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Despite recent progress toward elimination, persisting malaria transmission in the Americas continues to pose a risk for infection to 120 million persons (1). The Amazon Basin, spanning 9 countries of [...]

Abstract Background Physical activity and sleep are established modifiable lifestyle factors, but the optimal time of the day of these behaviours for health is unknown. This study examined the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality. Methods This prospective cohort study included 6,673 participants who have attended the accelerometer assessment in the 2011–2014 National Health and Nutrition Examination Surveys (NHANES). Diurnal patterns of accelerometer-measured physical activity and sleep were identified using K-means clustering analysis. All-cause mortality was ascertained from the accelerometer measurement to December 31, 2019 (median follow-up 6.8 years). Survey-weighted Cox proportional hazard models were performed to estimate the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality. Results Diurnal patterns identified were: early-morning (32.4%), midday (42.5%), and late-afternoon (25.1%) for physical activity; and irregular sleep (37.4%), morning lark (33.6%), and night owl (29.0%) for sleep. After adjusting for volume of physical activity, sleep duration and other potential covariates, the early-morning physical activity pattern (hazard ratio 1.36, 95% confidence interval 1.13–1.64) and irregular sleep pattern (1.42, 1.01–1.99) were independently associated with higher risk of all-cause mortality, compared with midday physical activity and morning lark sleep patterns, respectively. In addition, participants with the combined pattern of early-morning physical activity and irregular sleep had higher risk of all-cause mortality compared to those with midday physical activity combined with a morning lark sleep pattern (1.92, 1.33–2.78). Several sociodemographic differences were observed in the strength of these associations. Conclusions Wearable activity-rest monitoring data showed that peak physical activity in the early morning and irregular sleep diurnal patterns are associated with increased mortality risk, and the combination of these patterns further exaggerated the risk. Public health program should acknowledge that the diurnal patterns of physical activity and sleep, in addition to their duration and frequency, may play a crucial role in lifestyle-based health promotion and management strategies.

Malaria is increasingly diagnosed in urban centers across the Amazon Basin. In this study, we combined repeated prevalence surveys over a 4-year period of a household-based random sample of 2,774 persons with parasite genotyping to investigate the epidemiology of malaria in Mâncio Lima, the main urban transmission hotspot in Amazonian Brazil. We found that most malarial infections were asymptomatic and undetected by point-of-care microscopy. Our findings indicate that as malaria transmission decreases, the detection threshold of microscopy rises, resulting in more missed infections despite similar parasite densities estimated by molecular methods. We identified genetically highly diverse populations of Plasmodium vivax and P. falciparum in the region; occasional shared lineages between urban and rural residents suggest cross-boundary propagation. The prevalence of low-density and asymptomatic infections poses a significant challenge for routine surveillance and the effectiveness of malaria control and elimination strategies in urbanized areas with readily accessible laboratory facilities.

ABSTRACT: Cattle lameness remains a significant concern, causing economic losses and compromising animal welfare. Claw horn lesions have been identified as a major cause of lameness in dairy cows, but their correlation with high-energy diets and ruminal acidosis remains unclear. Hence, the primary objective of this study was to assess the effects of a high-starch diet and a conventional diet on the rumen environment, acute-phase proteins, and metabolic alterations, with a particular focus on insulin resistance and the consequent implications for the histology of the hooves in Holstein steers. A total of 16 animals were divided into the high-starch (HS; 37% starch) and conventional (CON; 16.8% starch) groups. Glucose tolerance tests (GTT), blood analyses, rumen fluid analyses, and histological evaluations of the hoof tissue were conducted over a 102-d experimental period. The HS group showed a lower ruminal pH than the CON group, and with values indicating SARA. The plasma glucose and IGF-1 concentrations were higher in the HS group, suggesting an anabolic state. Both groups exhibited an increase in the insulin area under the curve (AUC) after the GTT on d 102. Histological analysis of the hooves showed a reduction in the length and width of the epidermal lamella in both groups. We found a significant negative correlation between the insulin AUC and the length and width of the epidermal lamella. Because both groups were similarly affected, the hypothesis that histological alterations were caused by the experimental diets still needs confirmation. Additionally, the development of SARA was not essential for the observed histological changes in the hoof. Further studies are warranted to thoroughly investigate the role of insulin and IGF-1 imbalances in claw health.

