Hasil untuk "Internal medicine"

Adam P Wagner, Nicholas J Simmonds, Susan C Charman et al.

Introduction Yoga is an emerging exercise choice for people with cystic fibrosis (CF), but evidence of its effect in this population is scarce, with a recent systematic review advocating for further research. Yoga Outcomes Get Assessed in CF (YOGA-CF) is a real-world multicentre randomised controlled trial (RCT) investigating a bespoke CF-specific online 12-week yoga intervention, vers usual care, to determine effectiveness for adults with CF.Methods and analysis A multicentre RCT of adults with CF across the UK. Participants are randomised to usual care or a 12-week online bespoke yoga programme with an expectation of two classes completed weekly. Assessments of lung function, 1 min sit-to-stand, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and other trial questionnaires are completed preintervention and postintervention (0 and 12 weeks) and after 12 weeks of follow-up (week 24). The primary outcome is the difference in respiratory-related quality of life measured using the CFQ-R before and after yoga/control. Sample size was calculated based on detecting a minimally clinically important difference of 4 for the CFQ-R respiratory domain, with power of 80% and 5% significance level (total target, n=314).Ethics and dissemination Ethics approval gained from the South Yorkshire and Humber Research Ethics Committee (REC) (reference: 23/YH/0270, project ID 303898). Dissemination to involve direct participant feedback and lay webinar, scientific conference presentation and publication in a peer-reviewed journal.Trial registration number NCT06120465.

Amro Al Radaideh, Amritpal Jagra, Murad Qirem et al.

A biliopleural fistula (BPF) is a rare, potentially life-threatening complication of hepatobiliary interventions, often presenting as bilious pleural effusion. Prompt diagnosis is essential, particularly in immunocompromised patients. We report a 74-year-old male with thrombotic thrombocytopenic purpura (TTP) who developed acute acalculous cholecystitis during treatment with plasmapheresis and rituximab. Due to severe thrombocytopenia, a percutaneous cholecystostomy was performed. Two days later, he developed a right-sided pleural effusion with recurrent fever. Thoracentesis yielded bilious fluid, and imaging revealed a hepatic abscess with a fistulous tract. The patient was treated with chest tube drainage, broad-spectrum antibiotics and endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression. This multidisciplinary approach led to closure of the fistula and full clinical recovery. This case highlights the importance of considering BPF in patients with new pleural effusion following hepatobiliary procedures. Early pleural fluid bilirubin analysis, targeted imaging and coordinated management with drainage and ERCP are crucial for favourable outcomes in high-risk patients.

M. Camila Melo-Narvaez, Fee Gölitz, Eshita Jain et al.

Abstract Background Human precision-cut lung slices (hPCLS) are a unique platform for functional, mechanistic, and drug discovery studies in the field of respiratory research. However, tissue availability, generation, and cultivation time represent important challenges for their usage. Therefore, the present study evaluated the efficacy of a specifically designed tissue preservation solution, TiProtec, complete or in absence (-) of iron chelators, for long-term cold storage of hPCLS. Methods hPCLS were generated from peritumor control tissues and stored in DMEM/F-12, TiProtec, or TiProtec (-) for up to 28 days. Viability, metabolic activity, and tissue structure were determined. Moreover, bulk-RNA sequencing was used to study transcriptional changes, regulated signaling pathways, and cellular composition after cold storage. Induction of cold storage-associated senescence was determined by transcriptomics and immunofluorescence (IF). Finally, cold-stored hPCLS were exposed to a fibrotic cocktail and early fibrotic changes were assessed by RT-qPCR and IF. Results Here, we found that TiProtec preserves the viability, metabolic activity, transcriptional profile, as well as cellular composition of hPCLS for up to 14 days. Cold storage did not significantly induce cellular senescence in hPCLS. Moreover, TiProtec downregulated pathways associated with cell death, inflammation, and hypoxia while activating pathways protective against oxidative stress. Cold-stored hPCLS remained responsive to fibrotic stimuli and upregulated extracellular matrix-related genes such as fibronectin and collagen 1 as well as alpha-smooth muscle actin, a marker for myofibroblasts. Conclusions Optimized long-term cold storage of hPCLS preserves their viability, metabolic activity, transcriptional profile, and cellular composition for up to 14 days, specifically in TiProtec. Finally, our study demonstrated that cold-stored hPCLS can be used for on-demand mechanistic studies relevant for respiratory research. Graphical Abstract

Silvia Palombella, Silvia Lopa, Camilla Recordati et al.

