The effects of 6 wk of resistance training on the gut microbiome and cardiometabolic health in young adults with overweight and obesity.

Obesity is a known risk factor for the development of insulin resistance and other cardiometabolic disorders. Recently, the gut microbiome has been associated with obesity and subsequent health complications. Exercise has been regularly utilized as a therapeutic intervention to treat obesity and its associated comorbidities. This study examined the effects of a 6-wk resistance training exercise program (RT) on the diversity, composition, and metabolic pathways of the gut microbiome. Sedentary young adults (age 18-35 yr) with overweight and obesity (BMI 25-45 kg/m2) were recruited to participate in this randomized controlled trial. Participants were randomized to RT (n = 16), a 6-wk resistance training program (3 days/wk), or control (CT) (n = 16), a nonexercising control. Main outcomes of the study included gut microbiome measures (taxa abundances, diversity, and predicted function) and cardiometabolic outcomes [blood pressure (BP) and glucoregulation]. Increased abundances of Roseburia, a short-chain fatty acid (SCFA) producer were observed over 6 wk (W6) with RT compared with CT (group × week, P < 0.05, q < 0.25). RT also induced marginal alterations in predicted microbial metabolic and cell motility pathways compared with CT (group × week, P < 0.05, q < 0.25). However, RT did not significantly impact overall microbial diversity. Furthermore, RT resulted in higher quantitative insulin-sensitivity check index (QUICKI) and lower diastolic BP at W6 compared with CT [baseline (BL)-adjusted P < 0.05]. RT had mixed effects on the gut microbiome. Although RT increased abundances of Roseburia and induced minor changes in microbial pathways, it is important to consider these changes in the context of the overall stability observed in the microbiome composition.NEW & NOTEWORTHY Resistance training induces mixed changes in the gut microbiome, including an increase in the abundances of the Roseburia genus and minor alterations in microbial pathways. However, it is vital to interpret these changes in light of the broader context, where we observe stability in the overall microbiome composition. This stability may be attributed to the microbiome's resilience, demonstrating its capacity to withstand short-term physiological stressors.

Charcot arthropathy outcomes after early referral to a regional tertiary care foot clinic.

BACKGROUND: Community physicians may not encounter Charcot arthropathy frequently, and its symptoms and signs may be nonspecific. Patients often have a delay of several months before receiving a formal diagnosis and referral for specialty care. However, limited Canadian data are available. We evaluated the clinical history, treatment and outcomes of patients treated for Charcot arthropathy after prompt referral and diagnosis. METHODS: We performed a retrospective chart review of 76 patients with diabetes (78 feet) who received nonoperative treatment for Charcot arthropathy in a specialty foot clinic between Jan. 20, 2009, and Mar. 26, 2018. Patients were referred to the foot clinic by community physicians for evaluation or were pre-existing patients at the foot clinic with new-onset Charcot arthropathy. RESULTS: Of the 78 feet included in our analyses, 52 feet (67%) were evaluated initially by a community physician and referred to the foot clinic, where they were seen within 3 ± 5 weeks. The remaining 26 feet (33%) were already being treated at the foot clinic. Most feet had swelling, erythema, warmth, a palpable pulse and loss of protective sensation. Ulcers were present initially in 23 feet (29%). Sixty-four feet (82%) with Charcot arthropathy were in Eichenholtz classification stage 1 and most had midfoot involvement. Nonoperative treatment included total contact casting (60 feet, 77%). Mean duration of nonoperative treatment until resolution for 55 feet (71%) was 6 ± 5 months. Surgery was performed on 20 feet (26%) for the treatment of infection and recurrent ulcer associated with deformity, including 6 (8%) lower limb amputations. CONCLUSION: Charcot arthropathy may resolve in most feet with early referral and nonoperative treatment, but remains a limb-threatening condition.

Fire reduces eucalypt forest flowering phenology at the landscape-scale.

