A Haplotype-resolved reference genome of a long-distance migratory bat, Pipistrellus nathusii (Keyserling & Blasius, 1839).

We present a complete, chromosome scale reference genome for the long-distance migratory bat Pipistrellus nathusii. The genome encompasses both haplotypic sets of autosomes and separation of both sex chromosomes by utilising highly-accurate long-reads and preserving long-range phasing information through the use of 3-dimensional chromatin conformation capture sequencing (Hi-C). This genome, accompanied by a comprehensive protein-coding sequence annotation, provides a valuable genomic resource for future investigations into the genomic bases of long-distance migratory flight in bats as well as uncovering the genetic architecture, population structure and evolutionary history of Pipistrellus nathusii. The reference-quality genome presented here gives a fundamental resource to further our understanding of bat genetics and evolution, adding to the growing number of high quality genetic resources in this field. Here, we demonstrate its use in the phylogenetic reconstruction of the order Chiroptera and in particular, we present the resources to allow detailed investigations into the genetic drivers and adaptations related to long-distance migration.

Folding the human proteome using BioNeMo: A fused dataset of structural models for machine learning purposes.

Human proteins are crucial players in both health and disease. Understanding their molecular landscape is a central topic in biological research. Here, we present an extensive dataset of predicted protein structures for 42,042 distinct human proteins, including splicing variants, derived from the UniProt reference proteome UP000005640. To ensure high quality and comparability, the dataset was generated by combining state-of-the-art modeling-tools AlphaFold 2, OpenFold, and ESMFold, provided within NVIDIA's BioNeMo platform, as well as homology modeling using Innophore's CavitomiX platform. Our dataset is offered in both unedited and edited formats for diverse research requirements. The unedited version contains structures as generated by the different prediction methods, whereas the edited version contains refinements, including a dataset of structures without low prediction-confidence regions and structures in complex with predicted ligands based on homologs in the PDB. We are confident that this dataset represents the most comprehensive collection of human protein structures available today, facilitating diverse applications such as structure-based drug design and the prediction of protein function and interactions.

Investigation of Herb-Drug Interactions between Xylopia aethiopica, Its Principal Constituent Xylopic Acid, and Antidepressants.

Introduction: Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60-70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions. Objective: To investigate any potential herb-drug interaction that might exist between Xylopia aethiopica extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice. Methods: Dried, powdered fruits of Xylopia aethiopica were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of Xylopia aethiopica in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis. Results: XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the Xylopia aethiopica extract/fluoxetine (γXAE/FL = 0.502), Xylopia aethiopica extract/imipramine (γXAE/IP = 0.322), Xylopia aethiopica extract/venlafaxine (γXAE/VL = 0.601), xylopic acid/imipramine (γXA/IP = 0.556), xylopic acid/venlafaxine (γXA/VL = 0.451), and xylopic acid/fluoxetine (γXA/FL = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUCIP = 1966 ± 58.98 µg/ml.h) was significantly (P < 0.0001) reduced by Xylopia aethiopica extract (AUCIP = 1228 ± 67.40 µg/ml.h) and xylopic acid (AUCIP = 1250 ± 55.95 µg/ml.h), while the AUC of xylopic acid (AUCXA = 968.10 ± 61.22 µg/ml.h) was significantly (P < 0.0001) reduced by venlafaxine (AUCXA = 285.90 ± 51.92 µg/ml.h) and fluoxetine (AUCXA = 510.60 ± 44.74 µg/ml.h), possibly due to the effect of interfering agents on gastric emptying hence reducing oral absorption. Conclusion: Xylopia aethiopica extract and xylopic acid interacted synergistically with imipramine, fluoxetine, and venlafaxine and reduced the systemic circulation of imipramine.

Coenzyme A biosynthesis: mechanisms of regulation, function and disease.

