Decline In Function Research Articles

Environmental factors and chronic kidney disease: a case-control study

Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders causing abnormal renal function and progressive decline in the glomerular filtration rate (GFR). This study aimed to investigate the associations of several Environmental factors with CKD in the Iranian population. This is the second phase of a hospital-based case-control study, which was conducted on 700 participants (350 CKD cases and 350 controls, age and gender frequency matched). Multiple logistic regression was applied to measure the associations between the selected factors and CKD. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All p-values were two-sided and the results were considered statistically significant at p < 0.05. The results suggested that environmental factors including proximity of residence to mines (OR yes/no=3.98, 95%CI: 2.20–7.21, p < 0.001), proximity of residence to mobile antenna (OR yes/no=2.20, 95%CI: 1.24–3.89, p = 0.006), and exposure to chemicals (OR chemical/no=4.40, 95%CI: 2.27–8.53, p < 0.001), were significantly associated with a higher risk of CKD. The present study covered a large number of factors in association with CKD and highlighted the importance of some environmental factors in development of CKD.‌ One of the main causes of heat in the work environment being a risk factor is dehydration caused by high heat. In order to reduce damage to the kidneys in jobs that deal with high heat, the following tips are recommended: drinking fluids, reducing working hours and shifts, proper ventilation in the workplace, using suitable clothes and heat protection.

Economic Valuation of Ecosystem Services of Coastal Area of Kinondoni District, Tanzania

This study investigates the often overlooked economic values of ecosystem services in the coastal area of Kinondoni District, Tanzania, in the context of spatial and temporal changes in land use and land cover (LULC). The primary objectives were to assess how ecosystem services and functions have been affected by LULC changes over a 30-year period, from 1993 to 2023. The study employs a benefit transfer method, integrating local and global estimations of ecosystem service value (ESV) with field survey, remote sensing and GIS techniques. The findings reveal that the annual changes in ESV during the study period are estimated at US$ 0.024 million and US$ 0.034 million using local and global coefficients, respectively. Over the three decades, there has been a significant annual loss of US$ 0.72 million locally and US$ 2.11 million globally, primarily due to the degradation of mangrove forests and bushland. The decline in ecosystem functions is largely driven by reductions in regulating services, which account for 54.1% of the total decrease in local valuations and 31.6% in global valuations. Supporting services also experienced substantial declines, with reductions of 39.7% in local valuations and 55.8% in global valuations. The study underscores the urgent need to review and enhance management and conservation strategies to ensure the sustainability of the coastal ecosystems in Kinondoni District, Tanzania.

Detection of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease using home monitoring in the Netherlands (DecreaSSc): a prospective, observational study

In patients with systemic sclerosis, interstitial lung disease (ILD) is the leading cause of mortality. Early detection of progressive ILD associated with systemic sclerosis is warranted for timely adjustment of management strategies and improved prognosis. We aimed to investigate the validity of home spirometry to detect a decline in pulmonary function in patients with systemic sclerosis-associated ILD. DecreaSSc was a prospective, observational study done in two tertiary referral centres in the Netherlands. Eligible patients were aged 18 years or older, fulfilled the American College of Rheumatology-European Alliance of Associations for Rheumatology criteria for systemic sclerosis, had a disease duration from first non-Raynaud phenomenon symptom of 5 years or less, had high-resolution CT-confirmed diagnosis of ILD, and had a maximum immunosuppressive treatment duration of 8 weeks at baseline. Patients took weekly home spirometry measurements using a handheld spirometer for 1 year. At baseline and at semi-annual study visits, patients pulmonary function testing was done in the hospital and patients completed questionnaires on patient-reported outcome measurements. The primary outcome was the κ agreement between home and hospital measurements after 1 year to detect a decline in force vital capacity (FVC) of 5% or more, estimated using separate linear regression analyses for home-based and hospital-based FVC% predicted in individual patients. The sensitivity and specificity of home spirometry to detect an absolute decline in FVC% predicted of 5% or more was assessed using the hospital pulmonary function test as the gold standard. The longitudinal correlation between hospital and home measurements was assessed with regression analysis, whereas the cross-sectional correlation was assessed with the intraclass coefficient. People with lived experience were involved at several stages of the study. Between Jan 26, 2021, and Feb 27, 2023, 43 patients were enrolled, 35 of whom completed 6 months of follow-up and 31 of whom completed 12 months of follow-up. The last follow-up visit took place on March 28, 2024. 20 (57%) of patients were women and 15 (43%) were men; 32 (91%) were White. Mean age was 57·7 years (SD 10·7). The agreement between hospital and home measurements had a κ value of 0·40 (95% CI 0·01-0·79). The sensitivity of home spirometry to detect a decline in FVC% predicted of 5% or more was 60% (95% CI 44-76) and specificity was 87% (75-98). Regression analysis showed that the course of pulmonary function was not different between hospital and home assessment as the interaction term was not significant (-0·0003 [95% CI -0·0006 to 0·000008]; p=0·057) with a longitudinal correlation of 0·55 (95% CI 0·26-0·74; p=0·0070). The intraclass coefficient between both measurements was 0·85 (95% CI 0·73-0·92; p<0·0001) at baseline, 0·84 (0·71-0·92; p<0·0001) at 6 months, and 0·72 (0·50-0·86; p<0·0001) at 12 months. Home spirometry has the potential to detect a decline in pulmonary function in patients with systemic sclerosis-associated ILD earlier when used in addition to regular health care management. Future research could reveal whether home spirometry can contribute to improved outcomes of patients with systemic sclerosis-associated ILD. Galapagos and Boehringer Ingelheim.

