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). However, not much is known about the microbiome composition and its interactions in Huntington's disease (HD). This dominantly heritable, incurable neurodegenerative disease is caused by the expansion of CAG trinucleotide repeats in the huntingtin gene ( | [
"Huntington's disease is an inherited neurodegenerative disease described 150 years ago by George Huntington. The genetic defect was identified in 1993 to be an expanded CAG repeat on exon 1 of the huntingtin gene located on chromosome 4. In the following almost 30 years, a considerable amount of research, using ma... |
Strategies and mechanisms of induced pluripotent stem cell-derived small extracellular vesicles in the treatment of myocardial injury | Induced pluripotent stem cell (iPSC) therapy brings great hope to the treatment of myocardial injuries, while extracellular vesicles may be one of the main mechanisms of its action. iPSC-derived small extracellular vesicles (iPSCs-sEVs) can carry genetic and proteinaceous substances and mediate the interaction between iPSCs and target cells. In recent years, more and more studies have focused on the therapeutic effect of iPSCs-sEVs in myocardial injury. IPSCs-sEVs may be a new cell-free-based treatment for myocardial injury, including myocardial infarction, myocardial ischemia-reperfusion injury, coronary heart disease, and heart failure. In the current research on myocardial injury, the extraction of sEVs from mesenchymal stem cells induced by iPSCs was widely used. Isolation methods of iPSCs-sEVs for the treatment of myocardial injury include ultracentrifugation, isodensity gradient centrifugation, and size exclusion chromatography. Tail vein injection and intraductal administration are the most widely used routes of iPSCs-sEV administration. The characteristics of sEVs derived from iPSCs which were induced from different species and organs, including fibroblasts and bone marrow, were further compared. In addition, the beneficial genes of iPSC can be regulated through CRISPR/Cas9 to change the composition of sEVs and improve the abundance and expression diversity of them. This review focused on the strategies and mechanisms of iPSCs-sEVs in the treatment of myocardial injury, which provides a reference for future research and the application of iPSCs-sEVs. | [
"Bone defects caused by trauma, severe infection, tumor resection and skeletal abnormalities are common osteoporotic conditions and major challenges in orthopedic surgery, and there is still no effective solution to this problem. Consequently, new treatments are needed to develop regeneration procedures without sid... |
Why addressing lifestyle factors within cancer care is so important | A significant proportion of cancers could be prevented by adopting healthy lifestyle behaviours. In addition, healthy lifestyle factors can have a positive impact on cancer outcomes and survival. Yet, most physicians, including oncologists, do not dedicate a significant amount of time addressing these factors with their patients, who instead look to mainstream media and other non-medical sources for information. This has led to an increase in the number of 'influencers' in the wellness space who can accumulate a large and captive audience. At times, this has caused friction amongst healthcare professionals who feel that 'influencers' may overstate the potential benefits. The reality is that most people, physicians and the public alike, fail to recognise the immense power that lifestyle interventions hold. Rather than shy away from addressing these issues, we should be empowering our patients to take back control over their health. Here, we provide a personal perspective on why addressing lifestyle factors within cancer care is so important and that we can indeed work together with 'influencers' to amplify the message. | [
"This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new... |
Vitamin D receptor expression and insulin-like growth factor 1 receptor activation in breast cancer | Vitamin D receptor (VDR) and insulin-like growth factor 1 receptor (IGF1R) are known to be involved in breast cancer (BC) progression. Our previous work reported a correlation of differential localization of IGF1R with hormone receptor status in BC. A recent report described VDR and IGF1R as potential indicators of BC prognosis, but their interplay was not discussed. The present study focused on understanding the association of VDR expression with IGF1R activation, different molecular markers, and subtypes of BC. | [
"The nuclear receptor for 1α,25-dihydroxycholecalciferol (1,25D), the active form of vitamin D, has anti-tumor actions in many tissues. The vitamin D receptor (VDR) is expressed in normal mammary gland and in many human breast cancers suggesting it may represent an important tumor suppressor gene in this tissue. Wh... |
Drosophila fibroblast growth factor receptor heartless signaling disrupts glial phagocytosis of apoptotic neurons | Glial phagocytosis of apoptotic neurons is crucial for development and proper function of the central nervous system. Relying on transmembrane receptors located on their protrusions, phagocytic glia recognize and engulf apoptotic debris. Like vertebrate microglia, Drosophila phagocytic glial cells form an elaborate network in the developing brain to reach and remove apoptotic neurons. However, the mechanisms controlling creation of the branched morphology of these glial cells critical for their phagocytic ability remain unknown. Here, we demonstrate that during early embryogenesis, the Drosophila fibroblast growth factor receptor (FGFR) Heartless (Htl) and its ligand Pyramus are essential in glial cells for the formation of glial extensions, the presence of which strongly affects glial phagocytosis of apoptotic neurons during later stages of embryonic development. Reduction in Htl pathway activity results in shorter lengths and lower complexity of glial branches, thereby disrupting the glial network. Our work thus illuminates the important role Htl signaling plays in glial subcellular morphogenesis and in establishing glial phagocytic ability. | [
"The glial cells missing (gcm) gene in Drosophila encodes a novel nuclear protein that is transiently expressed early in the development of nearly all glia. In loss-of-function gcm mutant alleles, nearly all glia fail to differentiate, and, where we can follow them in the PNS, are transformed into neurons. In gain-... |
Expression of epithelial-to-mesenchymal transition-associated markers in mammary tumors of humans, dogs, and cats | Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties. EMT has been closely associated with cancer cell aggressiveness. The aim of this study was to evaluate the mRNA and protein expression of EMT-associated markers in mammary tumors of humans (HBC), dogs (CMT), and cats (FMT). Real-time qPCR for | [
"Downregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression. Using the EpFosER mammary tumour model we show that during EMT, upregulation of the transcriptional regulator deltaEF1 coincided with transcriptional repression of E-cadhe... |
Pathophysiological mechanism of 7,25-dihydroxycholesterol in osteoarthritis pathogenesis | This study aimed to exploring the pathophysiological mechanism of 7α,25-dihydroxycholesterol (7α,25-DHC) in osteoarthritis (OA) pathogenesis. 7α,25-DHC accelerated the proteoglycan loss in | [
"Cholesterol plays an important role in cellular homeostasis by maintaining the rigidity of cell membranes, providing a medium for signaling transduction, and being converted into other vital macromolecules, such as sterol hormones and bile acids. Epidemiological studies have shown the correlation between cholester... |
