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Mental fatigue is a psychophysiological state that adversely impacts performance in cognitive tasks, increasing risk of occupational hazards. Given its manifestation as a conscious sensation, it is often measured through subjective self-report. However, subjective measures are not always true measurements of objective fatigue. In this study, we investigated the relationship between objective and subjective fatigue measurements with the preventive AccessPoint fatigue assay in Chilean mine workers. Subjective fatigue was measured through the Samn-Perelli scale, objective fatigue through a neurocognitive reaction time task. We found that objective and subjective fatigue do not correlate (-0.03 correlation coefficient, p < 0.001). Moreover, severe fatigue cases often displayed absence of subjective fatigue coupled with worse cognitive performance, a phenomenon we denominated Perceptual Blindness to fatigue. These findings highlight the need for objective fatigue measurements, particularly in high-risk occupational settings such as mining. Our results open new avenues for researching mechanisms underlying fatigue perception and its implications for occupational health and safety., Competing Interests: HP, HA, KV, and CJ were employed by AlertPlus S.A. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Purto, Anabalon, Vargas, Jara D and de la Vega.)

Background: The venom of Bothrops lanceolatus, a viperid species endemic to the Lesser Antillean Island of Martinique, induces thrombosis in a number of patients. Previous clinical observations indicate that thrombotic events are more common in patients bitten by juvenile specimens. There is a need to develop an experimental model of this effect in order to study the mechanisms involved., Methodology/principal Findings: The venoms of juvenile and adult specimens of B. lanceolatus were compared by (a) describing their proteome, (b) assessing their ability to induce thrombosis in a mouse model, and (c) evaluating their in vitro procoagulant activity and in vivo hemostasis alterations. Venom proteomes of juvenile and adult specimens were highly similar, albeit showing some differences. When injected by the intraperitoneal (i.p.) route, the venom of juvenile specimens induced the formation of abundant thrombi in the pulmonary vasculature, whereas this effect was less frequent in the case of adult venom. Thrombosis was not abrogated by the metalloproteinase inhibitor Batimastat. Both venoms showed a weak in vitro procoagulant effect on citrated mouse plasma and bovine fibrinogen. When administered intravenously (i.v.) venoms did not affect classical clotting tests (prothrombin time and activated partial thromboplastin time) but caused a partial drop in fibrinogen concentration. The venom of juvenile specimens induced partial alterations in some rotational thromboelastometry parameters after i.v. injection. When venoms were administered i.p., only minor alterations in classical clotting tests were observed with juvenile venom, and no changes occurred for either venom in rotational thromboelastometry parameters. Both juvenile and adult venoms induced a marked thrombocytopenia after i.p. injection., Conclusions/significance: An experimental model of the thrombotic effect induced by B. lanceolatus venom was developed. This effect is more pronounced in the case of venom of juvenile specimens, despite the observation that juvenile and adult venom proteomes are similar. Adult and juvenile venoms do not induce a consumption coagulopathy characteristic of other Bothrops sp venoms. Both venoms induce a conspicuous thrombocytopenia. This experimental model reproduces the main clinical findings described in these envenomings and should be useful to understand the mechanisms of the thrombotic effect., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rucavado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Extensive research has shown that breastfeeding offers many benefits to children, including advantages in lifelong health, physical development, cognitive function, behavior, and brain development, compared to those not breastfed. In the Dominican Republic, the prevalence of exclusive breastfeeding among infants aged 0-6 months remains low, and the lack of a surveillance system has made it challenging to measure the impact of breastfeeding on early childhood development (ECD). This study aims to address the effect of ever breastfeeding on ECD. We conducted secondary data analysis from the Dominican System for Measuring Early Childhood Development (SIMEDID), a screening tool adapted and validated to the Dominican context that measures four areas of development: gross-motor, fine-motor, language, and socioemotional development. The data from SIMEDID can be cross-analyzed with other datasets generated by the National Institute for Early Childhood Comprehensive Care (INAIPI) that include information about breastfeeding. The children were evaluated during the standardization study of SIMEDID. To determine the breastfeeding impact, we: 1) conducted an analysis of covariance using ECD scores as dependent variables and ever breastfed as the independent variable, with age and sex as covariates (previously confirmed with an analysis of variance indicating the relevance of age and sex at birth in ECD); 2) analyzed the relative risk (RR) of developmental delay by breastfeeding status. We studied a sample of 699 Dominican children aged 12-36 months who receive services at INAIPI (the government institution responsible for administering comprehensive early childhood services). The results show that ever breastfed children had higher scores in overall ECD than those who were not; higher scores in language and fine motor development primarily drove this effect. The never breastfed group had a greater risk of developmental delay in fine motor and socioemotional development. These findings underscore the importance of promoting and supporting breastfeeding to improve child neurodevelopmental outcomes. This is particularly relevant in low-resource settings, where mothers may need additional support. Moreover, the study's results provide evidence of SIMEDID's validation, which can help inform future research and evidence-based decision-making toward optimal ECD in similar contexts., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

