Changes In Capacity Research Articles

Probiotics by Modulating Gut-Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole-Kindled Mice.

The microbiota-gut-brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications. In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non-treated animals. Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ-induced neuropsychiatric disturbances such as anxiety and depressive-like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network-driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3). Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti-seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug-resistant seizures.

Cognitive and Functional Capacity Assessment of Individuals Who Were Admitted to the Intensive Care Unit Due to COVID-19: A Prospective Cohort Study.

The goal of this study was to identify changes in cognitive and functional capacity after hospital discharge in those infected with COVID-19 who were admitted to the ICU. This is a prospective cohort study carried out with individuals who were admitted to a hospital, from July 2021 to May 2022. The evaluations happened in three moments: at hospital discharge, 30 days after discharge and 90 days after discharge. The instruments applied are the following: handgrip dynamometer, Montreal Cognitive Assessment Basic questionnaire (MoCA-B), Barthel Index (BI), timed up and go test (TUG), hospital anxiety and depressive scale (HADS) and 36-Item Short Form Health Survey questionary (SF-36). 74 individuals were eligible to participate in the study, 25 of which were followed for 90 days. Based on the results of the MoCA-b, there were no relevant cognitive changes after 3 months. According to the Barthel Index applied to each of the evaluations, the percentage of subjects that were classified as independent or minimally dependent was 48%, 92% then 96%, respectively, demonstrating that individuals can achieve a good degree of functional independence after 3 months. Despite that, the SF-36 demonstrated a score below the South Brazilian normal in some domains. The individuals studied did not present persistent cognitive changes after 3 months and functional capacity showed significant improvement during this period. However, when the assessment is about the self-perceived quality of life, the majority of domain values are still below expectations, deserving attention by the health professionals involved.

How does a Smoke-Free campus initiative generates changes in smoking? A theory-based evaluation

Abstract Background Smoke-free campuses (SFC) prohibit smoking and vaping on all university grounds and for all users. Despite their effectiveness in reducing smoking prevalence, passive smoking, and denormalizing tobacco use, the complex interplay between the programme activities and their impact on users and campus environments remain unclear. This study aims to improve our understanding of the transformation processes associated with SFC expected outcomes. Methods We conducted a retrospective qualitative study on the first SFC implemented in France by the EHESP School of Public Health. Guided by Mayne’s theory of change framework that includes ten dimensions of an impact pathway (e.g. activities, reach/reaction, capacity, behaviour changes, etc.), the research examined the chain of effects and hypotheses driving this SFC. Our dataset included internal documents (e.g. minutes of meetings, administrative documents) and semi-structured interviews with stakeholders (n = 16) involved in the development and implementation of the analysed SFC. Data is currently being analysed. Results Initial results suggest that the EHESP’s SFC activities included communication initiatives, student ambassadors, cessation support for smokers, installation of smoking shelters on campus periphery, etc. These activities were geared on capacity change (e.g. securing support and compliance among campus users, reduce smoking opportunities, promoting the use of cessation aids) and were intended to drive behaviour change (reducing smoking and facilitating cessation among students and staff). The goal of this SFC was not only to impact behaviors but also to educate future health service managers at EHESP to implement SFC policies and set an example for other institutions in France. Conclusions This study identifies some of the transformations that activities of the EHESP’s SFC can generate in students and staff in order to fulfil its outcomes. It also highlighted its expected impact on other institutions. Key messages • Understanding how a smoke-free campus generates its changes is essential in facilitating transferability of experiences to other universities. • Smoke-free campus policies can also generate a broader impact on other institutions.

Social ageing and higher-order interactions: social selectiveness can enhance older individuals' capacity to transmit knowledge.

In long-lived organisms, experience can accumulate with age, such that older individuals may act as repositories of ecological and social knowledge. Such knowledge is often beneficial and can spread via social transmission, leading to the expectation that ageing individuals will remain socially well-integrated. However, social ageing involves multiple processes that modulate the relationship between age and social connectivity in complex ways. We developed a generative model to explore how social ageing may drive changes in social network position and shape older individuals' capacity to transmit knowledge to others. We further employ novel hypernetwork analyses that capture higher-order interactions (i.e. involving ≥ 3 participants) to reveal potential relationships between age and sociality that conventional dyadic networks may overlook. We find that older individuals in our simulations effectively facilitate transmission across a range of scenarios, especially when transmission resembles a complex contagion or when social selectivity (i.e. prioritization of key relationships) rapidly emerges with age. These patterns result from the formation of tight-knit sets of older associates that co-occur in multiple groups, thereby reinforcing one another's capacity to transmit knowledge. Our findings suggest key avenues for future empirical work and illustrate the use of hypernetworks in advancing the study of social behaviour.This article is part of the discussion meeting issue 'Understanding age and society using natural populations'.

