A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.

Loci for insulin processing and secretion provide insight into type 2 diabetes risk.

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.

Circulatory levels of lysophosphatidylcholine species in obese adolescents: Findings from cross-sectional and prospective lipidomics analyses.

BACKGROUND AND AIMS: Obesity has reached epidemic proportions, emphasizing the importance of reliable biomarkers for detecting early metabolic alterations and enabling early preventative interventions. However, our understanding of the molecular mechanisms and specific lipid species associated with childhood obesity remains limited. Therefore, the aim of this study was to investigate plasma lipidomic signatures as potential biomarkers for adolescent obesity. METHODS AND RESULTS: A total of 103 individuals comprising overweight/obese (n = 46) and normal weight (n = 57) were randomly chosen from the baseline ORANGE (Obesity Reduction and Noncommunicable Disease Awareness through Group Education) cohort, having been followed up for a median of 7.1 years. Plasma lipidomic profiling was performed using the UHPLC-HRMS method. We used three different models adjusted for clinical covariates to analyze the data. Clustering methods were used to define metabotypes, which allowed for the stratification of subjects into subgroups with similar clinical and metabolic profiles. We observed that lysophosphatidylcholine (LPC) species like LPC.16.0, LPC.18.3, LPC.18.1, and LPC.20.3 were significantly (p < 0.05) associated with baseline and follow-up BMI in adolescent obesity. The association of LPC species with BMI remained consistently significant even after adjusting for potential confounders. Moreover, applying metabotyping using hierarchical clustering provided insights into the metabolic heterogeneity within the normal and obese groups, distinguishing metabolically healthy individuals from those with unhealthy metabolic profiles. CONCLUSION: The specific LPC levels were found to be altered and increased in childhood obesity, particularly during the follow-up. These findings suggest that LPC species hold promise as potential biomarkers of obesity in adolescents, including healthy and unhealthy metabolic profiles.

Exploring Barriers and Facilitators to COVID-19 Vaccination in People Planning Pregnancy, Trying to Conceive, Pregnant, and Postpartum: A Mixed-Methods Study.

Pregnant people are at higher risk of morbidity from COVID-19 infection, yet vaccine hesitancy remains prevalent. Our mixed-methods study utilised surveys and interviews to understand decision-making regarding COVID-19 vaccination surrounding pregnancy. The most trusted source of information was health care providers. Five themes relating to vaccination barriers and facilitators were identified: (1) COVID-19 vaccine-related policies; (2) pregnancy-specific considerations; (3) barriers, facilitators, and influencers to vaccination; (4) vaccination decisions based on personal health considerations; (5) attitudes toward COVID-19 and other vaccines. Our study underscores the importance of receiving high-quality information from a trusted source to increase vaccination.

Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect.

The endo-lysosomal two-pore channel (TPC2) has been established as an intracellular cation channel of significant physiological and pathophysiological relevance in recent years. For example, TPC2-/- mice show defects in cholesterol degradation, leading to hypercholesterinemia; TPC2 absence also results in mature-onset obesity, and a role in glucagon secretion and diabetes has been proposed. Infections with bacterial toxins or viruses e.g., cholera toxin or Ebola virus result in reduced infectivity rates in the absence of TPC2 or after pharmacological blockage, and TPC2-/- cancer cells lose their ability to migrate and metastasize efficiently. Finally, melanin production is affected by changes in hTPC2 activity, resulting in pigmentation defects and hair color variation. Here, we analyzed several publicly available genome variation data sets and identified multiple variations in the TPC2 protein in distinct human populations. Surprisingly, one variation, L564P, was found to be the predominant TPC2 isoform on a global scale. By applying endo-lysosomal patch-clamp electrophysiology, we found that L564P is a prerequisite for the previously described M484L gain-of-function effect that is associated with blond hair. Additionally, other gain-of-function variants with distinct geographical and ethnic distribution were discovered and functionally characterized. A meta-analysis of genome-wide association studies was performed, finding the polymorphisms to be associated with both distinct and overlapping traits. In sum, we present the first systematic analysis of variations in TPC2. We functionally characterized the most common variations and assessed their association with various disease traits. With TPC2 emerging as a novel drug target for the treatment of various diseases, this study provides valuable insights into ethnic and geographical distribution of TPC2 polymorphisms and their effects on channel activity.

A meta-analysis of mindfulness-based interventions for improving mental health and burden among caregivers of persons living with dementia.