For understanding a chemical compound's mechanism of action and its side effects, as well as for drug discovery, it is crucial to predict its possible protein targets. This study examines 15 developed target-centric models (TCM) employing different molecular descriptions and machine learning algorithms. They were contrasted with 17 third-party models implemented as web tools (WTCM). In both sets of models, consensus strategies were implemented as potential improvement over individual predictions. The findings indicate that TCM reach f1-score values greater than 0.8. Comparing both approaches, the best TCM achieves values of 0.75, 0.61, 0.25 and 0.38 for true positive/negative rates (TPR, TNR) and false negative/positive rates (FNR, FPR); outperforming the best WTCM. Moreover, the consensus strategy proves to have the most relevant results in the top 20 % of target profiles. TCM consensus reach TPR and FNR values of 0.98 and 0; while on WTCM reach values of 0.75 and 0.24. The implemented computational tool with the TCM and their consensus strategy at: https://bioquimio.udla.edu.ec/tidentification01/ . Scientific Contribution: We compare and discuss the performances of 17 public compound-target interaction prediction models and 15 new constructions. We also explore a compound-target interaction prioritization strategy using a consensus approach, and we analyzed the challenging involved in interactions modeling., (© 2024. The Author(s).)

Bifidobacterium adolescentis iVS-1 is a human-isolated strain known to possess several probiotic properties. Here, its genome was completely sequenced to examine genes associated with lactose metabolism and other potentially beneficial traits, such as the production of folate and gamma-aminobutyric acid (GABA)., Competing Interests: All authors are affiliated with Synbiotic Health, Inc. which supplied the funding for this study. T.A.A. and Z.T.L. are coinventors on a patent application (PCT/US23/61868) relating to iVS-1 and lactose digestion.

Recent advances in synthetic methodologies for selective, oxidative transformations using Bobbitt's salt (4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate, 1) and its stable organic nitroxide counterpart ACT (4-acetamidoTEMPO, 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl, 2) have led to increased applications across a broad array of disciplines. Current applications and mechanistic understanding of these metal-free, environmentally benign, and easily accessible organic oxidants now span well-beyond the seminal use of 1 and 2 in selective alcohol oxidations. New synthetic methodologies for the oxidation of alcohols, ethers, amines, thiols, C-H bonds and other functional groups with 1 and 2 along with the field's current mechanistic understandings of these processes are presented alongside our contributions in this area. Exciting new areas harnessing the unique properties of these oxidants include: applications to drug discovery and natural product total synthesis, the development of new electrocatalytic methods for depolymerization of lignin and modification of other biopolymers, in vitro and in vivo nucleoside modifications, applications in supramolecular catalysis, the synthesis of new polymers and materials, enhancements in the design of organic redox flow batteries, uses in organic fuel cells, applications and advancements in energy storage, the development of electrochemical sensors, and the production of renewable fuels.

Venom-induced consumption coagulopathy and thrombocytopenia are common and potentially severe manifestations of viperid snakebite envenoming since they contribute to local and systemic hemorrhage. Therefore, the assessment of the efficacy of antivenoms to neutralize coagulopathic and thrombocytopenic toxins should be part of the preclinical evaluation of these drugs. To evaluate the efficacy of the polyvalent (Crotalinae) antivenom produced in Costa Rica, in this study we have used a mouse model of coagulopathy and thrombocytopenia induced by the venom of Bothrops asper, based on the bolus intravenous (i.v.) injection of venom. When venom and antivenom were incubated before injection, or when antivenom was administered i.v. immediately after venom injection, venom-induced hemostatic alterations were largely abrogated. We also studied the recovery rate of clotting parameters in conditions where antivenom was administered when mice were coagulopathic. Some parameters recovered more rapidly in antivenom-treated mice than in control envenomed animals, but others showed a spontaneous recovery without antivenom. This is due to a rapid clearance of plasma venom levels in these experimental conditions. This implies that models based on the bolus i.v. injection of venom have limitations for assessing the effect of antivenom in the recovery of clotting alterations once coagulopathy has developed. It is suggested that alternative models should be developed based on a slower systemic absorption of venom. Overall, our findings provide a protocol for the preclinical evaluation of antivenoms and demonstrate that the polyvalent antivenom is effective in neutralizing the toxins of B. asper venom responsible for coagulopathy and thrombocytopenia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marilla Lamela Méndez works for Capris S.A., which distributes equipment and reagents for rotational thromboelastometry analysis.Erika Camacho, Alexandra Rucavado, Teresa Escalante, Mariángela Vargas, Álvaro Segura and José María Gutiérrez work at Instituto Clodomiro Picado, Universidad de Costa Rica, where the antivenom used in this study is manufactured., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Environmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats in the Neotropics: a region that supports over half of the world's species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem's ability to support biodiversity, and ultimately, global health. We present the largest database on Neotropical bird Hg concentrations (n = 2316) and establish exposure baselines for 322 bird species spanning nine countries across Central America, South America, and the West Indies. Patterns of avian Hg exposure in the Neotropics broadly align with those in temperate regions: consistent bioaccumulation across functional groups and high spatiotemporal variation. Bird species occupying higher trophic positions and aquatic habitats exhibited elevated Hg concentrations that have been previously associated with reductions in reproductive success. Notably, bird Hg concentrations were over four times higher at sites impacted by ASGM activities and differed by season for certain trophic niches. We developed this synthesis via a collaborative research network, the Tropical Research for Avian Conservation and Ecotoxicology (TRACE) Initiative, which exemplifies inclusive, equitable, and international data-sharing. While our findings signal an urgent need to assess sampling biases, mechanisms, and consequences of Hg exposure to tropical avian communities, the TRACE Initiative provides a meaningful framework to achieve such goals. Ultimately, our collective efforts support and inform local, scientific, and government entities, including Parties of the United Nations Minamata Convention on Mercury, as we continue working together to understand how Hg pollution impacts biodiversity conservation, ecosystem function, and public health in the tropics., (© 2023. The Author(s).)

