Functional Reserve Research Articles

Disrupted brain functional connectivity as early signature in cognitively healthy individuals with pathological CSF amyloid/tau

Alterations in functional connectivity (FC) have been observed in individuals with Alzheimer’s disease (AD) with elevated amyloid (Aβ) and tau. However, it is not yet known whether directed FC is already influenced by Aβ and tau load in cognitively healthy (CH) individuals. A 21-channel electroencephalogram (EEG) was used from 46 CHs classified based on cerebrospinal fluid (CSF) Aβ tau ratio: pathological (CH-PAT) or normal (CH-NAT). Directed FC was estimated with Partial Directed Coherence in frontal, temporal, parietal, central, and occipital regions. We also examined the correlations between directed FC and various functional metrics, including neuropsychology, cognitive reserve, MRI volumetrics, and heart rate variability between both groups. Compared to CH-NATs, the CH-PATs showed decreased FC from the temporal regions, indicating a loss of relative functional importance of the temporal regions. In addition, frontal regions showed enhanced FC in the CH-PATs compared to CH-NATs, suggesting neural compensation for the damage caused by the pathology. Moreover, CH-PATs showed greater FC in the frontal and occipital regions than CH-NATs. Our findings provide a useful and non-invasive method for EEG-based analysis to identify alterations in brain connectivity in CHs with a pathological versus normal CSF Aβ/tau.

Preoperative Ultrasound Radomics to Predict Posthepatectomy Liver Failure in Patients With Hepatocellular Carcinoma.

Posthepatectomy liver failure (PHLF) is a major cause of postoperative mortality in hepatocellular carcinoma (HCC) patients. The study aimed to develop a method based on the two-dimensional shear wave elastography and clinical data to evaluate the risk of PHLF in HCC patients with chronic hepatitis B. This multicenter study proposed a deep learning model (PHLF-Net) incorporating dual-modal ultrasound features and clinical indicators to predict the PHLF risk. The datasets were divided into a training cohort, an internal validation cohort, an internal independent testing cohort, and three external independent testing cohorts. Based on ResNet50 pretrained on ImageNet, PHLF-Net used a progressive training strategy with images of varying granularity and incorporated conventional B-mode and elastography images and clinical indicators related to liver reserve function. In total, 532 HCC patients who underwent hepatectomy at five hospitals were enrolled. PHLF occurred in 147 patients (27.6%, 147/532). The PHLF-Net combining dual-modal ultrasound and clinical indicators demonstrated high effectiveness for predicting PHLF, with AUCs of 0.957 and 0.923 in the internal validation and testing sets, and AUCs of 0.950, 0.860, and 1.000 in the other three independent external testing sets. The performance of PHLF-Net outperformed models of single- and dual-modal US. Preoperative ultrasound imaging combining clinical indicators can effectively predict the PHLF probability in patients with HCC. In the internal and external validation sets, PHLF-Net demonstrated its usefulness in predicting PHLF.

Significance of changes in tumor markers in patients treated with durvalumab plus tremelimumab combination therapy as a surrogate marker for tumor response to unresectable hepatocellular carcinoma.

When evaluating response to immune checkpoint inhibitor therapy, the tumor sometimes initially swells before shrinking and ultimately responding, also called pseudo-progression. In this study, we analyzed whether tumor markers were useful for reflecting the treatment response. Thirty-three patients who were treated with durvalumab plus tremelimumab combination therapy (Dur+Tre) were enrolled. Their functional reserve was Child-Pugh grade A. Their tumor markers α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), or AFP-Lectin 3 fraction (AFP-L3) were positive. Tumor markers were evaluated before treatment and at 1, 4, and 8weeks after the start of treatment. The first radiological evaluation was carried out at 4weeks and the second evaluation at 8-12weeks. The responders included those with complete response and partial response and the nonresponders included those with stable disease (SD) and progression disease at best response evaluated by Response Evaluation Criteria in Solid Tumors. In the responder group, the change ratio of AFP, DCP, and AFP-L3 specifically decreased at 8weeks. In the nonresponder group, the change ratio of DCP specifically increased at 4weeks. The optimal cut-off value to divide responders and nonresponders at 4weeks was approximately -40%. The ratio of responders was 72.7% in the patients whose AFP or DCP decreased over 40% at 4weeks. The change in tumor markers is a more useful predicter of tumor response to Dur+Tre than imaging evaluation alone.