Complete Genome Sequence and Comparative Genotypic Analysis of Burkholderia contaminans SK875 | The Burkholderia cepacia complex (BCC) is a Gram-negative bacterial, including Burkholderia contaminans species. Although the plain Burkholderia is pervasive from taxonomic and genetic perspectives, a common characteristic is that they may use the quorum-sensing (QS) system. In our previous study, we generated the complete genome sequence of Burkholderia contaminans SK875 isolated from the respiratory tract. To our knowledge, this is the first study to report functional genomic features of B. contaminans SK875 for understanding the pathogenic characteristics. In addition, comparative genomic analysis for five B. contaminans genomes was performed to provide comprehensive information on the disease potential of B. contaminans species. Analysis of average nucleotide identity (ANI) showed that the genome has high similarity (> 96%) with other B. contaminans strains. Five B. contaminans genomes yielded a pangenome of 8832 coding genes, a core genome of 5452 genes, the accessory genome of 2128 genes, and a unique genome of 1252 genes. The 186 genes were specific to B. contaminans SK875, including toxin higB-2, oxygen-dependent choline dehydrogenase, and hypothetical proteins. Genotypic analysis of the antimicrobial resistance of B. contaminans SK875 verified resistance to tetracycline, fluoroquinolone, and aminoglycoside. Compared with the virulence factor database, we identified 79 promising virulence genes such as adhesion system, invasions, antiphagocytic, and secretion systems. Moreover, 45 genes of 57 QS-related genes that were identified in B. contaminans SK875 indicated high sequence homology with other B. contaminans strains. Our results will help to gain insight into virulence, antibiotic resistance, and quorum sensing for B. contaminans species. | [
"Burkholderia sp. is a gram-negative bacterium that commonly exists in the environment, and can cause diseases in plants, animals, and humans. Here, a transposon mutant library of a Burkholderia lata isolate from a pig with swine respiratory disease in Korea was screened for strains showing attenuated virulence in ... |
Incidence and predictors of mortality among adult trauma patients admitted to intensive care units in Ethiopia | Trauma is the leading cause of morbidity and mortality among adult population in the world. Despite many improvements in technology and care, mortality among trauma patients in the intensive care unit is still high particularly in Ethiopia. However, there is limited evidence on the incidence and predictors of mortality among trauma patients in Ethiopia. Therefore, this study aimed to assess the incidence and predictors of mortality among adult trauma patients admitted to intensive care units. | [
"Surgical critical care is crucial to the care of trauma and surgical patients. This study was designed to provide a contemporary assessment of patient types, injuries, and conditions in intensive care units (ICU) caring for trauma patients. This was a multicenter prevalence study of the American Association for th... |
Serum electrolytes and acute kidney injury: a review | Acute kidney injury (AKI) affects up to 30% of all hospitalized patients in Central Europe and the USA. New biomarker molecules have been identified in recent years; most studies performed so far however aimed to identify markers for diagnostic purposes. Serum electrolytes such as sodium and potassium are quantified in more or less all hospitalized patients. Aim of the article is to review the literature on the AKI predictive role of four distinct serum electrolytes in evolving/progressing AKI. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, and Scopus. The period lasted from 2010 until 2022. The following terms were utilized: "AKI" AND "sodium" OR "potassium" OR "calcium" OR "phosphate" AND "risk" OR "dialysis" OR "recovery of kidney function" OR "renal recovery" OR "kidney recovery" OR "outcome". Finally, 17 references were selected. The included studies were mostly retrospective in nature. Particularly, hyponatremia has been shown to be associated with an overall poor clinical outcome. The association between dysnatremia and AKI is anything but consistent. Hyperkalemia and potassium variability are most likely AKI predictive. Serum calcium and AKI risk are associated in a U-shaped manner. Higher phosphate levels potentially predict AKI in non-coronavirus disease 2019 (COVID-19) patients. The literature suggests that admission electrolytes can offer valuable information about AKI onset during follow-up. Limited data are however available on follow-up characteristics such as the need for dialysis or the chance of renal recovery. These aspects are of particular interest from the nephrologist's perspective. | [
"The burden of AKI around the globe has not been systematically examined. A systematic review (2004-2012) of large cohort studies was conducted to estimate the world incidence of AKI and its stages of severity and associated mortality, and to describe geographic variations according to countries, regions, and their... |
The Repair Effects of the Repair Efficacy of a Multi-Agent System in a Multi-Agent System | This study evaluated the repair effects of | [
"Gut microbiota and their major metabolites, short-chain fatty acids (SCFAs), are recognized as important players in gut homeostasis and metabolic disease occurance. A convenient and sensitive detection method is needed to profile SCFAs in limited and complex biological samples. The gas chromatography/mass spectrom... |
Shigellosis in Low- and Middle-Income Countries (LMICs) | Shigellosis causes more than 200,000 deaths worldwide and most of this burden falls on Low- and Middle-Income Countries (LMICs), with a particular incidence in children under 5 years of age. In the last decades, | [
"The burden of shigellosis is greatest in resource-poor countries. Although this diarrheal disease has been thought to cause considerable morbidity and mortality in excess of 1,000,000 deaths globally per year, little recent data are available to guide intervention strategies in Asia. We conducted a prospective, po... |
Radiomics analysis as an adjuvant tool in the prognosis of disability after stroke | Stroke is a leading cause of disability and mortality, resulting in substantial socio-economic burden for healthcare systems. With advances in artificial intelligence, visual image information can be processed into numerous quantitative features in an objective, repeatable and high-throughput fashion, in a process known as radiomics analysis (RA). Recently, investigators have attempted to apply RA to stroke neuroimaging in the hope of promoting personalized precision medicine. This review aimed to evaluate the role of RA as an adjuvant tool in the prognosis of disability after stroke. We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase using the keywords: 'magnetic resonance imaging (MRI)', 'radiomics', and 'stroke'. The PROBAST tool was used to assess the risk of bias. Radiomics quality score (RQS) was also applied to evaluate the methodological quality of radiomics studies. Of the 150 abstracts returned by electronic literature research, 6 studies fulfilled the inclusion criteria. Five studies evaluated predictive value for different predictive models (PMs). In all studies, the combined PMs consisting of clinical and radiomics features have achieved the best predictive performance compared to PMs based only on clinical or radiomics features, the results varying from an area under the ROC curve (AUC) of 0.80 (95% CI, 0.75-0.86) to an AUC of 0.92 (95% CI, 0.87-0.97). The median RQS of the included studies was 15, reflecting a moderate methodological quality. Assessing the risk of bias using PROBAST, potential high risk of bias in participants selection was identified. Our findings suggest that combined models integrating both clinical and advanced imaging variables seem to better predict the patients' disability outcome group (favorable outcome: modified Rankin scale (mRS) ≤ 2 and unfavorable outcome: mRS > 2) at three and six months after stroke. Although radiomics studies' findings are significant in research field, these results should be validated in multiple clinical settings in order to help clinicians to provide individual patients with optimal tailor-made treatment. | [
"Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and sha... |
Prevalence, indications, and outcome of operative vaginal delivery in sub-Saharan Africa | This systematic review and meta-analysis is intended to assess the prevalence, indications, and fetal outcome of operative vaginal delivery in sub-Saharan Africa. | [
"Operative vaginal delivery refers to the use of measures to accomplish vaginal delivery through the use of instruments, mainly obstetric forceps and vacuum cups. In developed countries, the rate of cesarean section is increasing for fear of vaginal delivery complications, including instrumental delivery. This stud... |
Memory-guided decision-making in rat medial prefrontal cortex and dorsal hippocampal CA1 | Short-term memory enables incorporation of recent experience into subsequent decision-making. This processing recruits both the prefrontal cortex and hippocampus, where neurons encode task cues, rules, and outcomes. However, precisely which information is carried when, and by which neurons, remains unclear. Using population decoding of activity in rat medial prefrontal cortex (mPFC) and dorsal hippocampal CA1, we confirm that mPFC populations lead in maintaining sample information across delays of an operant non-match to sample task, despite individual neurons firing only transiently. During sample encoding, distinct mPFC subpopulations joined distributed CA1-mPFC cell assemblies hallmarked by 4-5 Hz rhythmic modulation; CA1-mPFC assemblies re-emerged during choice episodes but were not 4-5 Hz modulated. Delay-dependent errors arose when attenuated rhythmic assembly activity heralded collapse of sustained mPFC encoding. Our results map component processes of memory-guided decisions onto heterogeneous CA1-mPFC subpopulations and the dynamics of physiologically distinct, distributed cell assemblies. | [
"Correlated activity in cortico-basal ganglia circuits plays a key role in the encoding of movement, associative learning and procedural memory. How correlated activity is assembled by striatal microcircuits is not understood. Calcium imaging of striatal neuronal populations, with single-cell resolution, reveals sp... |
DNA alkylation adducts and DNA translesion synthesis | Nitrosamines occur widespread in food, drinking water, cosmetics, as well as tobacco smoke and can arise endogenously. More recently, nitrosamines have been detected as impurities in various drugs. This is of particular concern as nitrosamines are alkylating agents that are genotoxic and carcinogenic. We first summarize the current knowledge on the different sources and chemical nature of alkylating agents with a focus on relevant nitrosamines. Subsequently, we present the major DNA alkylation adducts induced by nitrosamines upon their metabolic activation by CYP450 monooxygenases. We then describe the DNA repair pathways engaged by the various DNA alkylation adducts, which include base excision repair, direct damage reversal by MGMT and ALKBH, as well as nucleotide excision repair. Their roles in the protection against the genotoxic and carcinogenic effects of nitrosamines are highlighted. Finally, we address DNA translesion synthesis as a DNA damage tolerance mechanism relevant to DNA alkylation adducts. | [
"N3-Methyladenine (3-MeA) is formed in DNA by reaction with S-adenosylmethionine, the reactive methyl donor, and by reaction with alkylating agents. 3-MeA protrudes into the DNA minor groove and strongly blocks synthesis by replicative DNA polymerases (Pols). However, the mechanisms for replicating through this les... |
Prevalence of vitamin D deficiency/insufficiency in hospitalized patients in Romania | Vitamin D deficiency is one of the most common medical conditions, with approximately one billion people having low vitamin D levels. Vitamin D is associated with a pleiotropic effect (immunomodulatory, anti-inflammatory and antiviral), which can be essential for a better immune response. The aim of this research was to evaluate the prevalence of vitamin D deficiency/insufficiency in hospitalized patients focusing on demographic parameters as well as assessing the possibility of its associations with different comorbidities. Of 11,182 Romanian patients evaluated in the study over 2 years, 28.83% had vitamin D deficiency, 32.11% insufficiency and 39.05% had optimal vitamin D levels. The vitamin D deficiency was associated with cardiovascular disorders, malignancies, dysmetabolic disorders and SARS-CoV2 infection, older age and the male sex. Vitamin D deficiency was prevalent and showed pathology association, while insufficiency of vitamin D (20-30 ng/mL) had lower statistical relevance and represents a grey zone in vitamin D status. Guidelines and recommendations are necessary for homogeneity of the monitoring and management of inadequately vitamin D status in the risk categories. | [
"To heighten awareness of the problems related to the high prevalence of suboptimal vitamin D status in hospitalized patients and the general population, including an overview of vitamin D biology, how vitamin D status is defined, the negative health issues associated with suboptimal vitamin D status, indications f... |
Effect of silicon on Cd accumulation and its physiological characteristics | Soil Cadmium (Cd) pollution has become a serious environmental problem. Silicon (Si) plays key roles in alleviating Cd toxicity in plants. However, the effects of Si on mitigation of Cd toxicity and accumulation of Cd by hyperaccumulators are largely unknown. This study was conducted to investigate the effect of Si on Cd accumulation and the physiological characteristics of Cd hyperaccumulator | [
"Silicon (Si), although not considered as an essential element for plants in general, can ameliorate the phytotoxicity induced by excess metal(loid)s whether non-essential (e.g. Cd, Pb, Cr, Al, As, and Sb) or essential (e.g. Cu, Ni, and Zn). The Si-enhanced resistance allowing plants to cope with this type of abiot... |
Effects of air pollution on metabolic dysfunction in mice | Air pollution has emerged as an unexpected risk factor for diabetes. However, the mechanism behind remains ill-defined. So far, the lung has been considered as the main target organ of air pollution. In contrast, the gut has received little scientific attention. Since air pollution particles can reach the gut after mucociliary clearance from the lungs and through contaminated food, our aim was to assess whether exposure deposition of air pollution particles in the lung or the gut drive metabolic dysfunction in mice. | [
"Large population cohort studies have indicated an association between exposure to particulate matter and cardiopulmonary morbidity and mortality. The inhalation of toxic environmental particles and gases impacts the innate and adaptive defense systems of the lung. Lung macrophages play a critically important role ... |
