Adverse Changes Research Articles

Lipid and glucose profiles in pregnant women with HIV on tenofovir-based antiretroviral therapy.

Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy is limited. We evaluated metabolic markers in pregnant women with HIV after starting TAF- vs TDF-based ART. We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC+DTG; n=217) or TDF/FTC+DTG (n=215). We measured non-fasting plasma concentrations of glucose, total-cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), lipoprotein (a), and triglycerides from samples collected eight weeks after enrollment. We employed linear regression models to estimate by-arm mean differences. 219 participants enrolled in the DTG arms in Zimbabwe and Uganda: 109 in the TAF/FTC+DTG and 110 in the TDF/FTC+DTG arms. At study entry, mean gestational age was 22.6 weeks, median HIV-1 RNA was 711 copies/mL, and mean age was 25.8 years. By eight weeks, mean total cholesterol was 12 mg/dL higher in women randomized to TAF/FTC+DTG versus TDF/FTC+DTG (95% CI 3.8, 21.1). Pregnant women in the TAF/FTC+DTG arm had higher mean LDL-C (7.1 mg/dL, 95% CI 0.2, 14.0), triglycerides (12.3 mg/dL, 95% CI 1.8, 22.7), lipoprotein (a) (7.3 mg/dL, 95% CI 1.1, 13.6), and lower mean HDL-C (2.8 mg/dL, 95% CI 0.1, 5.6) compared to the TDF/FTC+DTG arm. Pregnant women randomized to start TAF/FTC+DTG had higher lipids than those randomized to TDF/FTC+DTG within eight weeks of ART initiation. However, lipid levels were within normal reference ranges.

Adverse Childhood Experiences and Cognitive Change in Late-Life Depression

ObjectivesTo determine the relationship of adverse childhood experiences (ACEs) with change in cognitive performance over a 1-year period among older adults in treatment for depression. MethodsOlder depressed adults completed the ACEs questionnaire and the Consortium to Establish a Registry of Alzheimer's disease (CERAD) cognitive battery at baseline and were re-assessed with the CERAD 1 year later. ResultsChildhood physical abuse, sexual abuse, and verbal/emotional abuse, respectively, were reported by 25%, 17.5%, and 42% of participants. Total ACEs score was not associated with baseline cognitive performance or 1-year change. However, sexual abuse, physical abuse, and a measure of cumulative verbal/emotional, physical, and sexual abuse were inversely associated with 1-year change in total CERAD score. ConclusionsChildhood abuse may have long-term adverse effects, including placing depressed older adults at risk for progressive cognitive decline. ACEs should be considered in research and clinical management of depression in older adults.

P110 INITIAL TREATMENT WITH A SINGLE CAPSULE CONTAINING HALF-DOSE QUADRUPLE THERAPY VS STANDARD-DOSE DUAL THERAPY IN HYPERTENSIVE PATIENTS (QUADUAL): A RANDOMIZED, BLINDED, CROSSOVER TRIAL

Background and Objective: Guidelines recognized the dual combination in initial antihypertensive therapy. Studies demonstrated low-dose quadruple combination antihypertensive was superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown. Methods: A randomized blinded crossover trial was conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23·75 mg + amlodipine 2·5 mg + indapamide 1·25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension. Patients were randomly assigned in a 1:1 ratio to two crossover sequences. Each sequence received four-weeks of either half-dose quadruple antihypertensives or standard-dose dual antihypertensives, followed by a two-week washout and crossover for four-weeks. Participants and researchers were blinded, except for randomization and drug coding. The primary outcome was the reduction of mean 24-hour systolic blood pressure in ambulatory blood pressure monitoring. Safety outcomes were adverse events and changes in biochemistry after treatment. Analyses were per intention to treat. This trial was prospectively registered on www.clinicaltrials.gov (NCT05377203), and is now complete. Results: A total of 90 eligible participants were randomized between July 13, 2022, and April 20, 2023. The mean age of the population was 43.88 years, and 25.6% were women. The mean baseline 24-h blood pressure was 145.59/93.84 mm Hg. Half-dose quadruple treatment compared with standard-dose dual treatment further reduced mean 24-hour blood pressure by 4.72/4.17 mm Hg (P < 0.001 for both systolic and diastolic blood pressure). Except for fasting blood glucose (P = 0.029) and blood uric acid increased significantly (P < 0.001) in half-dose quadruple group, other adverse events and changes in laboratory values between the two treatments were not statistical different. Conclusions: Initiating treatment with half-dose quadruple combination therapy was more effective in lowering blood pressure than standard-dose dual therapy. The safety of half-dose quadruple therapy was comparable.

Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy

BackgroundAficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study. ObjectivesThe authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM. MethodsSerial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF). ResultsAmong 282 patients (mean age 59 ± 13 years; 41% female, 79% White, 19% Asian), mean LVEF was 75% ± 6% with resting and Valsalva LVOT gradients of 55 ± 30 mm Hg and 83 ± 32 mm Hg, respectively. Over 24 weeks, aficamten significantly lowered resting and Valsalva LVOT gradients, and improved left atrial volume index, lateral and septal eʹ velocities, and lateral and septal E/eʹ (all P ≤ 0.001). LV end-systolic volume increased and wall thickness decreased (all P ≤ 0.003). Aficamten resulted in a mild reversible decrease in LVEF (−4.8% [95% CI: −6.4% to −3.3%]; P < 0.001) and absolute LV global circumferential strain (−3.7% [95% CI: 1.8%-5.6%]; P < 0.0010), whereas LV global longitudinal strain was unchanged. Several measures, including LVEF, LVOT gradients, and E/eʹ returned to baseline following washout. Among those treated with aficamten, improved pVO2 and reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) were associated with improvement in lateral eʹ velocity and septal and lateral E/eʹ (all P < 0.03), whereas improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS) was associated with a decrease in both LVOT gradients (all P < 0.001). ConclusionsCompared with placebo, patients receiving aficamten demonstrated significant improvement in LVOT gradients and measures of LV diastolic function, and several of these measures were associated with improvements in pVO2, KCCQ-CSS, and NT-proBNP. A modest decrease in LVEF occurred yet remained within normal range. These findings suggest aficamten improved multiple structural and physiological parameters in oHCM without significant adverse changes in LV systolic function. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818)

A network design of a canola-to-biodiesel supply chain by considering the water-energy-food-land-ecosystem-undesirable climate change nexus

Global warming, adverse environmental consequences, and the rapid depletion of oil resources are some of the critical challenges that humanity presently confronts due to the utilization of fossil fuels. Replacing fossil fuels with renewable sources of energy such as biofuel is crucial for a clean environment. In addition to its numerous advantages, the production of biofuels has detrimental effects on natural resources as well. Water, energy, food, and land are all required to produce food and energy, which are inextricably linked as the essential inputs for agriculture and fuel production. Undesirable climate change and its impacts on ecosystems are also consequences of this process. This study offers a two-phase approach to designing a canola-to-biodiesel supply chain. The first phase is concerned with finding appropriate sites for canola cultivation in accordance with climatic, social, economic and design criteria. To achieve an ideal solution, the fuzzy best-worst method andthe fuzzy technique of order preference similarity to the ideal solution are simultaneously used. In the second phase, a new multi-objective integer programming model that involves a water-energy-food-land-ecosystem-undesirable climate change nexus is introduced. The suggested model enhances crop harvest from desirable agricultural areas, maximizes the profit, preserves ecosystem values, mitigates undesirable climate changes, and reduces water and energy consumption. An interactive fuzzy method is used to solve the model, and the efficiency of the proposed model is evaluated through a real case study for Iran. Sensitivity analyses are also performed on the key parameters. According to the findings, production activities are connected with the increase of network costs, adverse changes in climate, and increased use of energy. Thus, using high-yield catalysts, increasing the production scale, complying with environmental regulations, receiving government subsidies, investing in research to improve production technologies, and identifying cost-saving strategies can minimize harmful environmental effects and reduce biodiesel production costs, thereby boosting the profit. Furthermore, given Iran’s water scarcity and reduced rainfall, increasing the canola yield per hectare might lead to less land use and water consumption for irrigation. Utilizing specialized machinery, enhancing farmers’ skills in canola cultivation, supplying seeds on time, planting promptly, providing optimal nutrition, and promoting pest management are all effective methods to boost canola yields. The insights provided in this study can help managers in the canola-based biodiesel production sector make better decisions.

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biologic and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential change in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: 1) CT imaging of L3 prior to and after treatment, and 2) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher loss of SMMi after treatment (-11.1% vs. -6.3%, p = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs. -7.1%, p=0.04). In addition, HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs. 77.9, p=0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM were associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.

A multi-center, randomized, open label, two-arm study to evaluate safety & efficacy of nutraceutical tablet as adjuvant when compared with standard of care in patients with benign prostatic hyperplasia

BackgroundBenign Prostrate Hyperplasia (BPH) is a progressive disease of ageing men that may be associated with enlargement of the prostate and lower urinary tract symptoms (LUTS). Herbal/Nutraceutical formulations in addition to standard of care (SOC) could alleviate the symptoms, and thus improve the quality of life of patients. ObjectivesTo evaluate safety & efficacy of nutraceutical tablet as an adjuvant with SOC. Materials and MethodsThis was a prospective, randomized two-arm study aimed to assess the safety and efficacy of Herbal/Nutraceutical Formulation (IP) + SOC versus only SOC, in BPH patients. The primary efficacy endpoint was the change in international prostate symptom score (IPSS) within and between two arms. The safety was evaluated in terms of adverse events and change in prostate specific antigen (PSA) levels. Results140 eligible patients (70 / arm) were evaluated for efficacy and safety endpoints. The baseline characteristics of patients in two arms differed nonsignificantly. The change in IPSS-storage, voiding and QoL scores, from day 1 to 90 were statistically significant in both the arms (p < 0.0001). However, by day 90, the change in these scores in SOC+IP arm were significantly higher than that of SOC arm. Further, the change in International Index of Erectile Function (IIEF) scores was significant in SOC+IP arm (p < 0.05), while non-significant in SOC arm. The adverse events non-significantly differed between two arms. ConclusionThe herbal/nutraceutical formulation combined with SOC are safe and effective for the treatment of BPH. The combination therapy was effective in reducing urine-related symptoms and improving the QoL of BPH patients.

Silymarin mitigates toxic effects of cyclophosphamide on testicular tissue and sperm parameters in mice

Cyclophosphamide, a chemotherapy drug, increases oxidative stress in sperm and testicular tissue. This study evaluated the effect of silymarin, a potent antioxidant, on the quality of sperm and testicular tissue in mice treated with cyclophosphamide. NMRI adult male mice were divided into four groups: control; cyclophosphamide (intraperitoneal injection, 100 mg/kg, once a week); cyclophosphamide + silymarin; and silymarin (intraperitoneal injection, 200 mg/kg, every other day). After a 35-day treatment period, the caudal region of the epididymis was examined for sperm parameters, the right testis was used for stereological studies, and the left testis was used to assess biochemical factors. The data were statistically analyzed using SPSS software, one-way ANOVA and Tukey's test. In the cyclophosphamide group, there was a significant reduction in the mean total volume of testicular tissue, the average volume of seminiferous tubules and their components, and the average volume of interstitial tissue. Additionally, there was a notable decrease (p < 0.001) in the average number of Leydig cells, Sertoli cells, and sperm parameters. The mean concentration of testosterone hormone (p < 0.05) and total antioxidant capacity (TAC) level (p < 0.01) also significantly decreased, while the malondialdehyde (MDA) level increased significantly (p < 0.05). However, these adverse changes were mitigated in the cyclophosphamide + silymarin group compared to the cyclophosphamide group. Our results showed that silymarin as an antioxidant can mitigate the adverse effects of cyclophosphamide on testicular tissue and sperm parameters.

Aging Intensifies Myeloperoxidase Activity after Ischemic Stroke.

