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Abstract Background Gestational weight gain (GWG) is a critical issue related to postpartum health in newborns and mothers. In Brazil, pregnant women’s public health recommends monitoring GWG. Therefore, the objective of this study is to evaluate gestational weight gain and associated health factors of pregnant women monitored at Unified Health System (SUS) in the city of São Paulo between 2012 and 2020. Methods This is a retrospective cohort study of pregnant women seen from 2012 to 2020 in São Paulo, Brazil. The database used was from the Integrated Health Care Management System related to the Live Birth Information System. Data distribution was assessed using the Kolmogorov-Smirnov test. Comparisons between groups according to weight gain (LWG vs. AWG vs. EWG) were performed using analysis of variance (ANOVA) with Tukey post hoc. Inclusion criteria considered that pregnant women had a recorded initial weight before 13 weeks and up to 15 days before delivery and a single pregnancy. The final database includes 276.220 pregnant women. Results The frequency of women according to initial body mass index (BMI) was 12.004 (4.4%) underweight, 132.049 (48.3%) normal weight, 78.856 (28.8%) overweight, and 50.660 (18.5%) living with obesity. The population consisted of 59.881 (21.9%), 37.217 (13.6%) and 176.471 (64.5%) women with LWG, AWG and EWG, respectively. Weight gain was associated with initial BMI, type of birth, color/ethnicity, marital status, women’s age and antenatal care visits. Conclusion The proportion of pregnant women with inadequate weight gain is high, relating initial BMI, type of birth, color/ethnicity, marital status, women’s age and antenatal care visits. Interventions such as nutritional education should be suggested to help achieve adequate GWG.

Background Pediatric hypertension is linked to environmental factors like neighborhood noise disrupting sleep, which is crucial for health. The specific interaction between noise and sleep health in causing hypertension still needs to be explored. Methods and Results We analyzed data from 3320 participants of the ABCD (Adolescent Brain Cognitive Development) study, recruited across 21 US cities and monitored from 2018 to 2020 through 2020 to 2022. Participants with complete data on Fitbit‐tracked sleep, blood pressure, height, neighborhood noise, and covariates (biological sex, race and ethnicity, pubertal stage, waist circumference) were included. Hypertension was defined as average blood pressure ≥95th percentile for age, sex, and height. Sleep health was categorized on the basis of daily duration: healthy (9–12 hours), moderately healthy (±1 hour from optimal), and low (≥1 hour deviation). Noise exposure was measured as median nighttime anthropogenic noise levels by zip code. The incidence of hypertension increased from 1.7% (95% CI, 1.4–2.1) in 2018 to 2020 to 2.9% (95% CI, 2.4–3.6) in 2020 to 2022. Adolescents with healthier sleep had a lower risk of developing hypertension (relative risk, 0.63 [95% CI, 0.25–0.82]), while no significant effects were found for neighborhood noise alone or in combination with sleep health. Conclusions Adequate sleep significantly reduces the risk of hypertension in adolescents, independent of environmental noise exposure. These findings underscore the importance of promoting good sleep hygiene among youth to mitigate hypertension risk.

We investigate primordial magnetogenesis within a quantum bouncing model driven by a scalar field, focusing on various non-minimal couplings between the electromagnetic field and the scalar field. We test three cases: no coupling, a Cauchy coupling with gradual decay, and a Gaussian coupling with rapid fall-off. By exploring these scenarios, we assess a wide range of coupling strengths across different scales. The scalar field, with an exponential potential, behaves as pressureless matter in the asymptotic past of the contracting phase, as stiff matter around the bounce, and as dark energy during the expanding phase. Our findings reveal that, among the tested cases, only the Gaussian coupling can explain the generation of primordial magnetic fields on cosmological scales.

