Chronic Overload Research Articles

Predictors of school burnout among German high school students

Burnout refers to characteristic stress symptoms resulting from chronic overload at the workplace. However, increased stress and strain are observed already in adolescents in the context of school. Previous work shows that school burnout is associated with female gender, immigration background, higher academic achievement, and increasing grade level. We aimed at replicating these findings and extending them by investigating subjective stressors in a survey among 502 German high school students. Higher burnout scores related to all previously reported predictors, as well as the subjective stressors “homework” and “pressure to perform at school”, explaining up to 24% of the variance in burnout scores. These findings provide valuable evidence for effective prevention measures, optimal timing and target groups to combat school burnout.

Diuretics and mortality reduction in incident dialysis patients: a two-year observational study

Fluid overload predicts morbidity and mortality in dialysis patients. Diuretics can reduce fluid overload, but their effects on morbi-mortality following inception remain ill-defined. To determine whether diuretics reduce mortality and hospitalization rates in incident dialysis patients in the first 2 years after inception. Adult patients starting dialysis between 2009 and 2015 in the REIN registry were matched with the SNDS database and divided into four subgroups according to loop diuretics exposure: < 5%, 5–50%, 50–80% or > 80% over the observation period of each patient. The incidence of hospitalization was described based on the primary diagnoses of the discharge summaries and codes. In this study, which included 67,736 patients, 53,829 (79.5%) who had varying degrees of diuretic exposure exhibited a significantly lower mortality rate at 2 years compared to those without diuretic exposure (24.8% [95% CI 24.4–25.2], vs 37.5% [95% CI 36.7–38.3] respectively). However, the duration of diuretic exposure significantly impacted outcomes. The all-cause mortality rate at two years was highest in the group with ≥ 80% exposure (68.2% [95% CI 67.3–69.1]), followed by those with 50–80% exposure (15.7% [95% CI 15.0–16.4]), and those with 5–50% exposure (6.6% [95% CI 6.3–7.0]). An inverse probability weighting (IPW) propensity score analysis supported these findings. Stratified analyses showed consistent results regardless of a history of congestive heart failure and were similar for both hemodialysis and peritoneal dialysis patients. Additionally, the number of hospitalizations and length of stay were generally higher in the group with the longest exposure to loop diuretics. Diuretic exposure was generally associated with a lower mortality rate in dialysis patients. However, prolonged exposure (≥ 80%) was linked to an increased risk of mortality and hospitalization. This prolonged exposure may indicate residual diuresis at the cost of chronic fluid overload.

Body weight control via protein kinase CK2: diet-induced obesity counteracted by pharmacological targeting

BackgroundProtein kinase CK2 is a highly conserved enzyme implicated in the pathogenesis of various human illnesses including obesity. Despite compelling evidence for the involvement of this kinase in the pathophysiology of obesity, the molecular mechanisms by which CK2 might regulate fat metabolism are still poorly understood. Methods and resultsIn this study, we aimed to elucidate the role of CK2 on lipid metabolism by employing both in vitro and in vivo approaches using mouse pre-adipocytes and a mouse model of diet-induced obesity. We show that pharmacological inhibition of CK2 by CX-4945 results in premature upregulation of p27KIP1 preventing the progression of cells into mature adipocytes by arresting their development at the intermediate phase of adipogenic differentiation. Consistent with this, we show that in vivo, CK2 regulates the expression levels and ERK-mediated phosphorylation of C/EBPβ, which is one of the earliest transcription factors responsive to adipogenic stimuli. Furthermore, we demonstrate the functional implication of CK2 in the expression of late markers of adipogenesis and factors regulating lipogenesis in liver and white adipose tissue. Finally, we show that while mice subjected to high-fat diet increased their body weight, those additionally treated with CX-4945 gained considerably less weight. NMR-based body composition analysis revealed that this is linked to significant differences in body fat mass. ConclusionsTaken together, our study provides novel insights into the role of CK2 in fat metabolism in response to chronic lipid overload and confirms CK2 pharmacological targeting as a potentially powerful strategy for body weight control and/or the treatment of obesity and related metabolic disorders.