Abnormally elevated oxidative stress underlies many diseases and contributes to aging. The myeloid enzyme myeloperoxidase (MPO) generates oxidative stress and contributes to damage after stroke. How aging changes MPO in stroke has not been studied. We aimed to determine the effects aging has on MPO and how these changes contribute to age-related differences in outcomes after ischemic stroke. To investigate tissue MPO activity we developed MPO Activatable Fluorescent Agent (MAFA). We found that aged mice exhibited worse neurological outcomes and higher mortality within the first few days after stroke. Accordingly, neuronal loss was higher in aged mice on day 3. MAFA imaging revealed that aged brains have markedly higher MPO activity that increased after stroke on day 3 compared to young adult brains. Correspondingly, we found more Iba1+ cells in aged brains compared to young adult brains before and after stroke. Interestingly, we found decreased percentage of MPO+ cells and lower MPO protein levels in aged on day 3, suggesting that most Iba1+ cells in aged mice have degranulated and secreted MPO in response to stroke. By day 10 MPO activity and Iba1+ cells decreased in both age groups, although MPO activity remained higher in aged mice. MPO inhibition in aged mice decreased MAFA signal and Iba1+ cells and improved neurobehavioral outcomes to near young adult stroke mice levels and improved mortality rate. While aging is an unmodifiable risk, by uncovering the connection between aging and MPO-related changes after stroke, new therapies can be developed to mitigate these adverse changes brought upon by aging.

Predictors of Clinical Hematological Toxicities under Radiotherapy in Patients with Cervical Cancer-A Risk Analysis.

Cervical cancer ranks third in frequency among female cancers globally and causes high mortality worldwide. Concurrent chemoradiotherapy improves the overall survival in cervical cancer patients by 6% but it can cause significant acute and late toxicities affecting patient quality of life. Whole pelvis radiotherapy doses of 10-20 Gy can lead to myelosuppression and to subsequent hematological toxicities since pelvic bones contain half of bone marrow tissue. A total of 69 patients with IB-IVB-staged cervical cancer have been included in this retrospective cohort study. We analyzed clinical adverse events and changes in blood cell counts (hemoglobin, neutrophils, leukocytes, and platelets) during radiation or chemoradiotherapy received at the Oncological Institute of Bucharest from 2018 to 2021. Decreases in hemoglobin levels of over 2.30 g/dL during treatment were associated with BMI > 23.2 kg/m2 (OR = 8.68, 95%CI = [1.01, 75.01]), age over 53 years (OR = 4.60 95%CI = [1.10, 19.22]), with conformational 3D irradiation (OR = 4.78, 95%CI = [1.31, 17.40]) and with total EQD2 of over 66.1 Gy (OR = 3.67, 95%CI = [1.02, 13.14]). The hemoglobin decrease rate of 0.07 g/dL/day was related to 95% isodose volume (OR = 18.00). Neutropenia is associated frequently with gastrointestinal side effects and with the bowel and rectal V45 isodoses (OR = 16.5 and OR = 18.0, respectively). Associations of total external and internal radiation dose with the time durations calculated from the initiation of treatment to the onset of hematological adverse reactions were also obtained. The maximum drop in leukocytes was observed before day 35 from the RT initiation in patients who underwent treatment with 3D conformal radiotherapy (OR = 4.44, 95%CI = [1.25, 15.82]). Neutrophil levels under 2.2 × 103/μL and thrombocyte levels under 131 × 103/μL during the follow-up period were associated with a total planned dose of 54 Gy to the pelvic region volume (OR = 6.82 and OR = 6.67, respectively). This study shows the existence of clinical and blood predictors of hematological adverse reactions in cervical cancer patients. Thus, patients who are in a precarious clinical situation, with low hematological values (but not yet abnormal), should be monitored during days 29-35 after the initiation of RT, especially if they are obese or over 53 years of age.

Influence of SO4 and Rupestris du Lot (Monticola) Rootstocks on the Production of Tangra Dessert Vine Planting Material

The role of the vine rootstock and its correct selection is the main step in creating vine plantations to achieve a balance between vine growth, yield and grape quality. The studies in this direction are aimed at determining the most suitable rootstock for the different vine varieties, with the objective of their optimal development. In 2018–2021, the agrobiological parameters of vines of Tangra variety, grafted onto two rootstocks – SO4 (Berlandieri×Riparia selection Oppenheim 4) and Monticola (Rupestris du Lot), with different disposal of the root system and affecting the growth vigour and development of the vines, were studied in the Experimental nursery for grapevine rootings of IASS “Obratzov Chiflik”, Ruse, Bulgaria. The experiment was carried out in two variants, each in four replications with 50 grafted cuttings with drip irrigation and micro-jet irrigation in the first month after planting for rooting. The study aimed to recommend the most suitable rootstock for grafting Tangra dessert seedless variety to avoid adverse modification changes caused by it. Monticola rootstock was found to influence positively on the percentage of premium rooted vines, forming a better root system and inducing better growth and maturing of the increment in the production of vine planting material, compared to vines, grafted onto SO4 rootstock.

