High-protein high-konjac glucomannan diets changed glucose and lipid metabolism by modulating colonic microflora and bile acid profiles in healthy mouse models.

High protein and fiber diets are becoming increasingly popular for weight loss; however, the benefits or risks of high protein and fiber diets with a normal calorie level for healthy individuals still need to be elucidated. In this study, we explored the role and mechanisms of long-term high protein and/or konjac glucomannan diets on the metabolic health of healthy mouse models. We found that high konjac glucomannan contents improved the glucose tolerance of mice and both high protein and high konjac glucomannan contents improved the serum lipid profile but increased the TNF-α levels. In the liver, high dietary protein contents reduced the expression of the FASN gene related to fatty acid synthesis. Interactions of dietary protein and fiber were shown in the signaling pathways related to lipid and glucose metabolism of the liver and the inflammatory status of the colon, wherein the high protein and high konjac glucomannan diet downregulated the expression of the SREBF1 and FXR genes in the liver and downregulated the expression of TNF-α genes in the colon compared to the high protein diet. High konjac glucomannan contents reduced the colonic secondary bile acid levels including DCA and LCA; this was largely associated with the changed microbiota profile and also contributed to improved lipid and glucose homeostasis. In conclusion, high protein diets improved lipid homeostasis and were not a risk to metabolic health, while high fiber diets improved glucose and lipid homeostasis by modulating colonic microbiota and bile acid profiles, and a high protein diet supplemented with konjac glucomannan might improve hepatic lipid homeostasis and colonic inflammation in healthy mouse models through long-term intervention.

Pain Catastrophizing, Kinesiophobia and Exercise Adherence in Patients After Total Knee Arthroplasty: The Mediating Role of Exercise Self-Efficacy.

Purpose: To examine whether exercise self-efficacy mediates the contributions of pain catastrophizing and kinesiophobia to exercise adherence in patients after total knee arthroplasty. Patients and Methods: A cross-sectional study design was conducted. A total 211 post-total knee arthroplasty patients were recruited from three orthopedics units of a tertiary hospital in China. Participants were invited to complete questionnaires on pain catastrophizing, kinesiophobia, exercise self-efficacy, and exercise adherence. Mplus 8.3 software was used to construct mediation models. Results: Pain catastrophizing and kinesiophobia were negatively correlated with exercise adherence (r = -0.509, r = -0.605, p < 0.001 respectively), while exercise self-efficacy were positively associated with exercise adherence (r = 0.799, p < 0.001). The results found exercise self-efficacy mediated the correlations of pain catastrophizing and kinesiophobia with exercise adherence after adjusting for demographic and clinical covariates. Pain catastrophizing indirectly affected patients' exercise adherence through its effect on exercise efficacy (indirect effect: -0.412), while Kinesiophobia is directly associated with exercise adherence and also indirectly through exercise self-efficacy (direct effect: -0.184, indirect effect: -0.415). Conclusion: Patients after total knee arthroplasty who have high levels of psychological distress (pain catastrophizing and kinesiophobia) are vulnerable to be non-adherent to exercise behaviors. Exercise self-efficacy explains the effects of pain catastrophizing and kinesiophobia on exercise adherence and may be a key target for measures to improve exercise behaviors in patients after total knee arthroplasty.

Short-term statin treatment reduces, and long-term statin treatment abolishes chronic vascular injury by radiation therapy.

Background: The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. Objectives: Determine if irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared to long-term administration. Methods: C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy x-ray head-and-neck irradiation. Subsequently, they received pravastatin either for one additional day or for one year. Carotid arteries were tested for vascular reactivity and altered gene expression one year after irradiation. Results: Treatment with pravastatin for 24 hours reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction after IR. It reduced the expression of some markers associated with inflammation and oxidative stress and modulated that of subunits of the voltage and Ca2+ activated K+ (BK) channel in the carotid artery one year after irradiation. Treatment with pravastatin for one year completely reversed the changes caused by irradiation. Conclusions: In mice, short-term administration of pravastatin is sufficient to reduce chronic vascular injury after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.

Parametric optimization of culture chamber for cell mechanobiology research.

Mechanical signals influence the morphology, function, differentiation, proliferation, and growth of cells. Due to the small size of cells, it is essential to analyze their mechanobiological responses with an in vitro mechanical loading device. Cells are cultured on an elastic silicone membrane substrate, and mechanical signals are transmitted to the cells by the substrate applying mechanical loads. However, large areas of non-uniform strain fields are generated on the elastic membrane, affecting the experiment's accuracy. In the study, finite-element analysis served as the basis of optimization, with uniform strain as the objective. The thickness of the basement membrane and loading constraints were parametrically adjusted. Through finite-element cycle iteration, the "M" profile basement membrane structure of the culture chamber was obtained to enhance the uniform strain field of the membrane. The optimized strain field of culture chamber was confirmed by three-dimensional digital image correlation (3D-DIC) technology. The results showed that the optimized chamber improved the strain uniformity factor. The uniform strain area proportion of the new chamber reached 90%, compared to approximately 70% of the current chambers. The new chamber further improved the uniformity and accuracy of the strain, demonstrating promising application prospects.

Mechanisms by which statins protect endothelial cells from radiation-induced injury in the carotid artery.