Abstract Agricultural production assessments are crucial for formulating strategies for closing yield gaps and enhancing production efficiencies. While in situ crop yield measurements can provide valuable and accurate information, such approaches are costly and lack scalability for large-scale assessments. Therefore, crop modeling and remote sensing (RS) technologies are essential for assessing crop conditions and predicting yields at larger scales. In this study, we combined RS and a crop growth model to assess phenology, evapotranspiration (ET), and yield dynamics at grid and sub-county scales in Kenya. We synthesized RS information from the Food and Agriculture Organization (FAO) Water Productivity Open-access portal (WaPOR) to retrieve sowing date information for driving the model simulations. The findings showed that grid-scale management information and progressive crop growth could be accurately derived, reducing the model output uncertainties. Performance assessment of the modeled phenology yielded satisfactory accuracies at the sub-county scale during two representative seasons. The agreement between the simulated ET and yield was improved with the combined RS-crop model approach relative to the crop model only, demonstrating the value of additional large-scale RS information. The proposed approach supports crop yield estimation in data-scarce environments and provides valuable insights for agricultural resource management enabling countermeasures, especially when shortages are perceived in advance, thus enhancing agricultural production.

Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)-based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.

Malaria is among the world's deadliest diseases, predominantly affecting Sub-Saharan Africa and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae, as well as other anophelines, is among the most effective methods to control disease spread. Here, we develop a genetic population suppression system termed Ifegenia (inherited female elimination by genetically encoded nucleases to interrupt alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless (fle), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we demonstrate that Ifegenia males remain reproductively viable and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of nonbiting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system.

The creation of vacancies and/or pores into two‐dimensional materials, like graphene and MXenes, has shown to increase their performance for sustainable applications. However, a simple and affordable method with controlled and tailorable vacancy concentration and/or pores size remains challenging. Herein, a simple and reproducible method is presented for controlled synthesis of Mo1.74CTz MXene with randomly distributed vacancies and pores, obtained from selective etching of both Ga and Cr in the Cr‐alloyed MAX‐phase like precursor Mo1.74Cr0.26Ga2C. Structural and compositional analysis of the 3D alloy show ≈13% Cr on the metal site, homogeneously distributed between different particles and within the atomic structure. After etching, it translates to Mo1.74CTz MXene, exhibiting defect‐rich sheets. Notably, the incorporation of Cr facilitates a shorter etching time with an improved yield compared to Mo2CTz. The Mo1.74CTz MXene displays excellent electrochemical properties, almost doubling the capacitance values (1152 F cm−3 and 297 F g−1 at 2 mV s−1 scan rate), compared to its pristine counterpart Mo2CTz. The presented method and obtained results suggest defect engineering of MXenes through precursor alloying as a pathway that can be generalized to other phases, to further improve their properties for various applications.