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation

BackgroundAntenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks’ gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function.MethodsDate-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection.ResultsPreterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration (“Prion Disease”, “Alzheimer’s Disease”, “Arachidonic Acid metabolism”). Adverse changes were independent of respiratory function during ventilation.ConclusionsOur data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.

Regular Consumption of Green Tea as an Element of Diet Therapy in Drug-Induced Liver Injury (DILI).

The liver is a highly metabolically active organ, and one of the causes of its dysfunction is the damage caused by drugs and their metabolites as well as dietary supplements and herbal preparations. A common feature of such damage is drugs, which allows it to be defined as drug-induced liver injury (DILI). In this review, we analysed available research findings in the global literature regarding the effects of green tea and/or its phenolic compounds on liver function in the context of protective action during prolonged exposure to xenobiotics. We focused on the direct detoxifying action of epigallocatechin gallate (EGCG) in the liver, the impact of EGCG on gut microbiota, and the influence of microbiota on liver health. We used 127 scientific research publications published between 2014 and 2024. Improving the effectiveness of DILI detection is essential to enhance the safety of patients at risk of liver damage and to develop methods for assessing the potential hepatotoxicity of a drug during the research phase. Often, drugs cannot be eliminated, but appropriate nutrition can strengthen the body and liver, which may mitigate adverse changes resulting from DILI. Polyphenols are promising owing to their strong antioxidant and anti-inflammatory properties as well as their prebiotic effects. Notably, EGCG is found in green tea. The results of the studies presented by various authors are very promising, although not without uncertainties. Therefore, future research should focus on elucidating the therapeutic and preventive mechanisms of polyphenols in the context of liver health through the functioning of gut microbiota affecting overall health, with particular emphasis on epigenetic pathways.

Evaluating seasonal variation in macronutrient levels and their impact on water quality in urban coastal waters: A case study in nutrient management along the North Colombo coast of Sri Lanka

Macronutrients are vital for sustaining marine food webs and primary production. However, their overabundance through riverine inflows and untreated wastewater discharges causes adverse ecological changes, especially in developing countries, necessitating effective nutrient management for ecosystem preservation. We assessed macronutrient enrichment and dispersion patterns in the north Colombo coast of Sri Lanka, an urban estuary stressed by untreated wastewater discharge from sewer channels and macronutrients from the Kelani River. Maximum concentrations of NO3−−N, total dissolved nitrogen, PO43−−P and total dissolved phosphorus were 0.085, 0.74, 0.70, and 0.79 mg/L, respectively, while the dissolved oxygen levels and temperature ranged from 6.42 to 8.62 mg/L and from 28.1 to 30.8 0C during January 2023. The estuary was a nitrogen-limited ecosystem, with the Kelani River being the primary source of NO3−−N. Although nutrient levels were within water quality guidelines, understanding how pollutants disperse during a catastrophic discharge is crucial for risk management. Simulated dispersion patterns using Delft3D revealed that NO3−−N and other solutes introduced through the Kelani River accumulate near the breakwaters of the Colombo harbor complex during the Northeast monsoon, primarily due to seasonal wave and wind conditions. The accumulation of the limiting nutrient increased the risk of eutrophication and harmful algal blooms by non-indigenous toxic algae species introduced by untreated ballast water disposal. The findings elucidate the critical role of breakwaters in retaining solutes and emphasize the influence of morphological, climatic, and topographical factors on dispersion patterns in coastal ecosystems. The study provides an example for developing countries to integrate cost-effective monitoring technologies and numerical modelling into coastal management, facilitating data-driven decision making for effective environmental management.

Plasticity of the heart in response to changes in physical activity.