Usefulness of monitoring mycophenolic acid exposure in systemic sclerosis-related interstitial lung disease: a retrospective cohort study

BackgroundSystemic sclerosis-related interstitial lung disease (SSc-ILD) represents a significant cause of morbidity and mortality in Systemic Sclerosis (SSc). Mycophenolate mofetil (MMF) is currently the first line treatment for SSc-ILD. There is no recommendation on the dosage of mycophenolic acid (MPA) blood concentrations, so we aimed to study the correlation between MPA exposure and respiratory outcomes in this population.MethodsWe conducted a retrospective cohort study of SSc-ILD patients treated with MMF in our center. According to our policy, a complete patient evaluation was performed approximately one year after MMF initiation, during which the mycophenolic acid (MPA) residual rate (RR) was measured. We analyzed the association between RR and changes in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) over time.ResultsForty-three SSc-ILD patients were included. Patients with higher RR levels (≥ 1.5 mg/L) had a significantly better FVC evolution with a higher proportion of stabilization and lower proportion of FVC decrease (p = 0.024). RR above 1.5 mg/L was a predictive factor of reduced FVC decline compared with lower RR levels adjusting for MMF dose and duration of MMF exposure (p = 0.008). There was no difference regarding DLCO outcome.ConclusionOur study suggests that optimal MPA exposure, as indicated by RR levels, may better protect against FVC decline in SSc-ILD patients treated with MMF. Routine monitoring of MPA exposure could be beneficial in optimizing treatment outcomes. Prospective, multicenter studies are needed to further explore the relationship between MPA exposure and clinical outcomes in SSc-ILD.

Aerobic exercise capacity improvement of patients with human immunodeficiency virus one year post-treatment initiation by integrase inhibitors

Abstract Background Infection by Human Immunodeficiency Virus (HIV) leads to chronic inflammation and subsequently to the early development of cardiovascular (CV) disease in young adults. Initiation of antiretroviral therapy (ART) usually leads to patient’s body weight and blood pressure increase. Cardiopulmonary exercise test (CPET) evaluates aerobic exercise capacity and subsequently cardiovascular and respiratory function. Aim of this study is the investigation of any treatment-induced changes in aerobic exercise capacity in treatment naïve young HIV patients’ at 1-year post HIV treatment initiation by different ART agents. Methods We studied 46 recently diagnosed and treatment naïve young HIV patients (37+10 years, 87% males, 62% smokers) at baseline and 1-year post ART initiation (integrase or protease inhibitors). Twenty-six (26) patients were randomly treated by the newer integrase inhibitor Dolutegravir (Group A, mean age=36+9 years, 100% males, 77% smokers) while 19 patients by the older protease inhibitor Darunavir/Cobicistat (Group B, mean age=37+10 years, 90% males, 47% smokers). All patients were submitted in CPET at baseline and 1-year post ART initiation. We estimated any changes in body mass index (BMI), systolic blood pressure (SBP) and CPET parameters (peak VO2, Oxygen pulse, WorkLoad, VE/VCO2) at 1-year post ART initiation. Results At baseline and 1-year re-evaluation, we found no differences between groups regarding age, BMI and CPET parameters. In the whole HIV population, we found an increase in body weight (76+12 vs. 82+15kg, p<0.001), SΒΡ (124+12 vs. 132+14mmHg, p<0.001), WorkLoad (176+35 vs. 186+35watt, p<0.001) and peak VO2 (2171+437 vs. 2299+491ml/min, p=0.03) at 1-year re-evaluation. In Group A, body weight (p<0.001), SBP (p=0.07), WorkLoad (p=0.006) and peak VO2 (p=0.01) were increased while in Group B, body weight (p<0.001), SBP (p=0.001) και WorkLoad (p=0.01) were also increased. Conclusions Aerobic exercise capacity is improved 1-year post-treatment initiation by the newer integrase inhibitor Dolutegravir in treatment-naïve HIV patients despite the adverse BMI and SBP increase. The newer Dolutegravir probably exhibits a more favorable CV profile in HIV patients compared to the older Darunavir/Cobicistat.Re-evaluation 1-year post ART initiation

