Functional Assessment Research Articles

CANINE COGNITION ASSESSMENTS IN THE TEST OF RAPAMYCIN IN AGING DOGS (TRIAD)

Abstract The primary objective of the Dog Aging Project’s Test of Rapamycin in Aging Dogs (TRIAD), is to assess whether rapamycin treatment extends lifespan in healthy, middle-aged, medium-to-large companion dogs. A secondary objective is to determine whether rapamycin impacts cognitive function in aging dogs. This placebo-controlled, double-blinded, randomized clinical trial is underway; however, baseline data allows us to investigate relationships between demographic factors and cognitive function. Dogs who met medical records eligibility criteria for TRIAD were assessed during an in-person examination by veterinary neurologists. Baseline cognitive functional assessment involved two validated clinical assessments: the Sustained Gaze test (possible scores 1 to 60 seconds; higher scores indicate greater attention span), and the CAnine DEmentia Scale (CADES) (possible scores of 0-85; higher scores indicate greater impairment). Thirty-five dogs were examined for inclusion in TRIAD, including baseline assessment of cognitive function. The median age of evaluated dogs was 9.2 years (8.1-10.2) and the median weight was 27.7 kg (24.5-30.2). The median CADES score was 1.0 (0.0-4.0) and median Sustained Gaze score was 9.0 (5.3-14.0). Post hoc analysis did not identify significant correlations between age, weight, sex, or breed and scores for either cognitive test. CADES and Sustained Gaze tests do not reveal an influence of demographic factors on cognition at middle-age in dogs being assessed for enrollment in TRIAD. Accordingly, the TRIAD clinical trial will enable robust assessment of rapamycin’s impact on age-related cognitive decline.

Deep learning enhanced transmembranous electromyography in the diagnosis of sleep apnea

Obstructive sleep apnea (OSA) is widespread, under-recognized, and under-treated, impacting the health and quality of life for millions. The current gold standard for sleep apnea testing is based on the in-lab sleep study, which is costly, cumbersome, not readily available and represents a well-known roadblock to managing this huge societal burden. Assessment of neuromuscular function involved in the upper airway using electromyography (EMG) has shown potential to characterize and diagnose sleep apnea, while the development of transmembranous electromyography (tmEMG), a painless surface probe, has made this opportunity practical and highly feasible. However, experience and ability to interpret electrical signals from the upper airway are scarce, and much of the pertinent information within the signal is likely difficult to detect visually. To overcome this issue, we explored the use of transformers, a deep learning (DL) model architecture with attention mechanisms, to model tmEMG data and distinguish between electromyographic signals from a cohort of control, neurogenic, and sleep apnea patients. Our approach involved three strategies to train a generalizable model on a relatively small dataset including, (1) transfer learning using an audio spectral transformer (AST), (2) the use of 6,000 simulated EMG recordings, converted to spectrograms and using standard backpropagation for fine-tuning, and (3) application of regularization to prevent overfitting and enhance generalizability. This DL approach was tested using 177 transoral EMG recordings from a prior study’s database that included six healthy controls, five moderate to severe OSA patients, and five amyotrophic lateral sclerosis (ALS) patients with evidence of bulbar involvement (neurogenic injury). Sensitivity and specificity for classifying neurogenic cases from controls were 98% and 73%, respectively, while classifying OSA from controls were 88% and 64%, respectively. Notably, by averaging the predicted probabilities of each segment for individual patients, the model correctly classified up to 82% of control and OSA patients. These results not only suggest a potential to diagnose OSA patients accurately, but also to identify OSA endotypes that involve neuromuscular pathology, which has major implications for clinical management, patient outcomes, and research.

The Effect of Levetiracetam on Improving Cognitive Impairment in Relapsing-Remitting Multiple Sclerosis Patients: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial

Background: Cognitive impairment has been identified in all stages and affects all subtypes of multiple sclerosis (MS) (40 - 65% of people with clinically definite MS). A defined therapeutic strategy has not yet been determined. Objectives: This study aimed to assess the efficacy of levetiracetam (LEV) to improve cognitive impairments in patients with relapsing-remitting MS (RRMS). Methods: A Pilot randomized; double-blinded, placebo-controlled clinical trial was conducted. The patients with a definite diagnosis of RRMS treated with first-line drugs. They were assigned into two groups; LEV and the placebo for four months. The primary outcome was the changes in cognitive domains based on the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) compared to baseline. The MACFIMS was accomplished by seven tests: California verbal learning test-II (CVLT-II), paced auditory serial addition test (PASAT), symbol digit modalities testing (SDMT), brief visuospatial memory test-revised (BVMT-R), delis-Kaplan executive function system (D-KEFS), controlled oral word association test (COWAT), and judgment of line orientation (JLO). Results: A total of 32 patients entered the study and 28 patients completed the trial. The change in JLO score in the LEV group was significantly greater than in the placebo group (P-value = 0.03). After intervention in the LEV group, the SDMT and JLO scores were significantly higher than the baseline scores. Conclusions: This is the study to evaluate the effects of LEV on cognitive disorders in patients with MS. Levetiracetam was significantly effective in improving the JLO and SDMT scores in patients with RRMS compared to the placebo group.

Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion

ABSTRACT Introduction Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of immature myeloid cells. Among the genetic alterations in AML, the RUNX1- RUNX1T1 fusion, resulting from the t (8; 21) (q22; q22.1) translocation, is common and linked with a favorable prognosis. However, the complete mutational profile contributing to leukemogenesis remains unclear. This study characterizes the mutational profile of the RUNX1-RUNX1T1 fusion in AML using Next-Generation Sequencing (NGS). Methods Twenty-four newly diagnosed AML patients were selected. DNA and RNA were extracted from bone marrow aspirate samples, and libraries were prepared using the Ion AmpliSeq™ Library Kit. Sequencing was performed on the Ion S5™ system, and data were analyzed using Torrent Suite™ and Ion Reporter™ Software. Variants were annotated, and their clinical significance was assessed via ClinVar. In silico prediction tools, including SIFT and PolyPhen-2, were used for functional impact assessment. Results Patients with RUNX1-RUNX1T1 fusion (n = 3) demonstrated higher initial peripheral blood and bone marrow blast counts and a pronounced prevalence of CD56 and CD19 positivity. The average number of mutations in KIT and NF1 was higher in the fusion group (p = 0.021 and p = 0.049, respectively). In total, 228 genetic variants were identified, with most associated with transcription/kinase signaling pathways (36.8%). Epigenetic regulators were the next most common category (21.5%). ClinVar data revealed pathogenic variants predominantly in the KIT gene, including two missense mutations, p.Asp816Val and p.Asp816Ala, at exon 17. Unique variants were identified exclusively in RUNX1-RUNX1T1 patients, including eight non-reported variants. Among these, a TET2 variant (p.Pro1367Leu) was predicted to have deleterious effects based on in silico tools. Conclusion The molecular profiling of RUNX1-RUNX1T1 fusion offers crucial insights into AML’s genetic landscape. Identifying therapeutic targets and novel variants broadens our understanding of mutations, presenting new research opportunities and potential interventions.

Exploring the Levels of Stress, Anxiety, Depression, Resilience, Hope, and Spiritual Well-Being Among Greek Dentistry and Nursing Students in Response to Academic Responsibilities Two Years After the COVID-19 Pandemic.

Background: Dentistry and nursing students experience significant anxiety, negatively impacting their well-being and academic performance. Objectives: This study aims to assess the prevalence and relationships of stress, anxiety, depression, resilience, hope, and spiritual well-being among dentistry and nursing students, identify demographic influences and propose strategies to enhance resilience and well-being. Methods: This study surveyed 271 students attending Greece's departments of dentistry and nursing at the National and Kapodistrian University of Athens, using an electronic questionnaire aimed to assess stress, anxiety, and depression (depression, anxiety, stress scale-DASS-21); resilience (resilience assessment questionnaire-RAQ8, brief resilience scale-BRS); hope (adult hope scale-AHS); and spiritual well-being (functional assessment of chronic illness therapy-spiritual well-being scale-FACIT-Sp-12). The survey also collected demographic data to identify factors influencing these variables. Statistical analyses, including hierarchical multiple linear regression and t-tests, were performed to analyze the relationships between variables. Results: The sample included 145 dentistry and 126 nursing students, with 68.6% female and 80.1% undergraduate. Half of the students reported mild or higher levels of stress (48.7%), anxiety (51.3%), and depression (53.5%). The prevalence of depression was the highest in our sample, followed by anxiety and stress. Higher family wealth was associated with reduced stress levels, while female undergraduate students reported higher levels of anxiety than their male counterparts. Hope was a strong predictor of resilience, but stress and worry had a negative correlation. Conclusions: Promoting students' well-being and academic success requires effective stress-reduction and resilience-building techniques to improve students' performance and support future healthcare professionals' personal sustainability and holistic growth.