Diagnostic imaging findings in lame Warmblood horses with bone injuries of the medial proximal phalanx glenoid cavity.

This retrospective study aims to describe baseline and follow-up imaging findings in subchondral and trabecular bone damage occurring outside of the sagittal groove in the proximal phalanx (P1) glenoid in a case series of lame Warmblood horses. Thirteen lame horses (16 forelimbs) with standing magnetic resonance imaging (sMRI) evidence of nonsagittal groove glenoid subchondral and trabecular bone injury of P1 as the main lesion were included. All injuries were located at the medial aspect of the P1 glenoid. At sMRI, changes included subchondral bone plate thickening and trabecular sclerosis, bone marrow edema-like signal, subchondral bone resorption (11/16), and new bone production (8/16). Subchondral bone resorption in the transverse plane was linear (8/11), round (2/11), or ill-defined (1/11). Sclerosis, bone resorption, and new bone production were seen radiographically in 10, 4, and 5 limbs, respectively. All limbs had concurrent metacarpal condyle sMRI imaging abnormalities, osteophytosis, and joint effusion. Follow-up sMRIs were obtained in 8 of 16 limbs, five of which showing progression of the resorptive lesion. One horse encountered a comminuted fracture of the affected P1 18 months after the follow-up sMRI examination. The imaging appearance of the medial glenoid bone injuries of P1 in this case series is consistent with chronic bone overload. The linear configuration of bone resorption seen in eight lesions suggests short, incomplete stress fractures, which is supported by the ultimate catastrophic fracture occurring in one case.

Recurrence of Sigmoid Volvulus Associated With Constipation: A Retrospective Cohort Study.

Introduction Sigmoid volvulus is a gastrointestinal condition characterized by twisting the sigmoid colon, leading to obstruction and potentially severe complications. It is associated with factors such as advanced age, constipation, and the use of certain medications. Despite treatment, recurrence is common and significantly impacts patients' quality of life. This study aimed to identify factors influencing the recurrence of sigmoid volvulus to develop effective preventive strategies. Methods A retrospective cohort study was conducted at Fuchu Hospital, Osaka, including 44 patients diagnosed with sigmoid volvulus between May 2013 and May 2023. Data on variables such as age, gender, constipation, cardiac and neuropsychiatric diseases, hypertension, diabetes mellitus, sigmoid colon overgrowth, and BMI were collected from electronic medical records. Recurrence was defined as two or more diagnoses of sigmoid volvulus during the study period. Logistic regression analysis was used to identify significant predictors of recurrence. Results Of the 44 patients, 20 experienced recurrences. Single regression analysis identified constipation, neuropsychiatric disorders, and sigmoid colon overgrowth as significant factors. Logistic regression analysis confirmed constipation as an important predictor of recurrence (OR: 8.84, 95% CI: 2.05-38.1, p=0.0034). The area under thereceiver operating characteristic (ROC) curve for the model was 0.804 (95% CI: 0.67-0.938), indicating good predictive accuracy. Conclusion Constipation is a significant risk factor for the recurrence of sigmoid volvulus, likely due to chronic fecal overload leading to elongation and dilation of the sigmoid colon. Effective management of constipation is crucial in preventing recurrence. Future prospective studies with larger sample sizes are needed to validate these findings and explore additional preventive measures.

Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.

Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1-8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD. In this study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild-type) and A17 (OPMD) mice underwent a 6-week-long motorized treadmill protocol consisting in three sessions per week of running 20cm/s for 20min. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of gastrocnemius and soleus muscles was performed, inducing hypertrophy of the plantaris muscle. In both types of exercise, muscles of A17 and FvB mice were compared with those of respective sedentary mice. For all the groups, force measurement, muscle histology, and molecular analyses were conducted. Following the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates in both tibialis anterior (+24%, **P=0.0026) and gastrocnemius (+18%, ****P<0.0001) as well as enhanced collagen deposition (+20%, **P=0.0064 in the tibialis anterior; +35%, **P=0.0042 in the gastrocnemius) in the exercised A17 OPMD mice. In the supraphysiological resistance overload protocol, we also observed an increased collagen deposition (×2, ****P<0.0001) in the plantaris muscle of A17 OPMD mice which was associated with larger muscle mass (×2, ****P<0.0001) and fibre cross sectional area (×2, ***P=0.0007) and increased absolute maximal force (×2, ****P<0.0001) as well as a reduction in PABPN1 aggregate number (-16%, ****P<0.0001). Running exercise and mechanical overload led to very different outcome in skeletal muscles of A17 mice. Both types of exercise enhanced collagen deposition but while the running protocol increased aggregates, the OVL reduced them. More importantly OVL reversed muscle atrophy and maximal force in the A17 mice. Our study performed in a relevant model gives an indication of the effect of different types of exercise on OPMD muscle which should be further evaluated in humans for future recommendations as a part of the lifestyle of individuals with OPMD.

Abstract Mo098: LMNA R190W Mutation Associated With Dilated Cardiomyopathy Causes Hypercontractility in iPSC-derived Cardiomyocytes and Engineered Heart Muscles

Familial dilated cardiomyopathy (DCM) caused by mutations in sarcomeric proteins have been extensively studied in vitro , however less is known about DCM caused by alterations in non-sarcomeric genes like Lamin A (LMNA). LMNA is a ubiquitously expressed nuclear intermediate filament protein that regulates nuclear structure, chromatin access and gene expression. LMNA mutations account for 6% of DCM, and affected patients develop drug-therapy resistant severe heart failure and lethal arrythmias that are not amenable to currently available therapies. Most identified LMNA-cardiomyopathy mutations have been associated with severely depressed cardiac systolic function in patients and cardiomyocyte hypocontractility in vitro . However, the underlying mechanisms are incompletely understood. This project examines the mechanisms by which a patient-derived pathogenic mutation, LMNA R190W, leads to cardiac dysfunction at the cellular and tissue levels. We hypothesize that LMNA R190W mutation causes dysregulated expression of calcium handling genes, eventually leading to altered contractility. First, we investigated early disease pathogenesis using iPSC-derived cardiomyocytes. Intriguingly, single cardiomyocyte traction force microscopy studies showed cardiomyocyte hypercontractility, and calcium flux assays revealed prolonged calcium transients. Second, in human engineered heart muscle tissues, LMNA CMs were also consistently hypercontractile. Through gene expression studies, we identified upregulation of a cardiac-specific sarcomeric calcium regulator, calsequestrin 2 (CASQ2), which modulates intracellular calcium availability and localization, and thereby indirectly impacts calcium-dependent contraction and electrophysiology. siRNA-mediated knockdown of CASQ2 in iPSC-CMs decreased cellular calcium content, suggesting Casq2 is necessary for increased calcium and contractility in LMNA R190W cells. These findings suggest that in the initial stages of LMNA R190W-associated cardiomyopathy, cardiomyocyte contractility is not diminished, but actually augmented, and this may be related to aberrant calcium handling. We posit that chronic inappropriate calcium overload may eventually lead to cell death, and predispose to cardiomyopathy. Understanding the initial processes driving the development of LMNA cardiomyopathy will inform more accurate mechanism-based subclassification of mutations, and the rational development of precision therapies.