Formation of reactive nitrogen species promoted by iron ions through the photochemistry of a neonicotinoid insecticide

Abstract. Nitrous acid (HONO) and nitrogen oxides (NOx=NO+NO2) are important atmospheric pollutants and key intermediates in the global nitrogen cycle, but their sources and formation mechanisms are still poorly understood. Here, we investigated the effect of soluble iron (Fe3+) on the photochemical behavior of a widely used neonicotinoid (NN) insecticide, nitenpyram (NPM), in the aqueous phase. The yields of HONO and NOx increased significantly when NPM solution was irradiated in the presence of iron ions (Fe3+). We propose that the enhanced HONO and NO2 emissions from the photodegradation of NPM in the presence of iron ions result from the redox cycle between Fe3+ and Fe2+ and the generated reactive oxygen species (ROS) by electron transfer between the excited triplet state of NPM and molecular oxygen (O2). Using the laboratory-derived parameterization based on kinetic data and gridded downward solar radiation, we estimate that the photochemistry of NPM induced by Fe3+ releases 0.50 and 0.77 Tg N yr−1 of NOx and HONO, respectively, into the atmosphere. This study suggests a novel source of HONO and NOx during daytime and potentially helps to narrow the gap between field observations and model outcomes of HONO in the atmosphere. The suggested photochemistry of NPM can be an important contribution to the global nitrogen cycle affecting the atmospheric oxidizing capacity and climate change.

Shortened sleep duration impairs adipose tissue adrenergic stimulation of lipolysis in postmenopausal women.

The objective of this study was to examine the changes in adipose tissue lipolytic capacity and insulin signaling in response to shortened sleep duration (SSD) in postmenopausal women. Adipose tissue from a randomized crossover study of nine healthy postmenopausal women (mean [SD], age: 59 [4] years; BMI: 28.0 [2.6] kg/m2) exposed to four nights of habitual and SSD (60% of habitual sleep) while following a eucaloric diet was examined ex vivo. Tissue lipolytic capacity was determined by measurement of secreted glycerol. Cellular insulin signaling was determined by measuring insulin-mediated changes in Akt phosphorylation. RNA sequencing examined global transcriptional changes. With SSD, basal glycerol secretion was reduced, and isoproterenol-stimulated lipolysis was attenuated. Insulin concentration-dependent increases in phosphorylated Akt observed in samples after habitual sleep were abrogated after SSD. However, insulin-mediated suppression of lipolysis remained unaltered with changes in sleep duration. Increased transcription of genes involved in adipogenesis and fatty acid metabolism was observed after SSD. SSD blunts adrenergic stimulation of lipolysis without altering insulin-mediated suppression of lipolysis in postmenopausal women. These changes in adipose tissue may potentiate fat gain independent of caloric intake. Therefore, interventions promoting sleep may be considered to mitigate abdominal adiposity in postmenopausal women.

The state of psychological and immunological indicators in graduate students of a medical university