Background: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is an X-linked disorder affecting over 400 million people worldwide. Individuals with molecular variants associated with reduced enzymatic activity are susceptible to oxidative stress in red blood cells, thereby increasing the risk of pathophysiological conditions and toxicity to anti-malarial treatments. Globally, the prevalence of G6PDd varies among populations. Accordingly, this study aims to characterize G6PDd distribution within the Ecuadorian population and to describe the spatial distribution of reported malaria cases., Methods: Molecular variants associated with G6PDd were genotyped in 581 individuals from Afro-Ecuadorian, Indigenous, Mestizo, and Montubio ethnic groups. Additionally, spatial analysis was conducted to identify significant malaria clusters with high incidence rates across Ecuador, using data collected from 2010 to 2021., Results: The A- c.202G > A and A- c.968T > C variants underpin the genetic basis of G6PDd in the studied population. The overall prevalence of G6PDd was 4.6% in the entire population. However, this frequency increased to 19.2% among Afro-Ecuadorian people. Spatial analysis revealed 12 malaria clusters, primarily located in the north of the country and its Amazon region, with relative risks of infection of 2.02 to 87.88., Conclusions: The findings of this study hold significant implications for public health interventions, treatment strategies, and targeted efforts to mitigate the burden of malaria in Ecuador. The high prevalence of G6PDd among Afro-Ecuadorian groups in the northern endemic areas necessitates the development of comprehensive malaria eradication strategies tailored to this geographical region., (© 2023. The Author(s).)

Entomological research studies on mosquito vector biology, vector competence, insecticide resistance, dispersal, and survival (using mark-release-recapture techniques) often rely on laboratory-reared mosquito colonies to produce large numbers of consistently reared, aged, and sized mosquitoes. We developed a low-cost blood feeding apparatus that supports temperatures consistent with warm blooded animals, using commonly available materials found in low resource environments. We compare our system ("Caserotek") to Hemotek and glass/membrane feeding methods. Two experiments were conducted with Aedes aegypti (Linnaeus 1762) and one with Anopheles darlingi (Root 1926) (Diptera: Culicidae); 3 replicates were conducted for each experiment. Aedes aegypti female mosquitoes were provided chicken blood once per week for 30 min (Experiment #1) for 14 days or 1 hour (Experiment #2) for 21 days. Anopheles darlingi were fed once for 1 hour (Experiment #3). Blood-feeding rates, survival rates, and egg production were calculated across replicates. Caserotek had a significantly higher 30-min engorgement rate (91.1%) than Hemotek (47.7%), and the glass feeder (29.3%) whereas for 1-hour feeding, Hemotek had a significantly lower engorgement rate than either of the other two devices (78% versus 91%). Thirty-day survival was similar among the feeding devices, ranging from 86% to 99%. Mean egg production was highest for the Caserotek feeder (32 eggs per female) compared to the glass feeder and Hemotek device (21-22 eggs per female). Our new artificial feeding system had significantly higher blood feeding rates than for more expensive artificial systems and was equivalent to other fitness parameters. Caserotek only requires the ability to boil water to maintain blood temperatures using a Styrofoam liner. It can be easily scaled up to large production facilities and used under austere conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

This work details the production of solid composite particles by the aerosol-assisted chemical vapor deposition method. With this method it is feasible to produce at low temperature (450 °C) the tetragonal phase of zirconium oxide stabilizing it with yttrium oxide (YSZ) and cubic iron oxide (Fe 3 O 4 ) at the same time. The particles have a solid morphology in which both metal oxides coexist without mixing. The average size of the obtained particles is 329 ± 81 nm, moreover, each particle is formed by thousands of crystallites of size 2 ± 0.5 nm. The formation of solid structures is due to the amount of Zr and Y found in each particle. These particles can be applied as reinforcements of metallic structures. •A simple and low-cost method for producing composite particles to be applied as reinforcing agents for metal structures.•The particles are formed by two phases of tetragonal yttria-stabilized zirconia (t-YSZ) and cubic Fe 3 O 4 , which was synthesized following a one-step process via the aerosol-assisted chemical vapor deposition method (AACVD).•The tetragonal phase of ZrO 2 is obtained at 450 °C stabilizing it with ∼3.8% of yttrium oxide., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti , thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes -borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = -9.11) and 12.4% (95% CI 4.2%, ∞); z = -2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