Efficacy of personalized repetitive transcranial magnetic stimulation based on functional reserve to enhance ambulatory function in patients with Parkinson’s disease: study protocol for a randomized controlled trial

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson’s disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function.MethodsThis is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging.DiscussionThe study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD.Trial registrationClinicalTrials.gov NCT06350617. Registered on 5 April 2024.

Compatibility Analysis of Frequency Containment Reserve and Load Frequency Control Functions

The study focuses on investigating the behavior of Electric Power Systems (EPS) during desynchronization from a synchronous area, its stability in island mode operation, and its synchronization with Continental Europe (CE). The primary aim is to ensure and maintain the stability and reliable operation of self–operating individual EPSs by analyzing the technical requirements and prequalification procedures for Frequency Containment Reserves (FCR) and Load Frequency Control (LFC) reserves. The study employed numerical simulations to analyze the behavior of isolated EPSs after losing a certain amount of active power, to ensure reliable operation and avoid the effects of Under Frequency Load Shedding (UFLS). It examined the technical requirements for LFC reserve units, such as the ability to remain connected to the network during disturbances and provide necessary support. The research investigated the procedures for prequalifying reserve units to provide FCR and LFC services. This investigation contributes to ensuring that EPSs operate reliably during desynchronization and that reserve providers meet the necessary technical and operational standards.

Intrinsic capacity and recent falls in adults 80 years and older living in the community: results from the ilSIRENTE Study

BackgroundFalls in older adults significantly impact overall health and healthcare costs. Intrinsic capacity (IC) reflects functional reserve and is an indicator of healthy aging.AimsTo explore the association between IC and recent falls (≤ 90 days) in community-dwelling octogenarians from the Aging and Longevity in the Sirente geographic area (IlSIRENTE) study.MethodsThe Minimum Data Set for Home Care (MDS−HC) and supplementary questionnaires and tests were used to assess the five IC domains: locomotion, cognition, vitality, psychology, and sensory. Scores in each domain were rescaled using the percent of maximum possible score method and averaged to obtain an overall IC score (range 0−100).ResultsThe study included 319 participants (mean age 85.5 ± 4.8 years, 67.1% women). Mean IC score was 80.5 ± 14.2. The optimal IC score cut-off for predicting the two-year risk of incident loss of at least one activity of daily living (ADL) was determined and validated in a subset of 240 individuals without ADL disability at baseline (mean age 84.7 ± 4.4 years, 67.1% women). Participants were then stratified into low (< 77.6) and high (≥ 77.6) IC categories. Those with high IC (63.9%) were younger, more often males, and had lower prevalence of recent falls, disability, multimorbidity, and polypharmacy. Logistic regression models including IC as a continuous variable revealed a significant association between higher IC and lower odds of falls. This association was significant in the unadjusted (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94–0.98, p < 0.001), age- and sex-adjusted (OR 0.96, 95% CI 0.94–0.98, p < 0.001), and fully adjusted models (OR 0.96, 95% CI 0.93–0.99, p = 0.003). When considering IC as a categorical variable, unadjusted logistic regression showed a strong association between high IC and lower odds of falls (OR 0.31, 95% CI 0.16–0.60, p < 0.001). This association remained significant in both the age- and sex-adjusted (OR 0.30, 95% CI 0.15–0.59, p < 0.001) and fully adjusted models (OR 0.33, 95% CI 0.16–0.82, p = 0.007). The locomotion domain was independently associated with falls in the unadjusted (OR 0.98, 95% CI 0.97–0.99, p < 0.001), age- and sex-adjusted (OR 0.97, 95% CI 0.96–0.99, p < 0.001), and fully adjusted model (OR 0.98, 95% CI 0.96–0.99, p < 0.001).DiscussionThis is the first study using an MDS−HC-derived instrument to assess IC. Individuals with higher IC were less likely to report recent falls, with locomotion being an independently associated domain.ConclusionsLower IC is linked to increased odds of falls. Interventions to maintain and improve IC, especially the locomotion domain, may reduce fall risk in community-dwelling octogenarians.