The Braverman Nature Assessment and Exercise Behavior | The Braverman Nature Assessment (BNA) is intended to determine the dominant monoamine neurochemical that drives an individual's temperament and behavior. The measure has been colloquially praised for the ability to determine the most effective exercise protocols for an individual based on their "dominant nature." This study seeks to examine the proposed relationship between the Braverman Natures and exercise behavior. Seventy-three adults (57 females) between ages 18-65 (mean = 26 years) completed an online survey consisting of the BNA, Big Five Personality Inventory (BFI), and Aerobics Center Longitudinal Study Physical Activity Questionnaire (ACLSPAQ). All Natures showed significant correlations to unique sets of personality traits (BFI). Dopamine and Serotonin Nature scores (via BNA) showed positive correlations to total physical activity (PA)measures. Serotonin Nature had positive correlation with participation in resistance exercise ( | [
"Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity, and coordinates firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical... |
Intramedullary spinal anaplastic ganglioglioma | Gangliogliomas (GGs) are rare tumors of the central nervous system composed of neoplastic neural and glial cells and are typically low-grade. Intramedullary spinal anaplastic GGs (AGG) are rare, poorly understood, and often aggressive tumors that can result in widespread progression along the craniospinal axis. Due to the rarity of these tumors, data are lacking to guide clinical and pathologic diagnosis and standard of care treatment. Here, we present a case of pediatric spinal AGG to provide information on our institutional approach to work-up and to highlight unique molecular pathology. | [
"Gangliogliomas are rare, low-grade intra-axial tumors that exhibit both neuronal and glial components. Although the vast majority present as an intracranial lesion, a rare subset exist as isolated lesions of the spinal cord. Gangliogliomas have also been shown to harbor mutations in the p53 tumor suppressor gene a... |
Myelin integrity in brain donors exposed to repetitive head impacts from American football. | American football players and other individuals exposed to repetitive head impacts can exhibit a constellation of later-life cognitive and neuropsychiatric symptoms. While tau-based diseases such as chronic traumatic encephalopathy can underpin certain symptoms, contributions from non-tau pathologies from repetitive head impacts are increasingly recognized. We examined cross-sectional associations between myelin integrity using immunoassays for myelin-associated glycoprotein and proteolipid protein 1 with risk factors and clinical outcomes in brain donors exposed to repetitive head impacts from American football. Immunoassays for myelin-associated glycoprotein and proteolipid protein 1 were conducted on dorsolateral frontal white matter tissue samples of 205 male brain donors. Proxies of exposure to repetitive head impacts included years of exposure and age of first exposure to American football play. Informants completed the Functional Activities Questionnaire, Behavior Rating Inventory of Executive Function-Adult Version (Behavioral Regulation Index), and Barratt Impulsiveness Scale-11. Associations between myelin-associated glycoprotein and proteolipid protein 1 with exposure proxies and clinical scales were tested. Of the 205 male brain donors who played amateur and professional football, the mean age was 67.17 (SD = 16.78), and 75.9% ( | [
"Cerebrospinal fluid (CSF) protein analysis may facilitate detection and elucidate mechanisms of neurological consequences from repetitive head impacts (RHI), such as chronic traumatic encephalopathy. We examined CSF concentrations of total tau (t-tau), phosphorylated tau, and amyloid β1-42 and their association wi... |
UV-induced skin photoaging: cellular and molecular mechanisms and mechanistic insights | Skin areas exposed to ultraviolet radiation (UV) from sunlight are more prone to photoaging than unexposed areas evidenced by several signs which include skin dryness, irregular pigmentation, lentigines, hyperpigmentation, wrinkling, and decreased elasticity. Plant-based natural product ingredients with therapeutic potential against skin photoaging are gaining more attention. This article aims the reviewing the research work done in exploring the cellular and molecular mechanisms involved in UV-induced skin photoaging, followed by summarizing the mechanistic insights involved in its therapeutics by natural product-based ingredients. In the mechanistic section of the convoluted procedure of photoaging, we described the effect of UV radiation (UVR) on different cellular macromolecules (direct damage) and subsequently, the deleterious consequences of UVR-generated reactive oxygen species (indirect damage) and signaling pathways activated or inhibited by UV induced ROS generation in various cellular pathologies of skin photoaging like inflammation, extracellular matrix degradation, apoptosis, mitochondrial dysfunction, and immune suppression. We also discussed the effect of UV radiation on the adipose tissue, and transient receptor potential cation channel V of photoaging skin. In the past few decades, mechanistic studies performed in this area have deciphered various therapeutic targets, opening avenues for different available therapeutic options against this pathological condition. So the remaining portion of the review deals with various natural product-based therapeutic agents available against skin photodamage. | [
"In our investigations towards the isolation of potentially biologically active constituents from Orchidaceae, we carried out phytochemical and biological analyses of Vanda species. A preliminary biological screening revealed that Vanda coerulea (Griff. ex. Lindl) crude hydro-alcoholic stem extract displayed the be... |
Epidermal Threads in Hagfish Epidermis | When attacked, hagfishes produce a soft, fibrous defensive slime within a fraction of a second by ejecting mucus and threads into seawater. The rapid setup and remarkable expansion of the slime make it a highly effective and unique form of defense. How this biomaterial evolved is unknown, although circumstantial evidence points to the epidermis as the origin of the thread- and mucus-producing cells in the slime glands. Here, we describe large intracellular threads within a putatively homologous cell type from hagfish epidermis. These epidermal threads averaged ~2 mm in length and ~0.5 μm in diameter. The entire hagfish body is covered by a dense layer of epidermal thread cells, with each square millimeter of skin storing a total of ~96 cm threads. Experimentally induced damage to a hagfish's skin caused the release of threads, which together with mucus, formed an adhesive epidermal slime that is more fibrous and less dilute than the defensive slime. Transcriptome analysis further suggests that epidermal threads are ancestral to the slime threads, with duplication and diversification of thread genes occurring in parallel with the evolution of slime glands. Our results support an epidermal origin of hagfish slime, which may have been driven by selection for stronger and more voluminous slime. | [
"The \"thread keratins (TK)\" alpha and gamma so far have been considered highly specialized intermediate filament (IF) proteins restricted to hagfish. From lamprey, we now have sequenced five novel IF proteins closely related to TKalpha and TKgamma, respectively. Moreover, we have detected corresponding sequences ... |
Time Deficit and Divorce Rates in Low Income Couples | Shared time is a centrally important component of relationship maintenance, and over the past few decades, couples have reported spending increasingly more time together. However, over this same time period divorce rates have risen much higher for lower income couples compared to higher income couples. One theorized explanation for the disparity in divorce rates between lower and higher income couples is a difference across the socioeconomic strata in the quantity and quality of time couples spend together. This theory argues that lower income couples may experience a time deficit because they face a greater number of stressors that take up time, diminishing the | [