The aim of the present study was to evaluated hemoglobin A1c (HbA1c), the hemoglobin glycation index (HGI), and triglyceride and glucose (TG) index as predictive indicators for low feed intake in lactating sows due to glucose intolerance. Cactus (Opuntia ficus-indica) was included in sow diets as a modulating factor of glucose. Thirty-six sows were separated into three groups (Gs). Although the three groups received a conventional diet during gestation and lactation, 2.0 kg per sow per day of steam-cooked cactus (G1) and fresh cactus (G2) were added to the lactation diet as a glycemic modulating factor, with G3 serving as the control group. Glycemia was assessed via glucometer (blood glucose concentrations), HbA1c and HGI. For each indicator of glycemia the triglycerides and glucose (TG) index was evaluated. The highest blood glucose concentration was observed on day 3 of lactation (88.2 mg/dL). The average glycemic concentrations obtained from HbA1c on farrowing day (61.6 mg/dL) and day 21 of lactation (65.6 mg/dL) were lower (p<0.05) than those measured by a glucometer on the same days (71.8 and 77.7 mg/dL for farrowing day and day 21 of lactation, respectively). At farrowing, the TG index obtained from the HGI indicated that 83.0% of sows were glucose intolerant, compared to 100% according to the TG index obtained from a glucometer. At weaning, 50% of G2 did not show glucose intolerance when the TG index was calculated using the HGI, compared to 54% when it was calculated with blood glucose concentrations measured by a glucometer. All G3 sows presented glucose intolerance, regardless of the test used. The HbA1c, HGI, and TG index tests are viable alternatives to predict low feed intake due to glucose intolerance in lactating sows., Competing Interests: The authors have declared that no competing interests exist.

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals., (© 2022. The Author(s).)

Microbes (bacteria, yeasts, molds), in addition to plants and animals, were domesticated for their roles in food preservation, nutrition and flavor. Aspergillus oryzae is a domesticated filamentous fungal species traditionally used during fermentation of Asian foods and beverage, such as sake, soy sauce, and miso. To date, little is known about the extent of genome and phenotypic variation of A. oryzae isolates from different clades. Here, we used long-read Oxford Nanopore and short-read Illumina sequencing to produce a highly accurate and contiguous genome assemble of A. oryzae 14160, an industrial strain from China. To understand the relationship of this isolate, we performed phylogenetic analysis with 90 A. oryzae isolates and 1 isolate of the A. oryzae progenitor, Aspergillus flavus . This analysis showed that A. oryzae 14160 is a member of clade A, in comparison to the RIB 40 type strain, which is a member of clade F. To explore genome variation between isolates from distinct A. oryzae clades, we compared the A. oryzae 14160 genome with the complete RIB 40 genome. Our results provide evidence of independent evolution of the alpha-amylase gene duplication, which is one of the major adaptive mutations resulting from domestication. Synteny analysis revealed that both genomes have three copies of the alpha-amylase gene, but only one copy on chromosome 2 was conserved. While the RIB 40 genome had additional copies of the alpha-amylase gene on chromosomes III, and V, 14160 had a second copy on chromosome II and an third copy on chromosome VI. Additionally, we identified hundreds of lineage specific genes, and putative high impact mutations in genes involved in secondary metabolism, including several of the core biosynthetic genes. Finally, to examine the functional effects of genome variation between strains, we measured amylase activity, proteolytic activity, and growth rate on several different substrates. RIB 40 produced significantly higher levels of amylase compared to 14160 when grown on rice and starch. Accordingly, RIB 40 grew faster on rice, while 14160 grew faster on soy. Taken together, our analyses reveal substantial genome and phenotypic variation within A. oryzae ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chacón-Vargas, McCarthy, Choi, Wang, Yu and Gibbons.)