The tricarboxylic acid cycle, nutrient oxidation, histone acetylation and synthesis of lipids, glycans and haem all require the cofactor coenzyme A (CoA). Although the sources and regulation of the acyl groups carried by CoA for these processes are heavily studied, a key underlying question is less often considered: how is production of CoA itself controlled? Here, we discuss the many cellular roles of CoA and the regulatory mechanisms that govern its biosynthesis from cysteine, ATP and the essential nutrient pantothenate (vitamin B5), or from salvaged precursors in mammals. Metabolite feedback and signalling mechanisms involving acetyl-CoA, other acyl-CoAs, acyl-carnitines, MYC, p53, PPARα, PINK1 and insulin- and growth factor-stimulated PI3K-AKT signalling regulate the vitamin B5 transporter SLC5A6/SMVT and CoA biosynthesis enzymes PANK1, PANK2, PANK3, PANK4 and COASY. We also discuss methods for measuring CoA-related metabolites, compounds that target CoA biosynthesis and diseases caused by mutations in pathway enzymes including types of cataracts, cardiomyopathy and neurodegeneration (PKAN and COPAN).

Donor side effects experienced under minimal controlled ovarian stimulation (COS) with in vitro maturation (IVM) versus conventional COS for in vitro fertilization (IVF) treatment.

OBJECTIVE: To evaluate oocyte retrieval experiences and side effects under minimal controlled ovarian stimulation (COS) for in vitro maturation (IVM) compared to conventional COS. DESIGN: Retrospective Survey Study SETTING: Clinical in vitro fertilization (IVF) treatment center in Spain. SUBJECTS: Data were collected from subjects undergoing minimal COS (n=110; 600-800 IU FSH) for IVM and conventional COS for egg donation (n=48; 1800-2600 IU FSH) from April 2022 to November 2023. INTERVENTION/EXPOSURE: Minimal and conventional controlled ovarian stimulation. MAIN OUTCOME MEASURES: The most common side effects suffered during ovarian stimulation and after OPU, satisfaction level, and the likelihood of recommending or repeating minimal or conventional COS. Statistical analysis included Mann Whitney and Chi-square tests, with a significance level set at p<0.05. RESULTS: During minimal COS, most subjects did not experience breast swelling (86%), pelvic or abdominal pain (76%), nausea or vomiting (96%), and bleeding (96%). After oocyte pick-up, the majority (75%) reported no pelvic or abdominal pain. The most common side effect was abdominal swelling (52%). Compared to conventional COS cycles, minimal COS subjects reported significantly less post-retrieval pain, with 33% experiencing no pain (vs. 6%; p=0.0011) and with a reduced severe level of pain (5% vs.19%; p=0.0097), leading to fewer subjects requiring pain medication (25% vs. 54%; p=0.0003). Additionally, 85% of women were very satisfied with minimal stimulation and would recommend or repeat the treatment. CONCLUSION: Reducing the hormonal dose for ovarian stimulation has a beneficial effect on subjects, suggesting the combination of minimal COS with IVM techniques is a well-tolerated alternative for women who cannot or do not wish to undergo conventional controlled ovarian hyperstimulation.

Large-area, self-healing block copolymer membranes for energy conversion.

Membranes are widely used for separation processes in applications such as water desalination, batteries and dialysis, and are crucial in key sectors of our economy and society1. The majority of technologically exploited membranes are based on solid polymers and function as passive barriers, whose transport characteristics are governed by their chemical composition and nanostructure. Although such membranes are ubiquitous, it has proved challenging to maximize selectivity and permeability independently, leading to trade-offs between these pertinent characteristics2. Self-assembled biological membranes, in which barrier and transport functions are decoupled3,4, provide the inspiration to address this problem5,6. Here we introduce a self-assembly strategy that uses the interface of an aqueous two-phase system to template and stabilize molecularly thin (approximately 35 nm) biomimetic block copolymer bilayers of scalable area that can exceed 10 cm2 without defects. These membranes are self-healing, and their barrier function against the passage of ions (specific resistance of approximately 1 MΩ cm2) approaches that of phospholipid membranes. The fluidity of these membranes enables straightforward functionalization with molecular carriers that shuttle potassium ions down a concentration gradient with exquisite selectivity over sodium ions. This ion selectivity enables the generation of electric power from equimolar solutions of NaCl and KCl in devices that mimic the electric organ of electric rays.

Effects of tag mass on the physiology and behaviour of common noctule bats.