Background: The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. However, the mechanisms by which statins protect the vasculature from irradiation injury remain poorly understood. Objectives: Identify the mechanisms by which the hydrophilic and lipophilic statins pravastatin and atorvastatin preserve endothelial function after irradiation. Methods: Cultured human coronary and umbilical vein endothelial cells irradiated with 4 Gy and mice subjected to 12 Gy head-and-neck irradiation were pretreated with statins and tested for endothelial dysfunction, nitric oxide production, oxidative stress, and various mitochondrial phenotypes at 24 and 240 h after irradiation. Results: Both pravastatin (hydrophilic) and atorvastatin (lipophilic) were sufficient to prevent the loss of endothelium-dependent relaxation of arteries after head-and-neck irradiation, preserve the production of nitric oxide by endothelial cells, and suppress the cytosolic reactive oxidative stress associated with irradiation. However, only pravastatin inhibited irradiation-induced production of mitochondrial superoxide; damage to the mitochondrial DNA; loss of electron transport chain activity; and expression of inflammatory markers. Conclusions: Our findings reveal some mechanistic underpinnings of the vasoprotective effects of statins after irradiation. Whereas both pravastatin and atorvastatin can shield from endothelial dysfunction after irradiation, pravastatin additionally suppresses mitochondrial injury and inflammatory responses involving mitochondria. Clinical follow-up studies will be necessary to determine whether hydrophilic statins are more effective than their lipophilic counterparts in reducing the risk of cardiovascular disease in patients undergoing radiation therapy.

MethBank 4.0: an updated database of DNA methylation across a variety of species.

DNA methylation, as the most intensively studied epigenetic mark, regulates gene expression in numerous biological processes including development, aging, and disease. With the rapid accumulation of whole-genome bisulfite sequencing data, integrating, archiving, analyzing, and visualizing those data becomes critical. Since its first publication in 2015, MethBank has been continuously updated to include more DNA methylomes across more diverse species. Here, we present MethBank 4.0 (https://ngdc.cncb.ac.cn/methbank/), which reports an increase of 309% in data volume, with 1449 single-base resolution methylomes of 23 species, covering 236 tissues/cell lines and 15 biological contexts. Value-added information, such as more rigorous quality evaluation, more standardized metadata, and comprehensive downstream annotations have been integrated in the new version. Moreover, expert-curated knowledge modules of featured differentially methylated genes associated with biological contexts and methylation analysis tools have been incorporated as new components of MethBank. In addition, MethBank 4.0 is equipped with a series of new web interfaces to browse, search, and visualize DNA methylation profiles and related information. With all these improvements, we believe the updated MethBank 4.0 will serve as a fundamental resource to provide a wide range of data services for the global research community.

A Middle Aged Gentleman Presenting with Subacute Neurosyphilis: Report and Literature Review.

Syphilis is a sexually transmitted disease spread by spirochete Treponema Pallidum, it has a varied range of symptoms and is divided into stages primary, secondary and tertiary. Central nervous system (CNS) invasion occurs early in the disease in almost all the patients, and does not follow any particular stage. However, clinical manifestation depends on whether inflammatory response occurs. (1)(2) Early neurosyphilis typically affects cerebrospinal fluid (CSF) and meninges presenting like meningitis, while late affects the brain and spinal cord parenchyma, presenting as tabes dorsalis and paresis. Here we present a case of a patient with symptomatic neurosyphilis presenting with CSF findings of bacterial meningitis.

Tricuspid Endocarditis: A Case Report and Comprehensive Literature Review.

Infective endocarditis is a multisystem disease. Tricuspid valve endocarditis is frequently seen in patients with intravenous (IV) drug users. Cavitating lung nodules predominantly in a peripheral location in IV drug users indicate the possibility of septic emboli. Large vegetation and persistent bacteremia with septic embolic phenomena are the most common indication for surgery. We present a case of a 62-year-old male with a history of IV drug use who presented with epigastric abdominal pain, pleuritic chest pain, and shortness of breath. CT chest showed cavitating lung nodules suggestive of septic pulmonary emboli. A transesophageal echocardiogram (TEE) showed tricuspid valve vegetation despite a normal transthoracic echocardiogram. The patient was treated with intravenous antibiotics. He was deemed a poor surgical candidate; therefore, he was transferred to a tertiary center for AngioVAC (AngioDynamics, Latham, New York).

5q Deletion Myelodysplastic Syndrome in a Young Male Patient.

Myelodysplastic syndromes (MDS) are a diverse group of hematopoietic stem cell malignancies with various phenotypic variability that are categorized by abnormal differentiation of one or multiple cell lines of the bone marrow. A large part of the phenotypic heterogeneity is in part due to the wide set of genetic defects related to MDS. Though clinically, MDS is centered on diagnostic measures that do not incorporate molecular genetic data, an isolated deletion of the long arm of chromosome 5 (del(5q)) is the only subset of MDS to be identified by genetic defects. This distinctive phenotype is termed 5q-syndrome. We report a case of a 25-year-old with a past medical history of polydactyly, severe anemia, and thrombocytopenia who presented to the emergency department with a chief complaint of weakness and fatigue. Bone marrow biopsy showed myeloid neoplasm with complex genetic abnormalities, nearly 100% hyperplastic marrow with marked trilineage dysplasia, relative myeloid hyperplasia with increased abnormal eosinophilic precursors, erythroid left shift, and atypical megakaryocytes. Fluorescence in situ hybridization (FISH) panel showed deletion of 5q-. Herein, we address the clinical course and morphological characteristics as well as possible therapeutic options for 5q syndrome.