Diet-induced and age-related changes in rats: the impact of N-stearoylethanolamine intake on plasma lipoproteins, adiponectin, and adipocyte cholesterol-phospholipid composition

Adiponectin is secreted by adipose tissue, associated with lipoprotein (LP) metabolism, down-regulated­ in insulin resistance states, and reduced in individuals suffering from obesity and cardiovascular diseases. Phospholipids and cholesterol are the main components of cell membranes and play a critical role in storage and secretory adipocyte functions. N-stearoylethanolamine (NSE) is a minor lipid affecting cell membrane lipids’ composition. Our study aimed to investigate plasma levels of adiponectin and cholesterol of low- and high-density LP (LDL and HDL) and adipocyte cholesterol-phospholipid (Chol-PL) composition of different age rats with high-fat diet (HFD)-induced obesity and insulin resistance and their changes under NSE administration. Our study demonstrated that chronic dietary fat overloading leads to obesity accompanied by impairment of glucose tolerance, a manifestation of dyslipidemia, and changes in plasma adiponectin levels in rats from two age groups (10-month-old and and 24-month-old). Prolonged HFD led to a reduction in plasma adiponectin levels and the growth of adipocyte cholesterol content in rats of different ages. A significant increase in plasma LDL-Chol level and main adipocyte PLs (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine) was observed in younger rats, whereas not detected in elder animals after dietary fats overloading. The decrease in the content of anionic phospholipids (phosphatidylinositol + phosphatidylserine) was also detected in 10-month-old HFD rats compared to the control animals. NSE administration positively affected the normalization of adiponectin levels in both age HFD groups. It significantly impacted the reduction of LDL-Chol levels and the growth of HDL-Chol concentration in the blood plasma of 10-month-old rats as well as PL-composition of young HFD rats and anionic PL restoring in 24-month-old rats. The positive effect on investigated parameters makes NSE a prospective agent for treating diet-induced and age-related metabolic disorders threatening cardiovascular diseases. Keywords: adiponectin, adipose tissue, aging, cholesterol, dyslipidemia, lipoproteins, N-stearoylethanolamine, phospholipids

Modeling of the Effect of Subperiosteal Hydrostatic Pressure Conductivity between Joints on Decreasing Contact Loads on Cartilage and of the Effect of Myofascial Relief in Treating Trigger Points: The Floating Skeleton Theory.

Chronic overloading of the cartilage can lead to its irreversible destruction, as observed in people with osteoarthritis. The floating skeleton model previously introduced postulates that overloading begins and progresses when a joint is isolated from the hydrostatical connection with other joints. Such a connection occurs via the interstitial fluid in subperiosteal space and allows for pressure transmission between synovial capsules modulating intra-articular pressure. In the current study, a simple experiment was performed to model an obstruction in the subperiosteal hydrostatic pressure conductivity between joints to illustrate the effect of that obstruction on loads borne by the joint. When the obstruction was removed, the load experienced by the joint was reduced as it was redistributed throughout the model structure. The experiment demonstrated that contact pressures can be redistributed when the conditions of Pascal's Law are met.

Low-field magnetic resonance imaging of sagittal groove disease of the proximal phalanx in non-racing sport horses.

Injuries of the sagittal groove of the proximal phalanx (P1) in equine athletes are considered to predominantly occur due to chronic bone stress overload. To describe the range of abnormalities that is present in the sagittal groove in a large group of horses diagnosed with sagittal groove disease (SGD) on low-field MRI. Retrospective, cross-sectional. Medical records were searched to identify initial MRI images of horses diagnosed with SGD and these were blindly evaluated using a semi-quantitative grading scheme and novel SGD MRI classification system reflecting potential pathways of pathological progression and severity of stress injury. A total of 132 limbs from 111 horses were included in the study; predominantly warmbloods competing in showjumping (n = 83) and dressage (n = 18). SGD MRI classifications were: 0 (normal, n = 0), 1 (small subchondral defect, n = 2), 2 (osseous densification, n = 28), 3 (subchondral microfissure with osseous densification, n = 7), 4 (bone oedema-like signal within the subchondral ± trabecular bone and ± subchondral microfissure or demineralisation, n = 72), 5 (incomplete macrofissure/fracture, n = 23) and 6 (complete fracture, n = 0). Classification 4c (bone oedema-like signal with demineralisation) and 5 had higher proportions in the plantar third of hindlimbs (3% and 10%, respectively) compared with forelimbs (0% and 0%, respectively). SGD classification and extent of bone oedema-like signal were not significantly different between lame (n = 116) and non-lame limbs (n = 16) (both p > 0.05). Periosteal new bone and oedema-like signal were identified (either confidently or suspected) at the dorsoproximal aspect of P1 in 25% and 39% of limbs, respectively. Inclusion via diagnoses in original MRI reports, variable clinical history, small size of some classification groups. The presence or absence of lameness is not a dependable measure of the severity of SGD. The periosteal oedema-like signal of P1 has not previously been described in MRI of SGD and further supports the concept of bone stress injury.