BACKGROUND: External tags, such as transmitters and loggers, are often used to study bat movements. However, physiological and behavioural effects on bats carrying tags have rarely been investigated, and recommendations on the maximum acceptable tag mass are rather based on rules of thumb than on rigorous scientific assessment. METHODS: We conducted a comprehensive three-step assessment of the potential physiological and behavioural effects of tagging bats, using common noctules Nyctalus noctula as a model. First, we examined seasonal changes in body mass. Second, we predicted and then measured potential changes in flight metabolic rate in a wind tunnel. Third, we conducted a meta-analysis of published data to assess effects of different tag masses on the weight and behaviour of bats. RESULTS: Individual body mass of common noctules varied seasonally by 7.0 ± 2.6 g (range: 0.5-11.5 g). Aerodynamic theory predicted a 26% increase in flight metabolic rate for a common noctule equipped with a 3.8 g tag, equating to 14% of body mass. In a wind tunnel experiment, we could not confirm the predicted increase for tagged bats. Our meta-analysis revealed a weak correlation between tag mass and emergence time and flight duration in wild bats. Interestingly, relative tag mass (3-19% of bat body mass) was not related to body mass loss, but bats lost more body mass the longer tags were attached. Notably, relatively heavy bats lost more mass than conspecifics with a more average body mass index. CONCLUSION: Because heavy tags (> 3 g) were generally used for shorter periods of time than lighter tags (~ 1 g), the long-term effects of heavy tags on bats cannot be assessed at this time. Furthermore, the effects of disturbance and resource distribution in the landscape cannot be separated from those of tagging. We recommend that tags weighing 5-10% of a bat's mass should only be applied for a few days. For longer studies, tags weighing less than 5% of a bat's body mass should be used. To avoid adverse effects on bats, researchers should target individuals with average, rather than peak, body mass indices.

Non-invasive early detection on esophageal squamous cell carcinoma and precancerous lesions by microbial biomarkers combining epidemiological factors in China.

BACKGROUND: Microbiota may be associated with esophageal squamous cell carcinoma (ESCC) development. However, it is not known the predictive value of microbial biomarkers combining epidemiological factors for the early detection of ESCC and precancerous lesions. METHODS: A total of 449 specimens (esophageal swabs and saliva) were collected from 349 participants with different esophageal statuses in China to explore and validate ESCC-associated microbial biomarkers from genes level to species level by 16S rRNA sequencing, metagenomic sequencing and real-time quantitative polymerase chain reaction. RESULTS: A bacterial biomarker panel including Actinomyces graevenitzii (A.g_1, A.g_2, A.g_3, A.g_4), Fusobacteria nucleatum (F.n_1, F.n_2, F.n_3), Haemophilus haemolyticus (H.h_1), Porphyromonas gingivalis (P.g_1, P.g_2, P.g_3) and Streptococcus australis (S.a_1) was explored by metagenomic sequencing to early detect the participants in Need group (low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and ESCC) vs participants without these lesions as the Noneed group. Significant quantitative differences existed for each microbial target in which the detection efficiency rate was higher in saliva than esophageal swab. In saliva, the area under the curve (AUC) based on the microbial biomarkers (A.g_4 ∩ P.g_3 ∩ H.h_1 ∩ S.a_1 ∩ F.n_2) was 0.722 (95% CI 0.621-0.823) in the exploration cohort. Combining epidemiological factors (age, smoking, drinking, intake of high-temperature food and toothache), the AUC improved to 0.869 (95% CI 0.802-0.937) in the exploration cohort, which was validated with AUC of 0.757 (95% CI 0.663-0.852) in the validation cohort. CONCLUSIONS: It is feasible to combine microbial biomarkers in saliva and epidemiological factors to early detect ESCC and precancerous lesions in China.

Comparison of current to past outcomes in congenital diaphragmatic hernia using mri observed-to-expected total fetal lung volume.

BACKGROUND: Fetal Centers use imaging studies to predict congenital diaphragmatic hernia (CDH) prognosis and the need for fetal therapy. Given improving CDH survival, we hypothesized that current fetal imaging severity predictions no longer reflect true outcomes and fail to justify the risks of fetal therapy. METHODS: We analyzed our single-center contemporary data in a left-sided CDH cohort (n = 58) by prognostic criteria determined by MRI observed-to-expected total fetal lung volumes: severe <25%, moderate 25-35%, and mild >35%. We compared contemporary survival to prior studies and the TOTAL trials. RESULTS: Contemporary survival was significantly higher than past studies for all prognostic classifications (mild 100% vs 80-94%, moderate 95% vs 59-75%, severe 79% vs 13-25%; P < 0.01), and to either control or fetal therapy arms of the TOTAL trials. CONCLUSIONS: Current fetal imaging criteria are overly pessimistic and may lead to unwarranted fetal intervention. Fetal therapies remain experimental. Future studies will require updated prognostic criteria.

