Deleterious Effects Research Articles

Latino adolescents' experiences of residential risks on social media and mental health implications.

Despite alarms raised that adolescents' social media use can aggravate the harmful impact of residential risks (e.g. local violence) to their mental health, the mechanisms are poorly understood. To better understand potential mechanisms, we interviewed Latino adolescents living in a hypersegregated U.S. city, for whom social media may aggravate existing inequalities in residential risks to their mental health. Through an abductive analysis, we identified two processes suggesting how social media can amplify the deleterious impact of residential risks to their mental health. We refer to the first as additive, whereby social media heightens awareness of residential risks. The second is extension, whereby social media lengthens one's risk awareness, speeds up potential for risk awareness and multiplies who may become aware. We found evidence suggestive of parallel processes yielding diminution, whereby social media can minimise the deleterious effects of residential risks via adding and extending exposure to mental health resources, like collective efficacy. Further, the potential for extension (to both risks and resources) appears limited because social media practices (e.g. reposting, seeking viral attention) can foster indifference. Findings suggest the need to consider how adolescents activate resources via social media to avoid overstating its negative impact on mental health.

Produção e qualidade da couve folha hidropônica sob estresse salino e concentrações de KNO3

ABSTRACT Potassium is a nutrient with the potential to increase plant tolerance to salt stress. The aim of this study was to evaluate the production and quality of kale subjected to salt stress and potassium concentrations in a protected environment. The experimental design was in split plots, with plots composed of five nutrient solutions (control treatment, S1 - standard nutrient solution prepared in low-salinity water, 0.5 dS m-1 (500 mg L-1 of KNO3), and four nutrient solutions prepared in brackish waters (3.5 dS m-1) containing four concentrations of KNO3 (S2 - 500 mg L-1, S3 - 625 mg L-1, S4 - 750 mg L-1, S5 - 1,000 mg L-1), and subplots represented by two leaf kale cultivars (Manteiga and Manteiga da Geórgia). Leaf production variables and post-harvest physical and chemical qualities were evaluated. The saline nutrient solution with the addition of NaCl (S2) reduced production but did not reduce the post-harvest quality of kale. The extra addition of KNO3 at 25% (S3) was efficient in reducing the deleterious effects of salt stress on the variables leaf length, leaf area, leaf production, and number of bunches. The cv. Manteiga da Geórgia was more tolerant to salt stress than the cv. Manteiga.

Allelopathic interactions of Carthamus oxyacantha, Macrophomina phaseolina and maize: Implications for the use of Carthamus oxyacantha as a natural disease management strategy in maize.

Fungicides are used to control phytopathogens but all these fungicides have deleterious effects. Allelopathic interactions can be harnessed as a natural way to control the pathogens but there are no reports that show the allelopathic interactions of donor plant, recipient crop, as well as the target plant pathogen and the material used for inoculum production. So, in the present study, the suitability of Carthamus oxyacantha M. Bieb. was assessed against Macrophomina phaseolina, the cause of charcoal rot in maize. Among the various treatments in pot experiment, a negative control, 3 concentrations of inoculum (1.2×105, 2.4×105, and 3.6×105 colony forming units (CFU) mL-1, 3 concentrations (0.5, 1.0, and 1.5% w/w) of C. oxyacantha along with an autoclaved M. phaseolina (Mp) and C. oxyacantha alone were included to investigate their allelopathic effects on maize, not investigated earlier. Maximum suppression of the disease was observed by 1.5% (w/w) concentration of C. oxyacantha. Soil amendment with C. oxyacantha significantly suppressed the disease incidence (DI) and disease severity index (DSI) in charcoal rot of maize up to 40 and 55%, respectively over the strongest level of inoculum (Mp3). C. oxyacantha not only reduced area under disease incidence progress curve (AUDIPC) and area under disease severity progress curve (AUDSPC), but also improved the morphological, biochemical and physiological parameters of maize. The maximum increase of 48, 65, and 75% in values of shoot length (SL), shoot dry mass (SDM), and root dry mass (RDM), respectively was observed by application of the highest concentration of C. oxyacantha in the treatment Mp1+Co3, over infested control (Mp1). Photosynthetic pigments, such as chlorophyll a, chlorophyll b and carotenoids were increased to 58, 64, and 46%, respectively over Mp1, by the application of C. oxyacantha. Carbon assimilation rate (A), stomatal conductance (gs), rate of transpiration (E), and internal carbon dioxide concentration (Ci) were significantly increased to 58, 48, 48, and 20%, respectively over infested control (Mp3), by application of C. oxyacantha concentration 1.5 (w/w). Moreover, defense enzymes like superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities were boosted up to 27, 28, and 28% over Mp3, respectively. Positive allelopathy of C. oxyacantha towards maize and negative allelopathy towards M. phaseolina makes C. oxyacantha a suitable candidate for charcoal rot disease control in maize.

British Cardiovascular Intervention Society Training Culture Focus Group Position Statement: Bringing Trainees and Trainers Together

Unprofessional behaviour within cardiology has been well documented and commonly occurs within the cardiac catheterisation laboratory, with higher rates in interventional subspecialities. While most trainees have positive experiences and encounters within the catheterisation laboratory, around one in five report experiencing bullying. This not only has a significant negative impact on the individuals directly involved, but also on the wider multidisciplinary team; importantly, it will have a deleterious effect on patient safety. The British Cardiovascular Intervention Society established the Training Culture Focus Group in 2022 to analyse and offer potential solutions to this pressing issue. We recommend that a cohesive approach between trainers and trainees is the most effective way to reduce unprofessional behaviour incidents, thus improving departmental workplace culture and a subsequent reduction in adverse patient safety events. ,1,2 ,3 ,4 ,5 ,5 ,6,7 ,8 ,9 10 and ,1,2 on behalf of the

TGFβ2-Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions.

Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron-dependent regulated cell death, as a central mechanism driving postmenopausal salivary gland (SG) dysfunction. In the OVX-SGs, TGFβ signaling pathway is enhanced with the aberrant TGFβ2 expression in SG mesenchymal cells. Intriguingly, TGFβ2 treatment reduces iron-storing ferritin levels, leading to lipid peroxidation and ferroptotic death in SG epithelial organoids (SGOs). Mechanistically, TGFβ2 promotes the autophagy-mediated ferritin degradation, so-called ferritinophagy. A notable overexpression of the type III TGFβ receptor (TβRIII) is found in the OVX-SGs and TGFβ2-treated SGOs, while the silencing of TβRIII mitigates the ferroptosis-mediated deleterious effects of TGFβ2 on SGOs. Finally, administration of ferroptosis inhibitor, Liproxstatin-1 (Lip-1), improves saliva secretion in OVX mice. Present findings collectively suggest a link between TGFβ signaling, ferroptosis, and SG injury, offering new therapeutic avenues for postmenopausal xerostomia.

Susceptibility of Leishmania amazonensis Axenic Amastigotes to the Calpain Inhibitor MDL28170

Leishmaniasis encompasses a group of neglected diseases caused by flagellated protozoa belonging to the Leishmania genus, associated with high morbidity and mortality. The search for compounds with anti-Leishmania activity that exhibit lower toxicity and can overcome the emergence of resistant strains remains a significant goal. In this context, the calpain inhibitor MDL28170 has previously demonstrated deleterious effects against promastigote forms of Leishmania amazonensis, which led us to investigate its role on axenic amastigote forms. The calpain inhibitor MDL28170 was able to decrease the viability of amastigotes in a typically dose-dependent manner. The treatment with the IC50 dose (13.5 μM) for 72 h led to significant amastigote lysis and increased cell-to-cell aggregation. Ultrastructural analysis revealed several cellular alterations, including disruption of the trans-Golgi network and the formation of autophagosomes when treated with MDL28170 at ½ × IC50 dose. Additionally, mitochondrial swelling and the formation of concentric membranous structures inside the mitochondrion were observed after incubation with the IC50 dose. These results reinforce the potential application of the calpain inhibitor MDL28170 against L. amazonensis, highlighting its effectiveness and possible mechanism of action against the parasite.