A synoptic literature review of animal models for investigating the biomechanics of knee osteoarthritis.

Osteoarthritis (OA) is a common chronic disease largely driven by mechanical factors, causing significant health and economic burdens worldwide. Early detection is challenging, making animal models a key tool for studying its onset and mechanically-relevant pathogenesis. This review evaluate current use of preclinical in vivo models and progressive measurement techniques for analysing biomechanical factors in the specific context of the clinical OA phenotypes. It categorizes preclinical in vivo models into naturally occurring, genetically modified, chemically-induced, surgically-induced, and non-invasive types, linking each to clinical phenotypes like chronic pain, inflammation, and mechanical overload. Specifically, we discriminate between mechanical and biological factors, give a new explanation of the mechanical overload OA phenotype and propose that it should be further subcategorized into two subtypes, post-traumatic and chronic overloading OA. This review then summarises the representative models and tools in biomechanical studies of OA. We highlight and identify how to develop a mechanical model without inflammatory sequelae and how to induce OA without significant experimental trauma and so enable the detection of changes indicative of early-stage OA in the absence of such sequelae. We propose that the most popular post-traumatic OA biomechanical models are not representative of all types of mechanical overloading OA and, in particular, identify a deficiency of current rodent models to represent the chronic overloading OA phenotype without requiring intraarticular surgery. We therefore pinpoint well standardized and reproducible chronic overloading models that are being developed to enable the study of early OA changes in non-trauma related, slowly-progressive OA. In particular, non-invasive models (repetitive small compression loading model and exercise model) and an extra-articular surgical model (osteotomy) are attractive ways to present the chronic natural course of primary OA. Use of these models and quantitative mechanical behaviour tools such as gait analysis and non-invasive imaging techniques show great promise in understanding the mechanical aspects of the onset and progression of OA in the context of chronic knee joint overloading. Further development of these models and the advanced characterisation tools will enable better replication of the human chronic overloading OA phenotype and thus facilitate mechanically-driven clinical questions to be answered.

Temporal expression of mitochondrial life cycle markers during acute and chronic overload of rat plantaris muscles.

Skeletal muscle hypertrophy is generally associated with a fast-to-slow phenotypic adaptation in both human and rodent models. Paradoxically, this phenotypic shift is not paralleled by a concomitant increase in mitochondrial content and aerobic markers that would be expected to accompany a slow muscle phenotype. To understand the temporal response of the mitochondrial life cycle (i.e., biogenesis, oxidative phosphorylation, fission/fusion, and mitophagy/autophagy) to hypertrophic stimuli, in this study, we used the functional overload (FO) model in adult female rats and examined the plantaris muscle responses at 1 and 10weeks. As expected, the absolute plantaris muscle mass increased by ∼12 and 26% at 1 and 10weeks following the FO procedure, respectively. Myosin heavy-chain isoform types I and IIa significantly increased by 116% and 17%, respectively, in 10-week FO plantaris muscles. Although there was a general increase in protein markers associated with mitochondrial biogenesis in acute FO muscles, this response was unexpectedly sustained under 10-week FO conditions after muscle hypertrophy begins to plateau. Furthermore, the early increase in mito/autophagy markers observed under acute FO conditions was normalized by 10weeks, suggesting a cellular environment favoring mitochondrial biogenesis to accommodate the aerobic demands of the plantaris muscle. We also observed a significant increase in the expression of mitochondrial-, but not nuclear-, encoded oxidative phosphorylation (OXPHOS) proteins and peptides (i.e., humanin and MOTS-c) under chronic, but not acute, FO conditions. Taken together, the temporal response of markers related to the mitochondrial life cycle indicates a pattern of promoting biogenesis and mitochondrial protein expression to support the energy demands and/or enhanced neural recruitment of chronically overloaded skeletal muscle.