Rationale for the Potential Use of Recombinant Activated Factor VII in Severe Post-Partum Hemorrhage.

Severe post-partum hemorrhage (PPH) is a major cause of maternal mortality worldwide. Recombinant activated factor VII (rFVIIa) has recently been approved by the European Medicines Agency for the treatment of severe PPH if uterotonics fail to achieve hemostasis. Although large randomized controlled trials are lacking, accumulated evidence from smaller studies and international registries supports the efficacy of rFVIIa alongside extended standard treatment to control severe PPH. Because rFVIIa neither substitutes the activity of a missing coagulation factor nor bypasses a coagulation defect in this population, it is not immediately evident how it exerts its beneficial effect. Here, we discuss possible mechanistic explanations for the efficacy of rFVIIa and the published evidence in patients with severe PPH. Recombinant FVIIa may not primarily increase systemic thrombin generation, but may promote local thrombin generation through binding to activated platelets at the site of vascular wall injury. This explanation may also address safety concerns that have been raised over the administration of a procoagulant molecule in a background of increased thromboembolic risk due to both pregnancy-related hemostatic changes and the hemorrhagic state. However, the available safety data for this and other indications are reassuring and the rates of thromboembolic events do not appear to be increased in women with severe PPH treated with rFVIIa. We recommend that the administration of rFVIIa be considered before dilutional coagulopathy develops and used to support the current standard treatment in certain patients with severe PPH.

Toward solving the global green-green dilemma between wind energy production and bat conservation.

Wind energy production is growing rapidly worldwide in an effort to reduce greenhouse gas emissions. However, wind energy production is not environmentally neutral. Negative impacts on volant animals, such as bats, include fatalities at turbines and habitat loss due to land-use change and displacement. Siting turbines away from ecologically sensitive areas and implementing measures to reduce fatalities are critical to protecting bat populations. Restricting turbine operations during periods of high bat activity is the most effective form of mitigation currently available to reduce fatalities. Compensating for habitat loss and offsetting mortality are not often practiced, because meaningful offsets are lacking. Legal frameworks to prevent or mitigate the negative impacts of wind energy on bats are absent in most countries, especially in emerging markets. Therefore, governments and lending institutions are key in reconciling wind energy production with biodiversity goals by requiring sufficient environmental standards for wind energy projects.

Effect of EVAR on International Ruptured AAA Mortality-Sex and Geographic Disparities.

Background: We sought to investigate the differential impact of EVAR (endovascular aneurysm repair) vis-à-vis OSR (open surgical repair) on ruptured AAA (abdominal aortic aneurysm) mortality by sex and geographically. Methods: We performed a retrospective study of administrative data on EVAR from state statistical agencies, vascular registries, and academic publications, as well as ruptured AAA mortality rates from the World Health Organization for 14 14 states across Australasia, East Asia, Europe, and North America. Results: Between 2011-2016, the proportion of treatment of ruptured AAAs by EVAR increased from 26.1 to 43.8 percent among females, and from 25.7 to 41.2 percent among males, and age-adjusted ruptured AAA mortality rates fell from 12.62 to 9.50 per million among females, and from 34.14 to 26.54 per million among males. The association of EVAR with reduced mortality was more than three times larger (2.2 vis-à-vis 0.6 percent of prevalence per 10 percentage point increase in EVAR) among females than males. The association of EVAR with reduced mortality was substantially larger (1.7 vis-à-vis 1.1 percent of prevalence per 10 percentage point increase in EVAR) among East Asian states than European+ states. Conclusions: The increasing adoption of EVAR coincided with a decrease in ruptured AAA mortality. The relationship between EVAR and mortality was more pronounced among females than males, and in East Asian than European+ states. Sex and ethnic heterogeneity should be further investigated.

Trophic position determines the persistence of neotropical understory birds after forest disturbance.