Plant phenology describes the timing of reproductive events including flowering and fruiting, which for many species are affected by fire disturbance. Understanding phenological responses to fire provides insights into how forest demographics and resources may shift alongside increasing fire frequency and intensity driven by climate change. However, isolating the direct effects of fire on a species' phenology and excluding potential confounders (e.g. climate, soil) has been difficult due to the logistical challenges of monitoring species-specific phenological events across myriad fire and environmental conditions. Here, we use CubeSat-derived crown-scale flowering data to estimate the effects of fire history (time since fire and fire severity over a 15-year time span) on flowering of the eucalypt Corymbia calophylla across a Mediterranean-climate forest (814km2) in southwest Australia. We found that fire reduced the proportion of flowering trees at the landscape-scale, and flowering recovered at a rate of 0.15 % (±0.11% SE) per year. Further, this negative effect was significant due to high crown scorch fires (>20% canopy scorch), yet there was no significant effect from understory burns. Estimates were obtained using a quasi-experimental design which identifies the effect of time since fire and severity on flowering by comparing proportional flowering within target fire perimeters (treatment) and adjacent past fire perimeters (control). Given the majority of fires studied were managed fuel reduction burns, we applied the estimates to hypothetical fire regimes to compare flowering outcomes under more or less frequent prescribed burning. This research demonstrates the landscape-scale effects of burning on a tree species' reproduction, which could broadly impact forest resiliency and biodiversity.

A systematic review on the effects of exercise on gut microbial diversity, taxonomic composition, and microbial metabolites: identifying research gaps and future directions.

The gut microbiome, hosting a diverse microbial community, plays a pivotal role in metabolism, immunity, and digestion. While the potential of exercise to influence this microbiome has been increasingly recognized, findings remain incongruous. This systematic review examined the effects of exercise on the gut microbiome of human and animal models. Databases (i.e., PubMed, Cochrane Library, Scopus, and Web of Science) were searched up to June 2022. Thirty-two exercise studies, i.e., 19 human studies, and 13 animal studies with a minimum of two groups that discussed microbiome outcomes, such as diversity, taxonomic composition, or microbial metabolites, over the intervention period, were included in the systematic review (PROSPERO registration numbers for human review: CRD42023394223). Results indicated that over 50% of studies found no significant exercise effect on human microbial diversity. When evident, exercise often augmented the Shannon index, reflecting enhanced microbial richness and evenness, irrespective of disease status. Changes in beta-diversity metrics were also documented with exercise but without clear directionality. A larger percentage of animal studies demonstrated shifts in diversity compared to human studies, but without any distinct patterns, mainly due to the varied effects of predominantly aerobic exercise on diversity metrics. In terms of taxonomic composition, in humans, exercise usually led to a decrease in the Firmicutes/Bacteroidetes ratio, and consistent increases with Bacteroides and Roseburia genera. In animal models, Coprococcus, another short chain fatty acid (SCFA) producer, consistently rose with exercise. Generally, SCFA producers were found to increase with exercise in animal models. With regard to metabolites, SCFAs emerged as the most frequently measured metabolite. However, due to limited human and animal studies examining exercise effects on microbial-produced metabolites, including SCFAs, clear patterns did not emerge. The overall risk of bias was deemed neutral. In conclusion, this comprehensive systematic review underscores that exercise can potentially impact the gut microbiome with indications of changes in taxonomic composition. The significant variability in study designs and intervention protocols demands more standardized methodologies and robust statistical models. A nuanced understanding of the exercise-microbiome relationship could guide individualized exercise programs to optimize health. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=394223, identifier CRD42023394223.

Meta-Analysis Reveals Challenges and Gaps for Genome-to-Phenome Research Underpinning Plant Drought Response.

Severe drought conditions and extreme weather events are increasing worldwide with climate change, threatening the persistence of native plant communities and ecosystems. Many studies have investigated the genomic basis of plant responses to drought. However, the extent of this research throughout the plant kingdom is unclear, particularly among species critical for the sustainability of natural ecosystems. This study aimed to broaden our understanding of genome-to-phenome (G2P) connections in drought-stressed plants and identify focal taxa for future research. Bioinformatics pipelines were developed to mine and link information from databases and abstracts from 7730 publications. This approach identified 1634 genes involved in drought responses among 497 plant taxa. Most (83.30%) of these species have been classified for human use, and most G2P interactions have been described within model organisms or crop species. Our analysis identifies several gaps in G2P research literature and database connectivity, with 21% of abstracts being linked to gene and taxonomy data in NCBI. Abstract text mining was more successful at identifying potential G2P pathways, with 34% of abstracts containing gene, taxa, and phenotype information. Expanding G2P studies to include non-model plants, especially those that are adapted to drought stress, will help advance our understanding of drought responsive G2P pathways.

Acute kidney injury in sick neonates: a comparative study of diagnostic criteria, assessment of risk factors and outcomes.