"Although marital satisfaction starts high and declines for the average newlywed, some spouses may follow qualitatively distinct trajectories. Using eight self-reports of satisfaction collected over 4 years from 464 newlywed spouses, we identified five trajectory groups, including patterns defined by high intercept... |
Parent and Adolescent Emotional Variability and Adolescent Psychopathology | Emotional variability has been posited as a risk factor for adolescent psychopathology. However, it is unclear whether parent emotional variability may also function as a risk factor that heightens adolescent mental health problems. To fill this gap, the present study examined whether parent and adolescent emotional variability in both positive emotion (PE) and negative emotion (NE) is associated with adolescent psychopathology and potential sex differences in these associations. Participants were 147 adolescents and their parents in Taiwan who completed a baseline assessment, a 10-day daily diary study, and a 3-month follow-up assessment. The results indicated that parent NE variability was associated with risk for adolescent internalizing problems and depressive symptoms, after accounting for baseline levels, adolescent NE variability, parent internalizing problems, and mean levels of parent and adolescent NE. Adolescent PE variability was also associated with the risk for adolescent externalizing problems. Furthermore, higher parent PE variability was associated with more internalizing problems only for female but not male adolescents. The findings highlight the importance of assessing emotion dynamics in both parents and adolescents to better understand the development of adolescent psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved). | [
"Family-based assessments of risk factors for adolescent emotional, behavioral, and substance use problems can be used to identify adolescents who are at risk and intervene before problems cause clinically significant impairment. Expanding traditional methods for assessing risk, this study evaluates whether labilit... |
Discrete Fourier transform-based gene clustering | Within the realms of human thoughts on nature, Fourier analysis is considered as one of the greatest ideas currently put forwarded. The Fourier transform shows that any periodic function can be rewritten as the sum of sinusoidal functions. Having a Fourier transform view on real-world problems like the DNA sequence of genes, would make things intuitively simple to understand in comparison with their initial formal domain view. In this study we used discrete Fourier transform (DFT) on DNA sequences of a set of genes in the bovine genome known to govern milk production, in order to develop a new gene clustering algorithm. The implementation of this algorithm is very user-friendly and requires only simple routine mathematical operations. By transforming the configuration of gene sequences into frequency domain, we sought to elucidate important features and reveal hidden gene properties. This is biologically appealing since no information is lost via this transformation and we are therefore not reducing the number of degrees of freedom. The results from different clustering methods were integrated using evidence accumulation algorithms to provide in insilico validation of our results. We propose using candidate gene sequences accompanied by other genes of biologically unknown function. These will then be assigned some degree of relevant annotation by using our proposed algorithm. Current knowledge in biological gene clustering investigation is also lacking, and so DFT-based methods will help shine a light on use of these algorithms for biological insight. | [
"The major signal in coding regions of genomic sequences is a three-base periodicity. Our aim is to use Fourier techniques to analyse this periodicity, and thereby to develop a tool to recognize coding regions in genomic DNA. The three-base periodicity in the nucleotide arrangement is evidenced as a sharp peak at f... |
Neoadjuvant Chemotherapy: Imaging and Surgical Approaches | Neoadjuvant chemotherapy (NACT) today represents a cornerstone in the treatment of locally advanced breast cancer and highly chemo-sensitive tumors at early stages, increasing the possibilities of performing more conservative treatments and improving long term outcomes. Imaging has a fundamental role in the staging and prediction of the response to NACT, thus aiding surgical planning and avoiding overtreatment. In this review, we first examine and compare the role of conventional and advanced imaging techniques in preoperative T Staging after NACT and in the evaluation of lymph node involvement. In the second part, we analyze the different surgical approaches, discussing the role of axillary surgery, as well as the possibility of non-operative management after-NACT, which has been the subject of recent trials. Finally, we focus on emerging techniques that will change the diagnostic assessment of breast cancer in the near future. | [
"There is ongoing debate regarding the optimal sequence of sentinel lymph node (SLN) biopsy and neoadjuvant chemotherapy (CTX) for breast cancer. We report the accuracy of comprehensive pre-neoadjuvant CTX and post-neoadjuvant CTX axillary staging via ultrasound imaging, fine-needle aspiration (FNA) biopsy, and SLN... |
Upscaling cervical cancer screening and treatment services at a rural referral hospital in Tanzania | Cervical cancer (CC) is nearly always caused by persistent human papillomavirus (HPV) infection. It is the most common cancer among women living with HIV (WLWH) and is the leading cause of cancer-related death in women in East Africa, with 10,241 new cases reported in Tanzania in 2020. In 2019, the World Health Organization (WHO) presented a global strategy for the elimination of CC as a public health problem, proposing targets to meet by 2030 for HPV vaccine coverage (90% of all 15-year-old girls), CC screening (70% of all women once at 35 and again at 45 years of age) and treatment delivery, to be scaled at national and subnational levels with a context-sensitive approach. This study aims to evaluate the upscaling of screening and treatment services at a rural referral hospital in Tanzania in order to address the second and third WHO targets. | [
"Implementation of a novel, rapid, high-volume, see-and-treat cervical cancer screening programme using self-swab human papillomavirus (HPV) testing and digital colposcopy in underserved regions of Yunnan China. 480-980 women per day self-swabbed for high-risk HPV (hrHPV+). Four careHPV machines (Qiagen) were run s... |
Effects of Fenretinide on LDLR in Mice | Fenretinide is a synthetic retinoid that can prevent obesity and improve insulin sensitivity in mice by directly altering retinol/retinoic acid homeostasis and inhibiting excess ceramide biosynthesis. We determined the effects of Fenretinide on LDLR | [
"Differences in the composition of control diets may confound outcomes in studies investigating dietary effects. We compared the effects of two control diets commonly used in mice studies, chow (SD) and a purified low-fat diet (LFD), in relation to a chronic high-fat diet (HFD). We hypothesized that SD and LFD will... |