Habitat loss and degradation are key drivers of the current biodiversity crisis. Most research focuses on the question of which traits allow species to persist in degraded habitats. We asked whether a species' trophic position or niche width influences the resilience of species in degraded habitats and to what extent habitat degradation affects trophic interactions between species. We used nitrogen isotope ratios (15N:14N, expressed as δ15N value) to quantify and compare trophic positions and niche widths of understory birds inhabiting old-growth and young secondary forests in the Pacific lowlands of Costa Rica. We found that a species' trophic position rather than its trophic niche width determined its persistence in secondary forests. Species feeding at lower trophic levels in old-growth forests were less likely to persist in secondary forests than those occupying a higher trophic position in old-growth forests. This pattern is likely induced by the occurrence of relatively large-bodied habitat specialists with a flexible and high-trophic level diet in secondary forests. These habitat specialists likely caused generalist bird species to lower their trophic position relative to conspecifics in old-growth forests. Regarding trophic niche widths, species in secondary forests tend to have larger niche widths than old-growth forest species. However, as old-growth forest specialists and generalists did not differ in their niche widths, no systematic effect of trophic niche width on species persistence after forest disturbance was found. This is the first study that shows a systematic effect of trophic position on the persistence of a wide range of bird species in a disturbed forest ecosystem. It therefore provides important insights into species' responses to habitat degradation and the conservation value of secondary forests. To improve habitat quality for old-growth forest birds and facilitate avian seed dispersal, the creation of large contiguous forest patches should be prioritised when implementing reforestation measures.

Real-Time Electronic Patient Portal Use Among Emergency Department Patients.

Importance: Patients with inequitable access to patient portals frequently present to emergency departments (EDs) for care. Little is known about portal use patterns among ED patients. Objectives: To describe real-time patient portal usage trends among ED patients and compare demographic and clinical characteristics between portal users and nonusers. Design, Setting, and Participants: In this cross-sectional study of 12 teaching and 24 academic-affiliated EDs from 8 health systems in California, Connecticut, Massachusetts, Ohio, Tennessee, Texas, and Washington, patient portal access and usage data were evaluated for all ED patients 18 years or older between April 5, 2021, and April 4, 2022. Exposure: Use of the patient portal during ED visit. Main Outcomes and Measures: The primary outcomes were the weekly proportions of ED patients who logged into the portal, viewed test results, and viewed clinical notes in real time. Pooled random-effects models were used to evaluate temporal trends and demographic and clinical characteristics associated with real-time portal use. Results: The study included 1 280 924 unique patient encounters (53.5% female; 0.6% American Indian or Alaska Native, 3.7% Asian, 18.0% Black, 10.7% Hispanic, 0.4% Native Hawaiian or Pacific Islander, 66.5% White, 10.0% other race, and 4.0% with missing race or ethnicity; 91.2% English-speaking patients; mean [SD] age, 51.9 [19.2] years). During the study, 17.4% of patients logged into the portal while in the ED, whereas 14.1% viewed test results and 2.5% viewed clinical notes. The odds of accessing the portal (odds ratio [OR], 1.36; 95% CI, 1.19-1.56), viewing test results (OR, 1.63; 95% CI, 1.30-2.04), and viewing clinical notes (OR, 1.60; 95% CI, 1.19-2.15) were higher at the end of the study vs the beginning. Patients with active portal accounts at ED arrival had a higher odds of logging into the portal (OR, 17.73; 95% CI, 9.37-33.56), viewing test results (OR, 18.50; 95% CI, 9.62-35.57), and viewing clinical notes (OR, 18.40; 95% CI, 10.31-32.86). Patients who were male, Black, or without commercial insurance had lower odds of logging into the portal, viewing results, and viewing clinical notes. Conclusions and Relevance: These findings suggest that real-time patient portal use during ED encounters has increased over time, but disparities exist in portal access that mirror trends in portal usage more generally. Given emergency medicine's role in caring for medically underserved patients, there are opportunities for EDs to enroll and train patients in using patient portals to promote engagement during and after their visits.

Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes.

PURPOSE: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). METHODS: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. RESULTS: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. CONCLUSION: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.

Evaluation of the effect of Carica papaya seed on the growth performance of fattening rabbits.