The human heart is very adaptable, with chamber size, wall thickness and ventricular stiffness all modified by periods of inactivity or exercise training. Herein, we summarize the cardiac adaptations induced by changes in physical activity, ranging from bed rest and spaceflight to endurance exercise training, while also highlighting how the ageing process (a long-term model of inactivity) affects cardiac plasticity. Severe inactivity during bed rest or spaceflight leads to cardiac atrophy and ventriculo-vascular stiffening. Conversely, endurance training induces eccentric hypertrophy and enhances ventricular compliance, and can be used as an effective countermeasure to prevent adverse cardiac changes during prolonged periods of bed rest or spaceflight. With sedentary ageing, the heart undergoes concentric remodelling and irreversibly stiffens at advanced age. Specifically, older adults who initiate endurance training later in life are unable to improve ventricular compliance and diastolic function, suggesting reduced cardiac plasticity with advanced age; however, lifelong exercise training prevents age-associated cardiac remodelling and maintains cardiac compliance of older adults at a level similar to those of younger healthy individuals. Nevertheless, there are still many knowledge gaps related to cardiac remodelling and changes in cardiac function induced by bed rest, exercise training and spaceflight, as well as how these different stimuli may interact with advancing age. Future studies should focus on understanding what factors (sex, age, heritability, etc.) may influence the heart's responsiveness to training or deconditioning, as well as understanding the long-term cardiac consequences of spaceflight beyond low-Earth orbit with the added stimulus of galactic cosmic radiation.

β-Adrenergic blockade attenuates adverse adipose tissue responses after burn.

Severe burn injuries are defined by a prolonged hypermetabolic response characterized by increases in resting energy expenditure, systemic catabolism, and multi-organ dysfunction. The sustained elevation of catecholamines following a burn injury is thought to significantly contribute to this hypermetabolic response, leading to changes in adipose tissue such as increased lipolysis and the browning of subcutaneous white adipose tissue (WAT). Failure to mitigate these adverse changes within the adipose tissue has been shown to exacerbate the post-burn hypermetabolic response and lead to negative outcomes. Propranolol, a non-selective β-blocker, has been clinically administered to improve outcomes of pediatric and adult burn patients, but there is inadequate knowledge of its effects on the distinct adipose tissue depots. In this study, we investigated the adipose depot-specific alterations that occur in response to burn injury. Moreover, we explored the therapeutic effects of β-adrenoceptor blockade via the drug propranolol in attenuating these burn-induced pathophysiological changes within the different fat depots. Using a murine model of thermal injury, we show that burn injury induces endoplasmic reticulum (ER) stress in the epididymal (eWAT) but not in the inguinal (iWAT) WAT depot. Conversely, burn injury induces the activation of key lipolytic pathways in both eWAT and iWAT depots. Treatment of burn mice with propranolol effectively mitigated adverse burn-induced alterations in the adipose by alleviating ER stress in the eWAT and reducing lipolysis in both depots. Furthermore, propranolol treatment in post-burn mice attenuated UCP1-mediated subcutaneous WAT browning following injury. Overall, our findings suggest that propranolol serves as an effective therapeutic intervention to mitigate the adverse changes induced by burn injury, including ER stress, lipotoxicity, and WAT browning, in both adipose tissue depots. KEY MESSAGES: Burn injury adversely affects adipose tissue metabolism via distinct changes in both visceral and subcutaneous adipose depots. Propranolol, a non-selective β-adrenergic blocker, attenuates many of the adverse adipose tissue changes mediated by burn injury.

The Impact of Digital Transformation on Corporate Financial Performance: A Case Study of Luzhou Laojiao

With the development of the Internet and big data, the global economy is tending to the deep integration of digital economy and real economy. The state attaches great importance to the digital development strategy and has issued a number of policies to support the digital transformation of enterprises. Therefore, digital transformation has become a necessary means for enterprises to cope with internal and external adverse environmental changes and improve their survival and development. This paper selects Luzhou Laojiao, which has great development potential in the liquor industry, as the research object to sort out the background and path of its digital transformation, and then selects relevant indicators from four aspects of profitability, debt paying ability, operating ability and growth ability for analysis. This paper analyzes the impact of Luzhou Laojiao's digital transformation on its financial performance, and provides reference for other enterprises in the same industry undergoing digital transformation.

Effects of prenatal stress on reproductive function of male offspring through the KISS1 system.