The role of cognitive reserve and depression on executive function in older adults: A 10-year study from the Wisconsin Registry for Alzheimer’s Prevention

Objective: The current study examined the longitudinal relationship between cognitive reserve (CR), depression, and executive function (EF) in a cohort of older adults. Methods: 416 participants were selected from the Wisconsin Registry for Alzheimer’s Prevention. They were native English speakers, aged ≥50+, and cognitively unimpaired at baseline, with no history of neurological or other psychiatric disorders aside from depression. Depression was assessed with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). A composite score, based on the premorbid IQ (WRAT-3 Reading subtest) and years of education was used to estimate CR. Another composite score from four cognitive tests was used to estimate EF. A moderation analysis was performed to evaluate the effects of CR and Depression on EF at follow-up after controlling for age, gender, and APOE risk score. Moreover, a multinomial logistic regression was used to predict conversion to Mild Cognitive Impairment (MCI) from the healthy baseline. Results: The negative relationship between depression and EF was stronger in individuals with higher CR levels, suggesting a possible floor effect at lower CR levels. In the multinomial regression, the interaction between CR and depression predicted conversion to MCI status, indicating that lower CR paired with more severe depression at baseline was associated with a higher risk of subsequent impairment. Conclusions: This study sheds light on the intricate relationship between depression and EF over time, suggesting that the association may be influenced by varying levels of CR. Further studies may replicate these findings in clinical populations.

Neural ageing and synaptic plasticity: prioritizing brain health in healthy longevity.

Ageing is characterized by a gradual decline in the efficiency of physiological functions and increased vulnerability to diseases. Ageing affects the entire body, including physical, mental, and social well-being, but its impact on the brain and cognition can have a particularly significant effect on an individual's overall quality of life. Therefore, enhancing lifespan and physical health in longevity studies will be incomplete if cognitive ageing is over looked. Promoting successful cognitive ageing encompasses the objectives of mitigating cognitive decline, as well as simultaneously enhancing brain function and cognitive reserve. Studies in both humans and animal models indicate that cognitive decline related to normal ageing and age-associated brain disorders are more likely linked to changes in synaptic connections that form the basis of learning and memory. This activity-dependent synaptic plasticity reorganises the structure and function of neurons not only to adapt to new environments, but also to remain robust and stable over time. Therefore, understanding the neural mechanisms that are responsible for age-related cognitive decline becomes increasingly important. In this review, we explore the multifaceted aspects of healthy brain ageing with emphasis on synaptic plasticity, its adaptive mechanisms and the various factors affecting the decline in cognitive functions during ageing. We will also explore the dynamic brain and neuroplasticity, and the role of lifestyle in shaping neuronal plasticity.

Impaired Left Atrial Reserve Function in Heart Failure With Preserved Ejection Fraction.

Left atrial (LA) dysfunction is common in heart failure (HF) with preserved ejection fraction. However, data on the pathophysiologic impacts of impaired LA functional reserve remained limited. We sought to determine the association of abnormal LA dynamics during exercise with cardiovascular reserve, exercise capacity, and clinical outcomes. Patients with HF with preserved ejection fraction (n=231) and controls without HF (n=219) underwent exercise stress echocardiography with simultaneous expired gas analysis. LA function was assessed at rest and during exercise using speckle-tracking echocardiography. Patients with HF with preserved ejection fraction demonstrated less increase in LA reservoir and booster pump strain during exercise than those in controls. The degree of LA dilation was more closely related to exercise LA reservoir strain than to resting LA strain (Meng test, P=0.002). The presence of impaired LA reservoir strain during exercise was associated with poorer biventricular systolic reserve and cardiac output augmentation, more severe right ventricular-pulmonary artery uncoupling, and lower peak oxygen consumption. Patients with a lower exercise LA reservoir strain had a 2.7-fold increased risk of HF events (hazard ratio, 2.66 [95% CI, 1.32-5.38]; P=0.006). Among patients with follow-up echocardiography, initiation of guideline-directed medical therapy or atrial fibrillation ablation showed significant improvements in LA reservoir (P<0.001 and P=0.022) and booster pump strain (P=0.011 and 0.028) at rest and during exercise, respectively. Impaired LA reservoir function during exercise in HF with preserved ejection fraction is associated with biventricular reserve limitations, exercise intolerance, and increased risks of HF events.

Amino Acid Infusion for Perioperative Functional Renal Protection: A Meta-analysis

ObjectiveAcute kidney injury (AKI) is a common perioperative complication. To date, no single intervention has been proven effective for AKI prevention in this setting. However, intravenous amino acids (AA) administration may recruit renal functional reserve and, thereby, attenuate the perioperative loss of glomerular filtration rate. Accordingly, we performed a meta-analysis to assess the efficacy of AA infusion for perioperative renal functional protection. MethodsWe performed a meta-analysis of controlled studies in perioperative patients (P) evaluating intravenous AA infusion (I) versus any comparator (C). The primary outcome was AKI at longest follow-up (O). We performed a random effects meta-analysis on the relative risk (RR) scale to assess the effect of AA infusion. We used a Bayesian approach to estimate the probability of benefit (RR<1) for the primary outcome. Secondary outcomes included renal-replacement therapy, serum creatinine, and estimated glomerular filtration rate. Tertiary outcomes included mechanical ventilation duration, intensive care unit and hospital length of stay and mortality. (PROSPERO: CRD42024547225). ResultsWe identified 15 studies (14 RCTs and one prospective before-after study) reporting at least one outcome of interest (4,544 patients), with six studies (4,084 patients) reporting the primary outcome. AKI occurred 504/2,041 (24.7%) in AA patients vs 614/2,041 (30.1%) in controls (RR=0.66; 95% CI, 0.47 to 0.94; I2=50%; p=0.02), which corresponded to a 99.1% probability of AKI reduction with AA. Moreover, coherent with such findings, AA reduced serum creatinine, and hospital length of stay, and increased eGFR. ConclusionsThis meta-analysis suggests that AA administration likely reduces the perioperative incidence of AKI.

Evaluation of the Functional Reserve and Exercise Tolerance in Patients with CHF in Clinical Trials (Consent Document of the Editorial board of the Journal of Cardiology, the Board of the Society of Specialists in Heart Failure (SSHF) and Working Group "Non-drug treatment methods" of SSHF)

Assessing the functional capacity and exercise tolerance is an important and widely used research tool in patients with heart failure. It is used not only in cardiac rehabilitation and physical therapy, but also for inclusion criteria and outcome measures in studies of drug interventions. This document outlines the scope, guidelines for the implementation and interpretation, and limitations of the methods for assessing the functional capacity and exercise tolerance in clinical trials in patients with heart failure.

Noninvasive assessment of liver fibrosis in mini pigs using an 18F–AlF-NOTA-RGD2 PET/CT molecular probe

To evaluate the efficacy of the 18F–AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F–AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.

Computational framework for the generation of one-dimensional vascular models accounting for uncertainty in networks extracted from medical images.

One-dimensional (1D) cardiovascular models offer a non-invasive method to answer medical questions, including predictions of wave-reflection, shear stress, functional flow reserve, vascular resistance and compliance. This model type can predict patient-specific outcomes by solving 1D fluid dynamics equations in geometric networks extracted from medical images. However, the inherent uncertainty in in vivo imaging introduces variability in network size and vessel dimensions, affecting haemodynamic predictions. Understanding the influence of variation in image-derived properties is essential to assess the fidelity of model predictions. Numerous programs exist to render three-dimensional surfaces and construct vessel centrelines. Still, there is no exact way to generate vascular trees from the centrelines while accounting for uncertainty in data. This study introduces an innovative framework employing statistical change point analysis to generate labelled trees that encode vessel dimensions and their associated uncertainty from medical images. To test this framework, we explore the impact of uncertainty in 1D haemodynamic predictions in a systemic and pulmonary arterial network. Simulations explore haemodynamic variations resulting from changes in vessel dimensions and segmentation; the latter is achieved by analysing multiple segmentations of the same images. Results demonstrate the importance of accurately defining vessel radii and lengths when generating high-fidelity patient-specific haemodynamics models. KEY POINTS: This study introduces novel algorithms for generating labelled directed trees from medical images, focusing on accurate junction node placement and radius extraction using change points to provide haemodynamic predictions with uncertainty within expected measurement error. Geometric features, such as vessel dimension (length and radius) and network size, significantly impact pressure and flow predictions in both pulmonary and aortic arterial networks. Standardizing networks to a consistent number of vessels is crucial for meaningful comparisons and decreases haemodynamic uncertainty. Change points are valuable to understanding structural transitions in vascular data, providing an automated and efficient way to detect shifts in vessel characteristics and ensure reliable extraction of representative vessel radii.

Bu-Shen-Ning-Xin decoction ameliorates premature ovarian insufficiency by suppressing oxidative stress through rno_circRNA_012284/rno_miR-760–3p/HBEGF pathway

BackgroundPOI (premature ovarian insufficiency) refers to premature and rapid decline of ovarian reserve function in women before the age of 40, which can be manifested as menstrual disorders, endocrine abnormalities and low fertility. Bu-Shen-Ning-Xin decoction (BSNXD) has been found to have therapeutic effects on POI. Nevertheless, how it exerts therapeutic effects remains elusive. PurposeThis research aims to clarify the pharmacological mechanisms of BSNXD. MethodsWe applied Ultra Performance Liquid Chromatography (UPLC) to identify the main components of BSNXD.4-vinylcyclohexene diepoxide(VCD)was used to induce POI models. ELISA detected the serum level of hormones. H&E staining evaluated the morphology of ovarian tissues.CircRNA and mRNA expression profiles in the ovaries of both POI rats and those treated with BSNXD were detected. Then, dysregulated circRNAs and mRNAs that were potentially altered by BSNXD were screened. Network pharmacology analysis was performed to identify drug targets of BSNXD active ingredients. A circRNA-miRNA-mRNA network and an oxidative stress(OS)-related subnetwork were constructed. Expression of rno_circRNA_012284, rno_miR-760–3p, and HBEGF(Heparin-binding epidermal growth factor-like growth factor) was measured by RT-PCR and their binding were verified by dual-luciferase reporter assays. ROS was measured through DCFH-DA fluorescence probes. The HBEGF target was selected for molecular docking with key active ingredients.Surface plasmon resonance(SPR) was applied to verify the binding ability and affinity between components and HBEGF. ResultsUPLC analysis indicated that 6 chemical compounds including berberine, paeoniflorin, morroniside,gallic acid, loganin, baicalin were identified.Elevated FSH and LH levels, suppressed E2 and AMH levels in the serum, and inhibited follicles and corpus luteums in the ovarian tissues of VCD-induced rats were notably reversed by BSNXD.In total, 992 up- and 1135 down-regulated circRNAs, and 205 up- and 243 down-regulated mRNAs were found in POI rat ovaries following BSNXD administration. Furthermore, 198 drug targets of BSNXD were identified. An OS-related and BSNXD-targeted ceRNA subnetwork composed of rno_circRNA_012284/rno_miR-760–3p/HBEGF was established. rno_circRNA_012284 and HBEGF were up-regulated and rno_miR-760–3p was down-regulated in POI ovarian granulosa cells (OGCs) after BSNXD administration. rno_circRNA_012284 was a sponge of rno_miR-760–3p to elevate HBEGF expression. Moreover, rno_circRNA_012284 overexpression alleviated POI-induced excessive ROS generation in ovarian granulosa cells, while rno_circRNA_012284 inhibition exerted the opposite effect. Finally,molecular docking speculated active ingredients of each herb acted on HBEGF to reduce the OS. SPR tests showed that Berberine,Baicalein,Quercetin,Pachymic acid,Paeoniflorin exhibited satisfying affinity with HBEGF protein. ConclusionThis study demonstrates that BSNXD ameliorates POI partly by attenuating OS in ovarian granulosa cells via rno_circRNA_012284/rno_miR-760–3p/HBEGF axis, uncovering the pharmacological mechanisms of BSNXD in alleviating POI.