Neutrophil extracellular trap formation in myeloproliferative neoplasms | Myeloproliferative neoplasms (MPNs) are hematologic malignancies characterized by gene mutations that promote myeloproliferation and resistance to apoptosis via constitutively active signaling pathways, with Janus kinase 2-signal transducers and the activators of transcription (JAK-STAT) axis as a core part. Chronic inflammation has been described as a pivot for the development and advancement of MPNs from early stage cancer to pronounced bone marrow fibrosis, but there are still unresolved questions regarding this issue. The MPN neutrophils are characterized by upregulation of JAK target genes, they are in a state of activation and with deregulated apoptotic machinery. Deregulated neutrophil apoptotic cell death supports inflammation and steers them towards secondary necrosis or neutrophil extracellular trap (NET) formation, a trigger of inflammation both ways. NETs in proinflammatory bone marrow microenvironment induce hematopoietic precursor proliferation, which has an impact on hematopoietic disorders. In MPNs, neutrophils are primed for NET formation, and even though it seems obvious for NETs to intervene in the disease progression by supporting inflammation, no reliable data are available. We discuss in this review the potential pathophysiological relevance of NET formation in MPNs, with the intention of contributing to a better understanding of how neutrophils and neutrophil clonality can orchestrate the evolution of a pathological microenvironment in MPNs. | [
"Neutrophils cast neutrophil extracellular traps (NETs) to ensnare microbial pathogens. Nevertheless, the molecular rheostats that regulate NETosis in response to bacteria are not clearly established. We hypothesized that stress-activated protein kinase or c-Jun N-terminal Kinase (SAPK/JNK) is a molecular switch th... |
Systemic exposure to cisplatin and paclitaxel after adjuvant intraperitoneal administration in patients with advanced ovarian cancer who underwent primary debulking surgery | To determine the systemic exposure to cisplatin and paclitaxel after adjuvant intraperitoneal administration in patients with advanced ovarian cancer who underwent primary debulking surgery. This could provide an explanation for the high incidence of systemic adverse events associated with this treatment regimen. | [
"Plasma concentrations of cisplatin, total platinum, and total filterable platinum were monitored in 24 patients after either 50 or 100 mg/m2 of cisplatin by rapid intravenous injection. Half the patients at each dose were pretreated with mannitol. Total platinum levels declined in a triphasic fashion with a termin... |
The role of genetic counsellors in a highly specialised service for people with or suspected to have Ehlers Danlos syndrome | With genomic testing being increasingly integrated into every day clinical practice and a wide range of practitioners ordering genetic tests, it is important that the scope of the genetic counselling role continues to evolve alongside these changes. We present an exemplary role for genetic counsellors in a highly specialised service within England's National Health Service for people who have or are suspected to have rare genetic types of Ehlers Danlos syndrome. The service employs genetic counsellors and consultants from the fields of genetics and dermatology. The service also works closely with other specialists and related charities and patient organisations. The genetic counsellors in the service provide routine genetic counselling such as diagnostic and predictive testing, but their role also includes the writing of patient literature and emergency and well-being resources, delivering workshops and talks, and the development of qualitative and quantitative research on the patient experience. Data from such research has informed the development of patient self-advocacy and supportive resources, raised awareness amongst healthcare professionals and enhanced the standard of care and outcomes for patients. The service aims to be an example of innovation and accessibility and provides a model that can be potentially adopted by other highly specialised services of rare genetic diseases. | [
"Researchers define self-advocacy as the ability of an individual with cancer to overcome challenges in getting their preferences, needs, and values met. While imperative in all health care settings, self-advocacy is especially important in cancer care. The goal of this article is to present a conceptual framework ... |
Metabolites in pheochromocytoma/paraganglioma | Metabolites represent the highest layer of biological information. Their diverse chemical nature enables networks of chemical reactions that are critical for maintaining life by providing energy and building blocks. Quantification by targeted and untargeted analytical methods using either mass spectrometry or nuclear magnetic resonance spectroscopy has been applied to pheochromocytoma/paraganglioma (PPGL) with the long-term goal to improve diagnosis and therapy. PPGLs have unique features that provide useful biomarkers and clues for targeted treatments. First, high production rates of catecholamines and metanephrines allow for specific and sensitive detection of the disease in plasma or urine. Secondly, PPGLs are associated with heritable pathogenic variants (PVs) in around 40% of cases, many of which occur in genes encoding enzymes, such as succinate dehydrogenase (SDH) and fumarate hydratase (FH). These genetic aberrations lead to the overproduction of oncometabolites succinate or fumarate, respectively, and are detectable in tumors and blood. Such metabolic dysregulation can be exploited diagnostically, with the aim to ensure appropriate interpretation of gene variants, especially those with unknown significance, and facilitate early tumor detection through regular patient follow-up. Furthermore, SDHx and FH PV alter cellular pathways, including DNA hypermethylation, hypoxia signaling, redox homeostasis, DNA repair, calcium signaling, kinase cascades, and central carbon metabolism. Pharmacological interventions targeted toward such features have the potential to uncover treatments against metastatic PPGL, around 50% of which are associated with germline PV in SDHx. With the availability of omics technologies for all layers of biological information, personalized diagnostics and treatment is in close reach. | [
"Pheochromocytomas and paragangliomas (PPGLs) have a heterogeneous prognosis, the basis of which remains unclear. We, therefore, assessed disease-specific survival (DSS) and potential predictors of progressive disease in patients with PPGLs and head/neck paragangliomas (HNPGLs) according to the presence or absence ... |
Autophagy, phagocytosis and NETosis in diabetes | Type 2-diabetes, particularly poorly controlled diabetes, is a risk factor for several infections such as lower respiratory tract and skin infections. Hyperglycemia, a characteristic downstream effect of poorly controlled diabetes, has been shown to impair the function of immune cells, in particular neutrophils. Several studies have demonstrated that hyperglycemia-mediated priming of NADPH oxidase results in subsequent elevated levels of reactive oxygen species (ROS). In healthy neutrophils, ROS plays an important role in pathogen killing by phagocytosis and by induction of Neutrophil Extracellular Traps (NETs). Given the key role of ROS in autophagy, phagocytosis and NETosis, the relationship between these pathways and the role of diabetes in the modulation of these pathways has not been explored previously. Therefore, our study aimed to understand the relationship between autophagy, phagocytosis and NETosis in diabetes. We hypothesized that hyperglycemia-associated oxidative stress alters the balance between phagocytosis and NETosis by modulating autophagy. Using whole blood samples from individuals with and without type 2-diabetes (in the presence and absence of hyperglycemia), we demonstrated that (i) hyperglycemia results in elevated levels of ROS in neutrophils from those with diabetes, (ii) elevated levels of ROS increase LCIII (a marker for autophagy) and downstream NETosis. (iii) Diabetes was also found to be associated with low levels of phagocytosis and phagocytic killing of | [