Training future doctors for professional practice usually entails building awareness and embracing the significant responsibility inherent in the field. This, in turn, leads to significant psycho-emotional stress by the time of graduation from academic institution. With the aim of identifying the correlation between homeostatic system indicators, a comparative analysis was conducted to characterize the immunological and psychological parameters of final-year medical university students, contingent upon their respective training programs. The study involved sixth-year students of the Therapeutic and Preventive Faculty [TPF] (29 individuals) and the Military Training Center [MTC] (34 individuals) of Rostov State Medical University, a Federal State Budgetary Educational Institution of Higher Education. The exclusion criteria for all participants included the presence of chronic diseases and any infectious process of any origin within three months prior to the study. The groups were similar in terms of age (23.8±1.82 and 23.9±2.2 years, respectively), gender (all male), and corresponded to health group I. Psychological evaluation was conducted employing the Spielberger–Hanin Scale to gauge levels of personal and situational anxiety. The assessment of immunological status was carried out at the Scientific Research Institute of Clinical Immunology using standard methodological approaches. Registration cards for immunopathology analysis were used to characterize health status over the year. Analysis of the obtained data from psychological questionnaires revealed that students of the Therapeutic and Preventive Faculty, compared to their counterparts from the Military Training Center, demonstrated a higher degree of situational and, particularly, personal anxiety. Differences in the immune response system between the compared groups were identified with regards to indicators that characterize both adaptive and innate immunity. These differences were expressed in a more significant number of circulating regulatory T lymphocytes, a less pronounced lytic potential of effector cells, a greater number of TLR9+ monocytes with a decrease in the proportion of cells of the monocyte series carrying HLA-DR in medical students compared to their counterparts studying in the medical service officers’ program. Thus, the period of psychological preparation in a medical university for the commencement of professional activity varies based on the characteristics of the educational process and proves to be more effective for sixth-year students of MTC. Students from the TPF exhibit more pronounced psycho-emotional stress compared to their counterparts in military medical training, leading to evident signs of immune system dysregulation. It is imperative to develop strategies for timely detection of changes in both psychological and immunological adaptive capacities.

Chemical modification of Pinus walliichiana sawdust: Application in membrane system for efficient purification of groundwater containing Cd(II) and Ni(II)

In the Sargodha region of Pakistan, the concentrations of Cd(II) and Ni(II) ions are very high as compared to WHO and US EPA standards and may be one of the leading reasons for water-borne diseases in the population of this area. In the current research work, an eco-friendly, low-cost, effective, and reusable filter membrane system is developed. The cellulose sawdust of Pinus walliichiana (PWC) was treated with succinic anhydride to form Pinus walliichiana cellulose succinate (PWCS) and finally converted to sodic form (PWCS-Na) by treating with saturated sodium bicarbonate. The PWCS and PWCS-Na as obtained were characterized using FTIR, pHZPC, SEM, PXRD, and Brunauer–Emmett–Teller (BET) analysis. The BET surface area of the PWCS-Na was found to be 579.5 m2/g. Maximum sorption capacity values in the batch study for Cd(II) (235.2 ± 10.3 mg g−1) and Ni(II) (195.6 ± 15.2 mg g−1) were observed at 298 K, pH 6, sorbent dosage of 30 mg, and metal ion concentration of 70 mg/L. The filter membrane system was designed and employed for the purification of the flowing water system. Theoretical calculations show that 1 L of filter membrane containing 138.0 g of the adsorbent PWCS-Na can purify 532.8 L solution with Cd(II) concentration 70 mg/L and 278.2 L solution of Ni(II) with concentration 70 mg/L. The regeneration study proved the efficient reusability of sorbent after five cycles with a slight change in sorption capacity.

Seasonal refuge patterns of phytoplankton trigger irregular bloom events in a contaminated environment

Several experimental evidences and field data documented that zooplankton may alter its behavioral response in the presence of toxic phytoplankton, reducing its consumption to the point of starvation. This paper is devoted to the mathematical study of such interactions of toxic phytoplankton with grazer zooplankton. The non-toxic phytoplankton is assumed to adopt a density-dependent refuge strategy to avoid over-predation by zooplankton. Both groups of phytoplankton are assumed to suffer direct harm from anthropogenic toxicants, while zooplankton is affected indirectly by ingesting contaminated phytoplankton. We calibrate the proposed model with the field data from Talsari and Digha Mohana, India, and estimate some crucial model parameters consistent with the behavior of the observed data. Our results demonstrate that zooplankton grazing on toxic phytoplankton plays a key role in the emergence or mitigation of plankton blooms. We also highlight the system’s potential to exhibit multiple stable configurations under the same ecological conditions. The plankton system experiences significant regime shifts, which are explored through various bifurcation scenarios, such as transcritical and saddle-node bifurcations. These shifts are influenced by changes in refuge capacity, species growth rates, and environmental carrying capacity. Furthermore, we incorporate environmental variations due to seasonal periodic or almost periodic changes, allowing the refuge parameter to be time-dependent. We observe that the forced system exhibits double periodic solutions. Moreover, stronger seasonal variations in the refuge pattern lead to irregular chaotic blooms. In conclusion, the results offer valuable insights into the sustainability of biodiversity, potentially shedding light on the origin of diverse plankton bloom phenomena.

