Development and validation of a pulmonary function test data extraction tool for the US department of veterans affairs electronic health record.

OBJECTIVE: Pulmonary function test (PFT) results are recorded variably across hospitals in the Department of Veterans Affairs (VA) electronic health record (EHR), using both unstructured and semi-structured notes. We developed and validated a hospital-specific code to extract pre-bronchodilator measures of obstruction (ratio of forced expiratory volume in one second [FEV1] to forced vital capacity [FVC]) and severity of obstruction (percent predicted of FEV1). RESULTS: Among 36 VA facilities with the most PFTs completed between 2018 and 2022 from a parent cohort of veterans receiving long-acting controller inhalers, 12 had a consistent syntactical convention or template for reporting PFT data in the EHR. Of the 42,718 PFTs identified from these 12 facilities, the hospital-specific text processing pipeline yielded 24,860 values for the FEV1:FVC ratio and 23,729 values for FEV1. A ratio of FEV1:FVC less than 0.7 was identified in 17,615 of 24,922 studies (70.7%); 8864 of 24,922 (35.6%) had a severe or very severe reduction in FEV1 (< 50% of the predicted value). Among 100 randomly selected PFT reports reviewed by two pulmonary physicians, the coding solution correctly identified the presence of obstruction in 99 out of 100 studies and the degree of obstruction in 96 out of 100 studies.

Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

Collective antiretroviral protection: new dimensions of community HIV prevention practices at the intersection of U=U and PrEP.

Collective antiretroviral protection is an evolving sexual health strategy in HIV prevention, used in particular by gay, bisexual, and other men who have sex with men. The strategy involves HIV-negative individuals who engage in condomless sexual activities but, instead of using pre-exposure prophylaxis (PrEP) themselves, choose partners who either have undetectable viral loads or are on PrEP. This biomedical-sorting practice, rooted in the scientific principles of undetectable equals untransmittable (U=U) and PrEP, relies on an indirect protection strategy. Collective antiretroviral protection allows for HIV-negative individuals not on PrEP to benefit from their partner's antiretroviral use, without directly consuming antiretrovirals themselves for HIV prevention, during condomless sex. Empirical research is needed to evaluate the public health implications of this emerging sexual health approach. Research and public health initiatives should adopt a non-stigmatising approach to individuals engaging in collective antiretroviral protection and look beyond individual behaviour to understand the broader community-level effects of this innovative HIV prevention strategy.

Use of temporary tracheostomy occlusion to reduce the risk of sternal wound infection after sternotomy in congenital cardiac surgery.

OBJECTIVE: To describe a method of reducing the risk of sternal wound infection after sternotomy in children with a pre-existing tracheostomy. To report our outcomes using this method from 1 January, 2013 to 31 August, 2023. METHODS: We describe a method for temporarily occluding the tracheal stoma with a removable implant with the primary goal of reducing the risk of sternotomy wound infection by preventing soilage due to tracheostomal secretions. We then performed a retrospective review of all children who underwent temporary tracheostomal occlusion between 1 January, 2013 and 31 August, 2023 at our quaternary care children's hospital. Clinical variables were extracted from the hospital medical records. The rates of antibiotic use and minor and major complications during the period when the stoma plug was in place were recorded. RESULTS: Totally, 19 patients underwent tracheal stoma plugging prior to sternotomy and were included in our analysis. There were two cases of sternal wound infection; one case occurred while the stoma plug was in place, and one developed four days following plug removal. There was one minor complication, with one patient requiring stoma revision via serial dilation at bedside at the time of recannulation. There were no deaths. CONCLUSION: Temporary occlusion of the tracheal stoma with an impermeable plug is a viable option for reducing the risk of sternal wound infection in children with a pre-existing tracheostomy who are undergoing sternotomy.

Implications of Heat Stress-induced Metabolic Alterations for Endurance Training.