Triazole scaffold-based DPP-IV Inhibitors for the management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR.

Diabetes mellitus, characterized as a chronic metabolic disorder or a polygenic syndrome; is increasing at a very fast pace among every group of the population worldwide. It arises due to the inability of the body to produce enough insulin (the hormone responsible for controlling blood sugar levels) or inability to utilize the insulin, leading to hyperglycaemic condition, which, if left uncontrolled gives rise to chronic microvascular and macrovascular complications like retinopathy, neuropathy, nephropathy, coronary artery disease, cognitive impairment, etc. Several therapeutic approaches are available for the treatment of diabetes; among which dipeptidyl peptidase (DPP-IV) inhibitors (gliptins) hold a significant place. DPP-IV is a multifunctional enzyme or a serine exopeptidase that plays an imperative role in cleaving bioactive molecules. DPP-IV causes the breakdown of incretin hormone (GLP-1: Glucagon-like peptide 1 and GIP: Glucose-dependent insulinotropic peptide) that is essential for controlling glycaemic levels in the body. Inhibition of DPP-IV enzyme (DPP-IV inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin) prevents this breakdown, thereby controlling blood glucose levels and saving the patients from deleterious effects of prolonged hyperglycaemic conditions. Triazole-based DPP-IV inhibitors are a significant class of drugs used to treat Type 2 diabetes mellitus in a dose-dependent manner. Clinical trials have demonstrated their efficacy as monotherapy or in combination with other antidiabetic agents. This review highlights the molecular docking studies and structure-activity relationship of potential synthetic derivatives that may act as lead molecules for future drug discovery and yield drug molecules with enhanced efficacy, potency and reduced toxicity profile.

Geochemical study of heavy metals in samples from dumpsites at Onitsha, Anambra Basin, Southeastern Nigeria

Core (0-60cm) samples were collected from selected dumpsites at Onitsha and control site at Awka, Nigeria. Physiochemical parameters (particle size distribution, cation exchange capacity (CEC), pH, Organic Matter (OM in %)) and heavy metals (Lead (Pb), Copper (Cu), Zinc (Zn), Chromium (Cr), Nickel (Ni), Aluminium (Al), Cobalt (Co), Molybdenium (Mo), Cadmium (Cd), Manganese (Mn) and Silicon (Si)) were analyzed using standard methods. The result of the physiochemical analysis shows that the samples were generally sandy with acidic pH values (4.89-6.24); OM ranged from 5.693-27.71%; CEC ranged from 0.072-0.62(Cmol/kg). Comparatively, DS 5 (Obosi) has the highest levels of these heavy metals followed by DS 2 (Woliwo). The order is Bida < Okpoko <Obosi 1 < Woliwo < Obosi 2. The levels of these heavy metals were above the control values. They were equally above national and international guidelines. Enrichment Factor (EF) values varied between no enrichment to extremely severe enrichment. Pollution load index (PLI) indicated that all the sampled sites were polluted while the ecological risk of heavy metals varied between low contamination to high contamination. The prevailing indiscriminate disposal of wastes occasioned by nonexistence of appropriate disposal facilities is the direct cause of the situation. Proactive measures and regular environmental monitoring must be taken to minimize further deterioration as the contaminants pose serious deleterious effects on human and soil organisms.

Nifuroxazide rescues the deleterious effects due to CHCHD10-associated MICOS defects in disease models.