Prenatal stress can lead to the programming of the neuroendocrine system in male offspring, disrupting the hypothalamic testicular axis and adversely affecting the reproductive health of male offspring. This study aimed to determine the long-term effects of prenatal stress on the KISS1 system in male offspring and the effects on reproductive function in male offspring. Sixteen pregnant females were divided into a prenatal control group (PC, n = 8) and a prenatal stress group (PS, n = 8). The PS group was modeled with chronic unpredictable mild stress (CUMS) from day 1 of gestation to full-term delivery. Differences between the two groups in various maternal parameters, including glucocorticoid secretion, litter size, and the effects of male offspring birth weight, the KISS1 system, and reproductive function, were determined. Male offspring of PS dams had lower birth weights compared to prenatal controls.KISS1 gene expression is reduced at birth and in adult PS offspring, and its receptor KISS1-R protein is similarly reduced in PS offspring at birth and adulthood. In adulthood, PS male offspring show significantly reduced sex hormone production, altered testicular morphology, reduced maturation of their supporting cells, and decreased expression of connexin 43 (CX43), leading to an altered sperm microenvironment and reduced sperm quality. In conclusion, prenatal stress leads to adverse changes in the KISS1 system in male offspring and decreased reproductive function.

The Genetic Diversity of the Macrophyte Ceratophyllum demersum in Backwaters Reflects Differences in the Hydrological Connectivity and Water Flow Rate of Habitats.

Macrophytes often live in fluvial backwaters that have a variety of hydrological connections to a main river. Since the ability of these plants to adapt to changing environments may depend on the genetic diversity of the populations, it is important to know whether it can be influenced by habitat characteristics. We examined the microsatellite polymorphism of the submerged macrophyte Ceratophyllum demersum from various backwaters and showed that the genetic diversity of this plant clearly reflects habitat hydrological differences. The greatest genetic variability was found in a canal system where constant water flow maintained a direct connection between the habitats and the river. In contrast, an isolated backwater on the protected side of the river had the lowest plant genetic diversity. Oxbows permanently connected to the branch system with static or flowing water, and former river branches temporarily connected to the main bed contained populations with moderately high or low genetic variability. The results demonstrate that habitat fragmentation can be a result not only of the loss of direct water contact, but also of the lack of flowing water. Adverse hydrological changes can reduce the genetic diversity of populations and thus the ability of this macrophyte to adapt to changing environments.

Examining a decade-long trend in exposure to per- and polyfluoroalkyl substances and their correlation with lipid profiles: Insights from a prospective cohort study on the young Taiwanese population

Per- and polyfluoroalkyl substances (PFAS) are artificial chemicals extensively utilized in everyday products, and numerous cross-sectional epidemiological studies consistently link PFAS exposure with lipid profiles across diverse populations and age groups. In longitudinal studies, the findings also indicate a positive correlation between PFAS and lipid profiles; however, this association remains unexplored in adolescents and young adults. Notably, previous research has predominantly focused on conventional lipid biomarkers, with limited exploration of the relationship between PFAS and diverse lipoprotein subfractions. Furthermore, there is a lack of comprehensive investigation into the temporal trends in PFAS concentrations in Taiwan. To address this research gap, we conducted a prospective study following 592 adolescents and young adults (12–30 years old at enrollment) from the YOung TAiwanese Cohort (YOTA) over a duration of 10 years. During the follow-up period, we measured 11 types of PFAS and various lipid profile biomarkers (low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), low-density lipoprotein triglyceride (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, lipoprotein(a), triglyceride). Our results revealed a general decline in PFAS concentrations in the study population. Regarding the correlation between the average levels (averaged across the initial and second tracking periods) of PFAS and lipid profiles (during the second tracking period), we observed positive correlations with total cholesterol and LDL-C for perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), N-methylperfluorooctane sulfonamide acetic acid (N-MeFOSAA), and the sum of PFAS (sum of the 11 kinds of PFAS). Additionally, average levels of PFUdA, N-MeFOSAA, and the sum of PFAS exhibited positive associations with sdLDL-C. This study unveiled an overall decrease in PFAS concentrations and underscores a potential link between PFAS exposure and adverse changes in lipid profiles among young populations, emphasizing the need for further exploration into the mechanisms of PFAS on lipid metabolism and atherosclerosis.