Inducing a heat-acclimated phenotype via repeated heat stress improves exercise capacity and reduces athletes̓ risk of hyperthermia and heat illness. Given the increased number of international sporting events hosted in countries with warmer climates, heat acclimation strategies are increasingly popular among endurance athletes to optimize performance in hot environments. At the tissue level, completing endurance exercise under heat stress may augment endurance training adaptation, including mitochondrial and cardiovascular remodeling due to increased perturbations to cellular homeostasis as a consequence of metabolic and cardiovascular load, and this may improve endurance training adaptation and subsequent performance. This review provides an up-to-date overview of the metabolic impact of heat stress during endurance exercise, including proposed underlying mechanisms of altered substrate utilization. Against this metabolic backdrop, the current literature highlighting the role of heat stress in augmenting training adaptation and subsequent endurance performance will be presented with practical implications and opportunities for future research.

A cornucopia of diversity-Ranunculales as a model lineage.

The Ranunculales are a hyperdiverse lineage in many aspects of their phenotype, including growth habit, floral and leaf morphology, reproductive mode, and specialized metabolism. Many Ranunculales species, such as opium poppy and goldenseal, have a high medicinal value. In addition, the order includes a large number of commercially important ornamental plants, such as columbines and larkspurs. The phylogenetic position of the order with respect to monocots and core eudicots and the diversity within this lineage make the Ranunculales an excellent group for studying evolutionary processes by comparative studies. Lately, the phylogeny of Ranunculales was revised, and genetic and genomic resources were developed for many species, allowing comparative analyses at the molecular scale. Here, we review the literature on the resources for genetic manipulation and genome sequencing, the recent phylogeny reconstruction of this order, and its fossil record. Further, we explain their habitat range and delve into the diversity in their floral morphology, focusing on perianth organ identity, floral symmetry, occurrences of spurs and nectaries, sexual and pollination systems, and fruit and dehiscence types. The Ranunculales order offers a wealth of opportunities for scientific exploration across various disciplines and scales, to gain novel insights into plant biology for researchers and plant enthusiasts alike.

A new remarkable Early Cretaceous nelumbonaceous fossil bridges the gap between herbaceous aquatic and woody protealeans.

Dating back to the late Early Cretaceous, the macrofossil record of the iconic lotus family (Nelumbonaceae) is one of the oldest of flowering plants and suggests that their unmistakable leaves and nutlets embedded in large pitted receptacular fruits evolved relatively little in the 100 million years since their first known appearance. Here we describe a new fossil from the late Barremian/Aptian Crato Formation flora (NE Brazil) with both vegetative and reproductive structures, Notocyamus hydrophobus gen. nov. et sp. nov., which is now the oldest and most complete fossil record of Nelumbonaceae. In addition, it displays a unique mosaic of ancestral and derived macro- and micromorphological traits that has never been documented before in this family. This new Brazilian fossil-species also provides a rare illustration of the potential morphological and anatomical transitions experienced by Nelumbonaceae prior to a long period of relative stasis. Its potential plesiomorphic and apomorphic features shared with Proteaceae and Platanaceae not only fill a major morphological gap within Proteales but also provide new support for their unexpected relationships first suggested by molecular phylogenies.

Phylogenomic analyses of Sapindales support new family relationships, rapid Mid-Cretaceous Hothouse diversification, and heterogeneous histories of gene duplication.

Sapindales is an angiosperm order of high economic and ecological value comprising nine families, c. 479 genera, and c. 6570 species. However, family and subfamily relationships in Sapindales remain unclear, making reconstruction of the order's spatio-temporal and morphological evolution difficult. In this study, we used Angiosperms353 target capture data to generate the most densely sampled phylogenetic trees of Sapindales to date, with 448 samples and c. 85% of genera represented. The percentage of paralogous loci and allele divergence was characterized across the phylogeny, which was time-calibrated using 29 rigorously assessed fossil calibrations. All families were supported as monophyletic. Two core family clades subdivide the order, the first comprising Kirkiaceae, Burseraceae, and Anacardiaceae, the second comprising Simaroubaceae, Meliaceae, and Rutaceae. Kirkiaceae is sister to Burseraceae and Anacardiaceae, and, contrary to current understanding, Simaroubaceae is sister to Meliaceae and Rutaceae. Sapindaceae is placed with Nitrariaceae and Biebersteiniaceae as sister to the core Sapindales families, but the relationships between these families remain unclear, likely due to their rapid and ancient diversification. Sapindales families emerged in rapid succession, coincident with the climatic change of the Mid-Cretaceous Hothouse event. Subfamily and tribal relationships within the major families need revision, particularly in Sapindaceae, Rutaceae and Meliaceae. Much of the difficulty in reconstructing relationships at this level may be caused by the prevalence of paralogous loci, particularly in Meliaceae and Rutaceae, that are likely indicative of ancient gene duplication events such as hybridization and polyploidization playing a role in the evolutionary history of these families. This study provides key insights into factors that may affect phylogenetic reconstructions in Sapindales across multiple scales, and provides a state-of-the-art phylogenetic framework for further research.

Acute heat stress amplifies exercise-induced metabolomic perturbations and reveals variation in circulating amino acids in endurance-trained males.

NEW FINDINGS: What is the central question of this study? Whole-body substrate utilisation is altered during exercise in hot environments, characterised by increased glycolytic metabolism: does heat stress alter the serum metabolome in response to high intensity exercise? What are the main finding and its importance? Alongside increases in glycolytic metabolite abundance, circulating amino acid concentrations are reduced following exercise under heat stress. Prior research has overlooked the impact of heat stress on protein metabolism during exercise, raising important practical implications for protein intake recommendations in the heat. ABSTRACT: Using untargeted metabolomics, we aimed to characterise the systemic impact of environmental heat stress during exercise. Twenty-three trained male triathletes ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_2}{\rm{peak}}}}$  = 64.8 ± 9.2 ml kg min-1 ) completed a 30-min exercise test in hot (35°C) and temperate (21°C) conditions. Venous blood samples were collected immediately pre- and post-exercise, and the serum fraction was assessed via untargeted 1 H-NMR metabolomics. Data were analysed via uni- and multivariate analyses to identify differences between conditions. Mean power output was higher in temperate (231 ± 36 W) versus hot (223 ± 31 W) conditions (P < 0.001). Mean heart rate (temperate, 162 ± 10 beats min-1 , hot, 167 ± 9 beats min-1 , P < 0.001), peak core temperature (Trec ), core temperature change (ΔTrec ) (P < 0.001) and peak rating of perceived exertion (P = 0.005) were higher in hot versus temperate conditions. Change in metabolite abundance following exercise revealed distinct clustering following multivariate analysis. Six metabolites increased (2-hydroxyvaleric acid, acetate, alanine, glucarate, glucose, lactate) in hot relative to temperate (P < 0.05) conditions. Leucine and lysine decreased in both conditions but to a greater extent in temperate conditions (P < 0.05). Citrate (P = 0.04) was greater in temperate conditions whilst creatinine decreased in hot conditions only (P > 0.05). Environmental heat stress increased glycolytic metabolite abundance and led to distinct alterations in the circulating amino acid availability, including increased alanine, glutamine, leucine and isoleucine. The data highlight the need for additional exercise nutrition and metabolism research, specifically focusing on protein requirements for exercise under heat stress.

First evidence of ranunculids in Early Cretaceous tropics.

Early Cretaceous floras containing angiosperms were described from several geographic areas, nearly from the Arctic to the Antarctic, and are crucial to understand their evolution and radiation. However, most of these records come from northern mid-latitudes whereas those of lower paleolatitude areas, such as the Crato Fossil Lagerstätte in NE Brazil, are less studied. Here, we describe from this region of northern Gondwanan origin, two fossil-species of eudicots belonging to a new extinct genus Santaniella gen. nov. Together with several vegetative axes and leaves, anatomically well-preserved fruits with seeds and persistent perianth-like organs allowed us to reconstruct its potential affinities with ranunculids, and presumably Ranunculaceae. Previous records putatively assigned to Ranunculales are all from mid-latitudes, and their first unequivocal occurrence in a low-latitude area supports further the hypothesis of a widespread radiation of the earliest diverging eudicot lineage by this early age.

Assessing Anopheles vector species diversity and transmission of malaria in four health districts along the borders of Côte d'Ivoire.

BACKGROUND: Although malaria and Anopheles mosquito vectors are highly prevalent in Côte d'Ivoire, limited data are available to help understand the malaria vector density and transmission dynamics in areas bordering the country. To address this gap, the Anopheles mosquito species diversity, the members of the Anopheles gambiae complex and the transmission of malaria were assessed in four health districts along the borders of Côte d'Ivoire. METHODS: From July 2016 through December 2016 and July 2017 through December 2017, adult Anopheles mosquitoes were collected in four health districts of Côte d'Ivoire (Aboisso, Bloléquin, Odienné and Ouangolodougou) using standardized window exit trap (WET) and pyrethrum knockdown spray collection (PSC) methods. The collected mosquitoes were identified morphologically at species level and the members of the An. gambiae complex were separated using short interspersed nuclear element-based polymerase chain reaction (SINE-PCR). Anopheles gambiae sensu lato (s.l.), Anopheles funestus s.l. and Anopheles nili specimens were analysed for malaria Plasmodium parasite detection using the cytochrome oxidase I gene (COX-I), and malaria prevalence among human population through local Ministry of Health (MoH) statistical yearbooks. RESULTS: A total of 281 female Anopheles were collected in Aboisso, 754 in Bloléquin, 1319 in Odienné and 2443 in Ouangolodougou. Seven Anopheles species were recorded including An. gambiae s.l. (94.8-99.1%) as the main vector, followed by An. funestus s.l. (0.4-4.3%) and An. nili (0-0.7%). Among An. gambiae s.l., Anopheles coluzzii represented the predominant species in Aboisso (89.2%) and Bloléquin (92.2%), while An. gambiae sensu stricto (s.s.) was the major species in Odienné (96.0%) and Ouangolodougou (94.2%). The Plasmodium sporozoite infection rate in An. gambiae s.l. was highest in Odienné (11.0%; n = 100) followed by Bloléquin (7.8%, n = 115), Aboisso (3.1%; n = 65) and Ouangologoudou (2.5%; n = 120). In An. funestus s.l., Plasmodium falciparum sporozoite infection rate was estimated at 6.2% (n = 32) in Bloléquin, 8.7% (n = 23) in Odienné. No An. funestus s.l. specimens were found infected with P. falciparum sporozoite infection in Ouangolodougou and Aboisso. No P. falciparum sporozoite was detected in An. nili specimens in the four health districts. Among the local human populations, malaria incidence was higher in Odienné (39.7%; n = 45,376) and Bloléquin (37.6%; n = 150,205) compared to that in Ouangolodougou (18.3%; n = 131,629) and Aboisso (19.7%; n = 364,585). CONCLUSION: Anopheles vector species diversity, abundance and Plasmodium sporozoite infection were high within the health districts along the borders of the country of Côte d'Ivoire, resulting in high malaria transmission among the local populations. Anopheles gambiae s.l. and An. funestus s.l. were found to be highly infected with Plasmodium in the health districts of Bloléquin and Odienné where higher malaria incidence was observed than the other districts. This study provides important information that can be used to guide Côte d'Ivoire National Malaria Control Programme for vector control decision-making, mainly in districts that are at the country borders.

Mosquito-Associated Viruses and Their Related Mosquitoes in West Africa.

Mosquito-associated viruses (MAVs), including mosquito-specific viruses (MSVs) and mosquito-borne (arbo)viruses (MBVs), are an increasing public, veterinary, and global health concern, and West Africa is projected to be the next front for arboviral diseases. As in-depth knowledge of the ecologies of both western African MAVs and related mosquitoes is still limited, we review available and comprehensive data on their diversity, abundance, and distribution. Data on MAVs' occurrence and related mosquitoes were extracted from peer-reviewed publications. Data on MSVs, and mosquito and vertebrate host ranges are sparse. However, more data are available on MBVs (i.e., dengue, yellow fever, chikungunya, Zika, and Rift Valley fever viruses), detected in wild and domestic animals, and humans, with infections more concentrated in urban areas and areas affected by strong anthropogenic changes. Aedes aegypti, Culex quinquefasciatus, and Aedes albopictus are incriminated as key arbovirus vectors. These findings outline MAV, related mosquitoes, key knowledge gaps, and future research areas. Additionally, these data highlight the need to increase our understanding of MAVs and their impact on host mosquito ecology, to improve our knowledge of arbovirus transmission, and to develop specific strategies and capacities for arboviral disease surveillance, diagnostic, prevention, control, and outbreak responses in West Africa.

Carbohydrate improves exercise capacity but does not affect subcellular lipid droplet morphology, AMPK and p53 signalling in human skeletal muscle.

KEY POINTS: Muscle glycogen and intramuscular triglycerides (IMTG, stored in lipid droplets) are important energy substrates during prolonged exercise. Exercise-induced changes in lipid droplet (LD) morphology (i.e. LD size and number) have not yet been studied under nutritional conditions typically adopted by elite endurance athletes, that is, after carbohydrate (CHO) loading and CHO feeding during exercise. We report for the first time that exercise reduces IMTG content in both central and peripheral regions of type I and IIa fibres, reflective of decreased LD number in both fibre types whereas reductions in LD size were exclusive to type I fibres. Additionally, CHO feeding does not alter subcellular IMTG utilisation, LD morphology or muscle glycogen utilisation in type I or IIa/II fibres. In the absence of alterations to muscle fuel selection, CHO feeding does not attenuate cell signalling pathways with regulatory roles in mitochondrial biogenesis. ABSTRACT: We examined the effects of carbohydrate (CHO) feeding on lipid droplet (LD) morphology, muscle glycogen utilisation and exercise-induced skeletal muscle cell signalling. After a 36 h CHO loading protocol and pre-exercise meal (12 and 2 g kg-1 , respectively), eight trained males ingested 0, 45 or 90 g CHO h-1 during 180 min cycling at lactate threshold followed by an exercise capacity test (150% lactate threshold). Muscle biopsies were obtained pre- and post-completion of submaximal exercise. Exercise decreased (P < 0.01) glycogen concentration to comparable levels (∼700 to 250 mmol kg-1 DW), though utilisation was greater in type I (∼40%) versus type II fibres (∼10%) (P < 0.01). LD content decreased in type I (∼50%) and type IIa fibres (∼30%) (P < 0.01), with greater utilisation in type I fibres (P < 0.01). CHO feeding did not affect glycogen or IMTG utilisation in type I or II fibres (all P > 0.05). Exercise decreased LD number within central and peripheral regions of both type I and IIa fibres, though reduced LD size was exclusive to type I fibres. Exercise induced (all P < 0.05) comparable AMPKThr172 (∼4-fold), p53Ser15 (∼2-fold) and CaMKIIThr268 phosphorylation (∼2-fold) with no effects of CHO feeding (all P > 0.05). CHO increased exercise capacity where 90 g h-1 (233 ± 133 s) > 45 g h-1 (156 ± 66 s; P = 0.06) > 0 g h-1 (108 ± 54 s; P = 0.03). In conditions of high pre-exercise CHO availability, we conclude CHO feeding does not influence exercise-induced changes in LD morphology, glycogen utilisation or cell signalling pathways with regulatory roles in mitochondrial biogenesis.

Exposure to nanoplastics affects the outcome of infectious disease in phytoplankton.

Infectious diseases of humans and wildlife are increasing globally but the contribution of novel artificial anthropogenic entities such as nano-sized plastics to disease dynamics remains unknown. Despite mounting evidence for the adverse effects of nanoplastics (NPs) on single organisms, it is unclear whether and how they affect the interaction between species and thereby lead to ecological harm. In order to incorporate the impact of NP pollution into host-parasite-environment interactions captured in the "disease triangle", we evaluated disease outcomes in the presence of polystyrene NP using an ecologically-relevant host-parasite system consisting of a common planktonic cyanobacterium and its fungal parasite. NP at high concentrations formed hetero-aggregates with phytoplankton and inhibited their growth. This coincided with a significant reduction in infection prevalence, highlighting the close interdependency of host and parasite fitness. Lower intensity of infection in the presence of NP indicates that reduced disease transmission results from the parasite's diminished ability to establish new infections as NP formed aggregates around phytoplankton cells. We propose that NP aggregation on the host's surface acts as a physical barrier to infection and, by reducing host light harvesting, may also hamper parasite chemotaxis. These results demonstrate that the consequences of NP pollution go well beyond toxic effects at the individual level and modulate the intensity of species interactions, thereby potentially eliciting diverse cascading effects on ecosystem functioning.

How Thermal Aging Affects Ignition and Combustion Properties of Reactive Al/CuO Nanolaminates: A Joint Theoretical/Experimental Study.

The paper reports a joint experimental/theoretical study on the aging of reactive Al/CuO nanolaminates, investigating both structural modifications and combustion properties of aged systems. We first show theoretically that the long-term storage (over several decades) in ambient temperature marginally affects nanolaminates structural properties with an increase in an interfacial layer of only 0.3 nm after 30 years. Then, we observe that the first thermal aging step occurs after 14 days at 200 °C, which corresponds to the replacement of the natural Al/CuO interfaces by a proper ~11 nm thick amorphous alumina. We show that this aging step does impact the nanolaminates structure, leading, for thin bilayer thicknesses, to a substantial loss of the energetic reservoir: considering a stoichiometric Al/CuO stack, the heat of reaction can be reduced by 6-40% depending on the bilayer thickness ranging from 150 nm (40%) to 1 µm (6%). The impact of such thermal aging (14 days at 200 °C) and interfacial modification on the initiation and combustion properties have been evaluated experimentally and theoretically. Varying Al to CuO ratio of nanolaminates from 1 to 3, we show that ignition time of aged systems does not increase over 10% at initiation power densities superior to 15 W·mm-2. In contrast, burn rate can be greatly impacted depending on the bilayer thickness: annealing a stoichiometric nanolaminates with a bilayer thickness of 300 nm at 200 °C for 14 days lowers its burn rate by ~25%, whereas annealing a fuel rich nanolaminates with the same bilayer thickness under the same thermal conditions leads to a burn rate decrease of 20%. When bilayer thickness is greater than 500 nm, the burn rate is not really affected by the thermal aging. Finally, this paper also proposes a time-temperature diagram to perform accelerated thermal aging.

Reversible Soft Mechanochemical Control of Biaryl Conformations through Crosslinking in a 3D Macromolecular Network.

Tuning the dihedral angle (DA) of axially chiral compounds can impact biological activity, catalyst efficiency, molecular motor performance, or chiroptical properties. Herein, we report gradual, controlled, and reversible changes in molecular conformation of a covalently linked binaphthyl moiety within a 3D polymeric network by application of a macroscopic stretching force. We managed direct observation of DA changes by measuring the circular dichroism signal of an optically pure BINOL-crosslinked elastomer network. Stretching the elastomer resulted in a widening of the DA between naphthyl rings when the BINOL was doubly grafted to the elastomer network; no effect was observed when a single naphthyl ring of the BINOL was grafted to the elastomer network. We have determined that ca. 170 % extension of the elastomers led to the transfer of a mechanical force to the BINOL moiety of 2.5 kcal mol-1 Å-1 (ca. 175 pN) in magnitude and results in the opening of the DA of BINOL up to 130°.

Graded reductions in pre-exercise glycogen concentration do not augment exercise-induced nuclear AMPK and PGC-1α protein content in human muscle.

NEW FINDINGS: What is the central question of this study? What is the absolute level of pre-exercise glycogen concentration required to augment the exercise-induced signalling response regulating mitochondrial biogenesis? What is the main finding and its importance? Commencing high-intensity endurance exercise with reduced pre-exercise muscle glycogen concentrations confers no additional benefit to the early signalling responses that regulate mitochondrial biogenesis. ABSTRACT: We examined the effects of graded muscle glycogen on the subcellular location and protein content of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and mRNA expression of genes associated with the regulation of mitochondrial biogenesis and substrate utilisation in human skeletal muscle. In a repeated measures design, eight trained male cyclists completed acute high-intensity interval (HIT) cycling (8 × 5 min at 80% peak power output) with graded concentrations of pre-exercise muscle glycogen. Following initial glycogen-depleting exercise, subjects ingested  2 g kg-1  (L-CHO), 6 g kg-1 (M-CHO) or 14 g kg-1 (H-CHO) of carbohydrate during a 36 h period, such that exercise was commenced with graded (P < 0.05) muscle glycogen concentrations (mmol (kg dw)-1 : H-CHO, 531 ± 83; M-CHO, 332 ± 88; L-CHO, 208 ± 79). Exercise depleted muscle glycogen to <300 mmol (kg dw)-1 in all trials (mmol (kg dw)-1 : H-CHO, 270 ± 88; M-CHO, 173 ± 74; L-CHO, 100 ± 42) and induced comparable increases in nuclear AMPK protein content (∼2-fold) and PGC-1α (∼5-fold), p53 (∼1.5-fold) and carnitine palmitoyltransferase 1 (∼2-fold) mRNA between trials (all P < 0.05). The magnitude of increase in PGC-1α mRNA was also positively correlated with post-exercise glycogen concentration (P < 0.05). In contrast, neither exercise nor carbohydrate availability affected the subcellular location of PGC-1α protein or PPAR, SCO2, SIRT1, DRP1, MFN2 or CD36 mRNA. Using a sleep-low, train-low model with a high-intensity endurance exercise stimulus, we conclude that pre-exercise muscle glycogen does not modulate skeletal muscle cell signalling.

Low transmission of Wuchereria bancrofti in cross-border districts of Côte d'Ivoire: A great step towards lymphatic filariasis elimination in West Africa.

BACKGROUND: Lymphatic filariasis (LF) is widely endemic in Côte d'Ivoire, and elimination as public health problem (EPHP) is based on annual mass drug administration (MDA) using ivermectin and albendazole. To guide EPHP efforts, we evaluated Wuchereria bancrofti infection indices among humans, and mosquito vectors after four rounds of MDA in four cross-border health districts of Côte d'Ivoire. METHODOLOGY: We monitored people and mosquitoes for W. bancrofti infections in the cross-border health districts of Aboisso, Bloléquin, Odienné and Ouangolodougou, Côte d'Ivoire. W. bancrofti circulating filarial antigen (CFA) was identified using filariasis test strips, and antigen-positive individuals were screened for microfilaremia. Moreover, filarial mosquito vectors were sampled using window exit traps and pyrethrum sprays, and identified morphologically at species level. Anopheles gambiae s.l. and Culex quinquefasciatus females were analyzed for W. bancrofti infection using polymerase chain reaction (PCR) technique. PRINCIPAL FINDINGS: Overall, we found a substantial decline in W. bancrofti infection indices after four rounds of MDA compared to pre-MDA baseline data. CFA prevalence fell from 3.38-5.50% during pre-MDA to 0.00-1.53% after MDA interventions. No subjects had detectable levels of CFA in Ouangolodougou. Moreover, post-MDA CFA prevalence was very low, and below the 1% elimination threshold in Aboisso (0.19%) and Odienné (0.49%). Conversely, CFA prevalence remained above 1% in Bloléquin (1.53%). W. bancrofti microfilariae (Mf) were not found in Aboisso, Bloléquin, and Ouangolodougou, except for Odienné with low prevalence (0.16%; n = 613) and microfilaremia of 32.0 Mf/mL. No An. gambiae s.l. and Cx. quinquefasciatus pools were infected with W. bancrofti in Bloléquin and Ouangolodougou, while they exhibited low infection rates in Aboisso (1% and 0.07%), and Odienné (0.08% and 0.08%), respectively. CONCLUSIONS: In cross-border areas of Côte d'Ivoire, LF infection indices in humans and mosquito vectors substantially declined after four rounds of MDA. CFA prevalence fell under the World Health Organization (WHO)-established threshold (1%) in Aboisso, Ouangolodougou and Odienné. Moreover, W. bancrofti prevalence in mosquitoes was lower than WHO-established threshold (2%) in all areas. This might suggest the interruption of W. bancrofti transmission, and possible MDA cessation. However, a formal transmission assessment survey (TAS) and molecular xenomonitoring in mosquito vectors should be implemented before eventual MDA cessation. However, MDA should pursue in Bloléquin where W. bancrofti infection prevalence remained above 1%. Our results provided important ramifications for LF control efforts towards EPHP in Côte d'Ivoire.