도수치료와 저항밴드 운동이 65세 이상 노인의 근감소증 및 관절 기능에 미치는 효과: 무작위 대조 연구

Objective : This study aimed to evaluate the effects of combined manual therapy and resistance band exercises on sarcopenia and joint function in elderly individuals aged 65 years or older, providing scientific evidence for effective intervention programs to improve physical function. Methods : A randomized controlled trial was conducted with 32 older adults aged 65 and above, recruited from the G Welfare Center in Gwangju. Participants were randomly assigned to either the experimental group (manual therapy combined with exercise therapy) or the control group (manual therapy only), with 16 participants in each group. During the study, 12 participants dropped out, leaving 10 participants in each group for the final analysis. The intervention was conducted over six weeks, with a total of 12 sessions. The intervention effects were analyzed through various physical function assessments, including balance ability, gait speed, sit-to-stand performance, shoulder and pelvic height, and grip strength. Results : Following the combined intervention of manual therapy and resistance band exercises, the experimental group showed significant improvements in balance ability and ROM (p<0.05), as well as greater changes in sit-to-stand performance (p=0.003). Gait speed significantly increased only in the experimental group (p=0.046), while grip strength showed no significant changes in either group (p>0.05). Conclusion : The combined intervention of manual therapy and resistance band exercises demonstrated significant improvements in balance ability and lower limb function in older adults (p<0.05). This suggests a synergistic effect of manual therapy and resistance exercises, highlighting their potential as a rehabilitation protocol for reducing fall risk and enhancing physical function.

Personalized Human Astrocyte-Derived Region-Specific Forebrain Organoids Recapitulate Endogenous Pathological Features of Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a highly heterogeneous neurodevelopmental malformation, the underlying mechanisms of which remain largely elusive. In this study, personalized dorsal and ventral forebrain organoids (DFOs/VFOs) are generated derived from brain astrocytes of patients with FCD type II (FCD II). The pathological features of dysmorphic neurons, balloon cells, and astrogliosis are successfully replicated in patient-derived DFOs, but not in VFOs. It is noteworthy that cardiomyocyte-like cells correlated with dysmorphic neurons are generated through the high activation of BMP and WNT signaling in some of the FCD-organoids and patient cortical tissues. Moreover, functional assessments demonstrated the occurrence of epileptiform burst firing and propagative self-assembling neuronal hyperactivity in both FCD-DFOs and VFOs. Additionally, the heterotopic cardiomyocyte-organoids demonstrated the capacity for cardiomyocyte contraction and rhythmic firing. The presence of these cardiomyocytes contributes to the hyperactivity of neural networks in cardioids-DFOs assembly. In conclusion, the personalized region-specific forebrain organoids derived from FCD patient astrocytes effectively recapitulate heterogeneous pathological features, offering a valuable platform for the development of precise therapeutic strategies.

Advancing Drug Development in Myelodysplastic Syndromes.

Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the United States Food and Drug Administration (FDA), (e.g., luspatercept, ivosidenib, decitabine/cedazuridine and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories including criteria for risk stratification and eligibility, response definitions, time-to-event endpoints, transfusion endpoints, functional assessments, and biomarker development. Strategies to address these challenges and optimize future clinical trial design for patients with MDS are presented here.

Cardiovascular and Metabolic Adverse Events of Endocrine Therapies in Women with Breast Cancer: A Disproportionality Analysis of Reports in the FDA Adverse Event Reporting System