Successful breeding depends on feeding. The present study aims to evaluate the Carica papaya seed effect on the growth performance of rabbits. The zootechnical parameters studied are weight growth, average daily gain, Feed Conversion Ratio, and carcass characteristics of kits. The experiment was conducted on 48 rabbits, divided into 4 groups, for 6 weeks. Forty-eight rabbits were divided into four (04) groups of 3 repetitions of 4 rabbits. The animals were fed diets containing various levels of papaya seed powder at variable contents: 0% (group T0), 4% (group T1), 6% (group T2), and 8% (group T3). At the end of the experiment, three animals were slaughtered in each animal group to assess the quality of the carcasses and organs. 6% of the seeds of Carica papaya significantly improved (p < 0.05) the average daily gain of the kits: T2 (22.40 g / d) compared to the T0 group (11.32 g / d), T1 (12.20 g / d) and T3 (17.53 g / d). The best Feed Conversion Ratio (0.80) was recorded in the animals of group T2. In contrast, the highest carcass yield was recorded in the rabbits of group T3 (62.70%). In conclusion, 6% was optimal in the feed rations of fattened rabbits to improve production performance. Breeders can consider the benefits of introducing Carica papaya seeds into the rabbits' diet.

Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

AIMS: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. METHODS: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. RESULTS: Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B = -0.99, 95% confidence interval (CI) [-1.77, -0.20], P = .014) or at least a 2-level reduction (B = -0.80, 95% CI [-1.47, -0.14], P = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B = -1.01, 95% CI [-1.83, -0.20], P = .015; 2-level: B = -0.90, 95% CI [-1.59, -0.22], P = .010). CONCLUSIONS: Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted.

Variations in inter-specific and sex-related niche partitioning in pelagic boobies during their annual cycle.

Animals that co-occur in a region (sympatry) may share the same environment (syntopy), and niche differentiation is expected among closely related species competing for resources. The masked booby (Sula dactylatra) and smaller congeneric red-footed booby (Sula sula) share breeding grounds. In addition to the inter-specific size difference, females of both species are also larger than the respective males (reversed sexual size dimorphism). Although both boobies consume similar prey, sometimes in mixed-species flocks, each species and sex may specialize in terms of their diet or foraging habitats. We examined inter- and intra-specific differences in isotopic values (δ13C and δ15N) in these pelagically feeding booby species during the incubation period at Clarion Island, Mexico, to quantify the degrees of inter- and intra-specific niche partitioning throughout the annual cycle. During incubation, both species preyed mainly on flyingfish and squid, but masked boobies had heavier food loads than red-footed boobies. There was no overlap in isotopic niches between masked and red-footed boobies during breeding (determined from whole blood), but there was slight overlap during the non-breeding period (determined from body feathers). Female masked boobies had a higher trophic position than conspecific males during breeding; however, no such pattern was detected in red-footed boobies. These results provide evidence of inter- and intra-specific niche partitioning in these tropical seabird species, particularly during the breeding period and in the more-dimorphic species. Our results suggest that these closely related species use different strategies to cope with the same tropical marine environment.

Randomised, Placebo-Controlled Investigation of the Impact of Probiotic Consumption on Gut Microbiota Diversity and the Faecal Metabolome in Seniors.

Aging has been associated with a changed composition and function of the gut microbiota (GM). Here, we investigate the effects of the multi-strain probiotic HOWARU® Restore on GM composition and function in seniors. Ninety-eight healthy adult volunteers aged ≥75 years were enrolled in a randomised, double-blinded intervention (NCT02207140), where they received HOWARU Restore (1010 CFU) or the placebo daily for 24 weeks, with 45 volunteers from each group completing the intervention. Questionnaires monitoring the effects on gastro-intestinal discomfort and bowel movements were collected. Faecal samples for GM characterisation (qPCR, 16S rRNA gene amplicon sequencing) and metabolomics (GC-FID, 1H NMR) were collected at the baseline and after 24 weeks. In the probiotic group, self-reported gastro-intestinal discomfort in the form of flatulence was significantly decreased during the intervention. At the baseline, 151 'core species' (present in ≥95% of samples) were identified. Most core species belonged to the Lachnospiraceae and Ruminococcaceae families. Neither alpha diversity nor beta diversity or faecal metabolites was affected by probiotic intake. On the contrary, we observed high intra-individual GM stability, with 'individual' accounting for 72-75% of variation. In conclusion, 24 weeks of HOWARU Restore intake reduced gastro-intestinal discomfort in the form of flatulence in healthy seniors without significantly influencing GM composition or activity.