BACKGROUND: Mindfulness-based interventions are becoming increasingly popular and are effective in lowering depressive symptoms and caregiver burden. However, the overall efficacy of therapies in stress and anxiety management is unreported, and no study to date has performed a subgroup analysis to investigate the intervention dose response of outcomes. AIMS: To quantitatively identify the effectiveness of mindfulness-based interventions for caregivers of persons living with dementia. METHODS: A comprehensive literature search of six databases was undertaken from the date of inception to June 18, 2023. The DerSimonian-Laird model with random effects was used to examine the overall effect and its heterogeneity in the studies. Version 2 of the risk of bias (RoB 2) tool was employed to analyze the publication bias of each randomized study. Funnel and forest plots were created to represent the findings. RESULTS: Thirteen randomized trials were included in the meta-analysis. Mindfulness-based interventions significantly reduced stress and anxiety of caregivers of persons living with dementia. In addition, interventions provided for ≥8 weeks were beneficial in reducing depression in caregivers. However, mindfulness-based interventions did not offer significant benefits in reducing depression or caregiver burden immediately after the intervention. CONCLUSION: Mindfulness-based interventions have the potential to help caregivers of people living with dementia. This study could be used as a model for future research into and implementation of mindfulness-based therapies for caregivers. LINKING EVIDENCE TO ACTION: Mindfulness-based therapies appear to alleviate stress and anxiety but are ineffective in reducing depression and burden in caregivers of persons living with dementia. Well-designed RCTs with more rigorous methodology and a larger sample size should be conducted to firm the conclusion of the effectiveness of mindfulness-based interventions for caregivers of persons living with dementia.

Scale of population synchrony confirms macroecological estimates of minimum viable range size.

Global ecosystems are facing a deepening biodiversity crisis, necessitating robust approaches to quantifying species extinction risk. The lower limit of the macroecological relationship between species range and body size has long been hypothesized as an estimate of the relationship between the minimum viable range size (MVRS) needed for species persistence and the organismal traits that affect space and resource requirements. Here, we perform the first explicit test of this assumption by confronting the MVRS predicted by the range-body size relationship with an independent estimate based on the scale of synchrony in abundance among spatially separated populations of riverine fish. We provide clear evidence of a positive relationship between the scale of synchrony and species body size, and strong support for the MVRS set by the lower limit of the range-body size macroecological relationship. This MVRS may help prioritize first evaluations for unassessed or data-deficient taxa in global conservation assessments.

Ischaemic stroke in South Asians: The BRAINS study.

BACKGROUND AND PURPOSE: Studies on stroke in South Asian populations are sparse. The aim of this study was to compare differences in age of onset of ischaemic stroke in South Asian patients living in the United Kingdom and South Asian patients living in India versus White British stroke patients. METHODS: We studied the UK and Indian arms of the ongoing BRAINS study, an international prospective hospital-based study of South Asian stroke patients. The BRAINS study includes 4038 South Asian and White British patients with first-ever ischaemic stroke, recruited from sites in the United Kingdom and India. RESULTS: Of the included patients, 1126 were South Asians living in India (ISA), while 1176 were British South Asian (BSA) and 1736 were White British (WB) UK residents. Patients in the ISA and BSA groups experienced stroke 19.5 years and 7.2 years earlier than their WB counterparts, respectively (mean [interquartile range] age: BSA 64.3 [22] years vs. ISA 52.0 [18] years vs. WB 71.5 [19] years; p < 0.001). Patients in the BSA group had higher rates of hypertension, diabetes mellitus and hypercholesterolaemia than those in the ISA and WB groups. After adjustment for traditional stroke risk factors, an earlier age of stroke onset of 18.9 years (p < 0.001) and 8.9 years (p < 0.001) was still observed in the ISA and BSA groups, respectively. In multivariable stepwise linear regression analysis, ethnicity accounted for 24.7% of the variance in early age onset. CONCLUSION: Patients in the BSA and ISA groups experienced ischaemic stroke approximately 9 and 19 years earlier, respectively, than their WB counterparts. Ethnicity is an independent predictor of early age of stroke onset. Our study has considerable implications for public health policymakers in countries with sizable South Asian populations.

Tocophobia: a nosological quagmire.

Fear of childbirth exists on a continuum of severity, and the most severe form is commonly referred to as tocophobia. Although a rare entity, tocophobia is a common reason for requesting an elective cesarean section. It is generally considered a specific phobia but is not recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a diagnostic entity. To improve the assessment and treatment of tocophobia, research is warranted to clarify its relationship with commonly occurring psychiatric disorders in pregnancy.