Abstract Background Osteoarthritis is a common degenerative joint disease marked by cartilage degeneration and inflammation. This study investigates the therapeutic potential of adipose-derived stromal cells (ASCs) and their secretome in a rat model of osteoarthritis. Methods ASCs were extracted from human adipose tissue, cultured, and primed with human platelet lysate. The secretome was collected after 48 h of serum-free culture. Osteoarthritis was induced in rats using monosodium iodoacetate, and after 14 days, they were treated with saline solution, ASCs, or secretome. Over five weeks, body weight and histopathological changes were monitored. Results No clinical complications arose post-treatment, and all rats gained weight similarly. ASC treatment increased histopathological changes associated with osteoarthritis, including severe cartilage necrosis and bone remodeling. Conversely, the secretome treatment resulted in mild to moderate cartilage degeneration, similar to that observed in the control group. These findings suggest that ASCs may contribute to disease progression in this model, while the secretome did not show significant effects on cartilage histology compared to the control group. Further studies are needed to determine whether optimizing the secretome composition or dosing could enhance its therapeutic potential. Conclusions This study highlights the complexity of ASC interactions with the immune system, while secretome may be a well-tolerated treatment, further studies are needed to determine its potential therapeutic benefits.

Stanley E. Lazic

Reproducibility is central to the credibility of scientific findings, yet complete replication studies are costly and infrequent. However, many biological experiments contain internal replication, which is defined as repetition across batches, runs, days, litters, or sites that can be used to estimate reproducibility without requiring additional experiments. This internal replication is analogous to internal validation in prediction or machine learning models, but is often treated as a nuisance and removed by normalisation, missing an opportunity to assess the stability of results. Here, six types of internal replication are defined based on independence and timing. Using mice data from an experiment conducted at three independent sites, we demonstrate how to quantify and test for internal reproducibility. This approach provides a framework for quantifying reproducibility from existing data and reporting more robust statistical inferences in preclinical research.

Erik Horsdal

The forces that act internally in a trebuchet as it delivers a shot depend on the motions of throwing arm, counterweight and sling. These motions are considered known experimentally or theoretically and given in the form of time-dependent angular coordinates. Explicit expressions in terms of these coordinates and their derivatives to second order are derived for the internal forces. The forces that act immediately after a shot is initiated can be extracted from the equations of motion without solving them, and they are compared with static forces just prior to initiation. Required strengths of the different parts of a trebuchet depend on the internal forces, which also determine sliding friction losses. Illustrative results are given for a specific trebuchet.

Matthias Jung, Hanna Rieder, Marco Reisert et al.