ABSTRACTIntroductionEmerging evidence suggests potential cardiovascular toxicities from oral endocrine therapies (ETs); however, results are conflicting. This study comprehensively examined adverse reactions of ETs and investigated cardiovascular and metabolic safety signals within the FDA Adverse Event Reporting System (FAERS).MethodsReports in the FAERS through December 2023 were analyzed for documented reactions to tamoxifen, letrozole, anastrozole, and exemestane in female breast cancer patients. Standardized queries were used to identify cases of cardiovascular (myocardial infarction, heart failure, arrhythmia, stroke) and metabolic (hypertension, dyslipidemia, hyperglycemia) disorders. Descriptive and disproportionality analyses were performed to assess reports and detect safety signals.ResultsAmong 14,327 unique ET‐related reports, arthralgia (n = 1873 events) was the most prevalent reaction. We identified 2170 cardiovascular and 2252 metabolic events associated with ETs. Letrozole had the highest reporting rate of cardiac arrhythmia (7.7%) and showed positive signals for both arrhythmia (reporting odds ratio [ROR] = 2.2; 95% confidence interval [CI]: 1.8–2.5) and myocardial infarction (ROR = 1.9; 95% CI: 1.4–2.6). We also observed a significantly increased risk of heart failure with letrozole (ROR = 1.3; 95% CI: 1.1–1.6) and stroke with tamoxifen (ROR = 1.7; 95% CI: 1.5–2.1). Only anastrozole was significantly associated with metabolic dysfunctions with a notable hyperglycemia reporting rate of 12.2%.ConclusionOur findings provide valuable evidence on common reactions as well as controversial cardiovascular and metabolic abnormalities associated with the real‐world use of ETs for breast cancer. Ongoing benefit–risk assessment and close monitoring of cardiac function during treatment, particularly in high‐risk women, are warranted to optimize cancer outcomes while minimizing cardiovascular injury.

NIH Toolbox for assessment of neurocognitive, motor and emotional-behavioral function in childhood: a systematic review

NIH Toolbox for assessment of neurocognitive, motor and emotional-behavioral function in childhood: a systematic review

Mechanism of syncope: role of ambulatory blood pressure monitoring and cardiovascular autonomic function assessment.

Identifying the haemodynamic mechanism of autonomic syncope is the essential pre-requisite for effective and personalized therapy aimed at preventing recurrences. The present study assessed the diagnostic efficacy of a two-step assessment. Multicentre prospective, cross-sectional, observational study. Patients affected by severe autonomic syncope underwent a two-step assessment including 24-h ambulatory blood pressure monitoring and short cardiovascular autonomic function assessment (SCAFA). SCAFA consisted of carotid sinus massage (CSM), performed in patients ≥40 years old, a passive standing test, and a 'fast' head-up tilt test scheduled sequentially during one session on a tilt table. The study population consisted of 333 patients, 102 ≤ 40 years old and 231 > 40 years old. Any positive response was observed in 298 (89%) patients (92 [92%] in younger and 134 [89%] in older), with hypotensive phenotype accounting for 226 (68%), bradycardic phenotype for 21 (6%) and mixed phenotype for 51 (15%) of cases. The mean duration of the SCAFA procedure was 25 (IQR 20-32) min. Ambulatory blood pressure monitoring, CSM, passive standing, and head-up tilt test were positive in 60%, 15%, 3%, and 71% of patients, respectively. More than one test was positive in 51% and 49% of patients ≤40 and >40 years, respectively. Large inter-centre variability of CSM positivity rate, which remained significant after adjustment for demographic and clinical variables, was observed (P = .003). The standardized 2STEPS protocol offers an easy-to-perform and time-saving diagnostic work-up allowing identification of the haemodynamic mechanism of loss of consciousness in most patients with autonomic syncope. This protocol provides the necessary background for a personalized mechanism-specific therapy.

Sarcopenia and Spondyloarthritis activity and functional assessment

Background: Sarcopenia is progressive loss of muscle mass and strength; this may cause increased morbidity and mortality. Rheumatic diseases as spondyloarthropathies have greater risks of developing sarcopenia. Objectives: Assessment of sarcopenia in Egyptian patients with psoriatic arthritis (PSA) and axial spondyloarthritis (axSPA) and investigate the relation between sarcopenia and different factors. Methods: This study included 56 PSA (Group I), 58 axSPA patients (Group II), and 60 healthy controls (Group III). Demographic data were collected, disease activity was assessed using Disease Activity Index for Psoriatic Arthritis (DAPSA) score for PSA patients and ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) for axSPA patients. Functional assessment was done using Bath ankylosing spondylitis functional index (BASFI) for axSPA patients and Health Assessment Questionnaire (HAQ) for PSA patients. Sarcopenia was assessed by measuring Muscle mass, muscle strength and physical performance. Results: There was no significant difference between study groups regarding age, and BMI. None of the studied patients had definite sarcopenia, twelve PSA patients (21.43%), and fifteen axSPA patients (25.86%) had probable sarcopenia. While seven PSA, and five axSPA patients had pre-sarcopenia. We found significant differences between PSA and controls regarding muscle quantity, muscle strength, and muscle performance. While we found significant differences between axSPA and controls regarding muscle strength, and muscle performance. the risk of probable sarcopenia in axSPA patients increased with increasing age and ASDAS-CRP and in PSA patients it increased with increasing age, DAPSA and HAQ. Conclusions: probable sarcopenia was significantly increased in PsA and axSPA. Our analysis suggests that age, and disease activity were associated with the development of sarcopenia in PSA and axSPA.