Alcohol-associated liver disease increases the risk of muscle loss and mortality in patients with cirrhosis

BackgroundRapid skeletal muscle loss adversely affects the clinical outcomes of liver cirrhosis. However, the relationships between the annual changes in skeletal muscle area (ΔSMA/year) and the etiology of cirrhosis, factors associated with muscle loss, and risk of mortality remains unclear.MethodsA total of 384 patients who underwent multiple computed tomography (CT) scans between March 2004 and June 2021 were enrolled in this study (median age, 67 years; 64% men; median model for end-stage liver disease score, 9). Body composition and ΔSMA/year were estimated using a 3D image analysis system and data from at least two distinct CT scans. Differences in ΔSMA/year among different etiologies of cirrhosis, factors associated with rapid muscle loss (defined as ΔSMA/year ≤ − 3.1%), and the association between ΔSMA/year and mortality were examined.ResultsPatients with alcohol-associated liver disease (ALD) cirrhosis experienced more rapid muscle loss (ΔSMA/year, − 5.7%) than those with hepatitis B (ΔSMA/year, − 2.8%) and hepatitis C cirrhosis (ΔSMA/year, − 3.1%). ALD cirrhosis was independently associated with ΔSMA/year ≤ − 3.1% after adjusting for age, sex, and liver functional reserve. Over a median follow-up period of 3.8 years, ALD cirrhosis, ΔSMA/year ≤ − 3.1%, and low subcutaneous adipose tissue level were found to be significantly associated with reduced survival. ALD cirrhosis (hazard ratio [HR], 2.43; 95% confidence interval [CI] 1.12–5.28) and ΔSMA/year ≤ − 3.1% (HR, 3.68; 95% CI 2.46–5.52) were also predictive of mortality.ConclusionsThese results suggest that ALD cirrhosis increases the risk of rapid muscle loss and mortality in affected patients.

KIT in oocytes: a key factor for oocyte survival and reproductive lifespan

The KITL-KIT interaction is known as an important initiator in oocyte activation through the downstream pathway of PI3K-AKT-FOXO3 signalling. Previous studies utilising germ cell-specific Kit mutant knockin and kinase domain knockout models with Vasa-Cre suggested the crucial role of KIT in oocyte activation at the primordial follicle stage. We utilised mice with complete postnatal deletion of KIT expression in oocytes via Gdf9-iCre and conducted analyses on ovarian follicle development, specific markers, hormone assays, and fertility outcomes. Our findings reveal contrasting phenotypes compared to previous mouse models with prenatal deletion of Kit. Specifically, postnatal deletion of Kit exhibit no defects in germ cell nest breakdown, follicle activation, and folliculogenesis during development. Remarkably, upon reaching full maturity, mice with postnatal deletion of Kit experience a complete loss of ovarian reserve, growing follicles, and ovarian function. Furthermore, mice display smaller ovarian size and weight, delayed folliculogenesis, and phenotypes indicative of primary ovarian insufficiency (POI), including elevated serum levels of FSH, reduced AMH, and absence of ovarian follicles, ultimately resulting in infertility. Additionally, the ovaries exhibit randomly distributed expression of granulosa and theca cell markers such as Inhibin α, ACVR2B, and LHR. Notably, there is the uncontrolled expression of p-SMAD3 and Ki67 throughout the ovarian sections, along with the widespread presence of luteinised stroma cells and cleaved Caspase-3-positive dying cells. These genetic studies underscore the indispensable role of KIT in oocytes for maintaining the survival of ovarian follicles and ensuring the reproductive lifespan. This work was supported by National Institutes of Health grant R01HD096042 and startup funds from UNMC (S.Y.K.).