An overview of the relationship between inflammation and cognitive function in humans, molecular pathways and the impact of nutraceuticals

Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer’s disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.

Effects of Respiratory Training on Pulmonary Function, Cough, and Functional Independence in Patients with Amyotrophic Lateral Sclerosis

Background: Respiratory complications in patients with amyotrophic lateral sclerosis (ALS), due to the involvement of respiratory muscles, are the leading cause of death, and respiratory physiotherapy (RP) focuses on addressing these complications. Objectives: The objective was to evaluate the effectiveness of an RP intervention that combines the four specific techniques (inspiratory muscle training, lung volume recruitment, manually assisted coughing, and diaphragmatic breathing training) in patients with ALS. Methods: A quasi-experimental study was carried out, and a specific RP programme was implemented in 15 patients with ALS (12 sessions, 30 min/session, one session/week, duration of three months), based on directed ventilation techniques, lung volume recruitment, manually assisted coughing, and the use of incentive spirometry and a cough assist device, along with a daily home exercise programme. Respiratory functions were assessed (pre- and post-intervention, with follow-up at three months) using Forced Vital Capacity (FVC) and Peak Expiratory Cough Flow (PECF); functionality was assessed using the Revised ALS Functional Rating Scale (ALSFRS-R) and the Modified Barthel Index by Granger. Results: FVC experienced an increase after three months of the intervention initiation (p = 0.30), which was not sustained at the three-month follow-up after the intervention ended. All other variables remained practically constant after treatment, with their values decreasing at follow-up. Conclusion: A specific RP intervention could have beneficial effects on respiratory functions, potentially preventing pulmonary infections and hospitalisations in patients with ALS. It may improve FVC and help stabilize the patient's functional decline. Considering the progressive and degenerative nature of the disease, this finding could support the usefulness of these techniques in maintaining respiratory function.

Efficacy of obstructive sleep apnea treatment in reducing fall risk in older adults: study protocol for a clinical trial

BackgroundFalls are a major cause of hospitalization fractures and functional decline in older adults. Obstructive sleep apnea (OSA), a highly prevalent sleep breathing disorder in older adults, has emerged as a potentially modifiable risk factor for falls. A small number of uncontrolled studies suggest OSA therapy by continuous positive airway pressure (CPAP) may reduce fall risk. We aim to describe the design of a randomized clinical trial that will evaluate if six months of CPAP intervention can significantly reduce fall risk markers in older adults with OSA. Methods140 adults aged ≥60 years at risk of falls with diagnosed and untreated OSA will be randomized to receive CPAP and usual care for fall risk or only usual care for fall risk. The primary outcome will be the difference in fall risk scores, derived from the physiological profile assessment, between the two arms six months post-randomization. Secondary outcomes will include differences in gait, quality of life, sleep quality (self-reported and objective home-based monitoring), psychological well-being, cognitive function, physical performance, muscle strength, and body composition at six months post-randomization. ResultsData will be analyzed on an intention-to-treat basis. Ethical approval was obtained from Southern Adelaide Clinical Human Research Ethics Committee in July 2023 (reference: 2023/HRE00081). Outcomes will be disseminated through publication in peer-reviewed journals and presentations at international conferences. Trial registration number: Australian New Zealand Clinical Trials Registry (ACTRN) 12623000965606 ConclusionThe findings from this study will provide insight into the causal associations between OSA and fall risk and contribute to high quality evidence required to inform larger clinical trials and future guidelines for fall prevention