Resumo Fundamento: A Cardiomiopatia Chagásica Crônica (CCC) é causada por um processo inflamatório induzido pelo Trypanosoma cruzi, que leva à miocardite com fibrose reativa e reparativa. A CCC progride com alterações de perfusão miocárdica e eventos histopatológicos que afetam a Aptidão Cardiorrespiratória (ACR). Objetivos: Avaliamos os efeitos do Treinamento Físico Aeróbico (TFA) na perfusão miocárdica e nos comprometimentos morfológicos e funcionais relacionados à inflamação e fibrose em hamsters sírios com CCC. Como objetivo secundário, analisamos as áreas de secção transversa do músculo esquelético. Métodos: Hamsters com CCC e seus respectivos controles foram divididos em quatro grupos: CCC sedentário, CCC-TFA, controle sedentário e controle TFA. Sete meses após a infecção, os animais foram submetidos à ecocardiografia, à cintilografia de perfusão miocárdica e ao teste de esforço cardiopulmonar. TFA de intensidade moderada foi realizado durante cinquenta minutos, cinco vezes por semana, por oito semanas. Posteriormente, os animais foram reavaliados. A análise histopatológica foi realizada após os procedimentos acima mencionados. O nível de significância foi estabelecido em 5% em todas as análises (p

Abstract This article aims to fill an existing knowledge gap within the literature: the characteristics of networks of publication on innovation management research and its relationship with country’s innovativeness. The study is grounded in the theory that the creation of knowledge and collaboration within networks play a pivotal role in improving a nation’s innovation capacity. It presents and describes the characteristics of co-authorship networks of scientific publications among authors from different countries. The published articles were extracted from the Scopus and Web of Science databases, considering a period of 12 years. Following the identification of pivotal countries, the research proceeded to investigate whether their positioning within the network has an impact on their innovation capabilities. To underpin this analysis, data from the Global Innovation Index ranking were employed. Among the six countries demonstrating noteworthy centrality metrics throughout the entire period, Germany, the United States, and the United Kingdom are also categorized as innovators according to the Global Innovation Index. The overlap observed suggests a relationship between countries maintaining consolidated and resilient innovation networks and positive performance in terms of innovation. However, it should be noted that innovation is influenced by a range of factors, including strategies and policies on international collaboration.

Abstract Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC–MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.

Abstract Background The androgen/androgen receptor (AR)-signaling axis plays a central role in prostate cancer (PCa). Upon androgen-binding the AR dimerizes with another AR, and translocates into the nucleus where the AR-dimer activates/inactivates androgen-dependent genes. Consequently, treatments for PCa are commonly based on androgen deprivation therapy (ADT). The clinical benefits of ADT are only transitory and most tumors develop mechanisms allowing the AR to bypass its need for physiological levels of circulating androgens. Clinical failure of ADT is often characterized by the synthesis of a constitutively active AR splice variant, termed AR-V7. AR-V7 mRNA expression is considered as a resistance mechanism following ADT. AR-V7 no longer needs androgenic stimuli for nuclear entry and/or dimerization. Methods Our goal was to mechanistically decipher the interaction between full-length AR (AR-FL) and AR-V7 in AR-null HEK-293 cells using the NanoLuc Binary Technology under androgen stimulation and deprivation conditions. Results Our data point toward a hypothesis that AR-FL/AR-FL homodimers form in the cytoplasm, whereas AR-V7/AR-V7 homodimers localize in the nucleus. However, after androgen stimulation, all the AR-FL/AR-FL, AR-FL/AR-V7 and AR-V7/AR-V7 dimers were localized in the nucleus. Conclusions We showed that AR-FL and AR-V7 form heterodimers that localize to the nucleus, whereas AR-V7/AR-V7 dimers were found to localize in the absence of androgens in the nucleus.

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 biofuel derived from controlled fermentation and subsequent distillation of lignocellulosic biomass is commonly referred to as second-generation ethanol (2G). This energy production pathway has experienced exponential growth due to its dual role as an alternative additive to fossil fuels and a potential replacement for this environmentally detrimental energy source in the future. This study aimed to produce second-generation ethanol by utilizing cassava peel and manipueira through acid hydrolysis, followed by a 10-day fermentation process using the yeast Saccharomyces cerevisiae the fermenting microorganism. The process began with the mechanical pulverization of the biomass, followed by a triple round of acid hydrolysis using sulfuric acid at 100 °C for 10 minutes. Subsequently, fermentation occurred within sealed PET bottles, with each sample containing 10 g of yeast and 25 g of biomass, maintaining a 1:2.5 mass ratio of yeast to biomass, at an average room temperature of 35 °C for 10 days. After this incubation period, the fermented solutions were evaluated for °BRIX and pH levels, then filtered using a vacuum pump and distilled in a micro distillation apparatus to obtain ethanol 2G. The obtained results demonstrated the significant potential of cassava peel (Manihot esculenta) and manipueira biomass for second-generation ethanol production, with °Brix values of 4 % for cassava peel and 3% for manipueira, respectively. During the fermentation process, regular assessments of pH, sugar content, alcohol concentration, and corresponding ethanol mass percentage were conducted for each sample. These analyses revealed a gradual increase in alcohol levels over time, reaching a peak of 26.2 % for cassava peel and 24 % for manipueira after 10 days. These findings suggest that cassava and manipueira peels, as sources of lignocellulosic biomass, hold promise for second-generation ethanol production. This research directly contributes to the development of more efficient and sustainable processes for generating biofuels from agricultural waste, paving the way to produce clean and renewable energy.