Background: Healthcare-associated infections (HAIs) remain a major challenge in burn research and care. We aimed to describe the epidemiology and timeline of HAIs and to estimate the association of demographics and clinical characteristics with time to HAI among burn patients., Methods: A prospective cohort study was conducted in a referral burn unit in southwestern Colombia. Incidence rates were calculated for HAI types and microorganisms, using a Poisson regression model. Univariable and multivariable Cox proportional hazards regression was used to estimate the effect of risk factors on time to first HAI., Results: Of 165 burn patients, 46 (27.9%) developed at least one HAI (incidence rate of 21.8 per 1000 patient-days). The most frequent HAIs were burn wound infections, followed by bloodstream infections. The most common microorganisms were Staphylococcus aureus, Pseudomonas spp., and Acinetobacter baumannii. Whereas gram-negative bacteria were the most common microorganisms causing HAIs, gram-positive bacteria were the first microorganisms isolated after hospital admission. The independent risk factors associated with time to first HAI were burn size (TBSA>20%), burn mechanism (flames and scalds), central venous catheter use, and mestizo race., Conclusion: These data have implications toward generating empirical antibiotic guidelines and preventive strategies targeting the patients at highest risk for HAI., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Background: The use of chlorhexidine as a strategy to reduce nosocomial infections in patients has been proven useful. Bacterial contamination of health care worker's uniforms during routine patient care has been demonstrated to have potential for horizontal transmission of pathogens., Methods: We performed a prospective, open comparative trial. We included nurses who were in direct patient care and evaluated clothing microbial growth during 3 interventions: (1) participants were given a sterile surgical scrub (SSS) to put on the beginning of the shift, (2) they were instructed to take a chlorhexidine bath (CHG-B) before putting on the SSS, and (3) participants were given a chlorhexidine impregnated SSS (CI-SSS). Cultures were obtained from 3 areas (chest pocket, chest, and abdominal) at hour 0, 6, and 12 hours after the start of the shift., Results: A total of 306 cultures processed with 17 bacterial groups. The uniform area with the highest number of CFU was the abdomen (818 CFU), followed by the thorax (654 CFU). Over 50% of the bacterial load occurred at 12 hours (1,092 CFU at 12 hours, 766 CFU at 6 hours, and 184 CFU at 0 hour). There was a significant reduction in CFU when SSS was compared to CHG-B (CFU mean = 12.5 [0-118] vs CFU mean = 3.5 [0-22], P = .003); and SSS versus CI-SSS (CFU mean = 12.5 [0-118] vs CFU mean = 3 [0-39], P = .007). No severe adverse events were reported., Conclusions: Bacterial load in uniforms decreased when chlorhexidine was used (bathing of personnel or impregnation) when compared to the use of a sterile uniform., (Copyright © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Pulque is a culturally important 4,000-year-old traditional Mexican fermented drink. Pulque is produced by adding fresh aguamiel (agave sap) to mature pulque, resulting in a mixture of microbial communities and chemical compositions. We performed shotgun metagenomic sequencing of five stages of pulque fermentation to characterize organismal and functional diversity. We identified 6 genera (Acinetobacter, Lactobacillus, Lactococcus, Leuconostoc, Saccharomyces and Zymomonas) and 10 species (Acinetobacter boissieri, Acinetobacter nectaris, Lactobacillus sanfranciscensis, Lactococcus lactis, Lactococcus piscium, Lactococcus plantarum, Leuconostoc citreum, Leuconostoc gelidum, Zymomonas mobilis and Saccharomyces cerevisiae) that were present ≥ 1% in at least one stage of pulque fermentation. The abundance of genera and species changed during fermentation and was associated with a decrease in sucrose and increases in ethanol and lactic acid, suggesting that resource competition shapes organismal diversity. We also predicted functional profiles, based on organismal gene content, for each fermentation stage and identified an abundance of genes associated with the biosynthesis of folate, an essential B-vitamin. Additionally, we investigated the evolutionary relationships of S. cerevisiae and Z. mobilis, two of the major microbial species found in pulque. For S. cerevisiae, we used a metagenomics assembly approach to identify S. cerevisiae scaffolds from pulque, and performed phylogenetic analysis of these sequences along with a collection of 158 S. cerevisiae strains. This analysis suggests that S. cerevisiae from pulque is most closely related to Asian strains isolated from sake and bioethanol. Lastly, we isolated and sequenced the whole-genomes of three strains of Z. mobilis from pulque and compared their relationship to seven previously sequenced isolates. Our results suggest pulque strains may represent a distinct lineage of Z. mobilis.

Purpose: To present an evidence-based guideline for non-vital pulp therapies due to deep caries or trauma in primary teeth. Methods: The authors, working with the American Academy of Pediatric Dentistry, conducted a systematic review/meta-analysis for studies on non-vital primary teeth resulting from trauma or caries and used the GRADE approach to assess level of certainty of evidence for clinical recommendations. Results: GRADE was assessed from high to very low. Comparing teeth with/without root resorption, pulpectomy success was better (P<0.001) in those without preoperative root resorption. Zinc oxide plus iodoform plus calcium hydroxide ([ZO/iodoform/CH]; Endoflas TM ) and zinc oxide and eugenol (ZOE) pulpectomy success did not differ from iodoform (iodoform plus calcium hydroxide; Vitapex TM , Metapex TM ) (P=0.55) after 18-months; however, ZO/iodoform/CH and ZOE success rates remained near 90 percent while iodoform was 71 percent or less. Network analysis ratings showed ZO/iodoform/CH and ZOE better than iodoform. Lesion sterilization tissue repair (LSTR) was better (P<0.001) than pulpectomy in teeth with preoperative root resorption, but pulpectomy results were better (P=0.09) if roots were intact. Rotary instrumentation of root canals was significantly faster (P<0.001) than manual, but the quality of fill did not differ (P=0.09) and both had comparable success. Network analysis ranked ZO/iodoform/CH the best, ZOE second, and iodoform lowest at 18 months. Success rates were not impacted by method of obturation or root length determination, type of tooth, number of visits, irrigants, smear layer removal, or timing/type of final restoration. Conclusions: Pulpectomy 18-month success rates supported ZO/iodoform/CH and ZOE pulpectomy over iodoform. LSTR had limited indication for teeth with resorbed roots and requires close monitoring.

Staphylococcus aureus represent a serious threat to public health due to food safety, antibiotic resistance, and the potential zoonotic transmission of strains between dairy cattle and humans. Biofilm formation by S. aureus results in chronicity of the infections which confers protection against the immune response and antibiotics. Likewise, biofilm allows the exchange of mobile genetic material among different strains through microbial interactions inside the matrix. In Colombia, where S. aureus continues to be one of the main pathogens isolated from bovine intramammary infections and where milking by hand is highly frequent, there are knowledge gaps on the zoonotic potential of the strains. Therefore, the aim of this work was to characterize genotypically and phenotypically the S. aureus Sa1FB strain with strong biofilm production and to perform genomic and phenotypic comparisons with other relevant S. aureus strains (native and references strains). These results show a highly productive strain of biofilm and a low ability of cell invasion compared to the other two native strains. In addition, high genomic similarity between S. aureus Sa1FB and the reference strains was observed, despite of the differences reported at the clinical level. However, Sa1FB exhibited special features in terms of mobile genetic elements, highlighting its ability to accept foreign genetic material. Indeed, this could increase mutation, pathogenesis, and adaptability to new hosts, representing a risk for people in contact with the milk obtained from animals infected with these strains. These results present the relevance of surveillance for early detection of emergent clones with zoonotic potential, which reduces the risk of occupational exposure and their spread in the community., (Copyright © 2020 Torres, Vargas, Cuesta-Astroz, Reyes-Vélez and Olivera-Angel.)