Development of Machine Learning-Based Production Forecasting for Offshore Gas Fields Using a Dynamic Material Balance Equation

Offshore oil and gas fields pose significant challenges due to their lower accessibility compared to onshore fields. To enhance operational efficiency in these deep-sea environments, it is essential to design optimal fluid production conditions that ensure equipment durability and flow safety. This study aims to develop a smart operational solution that integrates data from three offshore gas fields with a dynamic material balance equation (DMBE) method. By combining the material balance equation and inflow performance relation (IPR), we establish a reservoir flow analysis model linked to an AI-trained production pipe and subsea pipeline flow analysis model. We simulate time-dependent changes in reservoir production capacity using DMBE and IPR. Additionally, we utilize SLB’s PIPESIM software to create a vertical flow performance (VFP) table under various conditions. Machine learning techniques train this VFP table to analyze pipeline flow characteristics and parameter correlations, ultimately developing a model to predict bottomhole pressure (BHP) for specific production conditions. Our research employs three methods to select the deep learning model, ultimately opting for a multilayer perceptron (MLP) combined with regression. The trained model’s predictions show an average error rate of within 1.5% when compared with existing commercial simulators, demonstrating high accuracy. This research is expected to enable efficient production management and risk forecasting for each well, thus increasing revenue, minimizing operational costs, and contributing to stable plant operations and predictive maintenance of equipment.

Dengue-mediated changes in the vectorial capacity of Aedes aegypti (Diptera: Culicidae): manipulation of transmission or infection by-product?

An arthropod's vectorial capacity summarizes its disease transmission potential. Life-history traits, such as fecundity or survival, and behavioral traits, such as locomotor activity, host-seeking and feeding behavior, are important components of vectorial capacity. Studies have shown that mosquito-borne pathogens may alter important vectorial capacity traits of their mosquito vectors, thus directly impacting their transmission and epidemic potential. Here, we compile and discuss the evidence supporting dengue-mediated changes in the yellow fever mosquito Aedes aegypti (L.), its primary vector, and evaluate whether the observed effects represent an evolved trait manipulation with epidemiological implications. Dengue infection appears to manipulate essential traits that facilitate vector-host contact, such as locomotor activity, host-seeking, and feeding behavior, but the underlying mechanisms are still not understood. Conversely, life-history traits relevant to vector population dynamics, such as survival, oviposition, and fecundity, appear to be negatively impacted by dengue virus. Overall, any detrimental effects on life-history traits may be a negligible cost derived from the virulence that dengue has evolved to facilitate its transmission by manipulating Ae. aegypti behavior and feeding performance. However, methodological disparities among studies render comparisons difficult and limit the ability to reach well-supported conclusions. This highlights the need for more standardized methods for the research into changes in virus-mediated traits. Eventually, we argue that the effects on life-history traits and behavior outlined here must be considered when assessing the epidemiological impact of dengue or other arbovirus-vector-host interactions.

Effects of an Exercise and Lifestyle Education Program in Brazilians living with prediabetes or diabetes: study protocol for a multicenter randomized controlled trial.

Patient education is a crucial strategy for promoting prevention and diabetes self-management since glycemic control achievement involves taking medications, medical nutrition therapy, physical exercise, and behavior changes. However, patient education programs are still barely implemented in low- and middle-income countries. This trial aims to investigate whether a lifestyle education intervention added to physical exercising is superior to sole physical exercising regarding functional capacity, disease-related knowledge, health behaviors, cardiometabolic health parameters, quality of life, depression, and diet quality in individuals with prediabetes or diabetes. Multicenter double-blinded randomized controlled trial with two parallel arms involving 12-week intervention and 6-month follow-up. The eligible individuals (≥ 18years, living with prediabetes or diabetes, literate, no clinical decompensation and/or physical and/or mental limitations that contraindicate physical exercising, written physician permission for exercise, no cognitive impairment, no vision limitations for reading, no confirmed diagnosis of unstable coronary disease or heart failure, no pacemaker and/or implantable cardioverter-defibrillator, no complex ventricular arrhythmias, no intermittent claudication, no recent cardiovascular event or cardiac surgery, and no currently enrolled in a structured exercise program) were recruited from two Brazilian cities and randomized to either (1) an Exercise and Lifestyle Education Program (ExLE) or (2) an Exercise Program (Ex), which can be delivered on-site or remotely based on the participants' internet access and technology literacy. The primary outcomes will be changes in functional capacity and disease-related knowledge. The secondary outcomes will involve changes in health behaviors (health literacy, physical activity level, exercise self-efficacy, and medication adherence) and cardiometabolic health parameters (glycemic control, anthropometric measures, and cardiac autonomic control). Program adherence, satisfaction with the program, diabetes-related morbidity, and changes in quality of life, depression, and diet quality will be the tertiary outcomes. Assessments will occur at baseline, post-intervention, and after 6-month follow-up. If superior effectiveness of ExLE compared to Ex program to improve the outcomes measures is found, this program could be delivered broadly in the Brazilian health system, especially in the primary care facilities where most individuals living with prediabetes and diabetes in our country are assisted. ClinicalTrials.gov, NCT03914924 . Registered on April 16, 2019.