Guideline No. 441: Antenatal Fetal Health Surveillance.

OBJECTIVE: To summarize the current evidence and to make recommendations for antenatal fetal health surveillance (FHS) to detect perinatal risk factors and potential fetal decompensation in the antenatal period and to allow for timely intervention to prevent perinatal morbidity and/or mortality. TARGET POPULATION: Pregnant individuals with or without maternal, fetal, or pregnancy-associated perinatal risk factors for antenatal fetal decompensation. OPTIONS: To use basic and/or advanced antenatal testing modalities, based on risk factors for potential fetal decompensation. OUTCOMES: Early identification of potential fetal decompensation allows for interventions that may support fetal adaptation to maintain well-being or expedite delivery. BENEFITS, HARMS, AND COSTS: Antenatal FHS in pregnant individuals with identified perinatal risk factors may reduce the chance of adverse outcomes. Given the high false-positive rate, FHS may increase unnecessary interventions, which may result in harm, including parental anxiety, premature or operative birth, and increased use of health care resources. Optimization of surveillance protocols based on evidence-informed practice may improve perinatal outcomes and reduce harm. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to January 2022, using medical subject headings (MeSH) and key words related to pregnancy, fetal monitoring, fetal movement, stillbirth, pregnancy complications, and fetal sonography. This document represents an abstraction of the evidence rather than a methodological review. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care team members who provide care for or education to obstetrical patients, including maternal fetal medicine specialists, obstetricians, family physicians, midwives, nurses, nurse practitioners, and radiologists. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 441 : Surveillance prénatale du bien-être fœtal.

OBJECTIF: Résumer les données probantes actuelles et formuler des recommandations pour la surveillance prénatale du bien-être fœtal afin de détecter les facteurs de risque périnatal et toute potentielle décompensation fœtale et de permettre une intervention rapide en prévention de la morbidité et la mortalité périnatales. POPULATION CIBLE: Personnes enceintes avec ou sans facteurs maternels, fœtaux ou gravidiques associés à des risques périnataux et à la décompensation fœtale. OPTIONS: Utiliser des examens prénataux par technologie de base et/ou avancée en fonction des facteurs de risque de décompensation fœtale. RéSULTATS: La reconnaissance précoce de toute décompensation fœtale potentielle permet d'intervenir de façon à favoriser l'adaptation fœtale pour maintenir le bien-être ou à accélérer l'accouchement. BéNéFICES, RISQUES ET COûTS: Chez les personnes enceintes ayant des facteurs de risque périnatal confirmés, la surveillance du bien-être fœtal contribue à réduire le risque d'issue défavorable. Compte tenu du taux élevé de faux positifs, la surveillance du bien-être fœtal peut augmenter le risque d'interventions inutiles, ce qui peut avoir des effets nuisibles, dont l'anxiété parentale, l'accouchement prématuré ou assisté et l'utilisation accrue des ressources de soins de santé. L'optimisation des protocoles de surveillance d'après des pratiques fondées sur des données probantes peut améliorer les issues périnatales et réduire les effets nuisibles. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données Medline, PubMed, Embase et Cochrane Library, de leur création jusqu'à janvier 2022, à partir de termes MeSH et de mots clés liés à la grossesse, à la surveillance fœtale, aux mouvements fœtaux, à la mortinaissance, aux complications de grossesse et à l'échographie fœtale. Le présent document est un résumé des données probantes et non pas une revue méthodologique. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les membres de l'équipe de soins qui prodiguent des soins ou donnent de l'information aux patientes en obstétrique, notamment les spécialistes en médecine fœto-maternelle, les obstétriciens, les médecins de famille, les sages-femmes, les infirmières, les infirmières praticiennes et les radiologistes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

A meta-analysis of studies of the effects of case management intervention for stroke survivors across three countries.