Introduction: Malaria is still an important vector-borne disease in the New World tropics. Despite the recent decline in malaria due to Plasmodium falciparum infection in Africa, a rise in Plasmodium infections has been detected in several low malaria transmission areas in Latin America. One of the main obstacles in the battle against malaria is the lack of innovative tools to assess malaria transmission risk, and the behavioral plasticity of one of the main malaria vectors in Latin America, Anopheles darlingi . Methods: We used human IgG antibodies against mosquito salivary gland proteins as a measure of disease risk. Whole salivary gland antigen (SGA) from Anopheles darlingi mosquitoes was used as antigen in Western blot experiments, in which a ~65 kDa protein was visualized as the main immunogenic band and sent for sequencing by mass spectrometry. Apyrase and peroxidase peptides were designed and used as antigens in an ELISA-based test to measure human IgG antibody responses in people with different clinical presentations of malaria. Results: Liquid chromatography-mass spectrometry revealed 17 proteins contained in the ~65 kDa band, with an apyrase and a peroxidase as the two most abundant proteins. Detection of IgG antibodies against salivary antigens by ELISA revealed a significant higher antibody levels in people with malaria infection when compared to uninfected volunteers using the AnDar&#95;Apy1 and AnDar&#95;Apy2 peptides. We also detected a significant positive correlation between the anti-peptides IgG levels and antibodies against the Plasmodium vivax and P. falciparum antigens PvMSP1 and PfMSP1. Odd ratios suggest that people with higher IgG antibodies against the apyrase peptides were up to five times more likely to have a malaria infection. Conclusion: Antibodies against salivary peptides from An. darlingi salivary gland proteins may be used as biomarkers for malaria risk., (At least a portion of this work is authored by Eric Calvo, Hugo O. Valdivia, Karin Escobedo-Vargas, Luz Romero, Maria Bosantes, Michael L. Fisher, Gissella M. Vásquez and Audrey E. Lenhart on behalf of the U.S. Government and, as regards Drs. Calvo, Valdivia, Escobedo-Varga, Romero, Bosantes, Fisher, Vásquez and Lenhart and the U.S. Government, is not subject to copyright protection in the United States. Foreign and other copyrights may apply.)

Prevention of canine heartworm disease caused by Dirofilaria immitis relies on chemoprophylaxis with macrocyclic lactone anthelmintics. Alarmingly, there are increased reports of D. immitis isolates with resistance to macrocyclic lactones and the ability to break through prophylaxis. Yet, there is not a well-established laboratory assay that can utilize biochemical phenotypes of microfilariae to predict drug resistance status. In this study we evaluated laboratory assays measuring cell permeability, metabolism, and P-glycoprotein-mediated efflux. Our assays revealed that trypan blue, propidium iodide staining, and resazurin metabolism could detect differences among D. immitis isolates but none of these approaches could accurately predict drug susceptibility status for all resistant isolates tested. P-glycoprotein assays suggested that the repertoire of P-gp expression is likely to vary among isolates, and investigation of pharmacological differences among different P-gp genes is warranted. Further research is needed to investigate and optimize laboratory assays for D. immitis microfilariae, and caution should be applied when adapting cell death assays to drug screening studies for nematode parasites., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of this systematic review and meta-analysis was to assess success rates for nonvital treatment in primary teeth for caries/trauma. Methods: Databases were searched between 1960 and 2020 for randomized controlled trials, cohorts, case series, and in vitro studies. The primary outcome was overall success (clinical and radiographic) for pulpectomy and lesion sterilization tissue repair (LSTR). Included articles were independently determined, agreed upon, data extraction assessed, risk of bias, meta-analyses, and assignment of quality of evidence (GRADE). Results: Comparing teeth with and without root resorption, pulpectomy success was better (P<0.001) in teeth without preoperative root resorption. Success with pulpectomies performed with zinc oxide eugenol [ZOE] and with Endoflas (ZOE plus iodoform plus calcium hydroxide) did not differ from that observed using Vitapex or Metapex (iodoform plus calcium hydroxide; P ≥ 0.50) after 18 months; however, Endoflas and ZOE success rates remained near 90 percent versus 71 percent or less for iodoform. Network analysis ratings showed Endoflas and ZOE performed better than iodoform alone. Also, LSTR performed better (P<0.001) than pulpectomies in teeth with preoperative root resorption, but pulpectomy results were superior (P=0.09) if roots were intact. Rotary instrumentation of root canals was significantly faster (P<0.001) than manual instrumentation. Success rates were not impacted by method of obturation or root length determination, type of tooth, number of visits, irrigants, smear layer removal, or timing/type of final restoration. Conclusions: Eighteen-month success rates support Endloflas and zinc oxide eugenol pulpectomies over iodoform pulpectomies. Lesion sterilization tissue repair had limited indication for teeth with resorbed roots.