Abstract: This study aimed to estimate the population-based Parkinson disease prevalence, and to explore potentially associated factors and conditions. A population-based survey was conducted in Northern Peru. Symptoms compatible with Parkinson’s were defined using a validated Spanish questionnaire (≥ 42 points suggest Parkinson’s). Potential factors (e.g., age, sex, etc.) and clinical conditions (e.g., depressive symptoms, perceived stress, etc.) associated with Parkinson’s were assessed. In total, 1,609 subjects were included, mean age of participants was 48.2 (SD: 10.6), and 810 (50.3%) were women. Parkinson’s prevalence was 1.6% (95%CI: 1.0; 2.4). Those aged ≥ 55 years, and those who reported using wood as fuel for household cooking had a Parkinson’s prevalence from 3.5 to 4 times greater than those who did not. The presence of depressive symptoms, anxiety symptoms, perceived stress, poor sleep quality, and cognitive impairment was more common among those with Parkinson’s, and quality of life in these participants was lower than those without Parkinson’s. In conclusion, 1.6% of the population shows symptoms compatible with Parkinson’s. Age and use of wood for household cooking were factors associated with Parkinson’s. Several mental health conditions and lower quality of life were more frequent among those with Parkinson’s. Appropriate strategies are required to detect, prevent, and manage Parkinson’s cases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a worldwide health epidemic with a global occurrence of approximately 30%. The pathogenesis of MASLD is a complex, multisystem disorder driven by multiple factors, including genetics, lifestyle, and the environment. Patient heterogeneity presents challenges in developing MASLD therapeutics, creating patient cohorts for clinical trials, and optimizing therapeutic strategies for specific patient cohorts. Implementing pre-clinical experimental models for drug development creates a significant challenge as simple in vitro systems and animal models do not fully recapitulate critical steps in the pathogenesis and the complexity of MASLD progression. To address this, we implemented a precision medicine strategy that couples the use of our liver acinus microphysiology system (LAMPS) constructed with patient-derived primary cells. We investigated the MASLD-associated genetic variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 (I148M variant) in primary hepatocytes as it is associated with MASLD progression. We constructed the LAMPS with genotyped wild-type and variant PNPLA3 hepatocytes, together with key non-parenchymal cells, and quantified the reproducibility of the model. We altered media components to mimic blood chemistries, including insulin, glucose, free fatty acids, and immune-activating molecules to reflect normal fasting (NF), early metabolic syndrome (EMS), and late metabolic syndrome (LMS) conditions. Finally, we investigated the response to treatment with resmetirom, an approved drug for metabolic syndrome-associated steatohepatitis (MASH), the progressive form of MASLD. This study, using primary cells, serves as a benchmark for studies using “patient biomimetic twins” constructed with patient induced pluripotent stem cell (iPSC)-derived liver cells using a panel of reproducible metrics. We observed increased steatosis, immune activation, stellate cell activation, and secretion of pro-fibrotic markers in the PNPLA3 GG variant compared to the wild-type CC LAMPS, consistent with the clinical characterization of this variant. We also observed greater resmetirom efficacy in the PNPLA3 wild-type CC LAMPS compared to the GG variant in multiple MASLD metrics, including steatosis, stellate cell activation, and the secretion of pro-fibrotic markers. In conclusion, our study demonstrates the capability of the LAMPS platform for the development of MASLD precision therapeutics, enrichment of patient cohorts for clinical trials, and optimization of therapeutic strategies for patient subgroups with different clinical traits and disease stages.

ABSTRACT Objective Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by metabolic, reproductive, and psychological manifestations. Growth and differentiation factor 15 (GDF-15) is a cytokine associated with metabolic and inflammatory disorders. Metformin is commonly used for the treatment of PCOS. We investigated the relationship between GDF-15 levels and PCOS, the effect of metformin on GDF-15 levels, and potential biologic pathways related to GDF-15. Subjects and methods The study included 35 women with PCOS and 32 women without PCOS (controls). Both groups were compared in terms of GDF-15 levels. Additional analysis was conducted on samples from 22 women with PCOS who were treated with either metformin (n = 7) or placebo (n = 15), retrieved from a previous randomized, controlled trial. Levels of GDF-15 were measured using MILLIPLEX. The biologic pathways related to GDF-15 were evaluated using the databases STRING, SIGNOR, and Pathway Commons. The statistical analysis was conducted using the software SPSS. Results Levels of GDF-15 were higher in the PCOS group compared with the non-PCOS group (p = 0.039). Among women with PCOS, GDF-15 levels were higher in those treated with metformin compared with placebo (p = 0.007). The proteins related to GDF-15 overlapped between the databases, and a significant interaction was found between GDF-15 and proteins related to PCOS and its complications, including those related to estrogen response, oxidative stress, ovarian infertility, interleukin (IL)-18, IL-4, the ratio of advanced glycation end products to their receptor (AGE/RAGE), leptin, transforming growth factor beta (TGF-β), adipogenesis, and insulin. Conclusion The findings of the present study suggest a relationship between GDF-15 and PCOS and a potential increase in GDF-15 levels with metformin treatment. An additional finding was that GDF-15 could be involved in biologic pathways related to PCOS complications.