Cognitive reserve and executive functions in dual task gait performance in Parkinson’s disease

A higher level of education was correlated with less severe motor impairment in Parkinson’s Disease (PD). Nevertheless, there is limited evidence on the relationship between cognitive reserve and motor performance in complex situations in PD. To investigate the association between cognitive reserve and the dual-task gait effect in PD. Additionally, we examined the relationship between executive function, clinical and sociodemographic variables and, dual-task gait effects. We conducted a cross-sectional study with 44 PD participants. We evaluated dual-task effect on cadence, stride length, and gait velocity. Dual-task effects were correlated with neurophysiological factors, including cognitive reserve (Cognitive Reserve Index Questionnaire), overall cognitive performance of executive functions, a specific executive function domain (Trail Making Test), and the global cognitive status (Montreal Cognitive Assessment and Mini-Mental State Examination). Age, gender, and disease severity were considered as variables to be examined for correlation. We found that cognitive reserve did not influence gait performance under dual-task conditions in this sample. However, executive functions, age, and disease severity were associated with the dual-task effect on gait. The overall cognitive performance with respect to the Trail Making Test showed an inverse relationship in the dual-task gait effect on cadence. Our study’s findings have important implications for understanding the association between executive functions, age, and disease severity with the dual-task effect on gait in PD. Pre-life factors, such as education, occupation, and leisure activity, did not contribute to coping with complex gait situations in PD.

Physiological Features of the Response of the Respiratory and Circulation Systems to Physical Load in Students Engaged in Winter Football

Adaptive changes in the circulatory and respiratory systems under the influence of winter football training were studied. 50 men aged 21-25 years — 3rd-4th year students — were examined: control group — 25 people specializing in “soccer” (S), main group — 25 people studying in the specialization “winter football” (WF). The examination was performed twice — before and after physical activity. Running (average pace, 180 steps/min) for 15 minutes was used as dosed physical activity. The loads were performed either indoors at a temperature of plus 22–24°C, or in winter outside at a temperature of minus 18–20°C. Indoor and outdoor surveys were carried out on different days. Assessment of peripheral blood flow in the lower extremities was performed using rheography; to assess the main blood flow in the femoral artery, Doppler ultrasound was used. The study of external respiration functions was carried out using pneumotachography. The lactate concentration in capillary blood was determined photometrically. It has been shown that physical activity performed in the cold in adapted athletes (WF group) promotes increased integration between the respiratory and circulatory systems, ensuring the formation of a functional system characterized by stronger connections for optimal adaptation to the combined effects of physical activity and cold. In athletes training indoors (group S) under conditions of a combination of physical activity and cold exposure, on the contrary, desynchronization of the interaction of the respiratory and circulatory systems occurs, which leads to a decrease in adaptive reserves. Thus, sports training in winter football triggers phenotypic adaptive changes and creates a number of physiological mechanisms that promote increased integration between the respiratory and circulatory systems, providing optimal adaptation to the combined effects of physical activity and cold. The obtained facts will be useful for the development of special training programs aimed at increasing the functional reserve of the cardiorespiratory system of athletes training in cold conditions.

Risk factors for diminished ovarian reserve in women: Current state of the problem

Ovarian reserve is the basis of female fertility. The main markers of ovarian reserve are the level of anti-Mullerian hormone and the number of antral follicles. In addition to the natural age-related loss of follicles, many women experience a premature diminished ovarian reserve associated with a number of factors. This can be caused by both various diseases and environmental factors, lifestyle, and social aspects.The aim of this review was to examine the influence of external factors on the ovarian reserve and women fertility. A systematic analysis of data from modern scientific literature, domestic and foreign sources was carried out. The search involved such resources as PubMed, MEDLINE, Science Direct, eLibrary, Scopus, Cyberleninka. A detailed analysis of the influence of environmental pollution, lifestyle (sleep, nutrition, physical activity), previous surgeries, bad habits, obesity, psychological and social factors on the ovarian reserve and reproductive function of women was carried out. Significantly diminished ovarian reserve was noted with low sleep quality, excessive physical activity, and an unbalanced diet poor with animal proteins. Regular consumption of alcohol, smoking and exposure to certain chemical environmental pollutants cause premature follicle apoptosis and the onset of menopause. Circadian dysrhythmia, chronic stress and obesity can lead to the ovarian menstrual cycle disorders and the development of infertility in women. Previous parovarium surgeries are a significant risk factor for diminished ovarian reserve. Further population-based studies are needed to determine the precise mechanisms of influence of various factors on female fertility.

Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure: A multicenter study.

Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model. To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model. This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score. A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score. This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.