The identification of a point mutation (p.Ser59Leu) in the CHCHD10 gene was the first genetic evidence that mitochondrial dysfunction can trigger motor neuron disease. Since then, we have shown that this mutation leads to the disorganization of the MItochondrial contact site and Cristae Organizing System (MICOS) complex that maintains the mitochondrial cristae structure. Here, we generated yeast mutant strains mimicking MICOS instability and used them to test the ability of more than 1600 compounds from 2 repurposed libraries to rescue the growth defect of those cells. Among the hits identified, we selected nifuroxazide, a broad-spectrum antibacterial molecule. We show that nifuroxazide rescues mitochondrial network fragmentation and cristae abnormalities in CHCHD10S59L/+ patient fibroblasts. This molecule also decreases caspase-dependent death of human CHCHD10S59L/+ iPSC-derived motor neurons. Its benefits involve KIF5B-mediated mitochondrial transport enhancement, evidenced by increased axonal movement and syntaphilin degradation in patient-derived motor neurons. Our findings strengthen the MICOS-mitochondrial transport connection. Nifuroxazide and analogues emerge as potential therapeutics for MICOS-related disorders like motor neuron disease. Its impact on syntaphilin hints at broader neurological disorder applicability for nifuroxazide.

Ambient Moisture-Induced Self Alignment of Polarization in Ferroelectric Hafnia.

The discovery of nanoscale ferroelectricity in hafnia (HfO2) has paved the way for next generation high-density, non-volatile devices. Although the surface conditions of nanoscale HfO2 present one of the fundamental mechanism origins, the impact of external environment on HfO2 ferroelectricity remains unknown. In this study, the deleterious effect of ambient moisture is examined on the stability of ferroelectricity using Hf0.5Zr0.5O2 (HZO) films as a model system. It is found that the development of an intrinsic electric field due to the adsorption of atmospheric water molecules onto the film's surface significantly impairs the properties of domain retention and polarization stability. Nonetheless, vacuum heating efficiently counteracts the adverse effects of water adsorption, which restores the symmetric electrical characteristics and polarization stability. This work furnishes a novel perspective on previous extensive studies, demonstrating significant impact of surface water on HfO2-based ferroelectrics, and establishes the design paradigm for the future evolution of HfO2-based multifunctional electronic devices.

Addressing weight bias among pediatric healthcare clinical staff

BackgroundChildren with obesity may experience weight-based discrimination as a result of weight bias and stigma, which can have deleterious effects on their health and wellbeing, including increased risk of dysregulated, maladaptive, and disordered eating such as restriction, purging, and binging. Prior work has shown that weight bias occurs from healthcare workers caring for adults, but less is known about the prevalence of weight bias in the pediatric healthcare setting.MethodsWe aimed to determine what proportion of pediatric healthcare professionals had attitudes of weight bias at our own institution by constructing a survey with questions from validated weight bias survey tools. Results revealed nearly half of all respondents had witnessed another healthcare professional make negative remarks about a patient with obesity, and many shared that they lacked the proper education/training and equipment to properly care for patients with obesity. Based on survey results, we created an electronic-based training module to educate healthcare professionals on weight bias and discrimination and how they may negatively affect care provided to children and families with obesity at our institution. Engagement with hospital leadership was a key strategy to ensure participation from medical and nursing/allied health staff in the survey, although only nursing/allied health leadership required the online training module resulting in limited physician engagement.ResultsFeedback received regarding the training module was overwhelmingly positive.ConclusionsOur efforts illustrate that weight bias and discrimination exist in pediatric institutions, and that participation in a tailored electronic-based training module may be viewed as a helpful tool to raise awareness of how weight-based discrimination and bias can negatively affect patient care.

Parenting, Cultural Capital, and COVID-19: The Role of Parental Support for Latiné First-generation College Students

Caregivers and families play a pivotal role in students’ college decision-making and ability to develop cultural capital (Carey, 2016). Although the deleterious effects of the COVID-19 pandemic required shifts and adjustments to parenting strategies, it is less clear how COVID-19 impacted parental support for emerging adults, particularly Latiné first-generation college students (FGCS). The current study used a qualitative, longitudinal method to examine how parental support informs cultural capital (Yosso, 2005) and whether it changed due to the pandemic for six (6) Latiné FGCS attending a medium-sized private university in the Midwest region of the United States. Interpretative phenomenological analysis revealed that Latiné FGCS caregivers fostered college-going familial capital, which facilitated the development of forms of cultural capital (aspirational and navigational capital) both before and after the transition to remote learning. Post pandemic, caregivers provided additional logistical and practical support related to students navigating physical space. Findings provide novel insight on the role caregivers provided Latiné FGCS at the onset of the pandemic. Strategies for how universities can engage caregivers and families in order to support Latiné FGCS is discussed.

Regulating lipid metabolism in osteoarthritis: a complex area with important future therapeutic potential

Background Osteoarthritis (OA), which is characterized by pain, inflammation and pathological changes, is associated with abnormal lipid metabolism. Extensive studies have been conducted on the potential functions of lipids including cholesterol, fatty acids (FAs) and adipokines. Materials and Methods By searching and screening the literature included in the PubMed and Web of Science databases from 1 January 2019 to 1 January 2024, providing an overview of research conducted on lipid metabolism and OA in the last 5 years. Results In addition to adiponectin, several studies on the effects of lipid metabolism on OA have been consistent and complementary. Total cholesterol, triglycerides, low-density lipoprotein cholesterol, adipsin, leptin, resistin, saturated FAs, monounsaturated FAs, FA-binding protein 4 and the ratios of the FAs hexadecenoylcarnitine (C16:1) to dodecanoylcarnitine and C16:1 to tetradecanoylcarnitine induced mostly deleterious effects, whereas high-density lipoprotein cholesterol and apolipoprotein A/B/D had a positive impact on the health of joints. The situation for polyunsaturated FAs may be more complicated, as omega-3 increases the genetic susceptibility to OA, whereas omega-6 does the opposite. Conclusion: Alterations in lipid or adipokine levels and the resulting pathological changes in cartilage and other tissues (such as bone and synovium) ultimately affect joint pain, inflammation and cartilage degradation. Lipid or adipokine regulation has potential as a future direction for the treatment of OA, this potential avenue of OA treatment requires high-quality randomized controlled trials of combined lipid regulation therapy, and more in-depth in vivo and in vitro studies to confirm the underlying mechanism.

Population ageing and health financing: A method for forecasting two sides of the same coin

Abstract There is a perception that population ageing will have deleterious effects on future health financing sustainability. Given the positive association between health care utilization and increasing calendar age, many analysts assume population ageing will result in considerable growth in health spending. Since this expenditure tends to be sourced primarily from public funds, there is great policy interest to quantify how population ageing is likely to affect health expenditure trends. We propose a new method-the Population Ageing financial Sustainability gap for Health systems (or alternatively, the PASH)-to explore how changes in the population age mix will affect health expenditures and revenues. Using a set of six countries in Europe and the Western Pacific representing a diverse range of health financing systems (Australia, Bulgaria, Japan, Slovenia, United Kingdom, Vietnam), we forecast the size of the ageing-attributable gap between health revenues and expenditures from 2020 to 2100 under current health financing arrangements. The largest gap by 2100 is expected to be in Vietnam, where the gap between revenues and expenditure is expected to increase by around $170 per person in 2018 PPPs or 2.3% of GDP; 87.1% of this increase is due to expected growth in expenditures. In Slovenia, where the gap is forecast in line with the forecast for Japan (the oldest country in the world), nearly half of the gap (44.2%) is due to reductions in revenue generation. All countries face some health financing gap due to ageing under current financing arrangements. The PASH analysis highlights the wide range of policy options available to manage health financing as the population ages, such as changing sources for health revenues and reducing expenditure by promoting healthy ageing.

Digoxin reduces senescence and restores dysfunctional endothelial-subcutaneous adipocyte cross-talk and dysregulated glucose homeostasis in patients with type 2 diabetes mellitus

Abstract Background Normal subcutaneous adipose tissue (SAT) function is dependent on SAT microvascular expansion. Heart failure with reduced ejection fraction (HF) and type 2 diabetes mellitus (DM) have a synergistic deleterious relationship and, of relevance to this, metabolic dysregulation may drive HF progression in DM. Chronic hyperinsulinemia is associated with adipocyte senescence, however any contributing role of SAT microvascular endothelial cell (SATMVEC) senescence on adverse microvascular expansion in type 2 diabetes mellitus (DM) remains unknown. Digoxin has been shown to have senolytic activity in murine cancer models. However, the potential therapeutic role of digoxin on SAT metabolic function is unexplored. Purpose We establish the presence of SATMVEC senescence and its effects on adipocyte function in people with HF and DM (HFDM). Moreover, we establish a therapeutic role for digoxin in targeting SATMVEC senescence, modulating SATMVEC-adipocyte crosstalk and restoring metabolic homeostasis. Methods We took pectoral SAT biopsies from 59 patients undergoing pacemaker implantation of whom 25 (42%) had HF and DM (HFDM). SATMVEC were isolated from SAT and were treated with 1ng/mL digoxin vs control for 24 hours before characterisation (cell function, expression of senescence-associated ß-galactosidase (ß-gal) and senescence associated secretory phenotype, SASP). Crosstalk between SATMVEC and subcutaneous white adipocytes were examined using co-culture techniques (Fig 1A). Paired digoxin vs control treated SATMVEC were seeded co-cultured with adipocytes for 24 hours, before adipocyte health was quantified, through 2-NBD-glucose uptake and expression of key adipogenic genes and proteins. Results Compared to HF alone, isolated SATMVEC from patients with HFDM had a senescent phenotype with increased SASP and ß-gal expression (p<0.05), reduced metabolic activity, ATP production, proliferative capacity, and impaired angiogenesis (p<0.05). In co-culture, SATMVEC from patients with HFDM had deleterious effects on adipocyte function: increasing expression of IL-6 (Fig 1C) and reducing 2-NBD-glucose uptake (p<0.05). Treatment of SATMVEC with digoxin reduced the SATMVEC senescent phenotype (Fig 1B) and increased 2-NBD-glucose adipocyte uptake (Figure 1D) (p<0.001). Conclusions SATMVEC from patients with HFDM have a senescent phenotype, and when in co-culture induce a proinflammatory adipocyte phenotype, resistant to glucose uptake. Digoxin reduces SATMVEC senescence, restores healthy adipocyte glucose homeostasis, and thus has the potential to repair dysfunctional SAT in patients with HFDM.

Predicting mortality of type-2 diabetes mellitus by applying machine learning to electronic medical records in the west of scotland and hong kong

Abstract Introduction Type 2 diabetes mellitus (T2DM) is associated with accelerated development of atherosclerosis and a reduced life expectancy. Using machine learning (ML) to identify novel characteristics from electronic medical records (EMRs) associated with prognosis may increase prognostic precision and find new targets for investigation and treatment. Aim We used a novel ML approach to investigate the use of EMRs to predict all-cause mortality in two ethnically and geographically different populations; one from the West of Scotland (WoS) and the other from Hong Kong. Methods We obtained EMRs including demographics, prior comorbidities, laboratory measurements, medications, and mortality. Multivariable Cox regression and time-dependent random forest model were used to identify predictors of all-cause mortality in patients with T2DM. Subsequently, we applied a state-of-the-art ML interpretability method, to gain further insight into the key predictors. Results In WoS, 46,031 individuals received a new diagnosis of T2DM between 2009 and 2019. Their median age was 66 (IQR: 56 to 75) years. Within 10 years, 11,727 (25%) deaths were recorded. In Hong Kong, 273,876 patients with a first-attendance with T2DM at public hospitals or clinics were included, with follow-up until December 2019. The median age of the patients was 64 (IQR: 57 to 72) years. Within 10 years, 91,155 (33%) deaths were recorded. For both cohorts, the strongest predictor for all-cause mortality was prescription of loop diuretics (Figure 1). For the WoS, other important predictors were greater age, lower serum albumin, elevated alanine transaminase (ALT), increased alkaline phosphatase (ALP), and lower estimated glomerular function rate (eGFR) (c-index: 0.83; Brier score: 0.07). For Hong Kong, predictive variables were remarkably similar and included greater age, lower eGFR, lower haemoglobin and lymphocytes, lower serum albumin, and elevated ALP (c-index: 0.85; Brier score: 0.06). Multivariable Cox regression adjusting for age and sex showed a higher mortality amongst those prescribed loop diuretics compared to those who were not (WoS: hazard ratio: 1.549, 95% CI: 1.521 to 1.575; Hong Kong: hazard ratio: 1.745 (95% CI: 1.721 to 1.769). Only a minority of patients prescribed loop diuretics had a diagnosis of heart failure, end-stage renal disease or resistant hypertension. Conclusion Amongst patients with recent-onset T2DM, prescription of loop diuretics was the most important predictor of all-cause mortality in both WoS and Hong Kong. Prescription of loop diuretics might be a pharmacological marker of congestion and undiagnosed heart failure or loop diuretics might have deleterious effects on the outcome of patients with T2DM.Fig 1:Predictors of all-cause Mortality

The COVID-19 Pandemic Increased the Risk of Eating Disorders and Emotional Eating Symptoms: A Review of the Current Clinical Evidence

Background: There has been recent evidence to suggest that people who suffer from eating disorders (EDs) or other eating behavior disturbances, such as emotional eating (EE), are particularly vulnerable post-COVID-19. This narrative literature review aims to comprehensively analyze and scrutinize the existing clinical studies regarding the effects of the COVID-19 pandemic on people with EDs or EE. Moreover, due to the COVID-19 pandemic, it is very important to find out whether a person’s emotional state may lead them to wrongly confront their emotional behavior with food consumption. Methods: A thorough search of several databases (PubMed, Scopus, Web of Science, Public Library of Science, Google Scholar, CINAHL Complete, PsycINFO, and Academic Search Complete) was performed to identify available clinical studies on the COVID-19 pandemic published between 2020 and 2024 using relevant keywords. Results: There is substantial evidence that the COVID-19 pandemic exerted negative effects on persons suffering from EDs, including those who are symptomatic, those who are in remission, and those with an EE behavior. Characteristically, people diagnosed with anorexia nervosa (AN), bulimia nervosa (BN), or binge eating disorder (BED) showed considerable symptomatic worsening after the first wave of the COVID-19 pandemic. Clinical studies investigating the effects of the COVID-19 pandemic on persons suffering from EE have also clearly demonstrated that their mood disturbances negatively affected their eating behaviors. These studies have also shown that vulnerable people were at greater risk of EE development and progression during the COVID-19 pandemic. Conclusion: The COVID-19 pandemic seems to have exerted a significant deleterious effect on people who have a history of suffering from EDs or EE. The COVID-19 pandemic has been related to the frequency of dysfunctional eating behaviors, thus decreasing therapeutic intervention efficiency in people with EDs as well as in those with disturbed eating behaviors such as EE. In this aspect, further clinical studies are strongly recommended to investigate the exact effects of the COVID-19 pandemic as well as to explore their potential long-term deleterious complications in the post-pandemic period. Public strategies and policies should be applied to provide special healthcare for this group of patients.

Fenebrutinib, a Bruton’s tyrosine kinase inhibitor, blocks distinct human microglial signaling pathways

BackgroundBruton’s tyrosine kinase (BTK) is an intracellular signaling enzyme that regulates B-lymphocyte and myeloid cell functions. Due to its involvement in both innate and adaptive immune compartments, BTK inhibitors have emerged as a therapeutic option in autoimmune disorders such as multiple sclerosis (MS). Brain-penetrant, small-molecule BTK inhibitors may also address compartmentalized neuroinflammation, which is proposed to underlie MS disease progression. BTK is expressed by microglia, which are the resident innate immune cells of the brain; however, the precise roles of microglial BTK and impact of BTK inhibitors on microglial functions are still being elucidated. Research on the effects of BTK inhibitors has been limited to rodent disease models. This is the first study reporting effects in human microglia.MethodsHere we characterize the pharmacological and functional properties of fenebrutinib, a potent, highly selective, noncovalent, reversible, brain-penetrant BTK inhibitor, in human microglia and complex human brain cell systems, including brain organoids.ResultsWe find that fenebrutinib blocks the deleterious effects of microglial Fc gamma receptor (FcγR) activation, including cytokine and chemokine release, microglial clustering and neurite damage in diverse human brain cell systems. Gene expression analyses identified pathways linked to inflammation, matrix metalloproteinase production and cholesterol metabolism that were modulated by fenebrutinib treatment. In contrast, fenebrutinib had no significant impact on human microglial pathways linked to Toll-like receptor 4 (TLR4) and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) signaling or myelin phagocytosis.ConclusionsOur study enhances the understanding of BTK functions in human microglial signaling that are relevant to MS pathogenesis and suggests that fenebrutinib could attenuate detrimental microglial activity associated with FcγR activation in people with MS.

Relationship Between Training Frequency and Training Session Duration on Vitality in Recreational Runners: A Cross-Sectional Study

Background: Running can improve health status from a biopsychosocial perspective. However, isolation strategies, like the COVID-19 pandemic-induced lockdown, produce deleterious effects on both health status and sport performance. The aim of our study was to investigate recreational runners’ sporting habits, subjective vitality (SV), and well-being after the COVID-19 pandemic-induced lockdown. Methods: After data filtration, 5542 recreational runners (74.5% men and 25.5% women, >18 years) were selected for further analyses. The participants answered preliminary questions regarding sporting habits and completed the validated Spanish version of the Subjective Vitality as a Dynamic Reflection of Well-Being questionnaire for assessing their SV after lockdown. Results: Subjective vitality scores did not differ between men and women, nor between age groups (p = 0.41 and p = 0.11, respectively). Subjective vitality was greater with weekly training frequency up to 5 days/week, where this enhancement plateaued, while average training session duration was positively related to SV, stabilizing at 91–120 min/session (p < 0.001 for both). Conclusions: There is a dose–response relationship between both weekly training frequency and training session duration, and mental health benefits in recreational runners. Further longitudinal studies are needed in order to determine the optimal dose–response relationship for simultaneously enhancing mental health outcomes and running performance in recreational runners, especially regarding weekly training frequency, training session duration, and exercise intensity.

Methamphetamine-induced cardiotoxicity: in search of protective transcriptional mechanisms.

Crystalline methamphetamine hydrochloride is an illegal drug with ahigh addictive potential, better known by its colloquial name "ice" or "crystal meth". The abuse of this drug has led to significant health problems worldwide. Like other amphetamine-type stimulants, chronic consumption of methamphetamine leads to direct toxic effects on the central nervous system, causing cognitive impairment, depressive behavior, and other severe neurological or psychiatric symptoms. Besides its neurotoxicity, the drug exhibits numerous deleterious effects on the cardiovascular system, including hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, and dilated cardiomyopathy with congestive heart failure and left ventricular dysfunction. The excessive release of catecholamines upon methamphetamine exposure causes vasoconstriction and vasospasm, which ultimately lead to hypertension, tachycardia, endothelial dysfunction, and cardiotoxicity. While numerous studies have focused on transcription factors expressed in the brain that cause the neurotoxic effects of the drug, much less is known about transcription factors involved in the development of methamphetamine-induced heart failure. In this article, we provide an overview of the Janus kinase-signal transducer and activator of transcription3 (JAK-STAT3) pathway involved in ischemia/reperfusion injury in the myocardium, which may be activated by the vasospasm-inducing action of the drug. However, much more work is needed to decipher the precise role of STAT protein family members, including the potentially cardioprotective STAT3, in the pathogenesis of methamphetamine-induced cardiotoxicity.