Background: Postoperative sore throat is one of the main postoperative complaints in patients undergoing tonsillectomy. As the primary outcome, we aimed to determine whether endotracheal tube cuffs filled with alkalinized lidocaine are associated with a lower incidence of postoperative sore throat and anesthesia emergence phenomena in children undergoing tonsillectomy or adenotonsillectomy. We also assessed the potential additional benefits of IV dexamethasone in reducing postoperative laryngotracheal morbidity. Methods: This is a clinical prospective, randomized, controlled trial. Patients were randomly allocated to one of four groups, as follows: air – endotracheal tube cuff filled with air; air/dex – endotracheal tube cuff filled with air and intravenous dexamethasone; lido – endotracheal tube cuff filled with alkalinized lidocaine; and lido/dex – endotracheal tube cuff filled with alkalinized lidocaine and intravenous dexamethasone. Perioperative hemodynamic parameters and the incidence of postoperative nausea and vomiting, coughing and hoarseness were recorded. Postoperative sore throat was assessed in the postanesthetic care unit and 24 hours post tracheal extubation. Results: In total, 154 children aged 4–12 years, ASA physical status I or II, undergoing general anesthesia for elective tonsillectomy and adenotonsillectomy, were assessed for postoperative sore throat in this study. The incidence of postoperative sore throat 24 hours after tracheal extubation was significantly lower in the lido/dex group compared to groups air and air/dex (p = 0.01). However, no additional reduction in these symptoms was observed from the intravenous administration of dexamethasone when comparing the lido and lido/dex groups. Similarly, there were no differences among groups regarding perioperative hemodynamic variables or postoperative nausea and vomiting, coughing, and hoarseness during the study period. Conclusion: Intracuff alkalinized lidocaine, associated with intravenous dexamethasone, might be effective in reducing sore throat 24 hours post-tonsillectomy or adenotonsillectomy in children when compared to the use of air as the cuff insufflation media.

Background The prevalence of overweight and obesity has increased fastest in low- and middle-income countries in the last decades. Together with this rising prevalence, pharmacological and surgical interventions for obesity have emerged. How many people need these treatments is unknown. We quantified the prevalence of people in need of pharmacological and surgical treatment for obesity in Peru between 2014 and 2022. Methods Repeated cross-sectional analysis of national health surveys in Peru was conducted. Eligibility for pharmacological treatment for obesity was: body mass index (BMI) ≥30 kg/m2 or BMI ≥27 kg/m2 alongside type 2 diabetes or hypertension (self-reported). Eligibility for bariatric surgery were BMI ≥40 kg/m2 or BMI between 35 to 39.9 kg/m2 linked to weight-related health problems. We used Poisson regressions to identify associated factors with eligibility for obesity management. Results Across years, 260,131 people (mean age 44.0 and 54.5% were women) were studied, 66,629 (27.7%; 95% CI: 27.4% - 28.1%) were eligible for obesity medication, and 5,263 (2.5%; 95% CI: 2.4% - 2.6%) were eligible for bariatric surgery. Female sex, older age, higher socioeconomic level and study year were associated with higher probability of eligibility for both obesity medication and bariatric surgery. Conclusions Eligibility for obesity management has increased over time in Peru. There is a need to strengthen policies to tackle overweight and obesity in Peru, acknowledging that some individuals may benefit from pharmacological and surgical interventions.

ABSTRACT The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others.

The antifouling booster biocides are frequently studied for toxic effects on the aquatic ecosystems. The present investigation proposes passive silicone rubber samplers as a collection method for biocides, once these methods can concentrate substances in aqueous matrices at very low levels. Through the passive sampler-water partition coefficient (Ksw) and the analyte chemical nature, we can optimize their extraction from the membrane to apply in the sample medium. We used the co-solvent method to determine the Ksw of three third-generation antifouling biocides, chlorothalonil, dichlofluanid, and dichlorooctylisothiazolinone (DCOIT), with log Ksw = 2.24, 4.01, and 2.38, respectively. Improving extraction also led to a recovery range higher than 70%, determinations were carried out by gas chromatography with an electron capture detector. Biocides concentration in seawater samples from Itaqui port (São Marcos Bay, northern Brazil) ranged from 0.058 to 0.72 µg L-1 for chlorothalonil, 0.001 to 0.008 µg L-1 for dichlofluanid, and 0.018 to 0.64 µg L-1 for DCOIT.