Event-related desynchronization of eeg sensorimotor rhythms in hemiparesis post-stroke patients

Motor impairment is one of the most prevalent consequences of a stroke, necessitating the implementation of efficacious diagnostic and rehabilitative techniques. An evaluation of alterations in sensorimotor cortical activity during the processes of movement preparation and execution can provide valuable insights into the state of motor circuits following a stroke and the potential for recovery. The objective of the present study was to evaluate the spatiotemporal characteristics of event-related desynchronization (ERD) of sensorimotor EEG rhythms in patients with hemiparesis following a stroke, during movements with the paretic and healthy hands. A total of 19 patients with hemiparesis following a stroke participated in the study. An EEG was recorded while the subject performed a visual-motor task. The analysis focused on the event-related desynchronization in the alpha (6–15 Hz) and beta (15–30 Hz) bands. An asymmetry in the ERD was observed, with a predominant response in the intact hemisphere, regardless of the hand performing the movement. The magnitude of the ERD in the affected hemisphere demonstrated a correlation with the Fugl-Meyer score. Furthermore, a notable correlation was identified between the magnitude of beta-ERD in the affected hemisphere during movements of the healthy limb and the degree of motor function recovery. The results demonstrate the utility of ERD pattern assessment for diagnosing the state of sensorimotor networks after stroke. The detection of a correlation between the magnitude of ERD during movements of the healthy arm and the assessment of sensorimotor functions of the patient expands the possibilities of using EEG to assess patients even with complete absence of movements in the paretic limb.

Dynamics of Clinical Manifestations and Social Functioning in Schizophrenia: A Non-interventional Observational Study of Paliperidone Palmitat Dosage Forms

BACKGROUND: Over the past seven years, the use of long-acting forms of antipsychotic medication has significantly increased in Russia. Specifically, in Moscow, from 2016 to 2021, the proportion of prescribed injectable long-acting antipsychotics had increased more than sevenfold (from 3% to 23%). Studies have shown that the correct selection of target groups for such therapy can reduce the frequency of relapses requiring hospitalization, lower the costs of inpatient care, and shift the focus of therapy from multiple drug administrations to psychosocial work. AIM: This study was aimed at evaluating changes over time in psychosocial functioning, as well as clinical and psychopathological manifestations, in patients with schizophrenia during early remission and while on therapy with different forms of paliperidone: oral paliperidone (OP), paliperidone palmitate administered once monthly (PP1M), and paliperidone palmitate administered once every three months (PP3M). METHODS: The observational study included 155 patients: 54 patients who had been treated with another second-generation antipsychotic received OP, 50 patients who had been treated with another antipsychotic received PP1M injections, and 51 patients who had been in remission for four months after treatment with PP1M received PP3M. The duration of the follow-up period was 12 months. Assessment of personal and social functioning was conducted five times: before the start of treatment, and 3, 6, 9, and 12 months later. RESULTS: Treatment in all groups led to a statistically significant reduction in the severity of positive symptoms (p 0.001). Hallucinations proved more susceptible to therapy (p 0.001), while persistent delusions showed greater treatment resistance. Significantly more patients in the PP1M and PP3M groups had completed the entire program (n=24; 48.0%, and n=30; 58.8%, respectively) compared to the OP group (n=11; 20.4%). The PP3M group demonstrated the highest treatment adherence, with the largest number of patients completing the study, and a similar rate of exacerbations or inadequate efficacy compared to the other groups. CONCLUSION: Treatment with different forms of paliperidone provides a roughly equal pace reduction in the severity of schizophrenia, including positive and negative symptoms. The PP3M group had better adherence and the highest number of patients who fully completed the study.

Risk, vulnerability, and HIV/AIDS among men who have sex with men: A behavioral analysis

HIV cases in Brazil and the city of São Paulo mainly occur among men who have sex with men (MSM) and within the age group 20–29. Considering that, this study aimed to investigate, from a behavior analysis perspective and an indirect functional assessment strategy (questionnaire): (a) possible present variables of the behavior of practicing condomless sex among eight MSM aged 20–29 in the District of República, in São Paulo, and (b) discourses on sexual behavior, risk-taking knowledge, prevention strategies, and information on HIV/AIDS into the same group. The results indicated inconsistent condom use with regular partners, knowledge about pre- and post-exposure prophylaxes for HIV, and non-stigmatizing discourses about MSM’s sexual behavior and HIV/AIDS. Reinforcing, potent, and immediate consequences, regarded as “greater pleasure” and “freedom,” for instance, may affect condomless sex, as well as countercontrolling variables.

Assessment of ovarian reserve function in patients with adenomyosis and ovarian endometriosis by three-dimensional transvaginal ultrasound and Anti-Müllerian hormone

We evaluated the impact of adenomyosis and ovarian endometriosis on ovarian reserve function through transvaginal three-dimensional ultrasound and anti-mullerian hormone testing. A total of 150 female patients who were admitted to our hospital from January 2023 to May 2024 were selected; 58 cases had adenomyosis (adenomyosis group), 36 had ovarian endometriosis (ovarian endometriosis group), and 56 were healthy (healthy group). There were no statistically significant differences in clinical baseline data among the three groups (all P > 0.05). However, significant overall differences were found in anti-Mullerian hormone levels, antral follicle count, ovarian volume, vascularization index, flow index, and vascularization flow index among the three groups (F values were 90.34, 146.50, 92.61, 63.87, 59.50, 49.36 respectively; all P < 0.001); compared to the healthy group, these indicators were all decreased in the adenomyosis group and ovarian endometriosis group (all P < 0.05). Pearson correlation analysis revealed that serum anti-mullerian hormone levels were positively correlated with antral follicle count, ovarian volume, vascularization index, flow index, and vascularization flow index (r = 0.80, 0.73, 0.50, 0.48, 0.45, respectively; all P < 0.01). These data suggest that adenomyosis and ovarian endometriosis can lead to a decline in ovarian reserve function in women of reproductive age compared to their peers. Also, antral follicle count and ovarian volume are the optimal indicators for evaluating ovarian reserve function in these patients.

Assessment of electron-proton correlation functionals for vibrational spectra of shared-proton systems by constrained nuclear-electronic orbital density functional theory.

Proton transfer plays a crucial role in various chemical and biological processes. A major theoretical challenge in simulating proton transfer arises from the quantum nature of the proton. The constrained nuclear-electronic orbital (CNEO) framework was recently developed to efficiently and accurately account for nuclear quantum effects, particularly quantum nuclear delocalization effects, in quantum chemistry calculations and molecular dynamics simulations. In this paper, we systematically investigate challenging proton transfer modes in a series of shared-proton systems using CNEO density functional theory (CNEO-DFT), focusing on evaluating existing electron-proton correlation functionals. Our results show that CNEO-DFT accurately describes proton transfer vibrational modes and significantly outperforms conventional DFT. The inclusion of the epc17-2 electron-proton correlation functional in CNEO-DFT produces similar performance to that without electron-proton correlations, while the epc17-1 functional yields less accurate results, comparable with conventional DFT. These findings hold true for both asymmetrical and symmetrical shared-proton systems. Therefore, until a more accurate electron-proton correlation functional is developed, we currently recommend performing vibrational spectrum calculations using CNEO-DFT without electron-proton correlation functionals.

Rehabilitation Assessment and Intervention to Facilitate Return to Work in Coronary Artery Disease Patients: A Narrative Review

Introduction: Coronary artery disease (CAD), causes significant changes in a person's life and is often accompanied by complex emotional reactions which further cause a decrease in the ability to complete work responsibilities, lower wages, and increase the risk of early dismissal. Promoting a return to work (RTW) program after CAD will improve economic burdens and the quality of life. This review aimed to explore the RTW program in CAD patients focused on the impact of CAD on the patients’ ability to back to their previous work and rehabilitation management to fulfill RTW criteria. Methods: Articles published in the last 10 years based on PubMed and Google Scholar databases were reviewed narratively. Keywords used were “coronary artery disease”, “ischemic heart disease”, “cardiovascular disease”, “cardiac rehabilitation”, “return to work”, and “return to vocational activity”. Results: The impact of CAD on RTW includes a decrease in the ability to RTW and work performance as well as an increase in the risk of premature dismissal. Factors that influence the RTW ability in CAD patients are sociodemographic, psychosocial, cardiovascular risk, medical history, complications during hospitalization, and clinical characteristics. Efforts to facilitate this process involve a wide range of assessments and interventions. The RTW ability can be determined through objective assessment of cardiac function, including exercise capacity and left ventricular ejection fraction, the presence or absence of comorbidities, job satisfaction, and other assessments of general well-being. Interventions aimed at promoting RTW consist of an initial CR (phase II CR) and an extended CR program. Conclusion: The rehabilitation assessments and interventions given to patients with CAD have shown good results for RTW rates and the quality of work.

Apolipoprotein E epsilon4 allele is associated with better performance language and visual memory in spinocerebellar ataxia type 3.

The regulatory role of the apolipoprotein E (APOE) ε4 allele in the clinical manifestations of spinocerebellar ataxia type 3 (SCA3) remains unclear. This study aimed to evaluate the impact of the APOE ε4 allele on cognitive and motor functions in SCA3 patients. This study included 281 unrelated SCA3 patients and 182 controls. APOE genotypes were analyzed using PCR amplification combined with Sanger sequencing. Additionally, 96 SCA3 patients were prospectively recruited for neuropsychological and motor function assessments. Neuropsychological phenotypes were evaluated using the modified Chinese version of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS). Motor function was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). The frequency of the APOE ε4 allele was increased in SCA3 patients compared to the control group. The APOE ε4 allele was associated with better performance in language and visual memory, but also with more severe speech disturbances in SCA3 patients. Furthermore, in SCA3, the expanded CAG repeat length was correlated with poorer language memory performance and slower information processing speed, as well as more severe gait disturbances, fast alternating hand movements, speech disturbance, and oculomotor disorders. The APOE ε4 allele may serve as a disease-modifying factor in SCA3, influencing both cognitive and motor functions.

Overall Survival and the Impact of Albumin-bilirubin Grade in Patients with Advanced Hepatocellular Carcinoma: Data from a Tertiary Care Hospital in a Lower-middle-income Country.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Most patients are diagnosed at an advanced stage, limiting their treatment options. The traditional assessment of liver function using the Child-Pugh score has limitations due to its subjectivity. The albumin-bilirubin (ALBI) grade delivers a more precise evaluation of liver function. This study examines overall survival (OS) in advanced HCC patients treated with first-line systemic therapy and the impact of ALBI grading on these outcomes. A total of 104 patients with advanced HCC treated between January 2017 and December 2023 with one of the three first-line therapy options: Sorafenib, lenvatinib or atezolizumab/bevacizumab were retrospectively analyzed. The Kaplan-Meier method was utilized to examine the survival results, and the log-rank test was employed to evaluate the variations in survival among ALBI grades and therapy types. Cox proportional hazards regression examined the impact of ALBI grading and other covariates on OS, with a significance threshold of p < 0.05 for the multivariable model. The median age of HCC patients was 58.5 years, with 70% males, and a primary etiology of hepatitis C (43%). The median OS and time to progression (TTP) in this cohort were 9 months and 3.25 months. In ALBI grade I patients, the OS was 21 months, while in grade II or III patients, it was just 5 months. Treatment-related side effects necessitated dose reductions in over 84% of patients. Albumin-bilirubin grade, Child-Pugh class, and treatment modifications due to adverse effects were significant predictors of survival. Lenvatinib appears to have better survival outcomes compared to other options. The albumin-bilirubin grading is a useful method for evaluating liver function and forecasting survival rates for individuals with HCC. Our findings support the use of ALBI grading in clinical decision-making for advanced HCC. Naviwala MSS, Tariq M, Ahmed F, et al. Overall Survival and the Impact of Albumin-bilirubin Grade in Patients with Advanced Hepatocellular Carcinoma: Data from a Tertiary Care Hospital in a Lower-middle-income Country. Euroasian J Hepato-Gastroenterol 2024;14(2):251-257.