"Rationale: Patients with newly diagnosed tuberculosis often have inconsistent glycemic measurements during and after treatment. Distinct glycemic trajectories after the diagnosis of tuberculosis are not well characterized, and whether patients with stress hyperglycemia have poor treatment outcomes is not known.Obj... |
Effect of acute atrial fibrillation on renal water and sodium metabolism in mice | To construct an animal model of atrial fibrillation and observe the effect of acute atrial fibrillation on renal water and sodium metabolism in mice. A total of 20 C57 mice were randomly assigned to 2 groups (n = 10/group): control group (CON) and atrial fibrillation group (AF). The mice model of atrial fibrillation was induced by chlorhexidine gluconate (CG) in combination with transesophageal atrial spacing. The urine of the two groups of mice was collected, and then we calculate the urine volume and urine sodium content. The expression of TGF-β and type III collagen in the atrial myocardium of the two groups was detected by immunohistochemistry and Western Blot. The levels of CRP and IL-6 in blood were observed by ELISA, and the NF-κB, TGF-β, collagen type III, AQP2, AQP3, AQP4, ENaC-β, ENaC-γ, SGK1 and NKCC proteins in the kidneys of the two groups of mice was observed by Western Blot. Compared with CON, the expression of TGF-β and type III collagen in the atrial myocardium of the mice in AF were increased, the levels of CRP and IL-6 in the blood in AF were increased, and the renal NF-κB, TGF-β, type III collagen AQP2, AQP3, ENaC-β, ENaC-γ, SGK1 and NKCC protein expression in AF were up-regulated. The level of urine volume and urine sodium content in AF were significantly reduced. In the acute attack of atrial fibrillation, the formation of renal inflammatory response and fibrosis is activated, and the renal water and sodium metabolism is hindered, which is related to the up-regulated of the expressions of renal NKCC, ENaC and AQPs. | [
"In heart failure, the renal responsiveness to exogenous and endogenous atrial natriuretic peptide (ANP) is blunted. The mechanisms of renal hyporesponsiveness to ANP are complex, but one potential mechanism is decreased expression of natriuretic peptide receptor-A (NPR-A) in inner medullary collecting duct (IMCD) ... |
The Effects of Sun-Dried Azolla (Azolla sativa L.) | This study investigated the effects of using sun-dried Azolla ( | [
"In the recent past,few studies have been carried out in chicken to assess the effect of Azolla meal and raw Azolla feeding on the performance of chicken. If turkeys effectively use unconventional feedstuffs like Azolla without reducing the performance, it will increase the profitability of turkey business. Hence, ... |
Chloramphenicol Resistance Mechanisms and Drug Resistance | Chloramphenicol is a broad-spectrum antibiotic widely used for treating ophthalmic infections, but concerns about rising bacterial resistance to chloramphenicol have been observed due to its frequent use as an over-the-counter medication. This review assessed the common ophthalmic bacterial pathogens, their chloramphenicol resistance mechanisms, and rates of drug resistance. | [
"Eye infections can cause loss or impairment of visual function and can lead to severe impairment. Bacteria are the most common pathogens that affect the structure of the eye. As a result, quick identification of the causative agents and testing of their medication susceptibility are essential for effective treatme... |
Quality Indicators for Gastroenterological Endoscopy | The quality and safety of gastrointestinal endoscopy varies considerably across regions and facilities worldwide. In this field, quality management has traditionally focused on individual performance of endoscopists, with most indicators addressing process measures and limited evidence of improvement in health outcomes. Indicators of quality can be classified according to their nature and sequence. The various professional societies and organizations have proposed many systems of indicators, but a universal system is necessary so that healthcare professionals are not overburdened and confused with a variety of quality improvement approaches. In this paper, we propose guidelines by the Saudi Gastroenterology Association pertaining to quality in endoscopic procedures aiming to improve the awareness of endoscopy unit staff toward important quality indications to enhance and standardize quality of care provided to our patients. | [
"The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology present a list of key performance measures for endoscopy services. We recommend that these performance measures be adopted by all endoscopy services across Europe. The measures include those related to the leadership, or... |
Mesenchymal stem cell-derived exosomes-based regimen for treating intrauterine adhesions | Intrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility globally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endometrium of IUA patients. Mesenchymal stem cell-derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis diseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, herein, we reported an exosome-based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently promote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and COL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides the theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery system in IUA patients. | [
"Transforming growth factor (TGF)‑β1 has a key role in the regulation of fibrosis and organ dysfunction. During the pathogenesis and progression of vital organ fibrosis, the microRNA (miR)‑29 family is irregularly downregulated and exogenous supplementation of miR‑29b has a strong anti‑fibrotic capacity. However, w... |
How does neural activity drive muscles to produce behavior? | How does neural activity drive muscles to produce behavior? The recent development of genetic lines in | [
"Glucose-stimulated insulin secretion is associated with transients of intracellular Ca(2+) concentration [Ca(2+)](i) in the pancreatic beta-cell. We identified the expression and function of specific small-conductance Ca(2+)-activated K(+) (SK) channel genes in insulin-secreting cells. The presence of mRNA for SK1... |
Fungal Population and Mycotoxins Level in Loose Tobacco Products | Smokeless tobacco products (STPs) contain several microbial communities which are responsible for the formation of carcinogens, like tobacco-specific nitrosamine (TSNAs). A majority of STPs are sold in loose/unpackaged form which can be loaded with a diverse microbial population. Here, the fungal population and mycotoxins level of three popular Indian loose STPs, Dohra, Mainpuri Kapoori (MK), and loose leaf-chewing tobacco (LCT) was examined using metagenomic sequencing of ITS1 DNA segment of the fungal genome and LC-MS/MS, respectively. We observed that Ascomycota was the most abundant phylum and Sterigmatomyces and Pichia were the predominant fungal genera in loose STPs. MK displayed the highest α-diversity being enriched with pathogenic fungi Apiotrichum, Aspergillus, Candida, Fusarium, Trichosporon, and Wallemia. Further, FUNGuild analysis revealed an abundance of saprotrophs in MK, while pathogen-saprotroph-symbiotroph were abundant in Dohra and LCT. The level of a fungal toxin (ochratoxins A) was high in the MK product. This study caution that loose STPs harbor various harmful fungi that can infect their users and deliver fungal toxins or disrupt the oral microbiome of SLT users which can contribute to several oral pathologies. | [