Recent studies have demonstrated mechanical, tribological and corrosion improvements properties on raw materials coated with stainless steel films produced by magnetron sputtering. However, few studies have reported the tribological behavior of thin austenitic stainless-steel films applied to the surface of carbon steels. The present study investigated the tribological behavior of AISI 1045 carbon steel coated with AISI 316 stainless steel film. Pin-on-disc dry sliding wear test was performed. The wear tracks were analyzed using a scanning electron and confocal microscopes. The corrosion resistance of coated and uncoated AISI 1045 were also assessed through an electrochemical test. Samples which presented a mixture of α-Ferrite and γ-iron, with predominant austenite parts, demonstrated lower friction coefficient, lower wear rates, and better corrosion resistance compared to substrate material. The results were also influenced by the variables used in the deposition process, as observed, heating the substrate and submitting to a higher powder density could improve the results. The results found corroborate to the academic and industrial research which looks for coating alternatives to AISI 1045 tools.

Abstract Background Staphylococcus spp and Microsporum canis are zoonotic microorganisms which can cause infections and systemic diseases. The bone infection is usually caused by invasion of pathogen through the hematologic route. Mixed osteomyelitis caused by bacteria and fungi is rare, and to date, there have been no reports of mixed osteomyelitis with Staphylococcus spp. and Microsporum canis. Case presentation This essay reports an atypical presentation of mixed osteomyelitis (Staphylococcus spp. and Microsporum canis) in a domestic cat. A 15-month-old female Persian cat was presented to a veterinary service; the main complaint was the appearance of a nodule in the mandibular ventral rostral region. A radiographic exam performed on the animal showed proliferative and osteolytic bone lesions. The patient was submitted to a biopsy for histopathological evaluation, along with bacterial and fungal cultures. Results showed mixed osteomyelitis by Staphylococcus spp. and Microsporum canis. Microbial Sensitivity Test was performed to choose a more suitable treatment. Two surgical procedures were executed to resect and curette the lesion, and treatments with anti-inflammatory, antibiotic, and antifungal drugs were established, showing a positive clinical evolution. After 8 months of treatment, the patient’s owner moved to a different city, and the animal was seen by other veterinarians, who followed along with the same treatment. However, due to complications and a diminishing quality of life over 4 years of diagnosis, the patient was euthanized. Conclusion Given the above, mixed osteomyelitis is difficult to treat and can cause losses of life quality resulting death, especially in infections where M. canis is the agent causing the disease. Bacterial osteomyelitis is more frequently reported. But the lack of investigation of microorganisms other than bacteria, such as fungal cases, may imply in underdiagnosed cases. Treatment of osteomyelitis can be difficult considering the difficulties in isolating the pathological agent, resistance to the drug used, prolonged treatment time, and cost.

Abstract Background Bacillus thuringiensis (Bt) is a widely used biopesticide. The bioinsecticide based on Bt is obtained by fermentation, but the substrates currently used for its production constitute ingredients of high commercial value. In this context, the use of agro-industrial residues as substrates is an alternative to make the fermentation process viable on a large scale, in addition to minimizing environmental problems and contributing to the destination of these residues for biotechnological purposes. Results In the first part of this study, a previously isolated spore forming soil bacteria (Bv5) harboring and expressing a novel cry 8A gene was confirmed as B. thuringiensis based on its morphological characteristics, Gram staining, scanning electron microscopy (SEM) and genome sequencing. Bv5 was established as a Gram-positive spore forming bacteria with ellipsoidal spores and small round toxins. Bv5 genome comprised of the 5.30 Mb chromosome and two megaplasmids of 450 kb and 261 kb, respectively, with cry 8A gene located on the smallest megaplasmid. In the second part of the study, the physiological profile of the Bv5 strain during fermentation in different agro-industrial biowastes (cassava wastewater, orange pulp wash and whey) was analyzed. The fermentation experiment was divided into two stages. In the first stage, the agro-industrial waste with or without salts with the best results for biomass, spores and proteins production was selected. In the second stage, the effect of the selected medium in original and diluted form with the C:N balance was evaluated, in two different fermentation times (72 h and 96 h). Pulp wash enriched with salts was selected as the most suitable medium for the growth of Bv5 strain in the first stage. In the second stage pulp wash (without dilution) with the addition of salts, and with nitrogen supplementation, was considered the best for cell growth, spore and toxin production by Bv5. Conclusions To conclude, our study provide a new alternative for bio-waste from the orange juice industry, as well as potential culture medium for the Bt commercial scale production.

Environmental contamination by potentially toxic elements (PTEs) poses a significant challenge, particularly in the metropolitan regions of developing countries. This issue arises from the high levels of pollution driven by industrial growth and the increased traffic from fossil fuel-powered vehicles. Even after the wastewater treatment in treatment plants, PTEs often persist, posing risks to stream structure and function. This form of pollution is persistent, long-term, and irreversible, presenting a significant challenge in terms of freshwater conservation. This study aimed to assess the water quality and PTE concentrations in urban streams in Santo André, SP, Brazil, to identify the PTEs relevant to stream pollution. We analyzed the water quality in seven catchments in the Santo André municipality, in the metropolitan region of São Paulo, Brazil. The samples were collected during the dry (2021) and rainy periods (2022), and the concentrations of potentially toxic elements (PTEs) were analyzed via inductively coupled plasma–mass spectrometry (ICP-MS). The results showed elevated electrical conductivity (429 ± 211 μS·cm) and low dissolved oxygen concentrations in the streams (2.3 ± 0.95 μg·L), indicating potential problems such as eutrophication and toxicity to aquatic organisms. PTE concentrations, particularly those of Mn (30.8 ± 22.3 μg·L), Fe (91.1 ± 72.1 μg·L), and Zn (38.1 ± 28.7 μg·L), were among the highest concentrations. Seasonal variations affected the PTE concentrations, with Cr and Fe predominating during the dry season and Zn increasing during the rainy season. Associations were found between the PTE concentrations and the water pH, indicating the importance of continuous monitoring and remediation efforts.

Abstract Background Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. Methods Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. Results Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1–16.1] in patients with poor adherence compared to 5.8% [5.0–6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8–2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3–15.2] in patients with poor adherence and 4.9% [4.1–5.8] in patients with full adherence; p

This study aimed to evaluate the toxicity of Piper hispidinervum essential oil (PHEO) against 11 Brazilian populations of Sitophilus zeamais (Coleoptera: Curculionidae). The effects of sublethal doses of PHEO on the behavior (walking and flying), respiration, and population growth (ri) of the insect populations were investigated. PHEO toxicity was determined through concentration–mortality bioassays, with mortality curves established using increasing PHEO concentrations ranging from 140.00 to 1000.00 μL kg−1. Behavior was evaluated based on walking distance, walking time, walking speed, walking time proportion, flight height, and flight takeoff success. Respiration was measured via the respiratory rate, while population growth (ri) was assessed through the instantaneous growth rate. All 11 populations of S. zeamais were susceptible to PHEO, showing no signs of resistance. The populations exhibited varying behavioral and physiological responses to sublethal exposure to PHEO, indicating different mitigation strategies. The results confirm that PHEO possesses insecticidal potential for controlling S. zeamais populations. However, the observed behavioral and physiological responses should be considered when establishing control measures in pest management programs for stored products.

This paper reports a rapid and sensitive sensor for the detection and quantification of the COVID-19 N-protein (N-PROT) via an electrochemical mechanism. Single-frequency electrochemical impedance spectroscopy was used as a transduction method for real-time measurement of the N-PROT in an immunosensor system based on gold-conjugate-modified carbon screen-printed electrodes (Cov-Ag-SPE). The system presents high selectivity attained through an optimal stimulation signal composed of a 0.0 V DC potential and 10 mV RMS−1 AC signal at 100 Hz over 300 s. The Cov-Ag-SPE showed a log response toward N-PROT detection at concentrations from 1.0 ng mL−1 to 10.0 μg mL−1, with a 0.977 correlation coefficient for the phase (θ) variation. An ML-based approach could be created using some aspects observed from the positive and negative samples; hence, it was possible to classify 252 samples, reaching 83.0, 96.2 and 91.3% sensitivity, specificity, and accuracy, respectively, with confidence intervals (CI) ranging from 73.0 to 100.0%. Because impedance spectroscopy measurements can be performed with low-cost portable instruments, the immunosensor proposed here can be applied in point-of-care diagnostics for mass testing, even in places with limited resources, as an alternative to the common diagnostics methods.

Since 2017, a new Neopestalotiopsis sp. has been reported causing severe Pestalotia leaf spot (PLS) outbreaks in Florida. The threat of this new species has forced several strawberry growers to destroy their fields early in the season. The need for a fast and accurate diagnosis of PLS came from growers’ concerns and the fact that PLS symptoms can be easily confused with leaf spots caused by other pathogens. Moreover, although N. rosae can be isolated from symptomatic tissues, it is not as aggressive as the new Neopestalotiopsis sp. in Florida. Therefore, this study aimed to develop a high-resolution melting (HRM) assay to accurately detect and differentiate Neopestalotiopsis spp. associated with strawberry and validate this assay for its practical application in a plant diagnostic clinic. Two sets of primers were designed based on the partial beta-tubulin gene (β-tub) and by cross-comparison of their HRM results. This molecular assay was able to differentiate Neopestalotiopsis spp. into three groups: the new Neopestalotiopsis sp. associated with PLS outbreaks, N. rosae, and other Neopestalotiopsis spp. represented by several other species within the genus. The HRM assay had a detection limit of 10 pg of genomic DNA or 10 conidia and was found to be efficient and accurate to be implemented in our plant diagnostic clinic, allowing for a quick turnaround of results. [Figure: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

BackgroundMalaria transmission modelling has demonstrated the potential impact of semiquantitative glucose-6-phosphate dehydrogenase (G6PD) testing and treatment with single-dose tafenoquine for Plasmodium vivax radical cure but has not investigated the associated costs. This study evaluated the cost-effectiveness of P. vivax treatment with tafenoquine after G6PD testing using a transmission model.Methods and findingsWe explored the cost-effectiveness of using tafenoquine after G6PD screening as compared to usual practice (7-day low-dose primaquine (0.5 mg/kg/day) without G6PD screening) in Brazil using a 10-year time horizon with 5% discounting considering 4 scenarios: (1) tafenoquine for adults only assuming 66.7% primaquine treatment adherence; (2) tafenoquine for adults and children aged >2 years assuming 66.7% primaquine adherence; (3) tafenoquine for adults only assuming 90% primaquine adherence; and (4) tafenoquine for adults only assuming 30% primaquine adherence. The incremental cost-effectiveness ratios (ICERs) were estimated by dividing the incremental costs by the disability-adjusted life years (DALYs) averted. These were compared to a willingness to pay (WTP) threshold of US$7,800 for Brazil, and one-way and probabilistic sensitivity analyses were performed. All 4 scenarios were cost-effective in the base case analysis using this WTP threshold with ICERs ranging from US$154 to US$1,836. One-way sensitivity analyses showed that the results were most sensitive to severity and mortality due to vivax malaria, the lifetime and number of semiquantitative G6PD analysers needed, cost per malaria episode and per G6PD test strips, and life expectancy. All scenarios had a 100% likelihood of being cost-effective at the WTP threshold. The main limitations of this study are due to parameter uncertainty around our cost estimates for low transmission settings, the costs of G6PD screening, and the severity of vivax malaria.ConclusionsIn our modelling study that incorporated impact on transmission, tafenoquine prescribed after a semiquantitative G6PD testing was highly likely to be cost-effective in Brazil. These results demonstrate the potential health and economic importance of ensuring safe and effective radical cure.

Category: Diabetes; Other Introduction/Purpose: A retrospective case series study was performed to evaluate the outcomes and risk factors of transtibial amputations (TTA) using a novel post operative treatment protocol. The study hypothesis is that a novel post operative treatment protocol could improve outcomes for TTAs. All patients who underwent a TTA from July 2019 through December 2022 were treated with this protocol. Outcomes identified included time to prosthetic fitting after surgery and complications including wound dehiscence and mortality at 30 days. Risk factors were also identified for the patients in this case series study. Methods: The novel post operative protocol includes a circumferential incisional negative pressure wound therapy (CiNPWT) dressing that covered with a novel residual limb shrinker (nRLS) and a limb protector (LP) applied after incision closure. The CiNPWT and nRLS were removed at the first follow up visit. Then the nRLS was applied as the primary dressing directly against the incision covering the residual limb. The nRLS was changed for wound cleansing and was sequentially decreased in size to facilitate consolidation of the residual limb. Results: There were 433 surgeries performed on 304 patients. This included 222 (73%) men and 81 (27%) women with an average age of 67 years (41-90 years). There were 129 revision surgeries including 25 above-the-knee amputations (AKA). The average time to prosthetic fitting for TTA was 8 weeks. The average study group BMI was 32 kg/m 2 , A1c 8.7%, albumin 2.6 g/dL and neutrophil to lymphocyte ratio (NLR) 4.9. Traumatic wound dehiscence from falls represented 26% of revision surgeries. Mortality at 30 days was 3.2% for all study participants. The early death average age was 70 years (41-90 years), 73% with end stage renal disease (ESRD) and 82% with diabetes mellitus (DM). Conclusion: The novel protocol for transtibial amputations decreased the 30 day mortality to 3.2% from a national average of 13.5%. The average time to prosthetic fitting was 8 weeks for the study group compared to 16 weeks for US Department of Veterans Affairs amputations. The early death group’s average albumin of 2.15 g/dL with a NLR of 8.9. The study demonstrated that a novel postoperative protocol may improve outcomes in transtibial amputations and that a few simple blood values may provide an indication of the diminished overall physiologic health of this patient population.

ABSTRACT Corticosteroids have become a choice for managing severe COVID-19, but the molecular mechanisms behind the response after corticosteroid administration remain incompletely understood. In order to unravel this, comparisons between temporal metabolic profiles in the plasma samples of methylprednisolone (MP)- and placebo-treated COVID-19 patients were performed at different time points. The patient plasma samples used were obtained from a double-blind, randomized, placebo-controlled Phase IIb clinical trial performed on severe COVID-19 patients in the Brazilian Amazon, where the patients received placebo or 0.5 mg/kg MP intravenously twice daily for 5 days. The MP treatment reduced the number of metabolites in the plasma of patients during follow-up. The longitudinal changes in the MP group were in eight metabolic pathways related to steroid hormones and eicosanoids. Direct comparison between the two groups, revealed differences at baseline, which peaked 5 days after initiation of MP treatment. The metabolic pathways differing between the two groups over time included galactose metabolism, glucose and gluconeogenesis, N-glycan metabolism, and prostaglandin formation from arachidonate. Deoxy-galactose, prostaglandin H2, sphingosine, and sphinganine exhibited differential trajectories by day 14 after initiating the MP treatment. Survival of MP-treated COVID-19 patients was associated with modulation of tryptophan metabolism and diminished levels of oxidized glutathione. Network analysis revealed that MP treatment is highly associated with alterations in pathways reflecting eicosanoid metabolism, such as arachidonic acid and prostaglandins. Curiously, there is a crosstalk between metabolomics, biochemistry, and cytokine components. Treatment of systemic and inflammatory conditions induced by SARS-CoV-2 viral infections with methylprednisolone modulates metabolic activity associated with tryptophan and inflammatory lipids.IMPORTANCEThe SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions and complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding of the metabolic and metabolomic pathway dysregulations while using intravenous corticosteroids in COVID-19 is limited. This study will help enlighten the metabolic and metabolomic pathway dysregulations underlying high daily doses of intravenous methylprednisolone in COVID-19 patients compared to those receiving placebo. The information on key metabolites and pathways identified in this study together with the crosstalk with the inflammation and biochemistry components may be used, in the future, to leverage the use of methylprednisolone in any future pandemics from the coronavirus family.