INTRODUCTION: Neonatal acute kidney injury (nAKI) poses unique challenges with diagnostic criteria specific to neonates evolving over time. Urine output (UOP) criterion has a special place in the diagnosis of nAKI although significant clarity on the ideal diagnostic threshold for UOP is not established. Risk factors peculiar to the tropical region for acute kidney injury (AKI) in neonates needs attention. It would be interesting to assess for kidney function in neonates who survived AKI during the dynamic phase of infancy. OBJECTIVES: To compare criteria of modified kidney disease improving global outcome (mKDIGO) and neonatal risk, injury, failure, loss, and end-stage criteria (nRIFLE) in diagnosing AKI in sick neonates; to study the risk factors for AKI and clinical outcomes at the end of neonatal ICU stay and during infancy. METHODS: This prospective study was conducted at a tertiary neonatal ICU that screened and staged sick neonates by applying mKDIGO and nRIFLE criteria. Risk factors were assessed and glomerular filtration rate was calculated by cystatin C in survivors of nAKI for 12 months post conception age. RESULTS: nAKI was observed in 30% (49/163) of sick neonates. The mKDIGO (94%) detected a higher number of neonates with AKI compared to nRIFLE (49%). Based on only UOP, nRIFLE diagnosed a higher proportion of neonates with mild AKI compared to mKDIGO (29% versus 16%), respectively. Besides known risk factors, hypernatremic dehydration (18%) was an important risk factor for AKI. With 20% mortality, the risk of developing AKI was comparable using either mKDIGO or nRIFLE diagnostic criteria. At the end of infancy, mean cystatin C eGFR of neonates was 101.3 ± 29.2 ml/1.73 m2/min. CONCLUSION: In sick neonates, mKDIGO criteria performed better than nRIFLE in detecting AKI. However, the risk of mortality was comparable using either diagnostic criterion. Hypernatremic dehydration was an important risk factor for AKI and renal function of neonates following complete recovery of AKI was normal at the end of infancy.

Evolution of the management of retrorectal masses: A retrospective cohort study.

AIM: Retrorectal masses are abnormalities located anatomically in the retrorectal space. A significant proportion are asymptomatic with no malignant potential while others cause symptoms due to mechanical pressure or malignant infiltration. We reviewed and categorised the retrorectal masses encountered over a 30-year time period in a specialist colorectal hospital and describe our management algorithm for consideration by other multidisciplinary teams (MDT). METHODS: This was a retrospective analysis of consecutive patients referred between 1984-2019. A detailed review of clinical presentation, imaging features, postoperative histology and impact on morbidity and anorectal function is reported. RESULTS: A total of 143 patients with median age of 46 years and female preponderance (74%) were reviewed. The commonest presenting symptom was pain (46%) and all malignant cases had symptoms (n = 17). Over the last decade, more asymptomatic patients have presented with a retrorectal mass (33%, p = 0.04) and more patients are opting for surveillance rather than resection (33%, p = 0.013). Increasing age and lesion size were associated with malignancy (p < 0.05). Radiological features associated with malignancy included: solid/heterogeneous component, lobulated borders or locally invasive. Following surgery, complications included chronic pain (40%), poor wound healing (23%) and bowel dysfunction (10%). CONCLUSIONS: The management of retrorectal masses remains complex. There are features, both clinical and radiological, that can help determine the best management strategy. Management should be in a high-volume tertiary centre and preferably through a complex rectal cancer MDT. Long-term sequelae such as chronic pain must be highlighted to patients. We advocate the establishment of an international registry to further record and characterise these rare, potentially troublesome lesions.

Hospital outbreak of New Delhi metallo-ß-lactamase type-1 (NDM-1) in Salmonella enterica with inter-species plasmid transmission.

New Delhi metallo-ß-lactamase (NDM) gene confers high-level resistance to an array of ß-lactams including carbapenems. Short- and long-read sequencing was used to investigate outbreaks of NDM-positive Enterobacterales including a potential horizontal gene transfer (HGT) event of an NDM-positive plasmid between Salmonella enterica and Klebsiella pneumoniae. Genomic analysis demonstrated a high degree of similarity between NDM-carrying plasmids from patient 1 in K. pneumoniae and patient 2 with S. enterica, K. pneumoniae and Klebsiella oxytoca, confirming an inter-species HGT event. The utility of whole-genome sequencing was demonstrated for in-hospital outbreaks, previously undetected using traditional infection-control surveillance.

G2PMineR: A Genome to Phenome Literature Review Approach.