PURPOSE: A stroke survivor who is discharged to home care faces many challenges during the transition from the hospital to home, including managing their care at home and engaging in rehabilitation and recovery. Case management was developed to ease the transition from hospital to home and help people with stroke cope with their care management challenges. However, the effects of case management intervention remain inconclusive. Case management was designed to direct care and may represent a novel method for reducing the burden of care. This study was designed to evaluate the effects of case management interventions on mental health outcomes, activities of daily living capacity, physical function, and social function among stroke survivors. DESIGN: Systematic review and meta-analysis. METHODS: This study included studies examining the impacts of case management interventions for stroke survivors that were published in English and identified by searching eight databases, from database inception to February 20, 2022. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to pool effect sizes using a random-effects model (in Stata 16.0). The revised Cochrane risk-of-bias tool for randomized trials (RoB-2) was used to assess the methodological quality of each study. FINDINGS: The inclusion criteria were satisfied by eight studies (including a total of 1119 stroke survivors). Case management had positive effects on mental health (SMD: 0.26; 95% CI: 0.07 to 0.45, p = 0.001) and activities of daily living (SMD: 0.68; 95% CI: 00.37 to 0.99, p < 0.001). However, no significant effects were observed for either physical function or social function. CONCLUSION: Case management appears to enhance the mental health and activities of daily living among stroke survivors. CLINICAL RELEVANCE: Case management interventions hold promise as efficient, cost-effective, and accessible strategies to positively influence care for stroke survivors. This intervention strategy could be applied to the hospital-to-home transition to guide care among this population.

Ionic liquid treated leaves of Juglans regia as an adsorbent for the removal of methyl orange dye: experimental, computational, and statistical approach.

The novel biosorbents prepared by surface modification from leaves of Juglans regia plant were exploited for removal of methyl orange dye from aqueous solution. The leaves in the form of dust and charcoal were separately impregnated with 1-butyl-3-methyl imidazolium bromide (I) to obtain adsorbents namely J. regia dust/charcoal impregnated with I (JRDI/JRCI) which were characterized using advanced analytical approaches. The impregnation of ionic liquid was confirmed by the appearance of new bands. Langmuir isotherm fitted well; the calculated adsorption capacity being 59.37 (JRDI) and 102.72 mg g-1 (JRCI). The kinetic study revealed that sorption obeyed the pseudo-first order model; the experimental adsorption capacity being 53.53 (JRDI) and 86.82 mg g-1 (JRCI) at selected conditions of pH 3, initial dye concentration 100 ppm, dosage of adsorbent 0.3 g and contact time 70 min. The mathematical models which predicted adsorption capacity as 51.5 (JRDI) and 82.1 mg g-1 (JRCI) were found at par with experimental values. Fukui condensed functions revealed that adsorbents had electron deficient electrophilic reaction sites while dye had electron-rich nucleophilic reaction sites. The structural properties and good adsorption capability of adsorbents indicate that they could be used as potential, eco-friendly adsorbents for the treatment of negatively charged dye pollutants.

The research work is the first study on the sorption of methyl orange dye from an aqueous solution using ionic liquid impregnated leaves of J. regia plant in powder and biochar form. Juglans regia leaves are eco-friendly and cheap precursors for selected adsorbents. Impregnation of ionic liquid which makes the adsorbent surface positively charged is responsible for enhancing the adsorption capacity for negatively charged methyl orange dye. To the best of our knowledge, the use of impregnated ionic liquid in the leaves of plants as an adsorbent for the efficient removal of dye is very sparse. This motivated us to fill the gap by choosing ionic liquid and demonstrating the enhanced adsorption capacity of dye.

Global increase in methane production under future warming of lake bottom waters.

Lakes are significant emitters of methane to the atmosphere, and thus are important components of the global methane budget. Methane is typically produced in lake sediments, with the rate of methane production being strongly temperature dependent. Local and regional studies highlight the risk of increasing methane production under future climate change, but a global estimate is not currently available. Here, we project changes in global lake bottom temperatures and sediment methane production rates from 1901 to 2099. By the end of the 21st century, lake bottom temperatures are projected to increase globally, by an average of 0.86-2.60°C under Representative Concentration Pathways (RCPs) 2.6-8.5, with greater warming projected at lower latitudes. This future warming of bottom waters will likely result in an increase in methane production rates of 13%-40% by the end of the century, with many low-latitude lakes experiencing an increase of up to 17 times the historical (1970-1999) global average under RCP 8.5. The projected increase in methane production will likely lead to higher emissions from lakes, although the exact magnitude of the emission increase requires more detailed regional studies.

Lakes in Hot Water: The Impacts of a Changing Climate on Aquatic Ecosystems.

Our planet is being subjected to unprecedented climate change, with far-reaching social and ecological repercussions. Below the waterline, aquatic ecosystems are being affected by multiple climate-related and anthropogenic stressors, the combined effects of which are poorly understood and rarely appreciated at the global stage. A striking consequence of climate change on aquatic ecosystems is that many are experiencing shorter periods of ice cover, as well as earlier and longer summer stratified seasons, which often result in a cascade of ecological and environmental consequences, such as warmer summer water temperatures, alterations in lake mixing and water levels, declines in dissolved oxygen, increased likelihood of cyanobacterial algal blooms, and the loss of habitat for native cold-water fisheries. The repercussions of a changing climate include impacts on freshwater supplies, water quality, biodiversity, and the ecosystem benefits that they provide to society.