NADPH oxidase 4 in mouse β cells participates in inflammation on chronic nutrient overload.

By exposing mice carrying a deletion of NADPH oxidase isoform 4, NOX4, specifically in pancreatic β cells (βNOX4-/-) to nutrient excess stimulated by a high-fat diet (HFD), this study aimed to elucidate the role of β-cell redox status in the development of meta-inflammation within the diabetic phenotype. The authors performed basic phenotyping of βNOX4-/- mice on HFD involving insulin and glycemic analyses, histochemistry of adipocytes, indirect calorimetry, and cytokine analyses. To characterize local inflammation, the study used caspase-1 activity assay, interleukin-1β immunochemistry, and real-time polymerase chain reaction during coculturing of β cells with macrophages. The phenotype of βNOX4-/- mice on HFD was not associated with hyperinsulinemia and hyperglycemia but showed accumulation of excessive lipids in epididymal fat and β cells. Surprisingly, mice showed significantly reduced systemic inflammation. Decreased interleukin-1β protein levels and downregulated NLRP3-inflammasome activity were observed on chronic glucose overload in βNOX4-/- isolated islets and NOX4-silenced INS1-E cells resulting in attenuated proinflammatory polarization of macrophages/monocytes in vitro and in situ and reduced local islet inflammation. Experimental evidence suggests that NOX4 pro-oxidant activity in β cells is involved in NLRP3-inflammasome activation during chronic nutrient overload and participates in local inflammatory signaling and perhaps toward peripheral tissues, contributing to a diabetic inflammatory phenotype.

Impacts of fighting against COVID-19 on critical care nurses’ psychological and physical health: a literature review

Abstract Objective To provide insight into the effects of the coronavirus disease (COVID-19) pandemic on the physical and psychological health of critical care nurses in adult units. Methods A systematic search through the CINAHL, MEDLINE, and EMbase databases were performed. Studies that addressed “critical care nurses,” “COVID-19,” “physical effect,” and “psychological effect” from different perspectives were reviewed. Results A total of 42 articles were reviewed based on 2 aspects: critical care nurses’ psychological and physical health. Negative emotions were the most common conditions: fear, anxiety, depression, and post-traumatic stress disorder (PTSD). Burnout, falling ill and having thoughts of self-harm, fatigue, physical burden, sleeping disorders, and chronic work overload also adversely affected the nurses’ health. The nurses’ health deteriorated because of the changes in the unfamiliar working environment and processes, colossal workload and chronic exhaustion, worries about themselves and their families, social response, and witnessing the death toll. Conclusions Critical care nurses experienced adverse effects of the institutional reaction, social response, and individuals’ reply to the COVID-19 pandemic upon their psychological and physical health. Supporting services and preparation for other unprecedented situations should be sustainably available.

Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism.

One-carbon metabolism is an essential branch of cellular metabolism that intersects with epigenetic regulation. In this work, we show how formaldehyde (FA), a one-carbon unit derived from both endogenous sources and environmental exposure, regulates one-carbon metabolism by inhibiting the biosynthesis of S-adenosylmethionine (SAM), the major methyl donor in cells. FA reacts with privileged, hyperreactive cysteine sites in the proteome, including Cys120 in S-adenosylmethionine synthase isoform type-1 (MAT1A). FA exposure inhibited MAT1A activity and decreased SAM production with MAT-isoform specificity. A genetic mouse model of chronic FA overload showed a decrease n SAM and in methylation on selected histones and genes. Epigenetic and transcriptional regulation of Mat1a and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units.

Mitral Stenosis Berat pada Penyakit Jantung Rematik

Rheumatic Heart Disease (RHD) has high morbidity and mortality. Cardiac valve disorders after rheumatic fever are the leading cause of heart failure in children and young adults. A comprehensive understanding of RHD can help early diagnosis and provide optimal management in the future. It has been reported that a 55-year-old man came to the heart clinic of Bhayangkara Hospital Denpasar for routine control of heart disease. The patient has been diagnosed with rheumatic heart disease since 2018. The patient complains of shortness of breath when walking long distances and doing strenuous activities. The patient was diagnosed with CHF FC II ec RHD + MS moderate-severe (Wilkins score 8) + AF NVR (CHA2DS2VASc 3) and treated with heart failure and antiplatelet medication. Mitral stenosis due to RHD produces the typical pathological features seen in Transthoracic echocardiography (TTE), including fibrous thickening and calcification of the valve leaflets, fusion of the commissures, and thickening and shortening of chordae tendineae. Chronic stress overload on the LA due to MS can cause LA dilatation and trigger AF. RHD patients with AF are recommended for anticoagulation for stroke prevention. Patients with acute rheumatic fever clinical features should be evaluated further and given long-term therapy to prevent more severe heart problems.Keywords: atrial fibrillation, mitral stenosis, rheumatic heart disease

Associations between central pulse pressure, microvascular endothelial function, and fluid overload in peritoneal dialysis patients

ABSTRACT Background Microcirculatory endothelial dysfunction is a complex phenomenon that contributes to the development of cardiovascular disease. However, the relationship between microcirculatory endothelial dysfunction and macrovascular disease remains incompletely understood. Fluid overload is a risk factor for cardiovascular mortality in patients undergoing peritoneal dialysis. Therefore, we investigated the effects of chronic fluid overload on both the microcirculation and macrocirculation in these patients. Methods Thirty patients undergoing peritoneal dialysis were included in this cross-sectional study. We measured their central blood pressure and pulse wave velocity, assessed their microvascular endothelial function using drug-induced iontophoresis with laser Doppler flowmetry, and determined the amount of fluid overload using bioimpedance. We conducted a Spearman correlation analysis, univariate analysis, and stepwise multivariate regression models to determine the associations among the hemodynamic parameters. Results Acetylcholine-induced iontophoresis with laser Doppler flowmetry showed a correlation with both brachial and central pulse pressure (PP), but not with pulse wave velocity. Fluid overload was associated with both central and brachial PP and remained an independent predictor of central PP even after adjusting for multiple factors. However, fluid overload was not associated with microcirculatory endothelial function. Conclusion In peritoneal dialysis patients, we observed a significant association between central PP and microvascular endothelial function, indicating a connection between macrocirculation and microcirculation. However, conclusive evidence regarding fluid overload as a mediator between these circulatory systems is lacking. Further research is needed to investigate this relationship.

The pathology of oxidative stress-induced autophagy in a chronic rotator cuff enthesis tear.

Partial-thickness rotator cuff tears (PTRCTs) are often found in daily orthopedic practice, with most of the tears occurring in middle-aged patients. An anaerobic process and imbalanced oxygenation have been observed in PTRCTs, resulting in oxidative stress. Studies have shown the roles of oxidative stress in autophagy and the potential of unregulated mechanisms causing disturbance in soft tissue healing. This article aims to review literature works and summarize the potential pathology of oxidative stress and unregulated autophagy in the rotator cuff enthesis correlated with chronicity. We collected and reviewed the literature using appropriate keywords, in addition to the manually retrieved literature. Autophagy is a normal mechanism of tissue repair or conversion to energy needed for the repair of rotator cuff tears. However, excessive mechanisms will degenerate the tendon, resulting in an abnormal state. Chronic overloading of the enthesis in PTRCTs and the hypovascular nature of the proximal tendon insertion will lead to hypoxia. The hypoxia state results in oxidative stress. An autophagy mechanism is induced in hypoxia via hypoxia-inducible factors (HIFs) 1/Bcl-2 adenovirus E1B 19-kDa interacting protein (BNIP) 3, releasing beclin-1, which results in autophagy induction. Reactive oxygen species (ROS) accumulation would induce autophagy as the regulator of cell oxidation. Oxidative stress will also remove the mammalian target of rapamycin (mTOR) from the induction complex, causing phosphorylation and initiating autophagy. Hypoxia and endoplasmic reticulum (ER) stress would initiate unfolded protein response (UPR) through protein kinase RNA-like ER kinase (PERK) and activate transcription factor 4, which induces autophagy. Oxidative stress occurring in the hypovascularized chronic rotator cuff tear due to hypoxia and ROS accumulation would result in unregulated autophagy directly or autophagy mediated by HIF-1, mTOR, and UPR. These mechanisms would disrupt enthesis healing.

Perceived stress of mental demands at work, objective stress and resilience – an analysis of the LIFE-Adult-study

BackgroundSo far, previous research suggests positive effects of mental demands at the workplace. However, it may depend on how stressfull these demands are perceived on an individual level.ObjectiveThe aim was to build on previous research by investigating how mental demands are related to stress, overload, and work discontent and whether this relationship is mediated by individuals resources, such as resilience.MethodA sub-sample of the LIFE Adult Cohort (n = 480) was asked to answer questions on sociodemographic characteristics, objective stress (using the Trier Inventory of Chronic Stress (TICS)), and perceptions of stress with regard to verbal and executive mental demands at work.ResultsAccording to generalized linear regression models, higher verbal as well as executive mental demands were associated with higher levels of chronic stress, work overload and discontent. Higher levels of resilience were associated with lower levels of these outcomes. Analyses regarding interaction effects revealed that the interaction between resilience and perceived stress of verbal mental demands was significant only in terms of work overload.ConclusionHigher perceived stressfulness of mental demands was associated with higher chronic stress, work overload and work discontent. Therefore, mental demands should be targeted by occupational interventions that aim to improve job conditions and employees‘ overall well-being. Besides resilience, other potential influencers or personal resources should be focused on in future studies to develop interventions.

FKBP25 regulates myoblast viability and migration and is differentially expressed in in vivo models of muscle adaptation.

FKBP25 (FKBP3 gene) is a dual-domain PPIase protein that consists of a C-terminal PPIase domain and an N-terminal basic tilted helix bundle (BTHB). The PPIase domain of FKBP25 has been shown to bind to microtubules, which has impacts upon microtubule polymerisation and cell cycle progression. Using quantitative proteomics, it was recently found that FKBP25 was expressed in the top 10% of the mouse skeletal muscle proteome. However, to date there have been few studies investigating the role ofFKBP25 in non-transformed systems. As such, this study aimed to investigate potential roles for FKBP25 in myoblast viability, migration and differentiation and in adaptation of mature skeletal muscle. Doxycycline-inducible FKBP25 knockdown in C2C12 myoblasts revealed an increase in cell accumulation/viability and migration in vitro that was independent of alterations in tubulin dynamics; however, FKBP25 knockdown had no discernible impact on myoblast differentiation into myotubes. Finally, a series of in vivo models of muscle adaptation were assessed, where it was observed that FKBP25 protein expression was increased in hypertrophy and regeneration conditions (chronic mechanical overload and the mdx model of Duchenne muscular dystrophy) but decreased in an atrophy model (denervation). Overall, the findings of this study establish FKBP25 as a regulator of myoblast viability and migration, with possible implications for satellite cell proliferation and migration and muscle regeneration, and as a potential regulator of in vivo skeletal muscle adaptation.