There is a gap in the conceptual framework linking genes to phenotypes (G2P) for non-model organisms, as most non-model organisms do not yet have genomic resources readily available. To address this, researchers often perform literature reviews to understand G2P linkages by curating a list of likely gene candidates, hinging upon other studies already conducted in closely related systems. Sifting through hundreds to thousands of articles is a cumbersome task that slows down the scientific process and may introduce bias into a study. To fill this gap, we created G2PMineR, a free and open source literature mining tool developed specifically for G2P research. This R package uses automation to make the G2P review process efficient and unbiased, while also generating hypothesized associations between genes and phenotypes within a taxonomical framework. We applied the package to a literature review for drought-tolerance in plants. The analysis provides biologically meaningful results within the known framework of drought tolerance in plants. Overall, the package is useful for conducting literature reviews for genome to phenome projects, and also has broad appeal to scientists investigating a wide range of study systems as it can conduct analyses under the auspices of three different kingdoms (Plantae, Animalia, and Fungi).

TRAIT2D: a Software for Quantitative Analysis of Single Particle Diffusion Data.

Single particle tracking (SPT) is one of the most widely used tools in optical microscopy to evaluate particle mobility in a variety of situations, including cellular and model membrane dynamics. Recent technological developments, such as Interferometric Scattering microscopy, have allowed recording of long, uninterrupted single particle trajectories at kilohertz framerates. The resulting data, where particles are continuously detected and do not displace much between observations, thereby do not require complex linking algorithms. Moreover, while these measurements offer more details into the short-term diffusion behaviour of the tracked particles, they are also subject to the influence of localisation uncertainties, which are often underestimated by conventional analysis pipelines. we thus developed a Python library, under the name of TRAIT2D (Tracking Analysis Toolbox - 2D version), in order to track particle diffusion at high sampling rates, and analyse the resulting trajectories with an innovative approach. The data analysis pipeline introduced is more localisation-uncertainty aware, and also selects the most appropriate diffusion model for the data provided on a statistical basis. A trajectory simulation platform also allows the user to handily generate trajectories and even synthetic time-lapses to test alternative tracking algorithms and data analysis approaches. A high degree of customisation for the analysis pipeline, for example with the introduction of different diffusion modes, is possible from the source code. Finally, the presence of graphical user interfaces lowers the access barrier for users with little to no programming experience.

Off-Pathway Assembly: A Broad-Spectrum Mechanism of Action for Drugs That Undermine Controlled HIV-1 Viral Capsid Formation.

The early and late stages of human immunodeficiency virus (HIV) replication are orchestrated by the capsid (CA) protein, which self-assembles into a conical protein shell during viral maturation. Small molecule drugs known as capsid inhibitors (CIs) impede the highly regulated activity of CA. Intriguingly, a few CIs, such as PF-3450074 (PF74) and GS-CA1, exhibit effects at multiple stages of the viral lifecycle at effective concentrations in the pM to nM regimes, while the majority of CIs target a single stage of the viral lifecycle and are effective at nM to µM concentrations. In this work, we use coarse-grained molecular dynamics simulations to elucidate the molecular mechanisms that enable CIs to have such curious broad-spectrum activity. Our quantitatively analyzed findings show that CIs can have a profound impact on the hierarchical self-assembly of CA by perturbing populations of small CA oligomers. The self-assembly process is accelerated by the emergence of alternative assembly pathways that favor the rapid incorporation of CA pentamers, and leads to increased structural pleomorphism in mature capsids. Two relevant phenotypes are observed: (1) eccentric capsid formation that may fail to encase the viral genome and (2) rapid disassembly of the capsid, which express at late and early stages of infection, respectively. Finally, our study emphasizes the importance of adopting a dynamical perspective on inhibitory mechanisms and provides a basis for the design of future therapeutics that are effective at low stoichiometric ratios of drug to protein.

Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding.

The influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored, and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will, in principle, be able to both contribute to curvature induction and sense curvature to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered-liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced.

Tea production characteristics of tea growers (plantations and smallholdings) and livelihood dimensions of tea workers in Assam, India.

This article provides summary data regarding tea production in Assam, India. Questionnaires were completed by tea producers and focus group discussions undertaken with tea workers. These data are presented for the four main tea growing regions of the state (Cachar, North Bank, South Bank and Upper Assam). Tables detail tea production characteristics of the tea plantations for both large- (> 10 ha) and small- (< 10 ha) holders. Figures provide supplementary information for research by Biggs et al. [1] regarding fertilizer application, landscape management strategies, healthcare provisioning and educational facilities within plantations, as well as detailing the livelihood dimensions of tea workers. The questions posed to producers are also included. For further context underpinning the research for which these data were collated, see 'The tea landscape of Assam: multi-stakeholder insights into sustainable livelihoods under a changing climate' by Biggs et al. [1].

Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane.