Securinine Induces Differentiation of Human Promyelocytic Leukemic HL-60 Cells through JNK-Mediated Signaling Pathway.

Acute myeloid leukemia is characterized by abnormal differentiation of hematopoietic stem cells, leading to the accumulation of immature myeloid cells. Differentiation therapy has been a successful treatment option for acute promyelocytic leukemia but suffers from adverse effects. Therefore, search for novel differentiation-inducing agents with minimal side effects is desirable. Securinine, a naturally-occurring alkaloid, induces differentiation in various leukemic cells and apoptosis in other types of cancers. However, the underlying molecular mechanism(s) remain elusive. Our study aimed to elucidate the possible molecular mechanism(s) and signaling events involved in securinine-induced differentiation of HL-60 cells. Securinine inhibited proliferation in a time- and dose-dependent manner and triggered differentiation. A higher CD14+ population indicated maturation toward monocytic lineage. Securinine caused cell cycle arrest at the G0/G1 phase and enhanced ROS generation. Quantitative gene expression analysis showed significant down-regulation of C/EBP-α, C/EBP-ε, GAΤΑ, and c-myc and up-regulation of the PU.1 gene. The expression of distinct protein kinases Lyn, Chk-2, Yes, FAK, c-Jun, and JNK were enhanced. Use of specific inhibitors of crucial intracellular signaling proteins indicated that JNK and ERK blockade resulted in a significant decline in differentiation. These data thus confirm that securinine induces differentiation through the activation of the JNK-ERK signaling pathway in HL-60 cells.

Effects of aluminium phosphide on larval morphometry of two important Chrysomya species.

Chrysomya megacephala and C. rufifacies are globally predominant species of blowflies that are amongst the primary colonisers of decomposing carcasses. The development of blowflies has been studied extensively to estimate the minimum postmortem interval (PMImin). This article evaluates the effect of aluminium phosphide (AlP) on the larval morphometry and life cycles of C. megacephala and C. rufifacies. The rabbits were given different dosages of AlP and their livers were excised to rear C. megacephala and C. rufifacies. Through multiple-regression analysis, we assessed the overall impact of varying dosages of AlP on larvae of both species. AlP accelerated development until pupation, whilst the time until emergence remained the same. At higher concentrations, AlP had a positive effect on the development of these species. Since both species are abundant, forensic entomology studies examining the effect of AlP on morphometry and developmental stages would provide valuable information to investigators assessing PMImin.

Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study.

BACKGROUND: Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. METHODS: A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. RESULTS: In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. CONCLUSIONS: In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.

The geography of metapopulation synchrony in dendritic river networks.

Dendritic habitats, such as river ecosystems, promote the persistence of species by favouring spatial asynchronous dynamics among branches. Yet, our understanding of how network topology influences metapopulation synchrony in these ecosystems remains limited. Here, we introduce the concept of fluvial synchrogram to formulate and test expectations regarding the geography of metapopulation synchrony across watersheds. By combining theoretical simulations and an extensive fish population time-series dataset across Europe, we provide evidence that fish metapopulations can be buffered against synchronous dynamics as a direct consequence of network connectivity and branching complexity. Synchrony was higher between populations connected by direct water flow and decayed faster with distance over the Euclidean than the watercourse dimension. Likewise, synchrony decayed faster with distance in headwater than mainstem populations of the same basin. As network topology and flow directionality generate fundamental spatial patterns of synchrony in fish metapopulations, empirical synchrograms can aid knowledge advancement and inform conservation strategies in complex habitats.

Idiopathic Intracranial Hypertension in Pregnancy.

Idiopathic intracranial hypertension (IIH) is a syndrome characterized by elevated intracranial pressure without an identifiable underlying cause. Pregnancy has unique and important diagnostic and therapeutic implications for patients with IIH. Despite these implications, there are no guidelines to assist clinicians in managing IIH during pregnancy. Our review aims to summarize the key considerations related to the diagnosis and management of IIH during pregnancy, to optimize the care of these patients and mitigate the risk of disease-related complications. The optimal management of IIH in pregnancy should include a multidisciplinary team, including an obstetrician (or maternal-fetal medicine specialist), a neurologist, and an ophthalmologist (or neuro-ophthalmologist).