Failure analysis of ternary lithium-ion batteries throughout the entire life cycling at high temperature

The operation life is a key factor affecting the cost and application of lithium-ion batteries. This article investigates the changes in discharge capacity, median voltage, and full charge DC internal resistance of the 25Ah ternary (LiNi0.5Mn0.3Co0.2O2/graphite) lithium-ion battery during full life cycles at 45 °C and 2000 cycles at 25 °C for comparison. The batteries before and after cycling were disassembled, and the structure, morphology, interface characteristics, element content of the cathode and anode plates of the battery were characterized. By analyzing the failure factors of the performance of the ternary batteries during the 45 °C cycling, a reaction mechanism for the rapid decline of high-temperature cycling performance of ternary batteries has been proposed. The results show that the performance degradation of the ternary lithium-ion batteries in the whole life operated at high temperature is characterized by slow decline in the initial stage and rapid drop in the latter stage. Further analysis of physical and chemical performance revealed irreversible damage to both the cathode and anode. The dissolution of transition metal ions from the cathode and their deposition on the anode surface catalyze the decomposition of electrolyte solvents to produce a large amount of gas. Gassing, accompanied by the deposition of Li2CO3 and the thickening of SEI, leads to an increase in the internal resistance of the battery. The coupling between gassing and increased internal resistance is responsible for the rapid drop in the performance of the ternary batteries during high-temperature cycling.

Determinants of Longitudinal Changes in Exercise Capacity in Patients with Independent Functioning on Hemodialysis.

Patients with chronic kidney disease reportedly have decreased muscle oxygen utilization, which most substantially decreases exercise capacity, followed by cardiac reserve. However, determinants of longitudinal changes in exercise capacity in patients on hemodialysis and the effects of long-term exercise interventions are unknown. This study was conducted to clarify these concerns. This was a prospective cohort study. Patients on hemodialysis that were not hospitalized were followed from baseline up to 2years, and cardiopulmonary exercise testing results, including peak oxygen uptake, peak work rate, heart rate reserve, and ventilatory equivalent for carbon dioxide slope, as well as implementation of exercise interventions were assessed. Based on the 2-year change in peak oxygen uptake, they were divided into improvement or declined groups. Forty-five patients who were not hospitalized completed the follow-up were analyzed. In the improvement group, the variation was determined by an increase in peak work rate, which is a peripheral factor (partial regression coefficient 0.08 [95% CI = 0.01 to 0.16]), while in the decline group, the variation was determined by a decrease in the ventilatory equivalent for carbon dioxide slope, which is a cardiac factor (partial regression coefficient = -0.12; 95% CI = -0.21 to -0.03). Moreover, exercise intervention was associated with the change in peak oxygen uptake (partial regression coefficient = 3.09; 95% CI = 1.45 to 4.72). Exercise intolerance even in patients on hemodialysis that were not hospitalized and stable progressed over time with deterioration of cardiac reserve, whereas exercise interventions were associated with improved exercise capacity through enhanced peripheral function. The results support the early measurement of cardiopulmonary or skeletal muscle reserve through cardiopulmonary exercise testing and the implementation of long-term exercise interventions based on the measurement results to address the potential deterioration in exercise capacity associated with reduced cardiac reserve, even in patients on hemodialysis that are asymptomatic and stable.