The packaging and budding of Gag polyprotein and viral RNA is a critical step in the HIV-1 life cycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth. We develop a coarse-grained (CG) computational model that is derived from subnanometer resolution structural data. Our simulations recapitulate contiguous and hexameric lattice assembly driven only by weak anisotropic attractions at the helical CA-SP1 junction. Importantly, analysis from CG and single-particle tracking photoactivated localization (spt-PALM) trajectories indicates that viral RNA and the membrane are critical constituents that actively promote Gag multimerization through scaffolding, while overexpression of short competitor RNA can suppress assembly. We also find that the CA amino-terminal domain imparts intrinsic curvature to the Gag lattice. As a consequence, immature lattice growth appears to be coupled to the dynamics of spontaneous membrane deformation. Our findings elucidate a simple network of interactions that regulate the early stages of HIV-1 assembly and budding.

Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly.

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies.

Outcome of HIV-infected Pregnant Women and Their Offspring in Barbados: A Five-year Study.

OBJECTIVES: To describe the outcome of HIV-infected pregnant women and their offspring during a five-year period. METHODS: The medical records of HIV-infected pregnant women who delivered between January 2007 and December 2011 and their HIV-exposed infants were reviewed. Demographics, outcome of pregnancy and infants, and clinic attendance were analysed. Data were entered on a Microsoft Excel spreadsheet. RESULTS: One hundred and forty-three women, aged 17-45 years (mean 27.3 years), were included in the study with 143 pregnancies and 142 pregnancy outcomes being recorded. One woman migrated before delivery. There were 122 live births and 18 (13%) terminations: 13 (9%) elective and five (4%) spontaneous. There was one ectopic pregnancy and one stillbirth. One hundred and twenty-two (85%) women were unmarried. Women were prescribed highly active antiretroviral therapy for prevention of mother-to-child transmission from the time of booking, apart from those opting for terminations or those who had spontaneous abortions. For clinic follow-up, 105 (73%) had regular attendance, 30 (21%) defaulted and could not be located despite intense tracking, four attended irregularly, and one refused to attend clinic. Four (3%) migrated after delivery. Two (1%) mothers died during the period of study. Two successive DNA polymerase chain reaction tests done within four months of age did not substantiate any cases of infant infection. CONCLUSION: This study revealed that there was a good outcome and compliance with follow-up of HIV-infected pregnant women and their offspring.

Elucidating the impact of temperature variability and extremes on cereal croplands through remote sensing.

Remote sensing-derived wheat crop yield-climate models were developed to highlight the impact of temperature variation during thermo-sensitive periods (anthesis and grain-filling; TSP) of wheat crop development. Specific questions addressed are: can the impact of temperature variation occurring during the TSP on wheat crop yield be detected using remote sensing data and what is the impact? Do crop critical temperature thresholds during TSP exist in real world cropping landscapes? These questions are tested in one of the world's major wheat breadbaskets of Punjab and Haryana, north-west India. Warming average minimum temperatures during the TSP had a greater negative impact on wheat crop yield than warming maximum temperatures. Warming minimum and maximum temperatures during the TSP explain a greater amount of variation in wheat crop yield than average growing season temperature. In complex real world cereal croplands there was a variable yield response to critical temperature threshold exceedance, specifically a more pronounced negative impact on wheat yield with increased warming events above 35 °C. The negative impact of warming increases with a later start-of-season suggesting earlier sowing can reduce wheat crop exposure harmful temperatures. However, even earlier sown wheat experienced temperature-induced yield losses, which, when viewed in the context of projected warming up to 2100 indicates adaptive responses should focus on increasing wheat tolerance to heat. This study shows it is possible to capture the impacts of temperature variation during the TSP on wheat crop yield in real world cropping landscapes using remote sensing data; this has important implications for monitoring the impact of climate change, variation and heat extremes on wheat croplands.

Highly Scalable and Memory Efficient Ultra-Coarse-Grained Molecular Dynamics Simulations.

The use of coarse-grained (CG) models can significantly increase the time and length scales accessible to computational molecular dynamics (MD) simulations. To address very large-scale phenomena, however, requires a careful consideration of memory requirements and parallel MD load balancing in order to make efficient use of current supercomputers. In this work, a CG-MD code is introduced which is specifically designed for very large, highly parallel simulations of systems with markedly non-uniform particle distributions, such as those found in highly CG models having an implicit solvent. The CG-MD code uses an unorthodox combination of sparse data representations with a Hilbert space-filling curve (SFC) to provide dynamic topological descriptions, reduced memory overhead, and advanced load-balancing characteristics. The results of representative large-scale simulations indicate that our approach can offer significant advantages over conventional MD techniques, and should enable new classes of CG-MD systems to be investigated.