"\"Cherry-red\" tobacco is the superior variant of tobacco, appearing with the apperance of red dapples on cured leaves due to the demethylation of nicotine to nornicotine during maturation and curing. Fungi are known to have the capacity to convert nicotine to nornicotine. However, an endophytic fungal community o... |
Performance of virtual monochromatic images with the same dose and iodine contrast | To investigate the performance of virtual monochromatic (VM) images with the same dose and iodine contrast as those for single-energy (SE) images using five dual-energy (DE) scanners with DE techniques: two generations of fast kV switching (FKS), two generations of dual source (DS), and one split filter (SF). | [
"Recent technologic advances have markedly enhanced the clinical applications of computed tomography (CT). While the benefits of CT exceed the harmful effects of radiation exposure in patients, increasing radiation doses to the population have raised a compelling case for reduction of radiation exposure from CT. St... |
Plasma gelsolin levels and extracellular vesicles in type 2 diabetes mellitus | The growing epidemic of the inflammation-related metabolic disease, type 2 diabetes mellitus, presents a challenge to improve our understanding of potential mechanisms or biomarkers to prevent or better control this age-associated disease. A gelsolin isoform is secreted into the plasma as part of the extracellular actin scavenger system which serves a protective role by digesting and removing actin filaments released from damaged cells. Recent data indicate a role for decreased plasma gelsolin (pGSN) levels as a biomarker of inflammatory conditions. Extracellular vesicles (EVs), a heterogeneous group of cell-derived membranous structures involved in intercellular signaling, have been implicated in metabolic and inflammatory diseases including type 2 diabetes mellitus. We examined whether pGSN levels were associated with EV concentration and inflammatory plasma proteins in individuals with or without diabetes. | [
"The discovery that submicron-sized extracellular vesicles (EVs) are generated by both prokaryotic and eukaryotic cells might have a profound effect on experimental and clinical sciences, and could pave the way for new strategies to combat various diseases. EVs are carriers of pathogen-associated and damage-associa... |
Moral views on non-treatment decisions in Norway | Decisions about appropriate treatment at the end of life are common in modern healthcare. Non-treatment decisions (NTDs), comprising both withdrawal and withholding of (potentially) life-prolonging treatment are in principle accepted in Norway. However, in practice they may give rise to significant moral problems for health professionals, patients and next of kin. Here, patient values must be considered. It is relevant to study the moral views and intuitions of the general population on NTDs and special areas of contention such as the role of next of kin in decision-making. | [
"Our objective was to investigate whether a consensus exists between the general public and health care providers regarding the reasoning and values at stake on the subject of life-sustaining treatment. A postal questionnaire was sent to a random sample of members of the adult population (n = 989) and to a random s... |
LibGuides: COVID19: Mental Health and Wellbeing | COVID19, and associated lockdown restrictions, have impacted on people's daily lives. Understanding the mental health and wellbeing implications of these impacts has been identified as a public health research priority. | [
"Environmental stressors such as mass disasters may contribute to an increased prevalence of depression within the population affected. We examined the prevalence of probable major depression and risk factors for depression in the 6-month period after the September 11, 2001, attacks on the World Trade Center among ... |
Human milk banks in Italy: a tool to standardize the organization, management and procedures | In Europe, an increasing number of human milk banks (HMBs) collect donor human milk to feed preterm infants when their mother's milk is not available or not enough. Moreover, donor milk is a bridge to breastfeeding, with positive clinical and psychological advantages for both mother and infant. Italy, with 41 HMBs actively operating in 2022, has the highest number of HMBs in Europe. The process of human milk donation is complex, so activity of HMBs must be regulated according to well-established rules. The present recommendations have been prepared as a tool to standardize the organization, management, and procedures of HMBs operating in Italy and to determine the minimal essential requirements to establish new HMBs. This article covers all the aspects of human milk donation and human milk banking, including general recommendations, donor recruitment and screening, expression, handling and storage of donor human milk, milk screening, and milk treatment (pasteurization). A pragmatic approach was taken to drafting the recommendations. Items for which there was consensus or robust published evidence on which to base recommendations were included. When there were differences that could not be resolved by reference to published research, a statement of explanation based on the expert opinion of the authors (all members of the Italian Association of Human Milk Banks) was included. Implementation of these recommendations can contribute to promotion of breastfeeding. | [
"Mother's own milk has long been accepted as the best source of nutrition for the newborn. In those cases where mother's milk is not available, the best choice is the human milk provided by selected donors. Human milk banks are the most institutionalized method of milk sharing and play a vital role for neonates tha... |
Early tumor recurrence in pilocytic astrocytomas. | Pilocytic astrocytomas (PAs) are benign tumors. However, clinically aggressive PAs despite benign histology have been reported, and histological and molecular risk factors for prognosis have not been elucidated. 38 PAs were studied for clinical, histological, and molecular factors, including tumor location, extent of resection, post-operative treatment, glioma-associated molecules (IDH1/2, ATRX, BRAF, FGFR1, PIK3CA, H3F3A, p53, VEGF, Nestin, PD-1/PD-L1), CDKN2A/B deletion, and chromosomal number aberrations, to see if there is any correlation with patient's progression-free survival (PFS). Brainstem/spinal location, extent of resection and post-operative treatment, and VEGF-A, Nestin and PD-L1 expression, copy number gain of chromosome 7q or 19, TP53 mutation were significantly associated with shorter PFS. None of the histological parameters was associated with PFS. Multivariate analyses demonstrated that high Nestin expression, gain of 7q or 19, and extent of removal were independently predictive for early tumor recurrence. The brainstem/spinal PAs appeared distinct from those in the other sites in terms of molecular characteristics. Clinically aggressive PAs despite benign histology exhibited high Nestin expression. Brainstem/spinal location, extent of resection and some molecular factors including Nestin expression and gains of 7q and 19, rather than histological parameters, may be associated with early tumor recurrence in PAs. | [
"Pilocytic astrocytoma (PA) is one of the most common glial neoplasms in the pediatric population, and its gross total resection can be curative. Treatment of partially resected or recurrent tumors is challenging, and the factors associated with increased recurrence risk are not well defined. Identification of favo... |
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