Patient scoring of outcomes for clinical trials that compare treatment options for bloodstream infections: a survey among adult inpatients

ObjectivesPatients' perspectives on outcomes of clinical trials is critical to the design of meaningful trials. As they are the primary recipients of treatment, it is important to focus on outcomes that are of value to the patients. We planned a study involving patients in defining and prioritizing endpoints for intervention trials for bloodstream infections (BSI). MethodsA survey was conducted at Rambam Health Care Campus, targeting hospitalized patients over 18 years old. Participants were asked to score the importance of various outcomes on a scale of 1 to 10, 10 being most important. We calculated the mean and median and dispersion measures per outcome. Results732 randomly selected patients were approached; 378 were not available due to technical reasons. Of the remaining 354 approached to take the survey, 300 consented and participated in the study. The median age was 51.9 years, with 55.3% female. Death was scored as the most important outcome, while the length of hospital stay was the least important. ConclusionsEliciting patient views on outcome importance was challenging but revealed key insights. Patients prioritized death, functional decline, and the development of secondary infections. Non-clinical outcomes, such as microbiological failure, were less clearly understood. Future studies should focus on clinical outcomes and include larger, more diverse patient populations to enhance the relevance of BSI trials.

In Silico Analysis of novel Phytocompounds targetting Dipeptidyl peptidase 4 Enzyme: A New Link between Prediabetes and its cardio-metabolic complications

BackgroundDPP-4 inhibitors, are widely used clinically for treatment of Diabetes. Increase in circulating DPP4 levels have been well demonstrated in patients with Type 2 Diabetes mellitus. The present study assessed the contribution of DPP-4 axis to the pathophysiology of Prediabetes and its cardiometabolic complications. In addition, in silico analysis of phytocompounds that target DPP 4 enzyme was undertaken to identify novel Phytocompounds with therapeutic potential in Prediabetes. MethodologyA novel experimental model of Prediabetes coexisting with hypertension and dyslipidemia was developed in experimental rats to elucidate the pathophysiological role of DPP-4 in Prediabetes and its resultant cardio-metabolic sequale. In the Prediabetic rats, DPP-4 levels, lipid profile, blood pressure readings, fasting blood sugar values, insulin resistance, beta cell function were measured and compared to Normal Control group. In addition, the DPP-4 Inhibitory activity of Phytocompounds (Arjunetin, Guggulsterone) was studied by molecular docking studies including Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), DPP 4 binding affinity and Protein-ligand simulation between the DPP4 and the Phytocompounds was performed. Results were compared to Vildagliptin, the synthetic DPP-4 inhibitor and metformin (Glucophage), the standard antidiabetic drug used in clinical settings. ResultsA statistically significant increase (p < 0.001) in DPP-4 levels along with a decline in bea cell function with increase in Insulin resistance was observed in Prediabetic rats. A positive correlation (p < 0.001) between serum DPP-4 with HbA1c, lipids, and systolic blood pressure was found. The novel model of Prediabetes co-existing with hypertension and dyslipidemia was successfully developed and validated. The silico active site interaction data from simulation studies demonstrated that Arjunetin and Guggulsterone shows effective and stable binding with DPP-4. Arjunetin maintains its contact with Glu205, Glu206, and Asn710 and by interacting with Val207 and His740, it effectively occupies the flanking residues of the active site area. Based on their protein-ligand contact report, Vildagliptin maintains its connection through Tyr547 and during simulation, Guggulsterone interacts with Ser630. ConclusionThe current study offers experimental evidence of DPP-4′s causal role in the development of cardio-metabolic consequences (dyslipidemia and hypertension) of Prediabetes. Arjunetin and Guggulsterone are two Phytocompounds whose potential as promising DPP-4 inhibitors has been further documented using in silico molecular docking studies.

Intramuscular injection of Bothrops jararaca venom provoked acute kidney injury (AKI): Underpinned by impaired renal filtration, Na+ handling, and tissue damage

Globally, about 2.5 million people are victims of snakebites annually. In Brazil, the most clinically relevant snake is the Bothrops jararaca. The symptoms of envenomation are acute inflammation at the bite site and bleeding disorders. Despite kidney failure being the main cause of death after envenomation, kidney damage is not completely understood, and there are no clinically representative in vivo models. This work aimed to characterize the acute kidney injury (AKI) induced by intramuscular injection (IM) of Bothrops jararaca (Bjc) venom in male Wistar rats. The control group received 0.9% saline solution. Three doses of venom (3.5, 6.0, and 8.0 mg/kg) were administered IM into the posterior region of the right knee. After the injection, the rats were kept in metabolic cages. The following parameters were analyzed after 24 h: the extent of muscle damage and kidney damage (urinary creatinine, proteinuria, plasma creatinine, and renal tissue histology). All rats presented a hemorrhagic lesion at the injection site in a dose-dependent manner. Biochemical parameters indicated kidney damage: plasma creatinine accumulation, decreased glomerular filtration rate, albuminuria and proteinuria, and disturbance in Na+ homeostasis. Histological analyses showed glomerular injury, tissue discontinuity more evident in the cortex and tubular dilatation, and collagen deposition. The decline in renal function and tissue damage indicated the occurrence of AKI. Therefore, a Bjc venom-induced in vivo model of renal injury has been established for future studies.

Early Alzheimer's disease diagnosis via handwriting with self-attention mechanisms.

The neurodegenerative diseases like Alzheimer's disease (AD) can result in progressive decline in both cognitive functions and motor skills, which have critical need for accurate early diagnosis. However, current diagnosis approaches primarily rely on timely clinical magnetic resonance imaging (MRI) scans, which impede widely application for potential patients. Leveraging handwriting as a diagnostic tool offers significant potential for identifying AD in its early stages. This study aims to develop an efficient, rapid, and accurate method for early diagnosis of AD by utilizing handwriting analysis, a promising avenue due to its association with compromised motor skills in neurodegenerative diseases. We propose a novel methodology that leverages self-attention mechanisms for the early diagnosis of AD. Our approach integrates data from 25 distinct handwriting tasks available in the DARWIN (Diagnosis AlzheimeR WIth haNdwriting) dataset. The Self-Attention model achieved an accuracy of 94.3% and an F1-score of 94.5%, outperforming other state-of-the-art models, including traditional machine learning and deep learning approaches. Specially, the Self-Attention model surpassed the previous best model, the convolutional neural networks, by approximately 4% in both accuracy and F1-score. Additionally, the model demonstrated superior precision (94.7%), sensitivity (94.5%), and specificity (94.1%), indicating high reliability and excellent identification of true positive and true negative cases, which is crucial in medical diagnostics. Handwriting analysis, powered by self-attention mechanisms, offers significant potential as a diagnostic tool for identifying AD in its early stages, providing an effective alternative to traditional MRI-based diagnosis.

Comparing 30 Versus 60min Cognitively Loaded Physical Exercise on Cognitive Function and Physical Health in Community-Dwelling Older Adults With Mild Cognitive Impairment: A Double-Blind Randomized Controlled Trial.

Mild cognitive impairment (MCI) is characterized by a mild decline in cognitive function and represents a risk stage for dementia in community-dwelling older adults. Exercise and dual-task training have been used to improve physical health, psychosocial health, and cognitive and learning functions in various subjects. However, the optimal time for these interventions has yet to be clearly identified. This study investigated the effects of cognitively loaded physical exercise (CLPE) on cognitive function and physical health in community-dwelling older adults with mild cognitive impairment and compared the differences according to exercise time. Fifty-one community-dwelling aged 60years or older with MCI were randomly assigned to 30-min CLPE (30CLPE, n=17), 60-min CLPE (60CLPE, n=17), and control (n=17) groups. The CLPE program consisted of a twice-weekly exercise program for 8weeks. During the exercise, a dual task was performed to assess cognitive load. The control group performed a typical exercise program at a dementia center during the same period. The Korean version of the Montreal Cognitive Assessment was used to evaluate cognitive function, and various physical health factors were assessed using the handgrip dynamometer and pinch gauge, Senior Fitness Test, dynamic and static balance abilities, and gait variables. After the intervention, both the 30CLPE and 60CLPE groups showed significant improvements in cognitive function, upper limb strength, senior fitness, balance, and gait (p<0.05), while the control group showed no significant changes in any of the variables (p>0.05). In between-group comparisons, both CLPE groups showed significantly improved cognitive and physical functions compared to the control group (p<0.05). However, there was no significant difference between the 30 CLPE and 60 CLPE groups (p>0.05). The results of this study demonstrate that cognitively loaded physical exercise is effective in improving cognitive and physical function in individuals with MCI. Both the 30-min and 60-min sessions resulted in significant improvements, with no statistically significant differences observed between the two durations. This suggests that persistence and consistency of exercise may be more important than the duration of individual sessions. Clinical Trials.gov: KCT0009053.