Strongyloides stercoralis hyperinfection syndrome is a medical emergency that requires a high level of suspicion. Immunocompromised patients are at high risk of hyperinfection syndrome; however, malnutrition, alcoholism, and diabetes mellitus also need to be considered as predisposing factors. The diagnosis and treatment of Strongyloides hyperinfection are challenging and patients often have severe complications. Consequently, mortality is overwhelmingly high, with proportions above 60%. Herein, we report a case of Strongyloides hyperinfection in a 40-year-old alcoholic diabetic patient living in México. Unfortunately, the late diagnosis resulted in his death despite the treatment and supportive measures. Increased awareness is needed to prevent the dire consequences of strongyloidiasis.

Tuberculosis (TB) remains the deadliest Infectious disease worldwide, partially due to the increasing dissemination of multidrug and extensively drug-resistant (MDR/XDR) strains. Drug regimens containing the new anti-TB drugs bedaquiline (BDQ) and delamanid (DLM) appear as a last resort for the treatment of MDR or XDR-TB. Unfortunately, resistant cases to these drugs emerged just one year after their introduction in clinical practice. Early detection of resistant strains to BDQ and DLM is crucial to preserving the effectiveness of these drugs. Here, we present a systematic review aiming to define all available genotypic variants linked to different levels of resistance to BDQ and DLM that have been described through whole genomic sequencing (WGS) and the available drug susceptibility testing methods. During the review, we performed a thorough analysis of 18 articles. BDQ resistance was associated with genetic variants in Rv0678 and atpE, while mutations in pepQ were linked to a low-level of resistance for BDQ. For DLM, mutations in the genes ddn, fgd1, fbiA , and fbiC were found in phenotypically resistant cases, while all the mutations in fbiB were reported only in DLM-susceptible strains. Additionally, WGS analysis allowed the detection of heteroresistance to both drugs. In conclusion, we present a comprehensive panel of gene mutations linked to different levels of drug resistance to BDQ and DLM.

The Ediacaran Weng'an Biota (Doushantuo Formation, 609 Ma old) is a rich microfossil assemblage that preserves biological structure to a subcellular level of fidelity and encompasses a range of developmental stages [1]. However, the animal embryo interpretation of the main components of the biota has been the subject of controversy [2, 3]. Here, we describe the development of Caveasphaera, which varies in morphology from lensoid to a hollow spheroidal cage [4] to a solid spheroid [5] but has largely evaded description and interpretation. Caveasphaera is demonstrably cellular and develops within an envelope by cell division and migration, first defining the spheroidal perimeter via anastomosing cell masses that thicken and ingress as strands of cells that detach and subsequently aggregate in a polar region. Concomitantly, the overall diameter increases as does the volume of the cell mass, but after an initial phase of reductive palinotomy, the volume of individual cells remains the same through development. The process of cell ingression, detachment, and polar aggregation is analogous to gastrulation; together with evidence of functional cell adhesion and development within an envelope, this is suggestive of a holozoan affinity. Parental investment in the embryonic development of Caveasphaera and co-occurring Tianzhushania and Spiralicellula, as well as delayed onset of later development, may reflect an adaptation to the heterogeneous nature of the early Ediacaran nearshore marine environments in which early animals evolved., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The prediction of cell-lines sensitivity to a given set of compounds is a very important factor in the optimization of in-vitro assays. To date, the most common prediction strategies are based upon machine learning or other quantitative structure-activity relationships (QSAR) based approaches. In the present research, we propose and discuss a straightforward strategy not based on any learning modelling but exclusively relying upon the chemical similarity of a query compound to reference compounds with annotated activity against cell lines. We also compare the performance of the proposed method to machine learning predictions on the same problem. A curated database of compounds-cell lines associations derived from ChemBL version 22 was created for algorithm construction and cross-validation. Validation was done using 10-fold cross-validation and testing the models on new data obtained from ChemBL version 25. In terms of accuracy, both methods perform similarly with values around 0.65 across 750 cell lines in 10-fold cross-validation experiments. By combining both methods it is possible to achieve 66% of correct classification rate in more than 26000 newly reported interactions comprising 11000 new compounds. A Web Service implementing the described approaches (both similarity and machine learning based models) is freely available at: http://bioquimio.udla.edu.ec/cellfishing., Competing Interests: The authors have declared that no competing interests exist.

Consensus scoring has become a commonly used strategy within structure-based virtual screening (VS) workflows with improved performance compared to those based in a single scoring function. However, no research has been devoted to analyze the worth of docking scoring functions components in consensus scoring. We implemented and tested a method that incorporates docking scoring functions components into the setting of high performance VS workflows. This method uses genetic algorithms for finding the combination of scoring components that maximizes the VS enrichment for any target. Our methodology was validated using a data set including ligands and decoys for 102 targets that have been widely used in VS validation studies. Results show that our approach outperforms other methods for all targets. It also boosts the initial enrichment performance of the traditional use of whole scoring functions in consensus scoring by an average of 45%. Our methodology showed to be outstandingly predictive when challenged to rescore external (previously unseen) data. Remarkably, CompScore was able not only to retain its performance after redocking with a different software, but also proved that the enrichment obtained was not artificial. CompScore is freely available at: http://bioquimio.udla.edu.ec/compscore/ .