Abstract Background There is increasing evidence that myosteatosis, which is currently not assessed in clinical routine, plays an important role in risk estimation in individuals with impaired glucose metabolism, as it is associated with the progression of insulin resistance. With advances in artificial intelligence, automated and accurate algorithms have become feasible to fill this gap. Methods In this retrospective study, we developed and tested a fully automated deep learning model using data from two prospective cohort studies (German National Cohort [NAKO] and Cooperative Health Research in the Region of Augsburg [KORA]) to quantify myosteatosis on whole‐body T1‐weighted Dixon magnetic resonance imaging as (1) intramuscular adipose tissue (IMAT; the current standard) and (2) quantitative skeletal muscle (SM) fat fraction (SMFF). Subsequently, we investigated the two measures for their discrimination of and association with impaired glucose metabolism beyond baseline demographics (age, sex and body mass index [BMI]) and cardiometabolic risk factors (lipid panel, systolic blood pressure, smoking status and alcohol consumption) in asymptomatic individuals from the KORA study. Impaired glucose metabolism was defined as impaired fasting glucose or impaired glucose tolerance (140–200 mg/dL) or prevalent diabetes mellitus. Results Model performance was high, with Dice coefficients of ≥0.81 for IMAT and ≥0.91 for SM in the internal (NAKO) and external (KORA) testing sets. In the target population (380 KORA participants: mean age of 53.6 ± 9.2 years, BMI of 28.2 ± 4.9 kg/m2, 57.4% male), individuals with impaired glucose metabolism (n = 146; 38.4%) were older and more likely men and showed a higher cardiometabolic risk profile, higher IMAT (4.5 ± 2.2% vs. 3.9 ± 1.7%) and higher SMFF (22.0 ± 4.7% vs. 18.9 ± 3.9%) compared to normoglycaemic controls (all P ≤ 0.005). SMFF showed better discrimination for impaired glucose metabolism than IMAT (area under the receiver operating characteristic curve [AUC] 0.693 vs. 0.582, 95% confidence interval [CI] [0.06–0.16]; P < 0.001) but was not significantly different from BMI (AUC 0.733 vs. 0.693, 95% CI [−0.09 to 0.01]; P = 0.15). In univariable logistic regression, IMAT (odds ratio [OR] = 1.18, 95% CI [1.06–1.32]; P = 0.004) and SMFF (OR = 1.19, 95% CI [1.13–1.26]; P < 0.001) were associated with a higher risk of impaired glucose metabolism. This signal remained robust after multivariable adjustment for baseline demographics and cardiometabolic risk factors for SMFF (OR = 1.10, 95% CI [1.01–1.19]; P = 0.028) but not for IMAT (OR = 1.14, 95% CI [0.97–1.33]; P = 0.11). Conclusions Quantitative SMFF, but not IMAT, is an independent predictor of impaired glucose metabolism, and discrimination is not significantly different from BMI, making it a promising alternative for the currently established approach. Automated methods such as the proposed model may provide a feasible option for opportunistic screening of myosteatosis and, thus, a low‐cost personalized risk assessment solution.

S. Navarro-Obregón, J. Queiruga

We study the sphaleron solutions in two deformations of the $φ^6$ model and analyze the oscillons originated from them. We find that the presence of internal modes plays a crucial role in the sphaleron collapse. The positive internal modes triggered by a squeezing of the sphaleron are able to change the direction of collapse. We provide an analytical understanding behind this phenomenon.

Noam Schiller, Hiromi Ebisu, Gil Refael et al.

We demonstrate that the effective internal entropy of quasiparticles within the non-Abelian fractional quantum Hall effect manifests in the heat current through a tunneling barrier. We derive the electric current and heat current resulting from voltage and heat biases of the junction, taking into account the quasiparticles' internal entropy. We find that when the tunneling processes are dominated by quasiparticle tunneling of one type of charge, the effective internal entropy can be inferred from the measurement of the heat current and the charge current. Our methods may be used to conclusively identify non-Abelian quasiparticles, such as the anyons that emerge in the $ν= 5/2$ fractional quantum Hall state.

Xiaoye Wang, Nicole Xi Zhang, Hongyu He et al.

Recent advancements in artificial intelligence (AI), particularly in large language models (LLMs), have unlocked significant potential to enhance the quality and efficiency of medical care. By introducing a novel way to interact with AI and data through natural language, LLMs offer new opportunities for medical practitioners, patients, and researchers. However, as AI and LLMs become more powerful and especially achieve superhuman performance in some medical tasks, public concerns over their safety have intensified. These concerns about AI safety have emerged as the most significant obstacles to the adoption of AI in medicine. In response, this review examines emerging risks in AI utilization during the LLM era. First, we explore LLM-specific safety challenges from functional and communication perspectives, addressing issues across data collection, model training, and real-world application. We then consider inherent safety problems shared by all AI systems, along with additional complications introduced by LLMs. Last, we discussed how safety issues of using AI in clinical practice and healthcare system operation would undermine trust among patient, clinicians and the public, and how to build confidence in these systems. By emphasizing the development of safe AI, we believe these technologies can be more rapidly and reliably integrated into everyday medical practice to benefit both patients and clinicians.

Lawrence A Leiter, David G Kallend, Wolfgang Koenig et al.

Therapeutic Area: ASCVD/CVD Risk Factors Background: Excessive bodyweight, often associated with dyslipidemia, may affect the pharmacology of drugs. Inclisiran, a small interfering RNA targeting PCSK9 hepatic mRNA, is an effective LDL-C lowering agent with twice-yearly subcutaneous dosing (after the initial and 3-month doses). The aim of this analysis was to assess the efficacy and safety of inclisiran in patients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent across body mass index (BMI) strata. Methods: In this post hoc analysis from ORION-9 (NCT03397121), ORION-10 (NCT03399370) and ORION-11 (NCT03400800), eligible patients were randomized 1:1 to receive 300 mg inclisiran sodium (equivalent to 284 mg inclisiran) or placebo at baseline, Day 90 and 6-monthly thereafter. Analysis was stratified by baseline BMI: <25, 25–<30, 30–<35 or ≥35 kg/m2. Percentage change in atherogenic lipids from baseline at Day 510 was evaluated. Safety was assessed over 540 days. Results: Baseline demographic and clinical characteristics including atherogenic lipid levels were mostly balanced between treatment arms and across BMI strata (Table). Percentage change in atherogenic lipids from baseline at Day 510 was significantly greater with inclisiran vs placebo within each BMI stratum (Table). Treatment-emergent adverse events (TEAE) and treatment-emergent serious adverse events were generally similar between treatment arms and were reported more frequently with increasing BMI strata (data not shown). Clinically relevant TEAEs at the injection site were reported more frequently with inclisiran vs placebo similarly across strata, but all were mild or moderate. Conclusion: Twice-yearly dosing with inclisiran (after the initial and 3-month doses) provided effective and sustained lipid lowering in patients, irrespective of their baseline BMI, and was generally well tolerated.

Rei Otsuki, Rei Otsuki, Rei Otsuki et al.

Daniel Alexis Zárate-Rendón, David Godoy Padilla, Samuel Pizarro Carcausto et al.

This study aimed to develop maps for Fasciola hepatica infection occurrence in dairy cattle in the districts of Matahuasi and Baños in the Peruvian central highlands. For this, a model based on the correlation between environmental variables and the prevalence of infection was constructed. Flukefinder® coprological test were performed in samples from dairy cattle from 8 herds, during both the rainy and wet season. Grazing plots were geo-referenced to obtain information on environmental variables. Monthly temperature, monthly rainfall, elevation, slope, normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), normalized difference water index (NDWI), distance to rivers, urban areas and roads were obtained by using remote sensor images and ArcGIS®. Multilayer perceptron Artificial Neural Networks modeling were applied to construct a predictive model for the occurrence of fasciolosis, based on the relationship between environmental variables and level of infection. Kappa coefficient (k > 0.6) was used to evaluate concordance between observed and forecasted risk by the model. Coprological results demonstrated an average prevalence from 20% to 100%, in Matahuasi, and between 0 and 87.5%, in Baños. A model with a high level of concordance between predicted and observed infection risk (k = 0.77) was obtained, having as major predicting variables: slope, NDWI, NDVI and EVI. Fasciolosis risk was categorized as low (p < 20%), medium (20% < p < 50%) and high (p ≥ 50%) level. Using ArcGIS 10.4.1, risk maps were developed for each risk level of fasciolosis. Maps of fasciolosis occurrence showed that 87.2% of Matahuasi area presented a high risk for bovine fasciolosis during the dry season, and 76.6% in the wet season. In contrast, 21.9% of Baños area had a high risk of infection during the dry season and 12.1% during the wet season. In conclusion, our model showed areas with high risk for fasciolosis occurrence in both districts during both dry and rainy periods. Slope, NDWI, NDVI and EVI were the major predictors for fasciolosis occurrence.

Takumi Hirose, Toshiki Takayama , Nobuto Shibata et al.

Aseel Alsouqi, Serpil Muge Deger, Melis Sahinoz et al.

Background Sodium (Na+) stored in skin and muscle tissue is associated with essential hypertension. Sodium magnetic resonance imaging is a validated method of quantifying tissue stores of Na+. In this study, we evaluated tissue Na+ in patients with elevated blood pressure or stage I hypertension in response to diuretic therapy or low Na+ diet. Methods and Results In a double‐blinded, placebo‐controlled trial, patients with systolic blood pressure 120 to 139 mm Hg were randomized to low sodium diet (<2 g of sodium), chlorthalidone, spironolactone, or placebo for 8 weeks. Muscle and skin Na+ using sodium magnetic resonance imaging and pulse wave velocity were assessed at the beginning and end of the study. Ninety‐eight patients were enrolled to undergo baseline measurements and 54 completed randomization. Median baseline muscle and skin Na+ in 98 patients were 16.4 mmol/L (14.9, 18.9) and 13.1 mmol/L (11.1, 16.1), respectively. After 8 weeks, muscle Na+ increased in the diet and chlorthalidone arms compared with placebo. Skin sodium was decreased only in the diet arm compared with placebo. These associations remained significant after adjustment for age, sex, body mass index, systolic blood pressure, and urinary sodium. No changes were observed in pulse wave velocity among the different groups when compared with placebo. Conclusions Diuretic therapy for 8 weeks did not decrease muscle or skin sodium or improve pulse wave velocity in patients with elevated blood pressure or stage I hypertension. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02236520.

N. A. Cherepanova, A. D. Erlikh, T. V. Pavlova et al.

Aim. To validate the SIRENA score  in assessing the risk of inhospital mortality in patients with pulmonary embolism (PE) in an independent sample.Material and methods. This retrospective, single-center study was based on the Samara Regional Cardiology Center. The risk of inhospital mortality was assessed using the SIRENA score, which includes such parameters as left ventricular ejection fraction &lt;40%,  immobilization in prior 12 months, creatinine clearance &lt;50 ml/min, syncope, cyanosis on admission. For each positive sign, 1 point is assigned. Low risk is set at score of 0-1, high — ≥2.Results. The study included 452 patients with PE hospitalized from 2004 to 2019, of which 221 (48,9%) were men (mean age, 60,0 years (50,5-70,0)).  With SIRENA score of 0, 1, 2, 3, and 4, inhospital mortality was 4,1%, 10,8%, 18,8%, 40,0%, and 100%, respectively. Mortality at SIRENA low risk (&lt;2) was 7,1%, and at high risk (≥2) — 20,5% (odds ratio (OR), 3,34; 95% confidence interval (CI), 1,74-6,43; p&lt;0,001).  The predictive sensitivity and specificity for inhospital mortality for the SIRENA score were 70,5% and 60,8%, respectively. Area under the ROC-curve for the SIRENA score was 0,71 (95% CI, 0,63-0,79), while for Simplified Pulmonary Embolism Severity Index (sPESI) — 0,69 (95%  CI, 0,60-0,77).  With high risk on both scales (sPESI and SIRENA), inhospital mortality was 24,2% (OR, 4,09, 95% CI, 2,07-8,09; p&lt;0,001).Conclusion. On an independent sample, the SIRENA score  showed  a high predictive ability in predicting adverse outcomes in patients with PE with a sensitivity of 70,5% and a specificity of 60,8% (AUC=0,71, 95% CI, 0,63-0,79), comparable with the sPESI.

Bruno Gonçalves Galdino da Costa, Jean-Philippe Chaput, Marcus Vinicius Veber Lopes et al.

Background: Physical activity, sleep, and sedentary behaviors compose 24-h movement behaviors and have been independently associated with depressive symptoms. However, it is not clear whether it is the movement behavior itself or other contextual factors that are related to depressive symptoms. The objective of the present study was to examine the associations between self-reported and accelerometer-measured movement behaviors and depressive symptoms in adolescents. Methods: Cross-sectional data from 610 adolescents (14–18 years old) were used. Adolescents answered questions from the Center for Epidemiological Studies Depression scale and reported time spent watching videos, playing videogames, using social media, time spent in various physical activities, and daytime sleepiness. Wrist-worn accelerometers were used to measure sleep duration, sleep efficiency, sedentary time, and physical activity. Mixed-effects logistic regressions were used. Results: Almost half of the adolescents (48%) were classified as being at high risk for depression (score ≥20). No significant associations were found between depressive symptoms and accelerometer-measured movement behaviors, self-reported non-sport physical activity, watching videos, and playing videogames. However, higher levels of self-reported total physical activity (odd ratio (OR) = 0.92, 95% confidence interval (95%CI): 0.86–0.98) and volume of sports (OR = 0.88, 95%CI: 0.79–0.97), in minutes, were associated with a lower risk of depression, while using social media for either 2.0–3.9 h/day (OR = 1.77, 95%CI: 1.58–2.70) or >3.9 h/day (OR = 1.67, 95%CI: 1.10–2.54), as well as higher levels of daytime sleepiness (OR = 1.17, 95%CI: 1.12–1.22), were associated with a higher risk of depression. Conclusion: What adolescents do when they are active or sedentary may be more important than the time spent in the movement behaviors because it relates to depressive symptoms. Targeting daytime sleepiness, promoting sports, and limiting social media use may benefit adolescents.

S. Ettinger, E. Feldman

Bárbara Otonín Rodríguez, Tania Lorca Sánchez

ABSTRACT At the end of 2019, a disease was identified, COVID-19, caused by a new type of easy and fast spreading virus, which led to the beginning of a worldwide pandemic. One of the most exposed groups to the virus and its psychosocial consequences is the healthcare workers, due to their implication in caring for affected people. Health workers are exposed to a fast and unpredictable situation that requires more human resources and materials than usual, however, the lack of means on account to this situation entails an increased probability of suffering different consequences, including the burnout syndrome, to which, generally, this professionals are already vulnerable. In addition, quarantine is added as a measure to prevent the spread of the pandemic, which is another handicap for healthcare workers. Quarantine means these professionals are more likely to suffer the foreseeable psychological consequences in general population, specifically, it has been observed that Post-Traumatic Stress Disorder (PTSD) is more prevalent, because of the stress load of the situation experienced.

Zahra Hassanzadeh-Rostami, Fatemeh Mirjalili, Monireh Panbehkar et al.

Background: Thiamine is an essential nutrient, and its deficiency is accompanied by nervous and cardiovascular disorders. This study aimed to assess the prevalence of thiamine deficiency and associated factors among adults in Shiraz, southern Iran. Methods: In a cross-sectional study using random multistage sampling method, 180 men and women who were 20-60 years old were enrolled. Demographic data were collected and a food frequency questionnaire was used to assess dietary intakes. Serum transketolase level was measured to estimate thiamine deficiency. Results: Mean serum transketolase level was 2.19±2.71 ng/dL, and the mean intake of thiamine was 1.39±0.58 mg/day. Overall serum transketolase level was in the normal range of 0.05-9 ng/dL; however, it was lower than 0.88 ng/dL among 50% of the subjects. No significant association was found between serum transketolase level and either dietary intake of thiamine and weekly intake of whole bread. Conclusion: Despite the normal serum transketolase level and dietary intake of thiamine, half of the participants were at lower levels of serum transketolase. Therefore, increasing the knowledge of the community about dietary sources of thiamine could prevent thiamine deficiency and enhance their health status.