Modulation of tyrosine receptor imposed by Estrogen in Memory and Cognition in Female Rats.

The present study aimed to investigate the potential role of estrogen in modulating the pathogenesis of dementia-type-AD phenotype, possibly by tyrosine kinase. Female Wistar rats were ovariectomized (OVX) and were treated with Diethylstilbesterol (DES), an estrogen analogue (20μg/kg/day, i.m.), and Imatinib, a tyrosine kinase inhibitor (30mg/kg/day, orally), for two months. Animals underwent surgical ovariectomy exhibited significant memory deficits in spatial memory assessment as mean dwell time, short-term memory as spontaneous alteration, and novel object recognition after a chronic period of 4 weeks. OVX animals administered with DES produced significant restoration of memory dysfunction in comparison to OVX, as exhibited by Morris water maze (p=0.0003), Y maze (p<0.0001), and NORT. Imatinib prior to DES treatment in OVX animals showed significant decline in memory functions, which confirms the potential involvement of tyrosine receptor kinase activity in improved memory functions offered by estrogen. Levels of estradiol were significantly (p<0.0001) lower in the OVX group compared to normal which was significantly (p<0.0001) restored in the OVX+E group. Biochemical estimations of TBARS, glutathione, and acetylcholinesterase levels in the brain showed a significant increase in oxidative stress among the OVX group. However, a significant restoration of oxidative changes with TBARS (p=0.0496), glutathione (p<0.0001), and acetylcholinesterase activity (p=0.0201) of OVX animals receiving DES was observed in comparison to animals receiving imatinib followed by DES. These implications in the brain signify that estrogen and tyrosine kinase play an important role in the pathogenesis of dementia. In conclusion, estrogen offers neurochemical mediation for cognition and memory possibly via modulation of tyrosine kinase signaling in female subjects.

Short-chain chlorinated paraffins induce liver injury in mice through mitochondrial disorders and disruption of cholesterol-bile acid pathway.

Short-chain chlorinated paraffins (SCCPs) are pervasive organic pollutants recognized for their persistence and bio-toxicity. This study investigated the hepatotoxic mechanisms of SCCPs at environmentally relevant concentration (0.7 μg/kg). The results showed that SCCPs exposure in mice resulted in dysregulated blood and liver lipids, marked by elevated cholesterol levels. Additionally, liver function was compromised, as indicated by increased levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Histopathological examination of liver tissue post-SCCPs exposure revealed hepatocyte enlargement, vacuolar degeneration, and mild ballooning degeneration. Mechanistically, SCCPs induced mitochondrial abnormalities, evidenced by heightened Hoechst 33258 fluorescence, and augmented reactive oxygen species and malondialdehyde levels in liver tissue. This was accompanied by a reduction in total antioxidant capacity, culminating in elevated apoptosis markers, including cytochrome C and caspase-3. Moreover, SCCPs perturbed hepatocellular energy metabolism, characterized by increased glycolysis, lactic acid, and fatty acid oxidation, alongside a disruption in the tricarboxylic acid cycle and a decline in mitochondrial energy metabolic function. Furthermore, SCCPs exposure downregulated the expression of genes involved in bile acid synthesis (cyp27a1, fxr, and shp), thereby precipitating the cholesterol-bile acid metabolism disorders and cholesterol accumulation. Collectively, these findings underscore that SCCPs, even at environmentally relevant levels, can induce lipid dysregulation, mitochondrial disorders and cholesterol deposition in the hepatocytes, contributing to liver damage. The study's insights contribute to a comprehension of SCCPs-induced hepatotoxicity and may inform potential preventative and treatment targets for hepatic damage associated with SCCPs exposure.

Effect of Behavioral Activation on Stigma and Quality of Life in Patients With Advanced Esophageal and Gastric Cancer: A Randomized Controlled Trial.

Esophageal cancer and gastric cancer patients require researchers' attention to address and resolve the issue of stigma. The aim of this study was to investigate whether behavioral activation (BA), an emerging psychosocial intervention method, can mitigate the stigma experienced by these patients and enhance their quality of life (QoL). One hundred fifty-three patients with advanced esophageal cancer and gastric cancer were recruited and randomly assigned to either the BA plus care as usual group (BA+CAU group) or the care as usual group (CAU group). Pre- and post-intervention questionnaires, including the Social Impact Scale (SIS), as well as all functional areas and global health and QoL modules from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version3). Generalized estimating equation analysis revealed that compared to usual care alone, combining BA with usual care significantly reduced stigma (time-by-group interaction, T1: β=-10.584, p<0.001; T2: β=-22.619, p<0.001) while improving physical, role, emotional, social functioning and global health and QoL particularly at T2 time point. Additionally, it also has the potential to decelerate the progressive decline of cognitive functioning. Furthermore, correlation analysis demonstrated a significant association between stigma levels and all functional areas as well as global health and QoL. The issue of stigma among esophageal cancer and gastric cancer patients warrants increased attention due to its close relationship with patient QoL. This study presents a promising psychosocial intervention approach suitable for clinical application that deserves further promotion among cancer patients. NCT06348940.

Efficacy of Radicava® IV (intravenous edaravone) in subjects with differing trajectories of disease progression in amyotrophic lateral sclerosis: Use of a novel statistical approach for post hoc analysis of a pivotal phase 3 clinical trial

IntroductionSubjects with amyotrophic lateral sclerosis (ALS) treated with Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [MTPA], hereafter “MTPA IV edaravone”) in Study MCI186–19 had a significantly slower physical functional decline vs placebo-treated subjects as measured by the revised ALS Functional Rating Scale (ALSFRS-R) and analyzed by the linear mixed model for repeated measures (MMRM). This Study 19 post hoc analysis of MTPA IV edaravone–treated and placebo-treated subjects evaluated linear and nonlinear latent class mixed models defining trajectories based on identifying the model with the lowest Bayesian information criterion. The best model differentiated 4 nonlinear trajectories in ALS subjects. ALSFRS-R total score in MTPA IV edaravone–treated and placebo-treated subjects was evaluated for these 4 nonlinear latent class trajectory groups. MethodsDisease trajectories of MCI186–19 MTPA IV edaravone–treated or placebo-treated ALS subjects who completed the double-blind period were investigated using latent class analysis (LCA) statistical models to identify potential unique nonlinear ALSFRS-R disease trajectories. ResultsALSFRS-R trajectories revealed 4 unique nonlinear trajectory latent classes per treatment group in MTPA IV edaravone–treated and placebo-treated ALS subjects completing the MCI186–19 double-blind period. Latent classes 2–4 had statistically significant slowing of ALSFRS-R total score decline in the predicted nonlinear trajectories of MTPA IV edaravone–treated vs placebo-treated ALS subjects. ConclusionsThis post hoc analysis suggests MTPA IV edaravone treatment results in slower ALSFRS-R decline vs placebo in most predicted nonlinear trajectories. LCA is a novel approach that may benefit future trial analyses.

Enhancement of physiology via adaptive transcription.

The enhancement of complex physiological functions such as cognition and exercise performance in healthy individuals represents a challenging goal. Adaptive transcription programs that are naturally activated in animals to mediate cellular plasticity in response to stimulation can be leveraged to enhance physiological function above wild-type levels in young organisms and counteract complex functional decline in aging. In processes such as learning and memory and exercise-dependent muscle remodeling, a relatively small number of molecules such as certain stimulus-responsive transcription factors and immediate early genes coordinate widespread changes in cellular physiology. Adaptive transcription can be targeted by various methods including pharmaceutical compounds and gene transfer technologies. Important problems for leveraging adaptive transcription programs for physiological enhancement include a better understanding of their dynamical organization, more precise methods to influence the underlying molecular components, and the integration of adaptive transcription into multi-scale physiological enhancement concepts.

Boston Naming Test as a Screening Tool for Early Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery.

The Boston naming test (BNT), as a simple, fast, and easily administered neuropsychological test, was demonstrated to be useful in detecting language function. In this study, BNT was investigated whether it could be a screening tool for early postoperative cognitive dysfunction (POCD). This prospective observational cohort study included 132 major noncardiac surgery patients and 81 nonsurgical controls. All participants underwent a mini-mental state examination (MMSE) and BNT 1 day before and 7 days after surgery. Early POCD was assessed by reliable change index and control group results. Seven days after surgery, among 132 patients, POCD was detected in 30 (22.7%) patients (95% CI, 15.5%-30.0%) based on MMSE, and 45 (34.1%) patients (95% CI, 26.3%-41.9%) were found with postoperative language function decline based on BNT and MMSE. Agreement between the BNT spontaneous naming and MMSE total scoring was moderate (Kappa .523), and the sensitivity of BNT spontaneous naming for detecting early POCD was .767. Further analysis showed that areas under receiver operating characteristics curves (AUC) did not show statistically significant differences when BNT spontaneous naming (AUC .862) was compared with MMSE language functional subtests (AUC .889), or non-language functional subtests (AUC .933). This study indicates the feasibility of implementing the BNT spontaneous naming test to screen early POCD in elderly patients after major noncardiac surgery.

Nomogram model based on clinical factors and autonomic nervous system activity for predicting residual renal function decline in patients undergoing peritoneal dialysis

Nomogram model based on clinical factors and autonomic nervous system activity for predicting residual renal function decline in patients undergoing peritoneal dialysis

Rheumatoid Arthritis-Associated Interstitial Lung Disease: Advancing the Identification and Management

BackgroundInterstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) that causes substantial morbidity and mortality. Effective, evidence-based strategies to screen for, and manage, RA-ILD are lacking. ObjectivesHighlight recent research advances in, and further opportunities to improve, the identification and management of RA-ILD. FindingsThe goals of RA-ILD screening are early disease detection while avoiding unnecessary testing. Such an approach requires the ability to accurate risk stratify RA patients. With only a few recognized clinical risk factors for RA-ILD, a growing body of evidence on peripheral biomarkers for RA-ILD appears well suited to support a precision medicine approach. There is a paucity of evidence to guide management after RA-ILD diagnosis. While initial trials of antifibrotics have been conducted in RA-ILD and show the potential to slow the rate of pulmonary function decline, there have been no randomized trials of immunomodulatory therapies in RA-ILD. Supporting such trials, and addressing the barriers to conducting them, is a high priority. ConclusionRobust characterization of peripheral biomarkers in large, RA populations is essential to inform a precision medicine approach to RA-ILD identification. Randomized trials of treatments and treatment strategies that consider the systemic nature of RA-ILD are necessary to inform evidence-based RA-ILD treatment.

Evaluating Repetitive Transcranial Magnetic Stimulation for Neuropsychiatric Symptoms in Long COVID: A Case Series.

To describe the immediate clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) in treating long COVID symptoms. Long COVID currently impacts approximately 5.3% of US adults, presenting with persistent fatigue, depression, anxiety, cognitive impairments, and social function decline. Repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex has improved these symptoms in some studies. Five patients (ages 52-63 years, 3 female patients) underwent accelerated rTMS using intermittent theta burst stimulation (600 pulses over 3 minutes 20 seconds, 80%-120% of resting motor threshold) to the left dorsolateral prefrontal cortex. The treatment consisted of twice-daily sessions over 20-30 treatments. Outcomes were measured using the Patient-Reported Outcomes Measurement and Information System (PROMIS) questionnaires, assessing fatigue, depression, anxiety, cognitive function, and social function at baseline and immediately posttreatment. One patient discontinued immediately due to intolerable scalp pain. Posttreatment PROMIS scores showed the following: fatigue decreased from 74.5 to 61.8, depression from 60.3 to 51.5, and anxiety from 62.0 to 54.0. Scores increased for cognitive (26.8 to 32.3) and social (31.0 to 32.5) function. These changes, although not statistically significant, indicate a trend toward symptom reduction. Subjectively, 3 of 4 patients who completed the rTMS course reported improvements. This case series suggests that rTMS may offer symptomatic relief in long COVID patients. Although the observed improvements in PROMIS were not statistically significant, even minimal improvements are clinically significant for patients enduring prolonged suffering. These preliminary findings are encouraging and underscore the need for further research with larger cohorts to validate the efficacy of rTMS in long COVID symptom relief.