Precision medicine has a long history dating to the early 20th century when inquiries into the biochemical basis of large person-to-person variations in susceptibility to human diseases and response to medicines had first begun. Yet, personalized medicine in the 21st century is far from being "future-proof." Emerging technologies such as artificial intelligence, and changing human values and preferences, call for anticipatory, rather than reactive, approaches to the governance of precision medicine futures. In this context, anticipatory governance is an innovative approach to understanding technology and innovation futures. Anticipatory governance and its corollary anticipatory ethics on emerging technologies require interdisciplinary collaboration and communication to cultivate shared language, imagination, and orientation toward plausible sociotechnical innovation trajectories. This study reports, for the first time in the literature to the best of our knowledge, an anticipatory governance experiment on "implementation precision medicine (IPM)" using scenario analysis and design fiction. Participants were undergraduate students and experts who collaboratively imagined the plausible futures of precision medicine. Given the long history of the precision medicine field, and recent calls for translating big data to real-life clinical applications, implementation was chosen as a key focus area of precision medicine futures. We report here several plausible future innovation scenarios of interest to precision medicine scientists and engineers and researchers in the fields of emerging technology governance, responsible innovation, and social studies of science. Of importance, we found that the playful quality of the design fiction methodology and the pedagogical orientation facilitated by undergraduate student involvement created an engaging creative safe space to build transdisciplinary dialog examining the social and anticipatory ethics dimensions of IPM. Demonstrating the possibilities of such cross-disciplinary dialog and differential expertise, this article is conceptualized and coauthored by all participants further attesting to the importance of co-designing and co-imagining innovation futures in IPM.

Opportunistic parasites are still important agents causing morbidity and mortality in immunocompromised patients, particularly those living with HIV/AIDS. Few studies in Mexico have attempted to determine the prevalence of opportunistic intestinal parasites causing diarrhea in immunocompromised patients. A study was conducted to determine the intestinal parasites in HIV-positive and HIV-negative immunocompromised patients with diarrhea admitted to a tertiary care hospital in Monterrey, Mexico, from 2014 to 2015. Stool samples were examined for trophozoites, cysts, and eggs using the EGRoPe sedimentation-concentration technique and special techniques (modified Ziehl-Neelsen stain, modified trichrome stain). A total of 56 patients were included. The overall prevalence of intestinal parasitism was 64% (36/56); 22/36 patients were HIV-positive. Prevalence of opportunistic parasites was 69% in HIV-infected patients compared to 44% in HIV-negative patients (P = 0.06). Microsporidia were the most frequently identified parasites (24/36, 67%), followed by Cryptosporidium sp. (6/36, 17%), Sarcocystis sp. (4/36, 11%), Cystoisospora belli (3/36, 8%), and Cyclospora cayetanensis (1/36, 3%). Overall prevalence rates of microsporidiosis and cryptosporidiosis were 43% and 11%, respectively. Among HIV-infected patients, prevalence rates of microsporidiosis and cryptosporidiosis were 48% and 14%, respectively. We also report the first cases of intestinal sarcocystosis in Mexico, all in HIV-infected patients. In conclusion, microsporidia and coccidia are major parasitic agents causing diarrhea in immunocompromised patients, particularly HIV-infected patients.

We identified individuals with variations in ACTL6B, a component of the chromatin remodeling machinery including the BAF complex. Ten individuals harbored bi-allelic mutations and presented with global developmental delay, epileptic encephalopathy, and spasticity, and ten individuals with de novo heterozygous mutations displayed intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.1027G>A (p.Gly343Arg) mutation. Human-derived neurons were generated that recaptured ACTL6B expression patterns in development from progenitor cell to post-mitotic neuron, validating the use of this model. Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development, a result recapitulated in two individuals with different bi-allelic mutations, and reversed on clonal genetic repair or exogenous expression of ACTL6B. Whole-transcriptome analyses and whole-genomic profiling of the BAF complex in wild-type and bi-allelic mutant ACTL6B neural progenitor cells and neurons revealed increased genomic binding of the BAF complex in ACTL6B mutants, with corresponding transcriptional changes in several genes including TPPP and FSCN1, suggesting that altered regulation of some cytoskeletal genes contribute to altered dendrite development. Assessment of bi-alleic and heterozygous ACTL6B mutations on an ACTL6B knock-out human background demonstrated that bi-allelic mutations mimic engineered deletion deficits while heterozygous mutations do not, suggesting that the former are loss of function and the latter are gain of function. These results reveal a role for ACTL6B in neurodevelopment and implicate another component of chromatin remodeling machinery in brain disease., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls., Methods: In total, 100 participants were included (71% women; average age, 70 years; range, 43⁻91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and APOE methylation., Results: MCI was diagnosed in 41 subjects (average age, 66.5 ± 9.6 years) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI ( p < 0.05). Higher CpG-227 methylation correlated with lower risk for MCI ( p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = -0.665; p = 0.008)., Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI.