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AIMS: The concept of atrial cardiomyopathy (AtCM) had been percolating through the literature since its first mention in 1972. Since then, publications using the term were sporadic until the decision was made to convene an expert working group with representation from four multinational arrhythmia organizations to prepare a consensus document on atrial cardiomyopathy in 2016 (EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication). Subsequently, publications on AtCM have increased progressively. METHODS AND RESULTS: The present consensus document elaborates the 2016 AtCM document further to implement a simple AtCM staging system (AtCM stages 1-3) by integrating biomarkers, atrial geometry, and electrophysiological changes. However, the proposed AtCM staging needs clinical validation. Importantly, it is clearly stated that the presence of AtCM might serve as a substrate for the development of atrial fibrillation (AF) and AF may accelerates AtCM substantially, but AtCM per se needs to be viewed as a separate entity. CONCLUSION: Thus, the present document serves as a clinical consensus statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) to contribute to the evolution of the AtCM concept.

Aging is increasingly thought to involve dysregulation of metabolism in multiple organ systems that culminate in decreased functional capacity and morbidity. Here, we seek to understand complex interactions among metabolism, aging, and systems-wide phenotypes across the lifespan. Among 2469 adults (mean age 74.7 years; 38% Black) in the Health, Aging and Body Composition study we identified metabolic cross-sectionally correlates across 20 multi-dimensional aging-related phenotypes spanning seven domains. We used LASSO-PCA and bioinformatic techniques to summarize metabolome-phenome relationships and derive metabolic scores, which were subsequently linked to healthy aging, mortality, and incident outcomes (cardiovascular disease, disability, dementia, and cancer) over 9 years. To clarify the relationship of metabolism in early adulthood to aging, we tested association of these metabolic scores with aging phenotypes/outcomes in 2320 participants (mean age 32.1, 44% Black) of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We observed significant overlap in metabolic correlates across the seven aging domains, specifying pathways of mitochondrial/cellular energetics, host-commensal metabolism, inflammation, and oxidative stress. Across four metabolic scores (body composition, mental-physical performance, muscle strength, and physical activity), we found strong associations with healthy aging and incident outcomes, robust to adjustment for risk factors. Metabolic scores for participants four decades younger in CARDIA were related to incident cardiovascular, metabolic, and neurocognitive performance, as well as long-term cardiovascular disease and mortality over three decades. Conserved metabolic states are strongly related to domain-specific aging and outcomes over the life-course relevant to energetics, host-commensal interactions, and mechanisms of innate immunity.

BackgroundImplementation science scholars have made significant progress identifying factors that enable or obstruct the implementation of evidence-based interventions, and testing strategies that may modify those factors. However, little research sheds light on how or why strategies work, in what contexts, and for whom. Studying implementation mechanisms-the processes responsible for change-is crucial for advancing the field of implementation science and enhancing its value in facilitating equitable policy and practice change. The Agency for Healthcare Research and Quality funded a conference series to achieve two aims: (1) develop a research agenda on implementation mechanisms, and (2) actively disseminate the research agenda to research, policy, and practice audiences. This article presents the resulting research agenda, including priorities and actions to encourage its execution.MethodBuilding on prior concept mapping work, in a semi-structured, 3-day, in-person working meeting, 23 US-based researchers used a modified nominal group process to generate priorities and actions for addressing challenges to studying implementation mechanisms. During each of the three 120-min sessions, small groups responded to the prompt: "What actions need to be taken to move this research forward?" The groups brainstormed actions, which were then shared with the full group and discussed with the support of facilitators trained in structured group processes. Facilitators grouped critical and novel ideas into themes. Attendees voted on six themes they prioritized to discuss in a fourth, 120-min session, during which small groups operationalized prioritized actions. Subsequently, all ideas were collated, combined, and revised for clarity by a subset of the authorship team.ResultsFrom this multistep process, 150 actions emerged across 10 priority areas, which together constitute the research agenda. Actions included discrete activities, projects, or products, and ways to shift how research is conducted to strengthen the study of implementation mechanisms.ConclusionsThis research agenda elevates actions to guide the selection, design, and evaluation of implementation mechanisms. By delineating recommended actions to address the challenges of studying implementation mechanisms, this research agenda facilitates expanding the field of implementation science, beyond studying what works to how and why strategies work, in what contexts, for whom, and with which interventions.

BackgroundAlthough social rejection is among the strongest proximal precipitants of major depressive disorder (MDD), little is known about the underlying neurobiological mechanisms and whether neural sensitivity to social rejection may help explain differences in MDD risk. To address this issue, we tested whether neural responses to social threat differed in female adolescents at high vs. low maternal risk for MDD.MethodFemale adolescents with (high-risk; n = 22, Mage = 14.68) and without (low-risk; n = 30, Mage = 15.07) a maternal history of depression were experimentally exposed to negative and neutral social evaluation while undergoing an fMRI scan. Neural responses were assessed by event-related activity and functional connectivity, as well as multivoxel pattern analysis. Activity and functional connectivity analyses focused on a priori-selected regions of interest implicated in self-referential processing and emotion regulation.ResultsCompared to low-risk female adolescents, high-risk female adolescents exhibited greater increases in self-reported depression and social disconnection following social evaluation. Moreover, compared to low-risk female adolescents, high-risk female adolescents exhibited greater amygdala responses to negative social evaluation and a differential pattern of functional connectivity in brain regions related to emotion regulation, self-referential processing, and negative affect. Additionally, these markers of neural threat reactivity were related to depressive symptoms.LimitationsA cross-sectional study design and relatively small, Western sample.ConclusionsThese results suggest that exaggerated neural reactivity to social threat-and an atypical pattern of related functional connectivity-is evident in individuals with a preclinical risk factor for depression. Targeting such responding may thus be a fruitful strategy for preventing depression in at-risk youth.

Surimi products are favored by domestic and foreign consumers due to their distinctive gelatinous texture, rich nutrition, and convenient consumption. Gel properties are key evaluation indicators for the quality of surimi products, which was mainly determined by the gel‐forming ability of the myofibrillar protein (MP). In recent years, the surimi processing industry has faced challenges in product quality that limits the further development, and how to effectively improve the gel properties of surimi products has become one of the key scientific problems to be solved in surimi processing industry. A viable strategy for improving the product quality involves combining surimi with exogenous additives, such as proteins, polysaccharides, and lipids, to enhance the gel‐forming ability of MP. At present, there is limited literature review to systematically investigate the role of these exogenous additives in interacting with MPs in surimi gel system and their effect on the gel properties of heat‐induced surimi. Therefore, in this review, we systematically discussed the formation mechanism and influencing factors of surimi gel, the interactions of exogenous biomolecules (proteins, polysaccharides, and lipids) with surimi protein, as well as their effects on the gel properties of surimi product. The aim of this review was to help us with a better understanding for the intrinsic action mechanisms of complex surimi system and provide some theoretical guidance for the improvement of gel quality and development of surimi products. [ABSTRACT FROM AUTHOR]

Two recent high‐profile publications reported the formation of Heck‐type arylated alkenes catalysed by MeDalPhosAuCl/AgOTf (J. Am. Chem. Soc. 2023, 145, 8810) and their cyclisation to tetralines (Angew. Chem. Int. Ed. 2023, e202312786). It was claimed that these were the first demonstrations in gold catalysis of alkene insertion into Au‐aryl bonds, β‐H elimination and chain‐walking by Au−H dications. We show here that in fact this chemistry is a two‐stage process. Only the first step, the production of an alkyl triflate ester as the primary organic product by the well‐known alkene heteroarylation sequence, involves gold. The subsequent formation of Heck‐type olefins and their cyclisation to tetralines represent classical H+‐triggered carbocationic chemistry. These steps proceed in the absence of gold with identical results. Literature claims of new gold reactivity such as chain walking by the putative [LAuH]2+ dication have no basis in fact. [ABSTRACT FROM AUTHOR]

Various problems and obstacles are encountered during pig farming, especially the weaning phase when switching from liquid to solid feed. Infection by pathogenic bacteria causes damage to the intestinal barrier function of piglets, disrupts the balance of the intestinal microbiota, and destroys the chemical, mechanical, and immune barriers of the intestinal tract, which is one of the main causes of gut inflammation or gut diseases in piglets. The traditional method is to add antibiotics to piglet diets to prevent bacterial infections. However, long-term overuse of antibiotics leads to bacterial resistance and residues in animal products, threatening human health and causing gut microbiota dysbiosis. In this context, finding alternatives to antibiotics to maintain pre- and post-weaning gut health in piglets and prevent pathogenic bacterial infections becomes a real emergency. The utilization of probiotics in piglet nutrition has emerged as a pivotal strategy to promote gut health and defend against pathogenic infections, offering a sustainable alternative to traditional antibiotic usage. This review introduces recent findings that underscore the multifaceted roles of probiotics in enhancing piglet welfare, from fortifying the gut barrier to mitigating the impacts of common bacterial pathogens. Meanwhile, this study introduces the functions of probiotics from different perspectives: positive effects of probiotics on piglet gut health, protecting piglets against pathogen infection, and the mechanisms of probiotics in preventing pathogenic bacteria. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion Avoidant/restrictive food intake disorder (ARFID) is an eating disorder characterized by a severely restrictive diet leading to significant physical and/or psychosocial sequelae. Largely owing to the phenotypic heterogeneity, the underlying pathophysiological mechanisms are relatively unknown. Recently, the communication between microorganisms within the gastrointestinal tract and the brain—the so‐called microbiota‐gut‐brain axis—has been implicated in the pathophysiology of eating disorders. This Spotlight review sought to investigate and conceptualize the possible ways that the microbiota‐gut‐brain axis is involved in ARFID to drive future research in this area.By relating core symptoms of ARFID to gut microbiota and its signaling pathways to the brain, we evaluated how the gut microbiota is potentially involved in the pathophysiology of ARFID.We hypothesized that the restricted type and amount of food intake characteristic of ARFID diminishes gut microbial diversity, including beneficial bacteria and their metabolites capable of signaling to the brain, to modulate biopsychological pathways relevant to ARFID: homeostatic signaling, food reward, interoception, sensory sensitivity, disgust, perseveration, fear‐based learning, and mood. Candidate signaling mechanisms include microbial‐induced effects on inflammation, cortisol, and neurotransmitters such as dopamine and serotonin.Through reviewing the extant evidence, we conceptualized a new theoretical framework of ARFID with an emphasis on microbiota‐gut‐brain axis signaling to inform future research. Although more research is necessary to evaluate this theoretical model, the tentative evidence suggests that therapeutics specifically targeting the gut microbiota for the treatment of ARFID symptomatology warrants more investigation. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive breast cancer may recur or metastasize years or decades after its diagnosis. Furthermore, hormone receptor expression may persist in relapsed or metastatic cancer cells. Endocrine therapy is one of the most efficacious treatments for hormone receptor-positive breast cancers. Nevertheless, a considerable proportion of patients develop resistance to endocrine therapy. Previous studies have identified numerous mechanisms underlying drug resistance, such as epigenetic abnormalities in the estrogen receptor (ER) genome, activation of ER-independent ligands, and alterations in signaling pathways including PI3K/AKT/mTOR, Notch, NF-κB, FGFR, and IRE1-XBP1. This article reviews the mechanisms of endocrine resistance in hormone receptor-positive advanced breast cancer, drawing from previous studies, and discusses the latest research advancements and prospects. [ABSTRACT FROM AUTHOR]

TET2 is a critical gene that regulates DNA methylation, encoding a dioxygenase protein that plays a vital role in the regulation of genomic methylation and other epigenetic modifications, as well as in hematopoiesis. Mutations in TET2 are present in 7%–28% of adult acute myeloid leukemia (AML) patients. Despite this, the precise mechanisms by which TET2 mutations contribute to malignant transformation and how these insights can be leveraged to enhance treatment strategies for AML patients with TET2 mutations remain unclear. In this review, we provide an overview of the functions of TET2, the effects of its mutations, its role in clonal hematopoiesis, and the possible mechanisms of leukemogenesis. Additionally, we explore the mutational landscape across different AML subtypes and present recent promising preclinical research findings. [ABSTRACT FROM AUTHOR]

This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors. [ABSTRACT FROM AUTHOR]

Hemerocallis citrina Borani is a traditional folk food used to promote the lactation of postpartum mothers in China; however, the active ingredients and corresponding mechanisms are still unknown. In this study, the lactogenic effect of alcoholic and aqueous extracts of H. citrina was primarily evaluated, and the aqueous extract (1,000 and 2,000 mg/kg) displayed significant lactation-promoting effects. Three eluates of the aqueous extract (0%, 30%, and 50%HCW) were further evaluated for their lactogenic effect, and 30% and 50% HCW showed significant lactation-promoting activity. Nineteen ingredients, including those with a high content of rutin and isoquercetin, were then identified from 30% and 50%HCW using the ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) method. Finally, the lactogenic effect of rutin and isoquercetin was evaluated, and both compounds displayed significant lactation-promoting activity. The mechanisms relative to the lactation-promoting active ingredients for H. citrina extracts and compounds are to stimulate the release of prolactin (PRL) and progesterone (P), as well as to induce the expression of prolactin receptor (PRLR) and improve the morphology of mammary tissue. This study first clarified the lactation-promoting active ingredients of H. citrina and the corresponding mechanisms, which provide a new insight into the new lactation-promoting drug and promote the high-value utilization of H. citrina resources. [ABSTRACT FROM AUTHOR]

Thyrotoxicosis appears to be a predisposing factor for cerebral venous thrombosis (CVT), which is a rare but important cause of stroke in young adults. The presentation of CVT is highly variable, ranging from a history of headaches (in the majority of cases) to deep coma, with the latter requiring invasive neurosurgical decompression. Although the long-term outcomes of CVT are favorable, multicenter cohort studies have shown that death may occur in up to 4% of cases in the acute phase and 8–10% of cases in the long term. It has been argued that the substantial decrease in mortality in patients with CVT that has been observed during the past few decades may be the result of an increased awareness of CVT among clinicians. Given that thyrotoxicosis is a risk factor for CVT, clinicians (and endocrinologists) should be alert to the possibility of CVT in patients with thyroid disease in order to prevent it whenever possible or treat it promptly. In this review, we provide an updated overview of the characteristics of patients with thyrotoxicosis who presented with CVT, the underlying mechanisms, and a few tips for clinicians. [ABSTRACT FROM AUTHOR]

Breast cancer is a public health concern worldwide, characterized by increasing incidence and mortality rates, requiring novel and effective therapeutic strategies. Curcumin is a bioactive compound extracted from turmeric with several pharmacological activities. Curcumin is a multifaceted anticancer agent through mechanisms including the modulation of signaling pathways, inhibition of cell proliferation, induction of apoptosis, and production of reactive oxygen species. However, the poor water solubility and bioavailability of curcumin create important barriers in its clinical application. This review elaborates on the therapeutic potential of curcumin in breast cancer treatment, focusing on the efficacy of different administration routes and synergistic effects with other therapeutic agents. The intravenous administration of curcumin-loaded nanoparticles significantly improves bioavailability and therapeutic outcomes compared to oral routes. Innovative formulations, such as nano-emulsifying drug delivery systems, have shown promise in enhancing oral bioavailability. While intravenous delivery ensures higher bioavailability and direct action on tumor cells, it is more invasive and expensive than oral administration. Advancing research on curcumin in breast cancer treatment is essential for improving therapeutic outcomes and enhancing the quality of life of patients. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of psychological interventions for bipolar disorder (BD) is well established, but much remains unknown about how change occurs. The primary objective of this exploratory study was to audit what is known about active components and mechanisms of action of psychological interventions for BD. Method: We conducted a systematic review (PROSPERO CRD42022323276). Two independent reviewers screened references from four databases and extracted data from eligible studies. Results: We included four component studies, six studies with mediation analyses and 26 studies presenting subjective experiences of how psychological interventions bring change. Ten mediators were examined across six studies, with only one putative mediator, medication adherence, tested in more than one study. Some initial support for mediation of varied outcomes by control over thoughts, positive non‐verbal behaviour, self‐esteem, post‐trauma growth and medication adherence. Some preliminary support was found in two components, human support and IPT. Studies exploring participant experiences of therapeutic change enumerated a range of potential active components, mechanisms of action and contextual factors potentially warranting investigation in future research. However, the evidence base for active components and mechanisms of action in psychological interventions for BD is unsatisfactory. Findings were inconsistent, studies homogenous with significant methodological limitations and statistical approaches failed to meet quality criteria. Conclusions: Preliminary identification of potential components and mechanisms via qualitative analyses and the insights emerging from this review will inform future research aimed at investigating how psychological interventions work in BD. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is highly prevalent in the Australian community, ranking amongst the highest globally. The consequences of AF are significant. Stroke, dementia and heart failure risk are increased substantially, hospitalisations are amongst the highest for all cardiovascular causes, and Australians living with AF suffer from substantial symptoms that impact quality of life. Australian research has made a significant impact at the global level in advancing the care of patients living with AF. However, new strategies are required to reduce the growing incidence of AF and its associated healthcare demand. The Australian Cardiovascular Alliance (ACvA) has led the development of an arrhythmia clinical theme with the objective of tackling major research priorities to achieve a reduction in AF burden across Australia. In this summary, we highlight these research priorities with particular focus on the strengths of Australian research and the strategies needed to move forward in reducing incident AF and improving outcomes for those who live with this chronic condition. [ABSTRACT FROM AUTHOR]

As the demand for multifunctional optoelectronic devices rises, the integration of electrochromic and energy storage functionalities represents a cutting‐edge pursuit in the electrochromic devices domain. The realm of conductive polymer‐based electrochromic energy storage devices (EESDs) stands as a vibrant area marked by ongoing research and development. Despite a plethora of individual research articles exploring various facets within this domain, there exists a conspicuous dearth of comprehensive reviews systematically scrutinizing the advancements, challenges, and potentials intrinsic to these systems. To fill this void, this review systematically outlines the latest progressions in EESDs centered on conductive conjugated polymers (CPs). The review commences with a thorough exploration of the foundational principles underpinning EESDs, encompassing their operational mechanisms, device configurations, and representative key performance indicators. Furthermore, the review categorizes diverse conductive polymers, shedding light on the latest advancements in EESD research utilizing these specific CP variants. This in‐depth analysis centers on their collaborative role in shaping electrochromic energy storage devices. Overall, this review is poised to captivate the interest of researchers toward state‐of‐the‐art CP‐based EESDs, establishing these pioneering technologies as pivotal contenders in defining the forthcoming landscape of wearable electronics, portable devices, and advanced energy storage systems. [ABSTRACT FROM AUTHOR]

The article discusses endocrine disorders in adult patients with inherited metabolic diseases, emphasizing the importance of diagnosis and long-term management. It highlights the prevalence of endocrine complications in patients with inherited metabolic diseases, such as diabetes mellitus, hypogonadism, adrenal insufficiency, and thyroid dysfunction. The study conducted at a tertiary referral center for endocrinology and inherited metabolic diseases reveals the need for specialized care and multidisciplinary approaches to address these complex health issues. The authors stress the significance of early detection, appropriate screening, and tailored management strategies for patients with inherited metabolic diseases and associated endocrine disorders. [Extracted from the article]

Understanding of the pathophysiology of heart failure with preserved ejection fraction (HFpEF) has advanced rapidly over the past two decades. Currently, HFpEF is recognized as a heterogeneous syndrome, and there is a growing movement towards developing personalized treatments based on phenotype-guided strategies. Left ventricular dysfunction is a fundamental pathophysiological abnormality in HFpEF; however, recent evidence also highlights significant roles for the atria, right ventricle, pericardium, and extracardiac contributors. Imaging plays a central role in characterizing these complex and highly integrated domains of pathophysiology. This review focuses on established evidence, recent insights, and the challenges that need to be addressed concerning the pathophysiology of HFpEF, with a focus on imaging-based evaluations and opportunities for further research. [ABSTRACT FROM AUTHOR]

Background To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects. Study Design We used data (n  = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path. Study Results CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101–0.304, P  < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = −0.010, 0.037, P  = .256). Total symptoms did not moderate the path to cognition (P  = .211) or the direct path to outcome (P  = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P  = .015) with high negative symptoms reducing the functional gains of improved cognition. Conclusions Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration. [ABSTRACT FROM AUTHOR]

Main conclusion: PPI analysis deepens our knowledge in critical processes like carbon fixation and nutrient sensing. Moreover, signaling networks, including pathways like MAPK/ERK and TOR, provide valuable information in how microalgae respond to environmental changes and stress. Additionally, species–species interaction networks for microalgae provide a comprehensive understanding of how different species interact within their environments. This review examines recent advancements in the study of biological networks within microalgae, with a focus on the intricate interactions that define these organisms. It emphasizes how network biology, an interdisciplinary field, offers valuable insights into microalgae functions through various methodologies. Crucial approaches, such as protein–protein interaction (PPI) mapping utilizing yeast two-hybrid screening and mass spectrometry, are essential for comprehending cellular processes and optimizing functions, such as photosynthesis and fatty acid biosynthesis. The application of advanced computational methods and information mining has significantly improved PPI analysis, revealing networks involved in critical processes like carbon fixation and nutrient sensing. The review also encompasses transcriptional networks, which play a role in gene regulation and stress responses, as well as metabolic networks represented by genome-scale metabolic models (GEMs), which aid in strain optimization and the prediction of metabolic outcomes. Furthermore, signaling networks, including pathways like MAPK/ERK and TOR, are crucial for understanding how microalgae respond to environmental changes and stress. Additionally, species–species interaction networks for microalgae provide a comprehensive understanding of how different species interact within their environments. The integration of these network biology approaches has deepened our understanding of microalgal interactions, paving the way for more efficient cultivation and new industrial applications. [ABSTRACT FROM AUTHOR]

Potassium voltage-gated channel subfamily a member 2 (Kv1.2, encoded by KCNA2) is highly expressed in the central and peripheral nervous systems. Based on the patch clamp studies, gain-of function (GOF), loss-of-function (LOF), and a mixed type (GOF/LOF) variants can cause different conditions/disorders. KCNA2-related neurological diseases include epilepsy, intellectual disability (ID), attention deficit/hyperactive disorder (ADHD), autism spectrum disorder (ASD), pain as well as autoimmune and movement disorders. Currently, the molecular mechanisms for the reported variants in causing diverse disorders are unknown. Consequently, this review brings up to date the related information regarding the structure and function of Kv1.2 channel, expression patterns, neuronal localizations, and tetramerization as well as important cell and animal models. In addition, it provides updates on human genetic variants, genotype–phenotype correlations especially highlighting the deep insight into clinical prognosis of KCNA2-related developmental and epileptic encephalopathy, mechanisms, and the potential treatment targets for all KCNA2-related neurological disorders. [ABSTRACT FROM AUTHOR]

A mechanism allocates one unit of an infinitely divisible commodity among agents reporting a number between zero and one. Nash, Pareto optimal Nash, and strong equilibria are analyzed for the case where the agents have single-dipped preferences. One main result is that when the mechanism satisfies anonymity, monotonicity, the zero–one property, and order preservation, then the Pareto optimal Nash and strong equilibria coincide and result in Pareto optimal allocations that are characterized by so-called maximal coalitions: members of a maximal coalition prefer an equal coalition share over obtaining zero, whereas the outside agents prefer zero over obtaining an equal share from joining the coalition. A second main result is an axiomatic characterization of the associated social choice correspondence as the maximal correspondence satisfying minimal envy Pareto optimality, equal division lower bound, and sharing index order preservation. [ABSTRACT FROM AUTHOR]

In the realm of healthcare and the advancing field of medical sciences, the development of efficient drug delivery systems become an immense promise to cure several diseases. Despite considerable advancements in drug delivery systems, numerous challenges persist, necessitating further enhancements to optimize patient outcomes. Smart nano-carriers, for instance, 2D sheets nano-carriers are the recently emerging nanosheets that may garner attention for targeted delivery of bioactive compounds, drugs, and genes to kill cancer cells. Within these advancements, Ti3C2TX-MXene, characterized as a two-dimensional transition metal carbide, has surfaced as a prominent intelligent nanocarrier within nanomedicine. Its noteworthy characteristics facilitated it as an ideal nanocarrier for cancer therapy. In recent advancements in drug delivery research, Ti3C2TX-MXene 2D nanocarriers have been designed to release drugs in response to specific stimuli, guided by distinct physicochemical parameters. This review emphasized the multifaceted role of Ti3C2TX-MXene as a potential carrier for delivering poorly hydrophilic drugs to cancer cells, facilitated by various polymer coatings. Furthermore, beyond drug delivery, this smart nanocarrier demonstrates utility in photoacoustic imaging and photothermal therapy, further highlighting its significant role in cellular mechanisms. [ABSTRACT FROM AUTHOR]

We argue that behavioural public policies (BPP) should be categorized by the kind of mechanism through which they operate, not by the kind of treatment they implement. Reviewing the energy consumption BPP literature, we argue (i) that BPPs are currently categorized by treatment; (ii) that treatment-based categories are subject to mechanistic heterogeneity : there is substantial variation of mechanisms within each treatment type; and (iii) that they also display mechanistic overlap : there is substantial overlap between mechanisms across treatment types. Consequently, current categorizations of BPPs do not reveal the conditions of their efficacy and should be revised to better reflect mechanistic information. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system CNS characterized by demyelination, inflammation, and neurodegenerative changes, making it the most common nontraumatic disabling neurological disease in young adults. While current pharmacological treatments primarily target immunomodulation or immunosuppression, exercise is gaining increasing attention from the scientific community as an adjunctive therapy. This review explores the potential biological mechanisms of exercise in animal models of MS, focusing on its effects on neuroprotection and inflammation. The review examines how exercise inhibits pro-inflammatory microglial reactivity, stabilizes the blood–brain barrier, and enhances neurotrophic factor expression in animal studies. Future research directions are proposed by summarizing the evidence and limitations of existing animal models of MS, emphasizing the need to further validate these mechanisms in humans to better integrate exercise into the comprehensive management of MS. Additionally, investigating exercise-induced biomarkers for MS symptom reduction may provide a scientific basis for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objectives Method Results Conclusions The trauma and social pathways model of psychosis proposes interactions between trauma, attachment, social rank and dissociation in pathways to psychosis, though this model has yet to be empirically investigated. The primary aim of this study was to examine the overall predictive value of the trauma and social pathways model using regression analysis. A secondary aim was to delineate hypothesized pathways between trauma and positive symptoms of psychosis using serial mediation analysis.This was a cross‐sectional study of people attending mental health services for a psychosis‐related diagnosis (N = 71). Measures of trauma, positive symptoms of psychosis, attachment, social comparison and dissociation were completed.A model of recurrent trauma, insecure attachment, social rank and dissociation predicted 23.2% of the variance in positive symptoms of psychosis. Recurrent trauma, attachment and dissociation contributed significantly to the model, while social rank did not. Further, serial mediation analysis indicated that the sequence of disorganized attachment and dissociation fully mediated the relationship between recurrent trauma and positive symptoms.Results provide preliminary support for the trauma and social pathways model of psychosis, specifically as it relates to recurrent trauma, insecure attachment and dissociation. Results did not support the social rank component of this model, however. These findings provide clear targets for the development of next‐wave psychological interventions that focus on trauma‐related variables in psychosis. Future studies should replicate these findings with a larger clinical sample, and consider a measure of shame to further elucidate social processes in pathways to psychosis. [ABSTRACT FROM AUTHOR]

Global reliance on fossil fuel combustion for energy production has contributed to the rising concentration of atmospheric CO2, creating significant global climate challenges. In this regard, direct air capture (DAC) of CO2 from the atmosphere has emerged as one of the most promising strategies to counteract the harmful effects on the environment, and the further development and commercialization of this technology will play a pivotal role in achieving the goal of net‐zero emissions by 2050. Among various DAC adsorbents, metal–organic frameworks (MOFs) show great potential due to their high porosity and ability to reversibly adsorb CO2 at low concentrations. However, the adsorption efficiency and cost‐effectiveness of these materials must be improved to be widely deployed as DAC sorbents. To that end, this perspective provides a critical discussion on several types of benchmark MOFs that have demonstrated high CO2 capture capacities, including an assessment of their stability, CO2 capture mechanism, capture‐release cycling behavior, and scale‐up synthesis. It then concludes by highlighting limitations that must be addressed for these MOFs to go from the research laboratory to implementation in DAC devices on a global scale so they can effectively mitigate climate change. [ABSTRACT FROM AUTHOR]

Background: Recurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL. Methods: Immune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. The metabolic pathways of the differential metabolites were analyzed, and specific metabolites were validated through targeted profiling. Potential biomarkers were identified, and the relationships between immune cytokines and differential metabolites were explored. Results: In the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-g were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-Ltryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis. Conclusion: The study highlights the role of amino acid metabolism in RPL pathogenesis, suggesting that PPA and 5-HTP may be potential predictive indicators, while cystine and tyrosine may potentially regulate immune responses related to RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL. [ABSTRACT FROM AUTHOR]

Since December 2019, coronavirus disease 2019 (COVID-19) has been spreading worldwide with devastating immediate or long-term effects on people's health. Although the lungs are the primary organ affected by COVID-19, individuals infected with SARS-CoV-2 also develop systemic lesions involving multiple organs throughout the body, such as the cardiovascular system. Emerging evidence reveals that COVID-19 could generate myocardial fibrosis, termed "COVID-19-associated myocardial fibrosis." It can result from the activation of fibroblasts via the renin-angiotensin-aldosterone system (RAAS), transforming growth factor-ß1 (TGF-ß1), microRNAs, and other pathways, and can also occur in other cellular interactions with SARS-CoV-2, such as immunocytes, endothelial cells. Nonetheless, to gain a more profound insight into the natural progression of COVID-19-related myocardial fibrosis, additional investigations are necessary. This review delves into the underlying mechanisms contributing to COVID-19-associated myocardial fibrosis while also examining the antifibrotic potential of current COVID-19 treatments, thereby offering guidance for future clinical trials of these medications. Ultimately, we propose future research directions for COVID-19-associated myocardial fibrosis in the post-COVID-19 era, such as artificial intelligence (AI) telemedicine. We also recommend that relevant tests be added to the follow-up of COVID-19 patients to detect myocardial fibrosis promptly. [ABSTRACT FROM AUTHOR]

Due to the heterogeneous nature of depression, the underlying etiological mechanisms greatly differ among individuals, and there are no known subtype-specific biomarkers to serve as precise targets for therapeutic efficacy. The extensive research efforts over the past decades have not yielded much success, and the currently used first-line conventional antidepressants are still ineffective for close to 66% of patients. Most clinicians use trial-and-error treatment approaches, which seem beneficial to only a fraction of patients, with some eventually developing treatment resistance. Here, we review evidence from both preclinical and clinical studies on the pathogenesis of depression and antidepressant treatment response. We also discuss the efficacy of the currently used pharmacological and non-pharmacological approaches, as well as the novel emerging therapies. The review reveals that the underlying mechanisms in the pathogenesis of depression and antidepressant response, are not specific, but rather involve an interplay between various neurotransmitter systems, inflammatory mediators, stress, HPA axis dysregulation, genetics, and other psycho-neurophysiological factors. None of the current depression hypotheses sufficiently accounts for the interactional mechanisms involved in both its etiology and treatment response, which could partly explain the limited success in discovering efficacious antidepressant treatment. Effective management of treatment-resistant depression (TRD) requires targeting several interactional mechanisms, using subtype-specific and/or personalized therapeutic modalities, which could, for example, include multi-target pharmacotherapies in augmentation with psychotherapy and/or other non-pharmacological approaches. Future research guided by interaction mechanisms hypotheses could provide more insights into potential etiologies of TRD, precision biomarker targets, and efficacious therapeutic modalities. [ABSTRACT FROM AUTHOR]

The implementation of adaptation to climate change lags behind necessary adaptation. Implementation of adaptation often takes place at the local level, influenced by local factors and mechanisms producing mainstreamed or standalone adaptation outcomes. Because mainstreaming adaptation is seen as accelerating adaptation, understanding this process is crucial for expediting its implementation. The lack of insight into the influence of context on mainstreaming and its respective outcomes hinders the transfer of lessons between different contexts. To address this gap, we investigate the question “Why do municipal policy processes lead to either standalone or mainstreamed adaptation implementation decisions?” We apply the Multiple Streams Framework to explain local adaptation implementation decisions to compare adaptation in Enschede and Zwolle, two Dutch adaptation frontrunners. We conclude that issue-linking with locally salient issues facilitates adaptation mainstreaming in a case without problem urgency, whereas a focusing event leads to standalone adaptation implementation if crisis-framing is applied. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo describe the incidence, mechanisms, and clinical characteristics of patients diagnosed with traumatic iritis in a U.S. Midwestern county population.Retrospective population-based cohort of all residents of Olmsted County, Minnesota diagnosed with traumatic iritis from January 1, 2006, to December 31, 2015. The medical records of patients with traumatic iritis were identified using the Rochester Epidemiology Project database, which contains virtually all medical care in the county. Medical records were reviewed for demographics, presentation, and follow-up data. Incidence rates were calculated per 100,000 per year.There were 156 incident diagnoses of traumatic iritis during the 10-year study period, yielding an age- and sex-adjusted incidence rate of 10.7 per 100,000 per year. Traumatic iritis disproportionately occurred in male (p < 0.001) and Black (p < 0.001) patients. The mean age of diagnosis was 33 years (range: 4–96 years), mean number of traumatic iritis-specific follow-up visits was 2.1 (range: 0–26), and median duration of traumatic iritis-specific follow-up was 11 days (range: 1 day-1.6 years). There were 155 (99.4%) patients with unilateral disease. The most frequent mechanisms of traumatic iritis were sports-related (N = 29, 18.6%), assault-related (N = 23, 14.7%), scratch (N = 22, 14.1%), and work-related (N = 21, 13.5%) injuries. The mean initial and final best-corrected visual acuity (BCVA) of the affected eye was 20/40 and 20/30, respectively. Loss of follow-up was more frequently observed in Black patients (p < 0.001) and patients with smoking history (p = 0.004).Traumatic iritis was most frequently observed in younger males and Black patients. Common mechanisms included sports, assault, scratch, and work-related injuries. [ABSTRACT FROM AUTHOR]

Capillary flow-related hydrovoltaic technology is an emerging research field for sustainable electricity generation. Despite great progress in the last decade, the mechanisms behind electricity generation remain unclear. In this review, we provide an overview of the current proposed mechanisms for electricity generation induced by water evaporation and moisture absorption. We explore key mechanisms, including streaming potential, ion concentration gradient, microbial electricity, ionovoltaic effect, pseudo-streaming, evaporating potential, and upstream proton diffusion. Each offers distinct insights and faces specific challenges that require further study. Unlike previous reviews, we focus specifically on the detailed mechanistic understanding of capillary flow-related electricity generation and highlight the interplay of different mechanisms. Additionally, we identify critical gaps in current research, particularly the need for empirical validation through advanced characterization techniques, such as spectroscopy, microscopy, and electrochemical analysis. Moreover, we discuss the practical applications of capillary flow-related hydrovoltaic technology in energy harvesting systems and self-powered sensors, highlighting its potential to convert water evaporation and environmental moisture into sustainable energy. We believe this review can serve as a starting point for further efforts aimed at addressing these challenges, thus paving the way for the commercialization of this technology and its contribution to sustainable development goals. [ABSTRACT FROM AUTHOR]

Objectives: Analyse reported processes of co-design and co-production in the context of health and social care to explore the underlying mechanisms that enable inclusive and reciprocal engagement. Search strategy: Peer review research was obtained from a prior scoping review searching eight databases consisting of all methodologies relevant to co-design or co-production in the context of health and social care services and involving service-users. Methods of selection: Articles were included for synthesis if they reported a process of dialogue, with mutuality, insight and clarification in their engagement process. Ninety-three peer-review articles informed our programme theory development. Analysis: Data relating to co-design and co-production processes were extracted and analysed through inductive, abductive, and deductive analysis leading to the development of an initial programme theory. Main results: This realist synthesis finds that co-design and co-production can occur at different times, in part or all of the research and participatory process. There is an over reliance on the term 'co-design' or 'co-production' to convey complex engagement or participatory processes. We identified six mechanisms (intention, assets, dialogue, documentation, interpretation and understanding). Interaction between these six identified mechanisms in context, even if only brief, is important for supporting meaningful engagement, alignment and agreement within a co-design or co-production process. Implications for practice: The initial programme theory presented in this article provides clarity by identifying essential mechanisms which can guide the design and implementation of a range of participatory approaches. Rather than relying on a single label to convey complex participatory methods or processes, the values and principles of co-design or co-production, in combination with this programme theory, could be applied to guide implementation and reporting of specific activities within a range of research or participatory methods. Patient and public contribution: The initial programme theory was presented and piloted in a series of collaborative workshops between May 2023 and March 2024 with patient and public contributors, health professionals and researchers. This engagement process is currently underway to refine the programme theory and it is anticipated that this next phase will be completed in September 2024. Plain English summary: The aim of this review was to understand what needs to happen for meaningful engagement to take place by exploring how co-design and co-production in health and social care has been reported in published research. Ninety-three research articles were selected as these reported engagement processes with exchanges of mutual insight. Articles which only stated that engagement took place, without reporting details, were excluded. Any information relating to co-design and co-production processes were then extracted and analysed. The findings from this review were that co-design and co-production can occur at different times, in part or all of the research and engagement process. We identified that interaction between six key elements (intention, assets, dialogue, documentation, interpretation and understanding) in context, even if only brief, are important for meaningful engagement to occur within a co-design or co-production process. We also found that there is an over reliance on the term 'co-design' or 'co-production' to convey complex processes for engagement. Rather than relying on a single word to convey such complex methods or processes, the values and principles of co-design or co-production, in combination with the key elements identified, could be applied to guide implementation, and reporting of specific activities within a range of research methods. [ABSTRACT FROM AUTHOR]

Elucidating the speciation (in terms of concentration versus pH) and understanding the formation mechanisms of polyoxometalates remains a significant challenge, both in experimental and computational domains. POMSimulator is a new methodology that tackles this problem from a purely computational perspective. The methodology uses results from quantum mechanics based methods to automatically set up the chemical reaction network, and to build speciation models. As a result, it becomes possible to predict speciation and phase diagrams, as well as to derive new insights into the formation mechanisms of large molecular clusters. In this work we present the main features of the first open‐source version of the software. Since the first report [Chem. Sci. 2020, 11, 8448‐8456], POMSimulator has undergone several improvements to keep up with the growing challenges that were tackled. After four years of research, we recognize that the source code is sufficiently stable to share a polished and user‐friendly version. The Python code, manual, examples, and install instructions can be found at https://github.com/petrusen/pomsimulator. [ABSTRACT FROM AUTHOR]

Hemerocallis citrina Borani is a traditional folk food used to promote the lactation of postpartum mothers in China; however, the active ingredients and corresponding mechanisms are still unknown. In this study, the lactogenic effect of alcoholic and aqueous extracts of H. citrina was primarily evaluated, and the aqueous extract (1,000 and 2,000 mg/kg) displayed significant lactationpromoting effects. Three eluates of the aqueous extract (0%, 30%, and 50%HCW) were further evaluated for their lactogenic effect, and 30% and 50%HCWshowed significant lactation-promoting activity. Nineteen ingredients, including those with a high content of rutin and isoquercetin, were then identified from 30% and 50%HCW using the ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) method. Finally, the lactogenic effect of rutin and isoquercetin was evaluated, and both compounds displayed significant lactation-promoting activity. The mechanisms relative to the lactation-promoting active ingredients for H. citrina extracts and compounds are to stimulate the release of prolactin (PRL) and progesterone (P), as well as to induce the expression of prolactin receptor (PRLR) and improve the morphology of mammary tissue. This study first clarified the lactation-promoting active ingredients of H. citrina and the corresponding mechanisms, which provide a new insight into the new lactation-promoting drug and promote the high-value utilization of H. citrina resources. [ABSTRACT FROM AUTHOR]

Having a job is important for the well-being and inclusion of people with limited capability for work (LCW) due to physical and/or mental disability. This study explores salutogenic mechanisms that contribute to work-related sense of coherence (Work-SoC) of employees with LCW, i.e. perceiving their work in nature as manageable, comprehensible and meaningful. Semi-structured interviews (26 in total) were conducted with employees with LCW, employee supervisors, job coaches and foresters, all working in nature management. Interviews were held at four worksites of a governmental organisation in the Netherlands that provides permanent jobs for people with LCW. Employees with LCW contributed to the design and analysis of the study as co-researchers. Thematic analysis was used and member checks were carried out on preliminary findings. We identified six salutogenic mechanisms that contribute to nature-based Work-SoC of employees with LCW: (i) having constructive working relationships, (ii) experiencing structure and clarity, (iii) receiving practical and emotional support, (iv) support in the creation of meaning, (v) experiencing and learning in practice and (vi) physical activity and (absence of) stimuli. Identified mechanisms can create a positive effect when leveraged, thereby boosting (new) salutogenic mechanisms. Our findings illustrate that nature-based work can provide resources that promote Work-SoC of employees with LCW through the identified mechanisms. However, employees with LCW, colleagues, supervisors and stakeholders must recognize, mobilize and use these resources to leverage identified mechanisms in order to facilitate health-promoting workplaces for people with LCW. This, in turn, can contribute to sustainable inclusion through enablement. [ABSTRACT FROM AUTHOR]

A pandemic known as anti-microbial resistance (AMR) poses a challenge to contemporary medicine. To stop AMR's rise and quick worldwide spread, urgent multisectoral intervention is needed. This review will provide insight on new and developing treatment approaches for AMR. Future therapy options may be made possible by the development of novel drugs that make use of developments in "omics" technology, artificial intelligence, and machine learning. Vaccines, immunoconjugates, antimicrobial peptides, monoclonal antibodies, and nanoparticles may also be intriguing options for treating AMR in the future. Combination therapy may potentially prove to be a successful strategy for combating AMR. To lessen the impact of AMR, ideas like drug repurposing, antibiotic stewardship, and the one health approach may be helpful. [ABSTRACT FROM AUTHOR]

Titanium dioxide nanoparticles, or TiO2 NPs, have shown potential in the fight against a range of diseases, including bacteria, viruses, fungi and parasites. Doping metals with nanoparticles modify their size and magnetic characteristics by decreasing the energy band gap and mixing spins and electrical charges. Furthermore, it has been shown that owing to their higher surface-to-volume ratio and improved ability to interact with bacterial cells, smaller metal-doped nanoparticles have better antibacterial action. Due in large part to their production, TiO3-NPs have outstanding antifungal and antibacterial capabilities. The major mechanism of TiO3-NPs' antibacterial activity is their potent oxidizing capacity, which produces superoxide and hydroxyl anion radicals. Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli are just a few of the pathogens against which TiO2 NPs have been shown to have antibacterial ability. Review topics will include the most recent discoveries in the sectors of water treatment, agriculture and medicine as well as the synthesis of TiO3- nanoparticles and their antimicrobial actions. TiO2 NPs as antibacterial agents: prospects and challenges will also be highlighted in the review. [ABSTRACT FROM AUTHOR]

Simple Summary: The SARS-CoV-2 virus that caused COVID-19 devastated families, social structures, and economies worldwide. This pandemic has overwhelmed healthcare systems, increased deaths and disabilities, and triggered a global socio-economic crisis. Although the COVID-19 vaccines were developed rapidly, their effectiveness significantly decreased by the end of 2021 due to mutated viruses evading the immune system. As a result, despite high vaccination rates in industrialized countries, significant outbreaks occurred due to immune evasion associated with viral mutations. Over 300 clinical studies have shown that vitamin D (and ivermectin) are widely available and economical agents that promote immune system function. Proper doses of vitamin D effectively prevent and treat SARS-CoV-2, reducing complications, hospitalizations, and deaths by approximately 50%. Those with vitamin D deficiency fare the worse. SARS-CoV-2 activates the renin-angiotensin system by increasing renin expression, leading to elevated levels of the inflammatogenic and vasoconstrictor peptide angiotensin-II. SARS-CoV-2 viruses cause widespread inflammation, blood clots, and lung damage through multiple mechanisms, leading to impaired tissue oxygenation and death. In addition to enhancing the immune system, vitamin D increases ACE-2 enzyme levels, which breaks down angiotensin-II and reduces SARS-CoV-2-induced inflammation. It also lowers blood pressure and mitigates abnormal clotting. While the virus enters human cells through ACE-2 receptors, excess ACE-2 spills into the bloodstream and neutralizes viruses. This manuscript discusses how vitamin D mitigates the harmful effects of COVID-19. The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses in circulation and mitigating inflammation. While SARS-CoV-2 reduces ACE-2 expression, vitamin D increases it, counteracting the virus's harmful effects. Vitamin D's beneficial actions are mediated through complex molecular mechanisms involving innate and adaptive immune systems. Meanwhile, vitamin D status [25(OH)D concentration] is inversely correlated with severity, complications, and mortality rates from COVID-19. This study explores mechanisms through which vitamin D inhibits SARS-CoV-2 replication, including the suppression of transcription enzymes, reduced inflammation and oxidative stress, and increased expression of neutralizing antibodies and antimicrobial peptides. Both hypovitaminosis D and SARS-CoV-2 elevate renin levels, the rate-limiting step in the renin-angiotensin-aldosterone system (RAS); it increases ACE-1 but reduces ACE-2 expression. This imbalance leads to elevated levels of the pro-inflammatory, pro-coagulatory, and vasoconstricting peptide angiotensin-II (Ang-II), leading to widespread inflammation. It also causes increased membrane permeability, allowing fluid and viruses to infiltrate soft tissues, lungs, and the vascular system. In contrast, sufficient vitamin D levels suppress renin expression, reducing RAS activity, lowering ACE-1, and increasing ACE-2 levels. ACE-2 cleaves Ang-II to generate Ang(1–7), a vasodilatory, anti-inflammatory, and anti-thrombotic peptide that mitigates oxidative stress and counteracts the harmful effects of SARS-CoV-2. Excess ACE-2 molecules spill into the bloodstream as soluble receptors, neutralizing and facilitating the destruction of the virus. These combined mechanisms reduce viral replication, load, and spread. Hence, vitamin D facilitates rapid recovery and minimizes transmission to others. Overall, vitamin D enhances the immune response and counteracts the pathological effects of SARS-CoV-2. Additionally, data suggests that widely used anti-hypertensive agents—angiotensin receptor blockers and ACE inhibitors—may lessen the adverse impacts of SARS-CoV-2, although they are less potent than vitamin D. [ABSTRACT FROM AUTHOR]

Air and bone conduction thresholds are used to differentiate between conductive and sensori-neural hearing losses because bone conduction is thought to bypass the conductive apparatus, directly activating the inner ear. However, the suggested bone conduction mechanisms involve the outer and middle ears. Also, normal bone conduction thresholds have been reported in cases of lesions to the conduction pathway. Therefore, further investigation of bone conduction mechanisms is required. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a form of age-related, non-inflammatory, degenerative joint disease. It is characterized by pain, swelling, and bone hyperplasia; osteoarthritis has a high morbidity and high disability rate, which has a significant impact on the quality of life of patients worldwide. Engaging in sports has been demonstrated to reduce the risk of developing obesity, diabetes mellitus, and other metabolic diseases, additionally, it has been shown to enhance muscle quality, stabilize joints, improve motor coordination abilities, reduce pain, and improve joint function in individuals with osteoarthritis, these findings highlight the potential for sports to play an important role in the management of osteoarthritis. In this review, we presented an overview of the pathogenesis of osteoarthritis, provided a summary of advancements in the utilization of sports in the management of osteoarthritis, and discussed the underlying mechanisms and future application limitations, hoping to provide the foundation for the prevention and treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

When does a model explain? When does it promote understanding? A dominant approach to scientific explanation is the interventionist view. According to this view, when X explains Y, intervening on X can produce, prevent or alter Y in some predictable way. In this paper, I argue for two claims. First, I reject a position that many interventionist theorists endorse. This position is that to explain some phenomenon by providing a model is also to understand that phenomenon. While endorsing the interventionist view, I argue that explaining and understanding are distinct scientific achievements. Second, I defend a novel theory of scientific understanding. According to this view, when some model M promotes understanding, M makes available a distinctive mental state. This state is of the same psychological kind as when we grasp events in a narrative as bearing on some ultimate conclusion. To conclude, I show that, given this view, mechanistic explanations often provide a powerful source of understanding that many causal-historical models lack. This paper will be of interest to both philosophers of science and epistemologists engaged in the topics of explanation and understanding. [ABSTRACT FROM AUTHOR]

Summary: This narrative review describes the current state of the literature that has examined associations between non‐sexual social touch (i.e., affectionate touch, touch therapies, touch with animals and inanimate objects that mimic social touch) and sleep quality. It also highlights areas for future research to clarify the links and to identify underlying mechanisms. Most existing studies have focussed on and shown positive effects of touch therapies (e.g., massage, therapeutic touch) on sleep quality in clinical populations. Although there are fewer studies examining how other forms of social touch are linked with sleep quality, the existing research provides preliminary evidence supporting affectionate touch (e.g., hugging, skin‐to‐skin contact) and tactile contact with animals (e.g., dogs) and objects that mimic social touch (e.g., robots, weighted blankets) as predictors of better sleep quality, while touch deprivation and touch aversion are associated with worse sleep quality. Informed by the existing literature, we additionally reviewed potential relational‐cognitive (e.g., felt‐security) and neurobiological (e.g., oxytocin) mechanisms likely to underlie associations between social touch and sleep quality. Overall, current research supports associations between non‐sexual social touch and sleep quality. However, future research is needed to establish these links for specific forms of social touch (and in various populations), to test explanatory mechanisms, and to identify boundary conditions. Understanding associations between non‐sexual social touch and sleep quality can inform the development of touch‐based interventions to improve sleep quality and health. [ABSTRACT FROM AUTHOR]

As our population ages, the medical challenges it faces become increasingly acute, with chronic kidney disease (CKD) becoming more prevalent among older adults. Frailty is alarmingly more common in CKD patients than in the general populace, putting the elderly at high risk of both physical and cognitive decline. CKD not only accelerates physical deterioration, but also heightens vascular dysfunction, calcification, arterial rigidity, systemic inflammation, oxidative stress, and cognitive impairment. Cognitive frailty, a distinct syndrome marked by cognitive deficits caused by physiological causes (excluding Alzheimer's and other dementias), is a critical concern. Although cognitive impairment has been well-studied, the molecular mechanisms driving cognitive frailty remain largely uncharted. Comprehensive interventions, including cutting-edge pharmaceuticals and lifestyle changes, are pivotal and effective, especially in the early stages of CKD. Recent research suggests that systematic exercise could counteract cognitive decline by improving brain blood flow, boosting neuroplasticity through the brain-derived neurotrophic factor (BDNF), and by triggering the release of neurotrophic factors such as insulin-like growth factor (IGF-1). This review delves into the molecular pathways of cognitive frailty in CKD, identifies key risk factors, and highlights therapeutic approaches, particularly the potent role of exercise in enhancing cognitive health. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) has been receiving a lot of attention from scientists and clinicians because it is an extremely common clinical condition. Due to its special hemodynamic changes, AF has a high rate of disability and mortality. So far, although AF has some therapeutic means, it is still an incurable disease because of its complex risk factors and pathophysiologic mechanisms, which is a difficult problem for global public health. Age is an important independent risk factor for AF, and the incidence of AF increases with age. To date, there is no comprehensive review on aging‐associated AF. In this review, we systematically discuss the pathophysiologic evidence for aging‐associated AF, and in particular explore the pathophysiologic mechanisms of mitochondrial dysfunction, telomere attrition, cellular senescence, disabled macroautophagy, and gut dysbiosis involved in recent studies with aging‐associated AF. We hope that by exploring the various dimensions of aging‐associated AF, we can better understand the specific relationship between age and AF, which may be crucial for innovative treatments of aging‐associated AF. [ABSTRACT FROM AUTHOR]

Elevation‐dependent warming (EDW) has been a topic of intense debate due to limited observed data in global highland areas. This study aims to fill this gap by utilizing CRU and ERA5 datasets from 1981 to 2021 to explore the trends of climate change and its elevation dependency. The anomalies of temperature indicators (Tmean, Tmax, and Tmin) in both ERA5 and CRU showed significant warming trends over global highlands. Moreover, the response of temperature indicators to elevation across global highlands is not spatially uniform. The linear regression model based on the elevation showed significant warming signals for the temperature indicators at various elevations over the global highlands. On a regional scale, Tmean and Tmax predominantly showed linear EDW over EU highlands, while Tmean in Asian highlands exhibited EDW signals at 4–5 km. Tmin showed EDW at 2.5–5.5 km with ERA5 and 3–5 km with CRU. In the Andes, EDW was prominent at 2.5–4 km. Overall, EDW signals are evident in all studied regions but vary across them. While assessing the driving factors, the results of this study indicate that total column water vapour (TCWV), snow depth (SD), snow albedo, and normalized difference vegetation index (NDVI) correlated positively with the temperature indicators. These findings emphasize the significance of elevation‐specific interactions between environmental factors and temperature in forecasting temperature changes in mountainous areas. Additionally, temperature exhibited coherence with teleconnection indices from the Atlantic and Pacific Oceans. Asian and European (EU) highlands exhibited interzonal coherence with the Pacific and Atlantic Oceans, while North American (NA) highlands showed coherence, followed by South American (SA) highlands. These findings provide a comprehensive understanding of EDW and its implications for highland regions globally, including the potential for more severe depletion of snow/ice resources in a warmer future. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in the benefits of group models of antenatal care. Although clinical reviews exist, there have been few reviews that focus on the mechanisms of effect of this model. Methods: We conducted a realist review using a systematic approach incorporating all data types (including non-research and audiovisual media), with synthesis along Context-Intervention-Mechanism-Outcome (CIMO) configurations. Results: A wide range of sources were identified, yielding 100 relevant sources in total (89 written and 11 audiovisual). Overall, there was no clear pattern of 'what works for whom, in what circumstances' although some studies have identified clinical benefits for those with more vulnerability or who are typically underserved by standard care. Findings revealed six interlinking mechanisms, including: social support, peer learning, active participation in health, health education and satisfaction or engagement with care. A further, relatively under-developed theory related to impact on professional practice. An overarching mechanism of empowerment featured across most studies but there was variation in how this was collectively or individually conceptualised and applied. Conclusions: Mechanisms of effect are amplified in contexts where inequalities in access and delivery of care exist, but poor reporting of populations and contexts limited fuller exploration. We recommend future studies provide detailed descriptions of the population groups involved and that they give full consideration to theoretical underpinnings and contextual factors. Registration: The protocol for this realist review was registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42016036768). [ABSTRACT FROM AUTHOR]