Improved functional oral intake and exercise training attenuate decline in aerobic capacity following chemoradiotherapy in patients with esophageal cancer.

To investigate the impact of chemoradiotherapy on the physical fitness of patients with oesophageal cancer, and the clinical factors influencing it. A total of 67 participants successfully completed the study, with 18 of them engaging in supervised, in-hospital aerobic training at moderate intensity for a minimum of 20 sessions. Cardiopulmonary exercise testing, hand grip strength, body composition assessed via bioelectrical impedance analysis, patient-generated subjective global assessment, albumin, and the Functional Oral Intake Scale (FOIS) were evaluated before chemoradiotherapy and 6-8 weeks after its completion. Among the participants, cardiopulmonary fitness, hand grip strength, and phase angle of BC-BIA declined during chemoradiotherapy. Before and after chemoradiotherapy, V̇O2peak was 19.6 ± 4.4 and 17.4 ± 3.9 mL/min/kg respectively. The improvement in FOIS during chemoradiotherapy showed a positive correlation with changes in aerobic capacity. Additionally, exercise training was associated with attenuating the decline in aerobic capacity. Physical fitness deteriorated in patients with oesophageal cancer following chemoradiotherapy. Improvement in dysphagia helps maintain aerobic capacity. Additionally, exercise training has the potential to mitigate the decline. This discovery can serve as a reference for enhancing holistic care for patients with oesophageal cancer.

Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression.

Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival. Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO2, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival. The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.

Changes of microbial active ingredients and antioxidant capacity during fermentation process of dark tea

Dark tea, a traditional fermented tea in China, is known for its unique flavor and enhanced health potential due to its fermentation process. However, previous studies on the evolution of its active ingredients and antioxidant properties have been limited by inadequate sample collection, single analytical methods, and insufficient data processing. To address these challenges, this study employed a comprehensive strategy to analyze the dynamic changes of active compounds and antioxidant efficacy during dark tea fermentation using refined sampling, diverse assay techniques, and advanced data analysis. A multi-point temporal sampling method was used to capture key stages of fermentation, ensuring comprehensive data. High-Performance Liquid Chromatography (HPLC) and various antioxidant assays (1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Ferric ion reducing antioxidant power (FRAP)) enabled precise quantification of tea polyphenols, catechins, theaflavins, and thearubigins. Multivariate statistical analysis revealed that tea polyphenols and catechins decreased, theaflavins increased then slightly declined, and thearubigins steadily rose as fermentation progressed. These changes were linked to fluctuations in antioxidant capacity, peaking at around 30 mg/g of phenolic compounds. The study also explored optimizing fermentation to enhance the retention of beneficial components, maximizing antioxidant properties and improving product quality. This research advances the understanding of dark tea fermentation and supports the sustainable development of the dark tea industry.

Hispolon-loaded lipid nanocapsules for the management of hepatocellular carcinoma: comparative study with solid lipid nanoparticles and suspension.

Aim: The present study aims to develop, optimize and assess hispolon (HPN) lipid nanocapsules (LNCs), solid lipid nanoparticles (SLNs) and suspension for treating hepatocellular carcinoma (HCC).Materials & methods: It included UPLC-MS/MS, solubility, optimization, characterization, stability, in vitro and in vivo studies.Results: HPN-loaded LNCs were developed using phase-inversion and temperature cycling, while SLNs and suspension using hot homogenization and trituration methods. HPN-LNCs had a particle size (PS) of 196.9nm, a PDI of 0.315 and a zeta potential of -24.3mV. HPN-S2 had a PS of 199.90nm, a PDI of 0.381 and a zeta potential of -19.1mV. HPN-SPN3 showed a PS of 946.60nm, a PDI of 0.31 and a zeta potential of -0.1945mV. Stability tests over 3 months and gastric stability testing in different media showed no significant changes in PS, PDI, entrapment efficiency (EE) and loading capacity (LC). HPN-LNCs demonstrated 96.22% sustained drug release over 25h, outperforming HPN-S2 (87.12%) and HPN-SPN3 (22% within 2h). HPN-loaded LNCs improved oral bioavailability by 2.03-times, the most effective hepatoprotective action and higher localization in liver tumors over HPN-S2 and HPN-SPN3.Conclusion: HPN-Loaded LNCs results are promising, but more safety data needed in the future.