Abstract Phytophthora crown rot (PhCR) caused by Phytophthora cactorum is one of the most damaging diseases of strawberry worldwide. Mefenoxam is one of the major fungicides currently used to manage PhCR. However, the emergence and spread of resistant isolates have made controlling the pathogen in the field problematic. In the present study, using whole genome sequencing analysis, mutations associated with mefenoxam-resistant isolates were identified in six different genomic regions of P. cactorum. The 95.54% reads from a sensitive isolate pool and 95.65% from a resistant isolate pool were mapped to the reference genome of P. cactorum P414. Four point mutations were in coding regions while the other two were in noncoding regions. The genes harboring mutations were functionally unknown. All mutations present in resistant isolates were confirmed by sanger sequencing of PCR products. For the rapid diagnostic assay, SNP-based high-resolution melting (HRM) markers were developed to differentiate mefenoxam-resistant P. cactorum from sensitive isolates. The HRM markers R3-1F/R3-1R and R2-1F/R2-1R were suitable to differentiate both sensitive and resistant profiles using clean and crude DNA extraction. None of the mutations associated with mefenoxam resistance found in this study were in the RNA polymerase subunit genes, the hypothesized target of this compound in oomycetes. Our findings may contribute to a better understanding of the mechanisms of resistance of mefenoxam in oomycetes since serves as a foundation to validate the candidate genes as well as contribute to the monitoring of P. cactorum populations for the sustainable use of this product.

Background: Patellofemoral pathology resulting from improper biomechanics is difficult to treat, and lateral patellar instability requires individualized treatment, which may include tibial tubercle osteotomy (TTO) with anteromedial repositioning. Indications: Symptomatic patellofemoral instability with maltracking, particularly in cases with a tibial tuberosity-trochlear groove distance >16 mm. Technique Description: We describe an oblique osteotomy from medial to lateral. A careful completion of the osteotomy is made with an osteotome, and the resulting fragment is mobilized to achieve anteromedial repositioning—as well as distalization in cases of patella alta. Two bicortical screws with a washer are used for fixation of the tibial tubercle following anteromedialization. Results: Systematic reviews demonstrated that the treatment of the lateral patellar instability requires an individual treatment and the anteromedial TTO is a very important procedure alone or in association with medial patellofemoral ligament. Discussion/Conclusion: Recurrent lateral patellar instability is a challenging condition with complex causes and various treatment options, but anteromedial TTO provides an effective way to improve clinical outcomes and correct patellar maltracking, with relatively low complication rates. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Meniscal radial tears are associated with altered contact mechanics, as they have the potential to disrupt the meniscal hoop stress mechanism. In prior studies, radial tears are associated with higher grade of cartilage damage, as well as higher rate and severity of meniscal extrusion in knees with a radial tear relative to other types of tears. Improved understanding of the meniscus biological potential together with modern developments in surgical technique has paved the way for the current emphasis on repairing even radial tears. Indication: Large or complete radial tears of the meniscus without prohibitive joint space narrowing or severe cartilage damage. Technique Description: A hybrid technique of meniscal radial repair is described, combining (1) 2 transtibial pullout cinch-loop sutures, (2) 2 inside-out vertical rip-stop sutures and 2 oblique sutures in a “cross-tag” configuration, and (3) 1 horizontal mattress all-inside suture. The repair is biologically augmented with a notch marrow-venting procedure. Results: Recent evidence has demonstrated significant biomechanical benefit in terms of increased load to failure and construct strength when adding transtibial tunnel augmentation to radial repairs. In addition, rip-stop sutures decrease the chance of cut-out relative to nonreinforced repairs. Those biomechanical advancements are reflected in excellent patient-reported outcomes as well as healing rates following radial repair. Discussion/Conclusion: We present a hybrid technique encompassing the most biomechanically effective novel radial repair techniques, backed by excellent clinical outcomes following radial repair in the current literature. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Despite extensive evidence of excellent biomechanical and clinical outcomes of ligament reconstructions with bone-patellar tendon-bone, hamstring tendon, and quadriceps tendon autografts, these are not without limitations, including knee-related donor site morbidity, decreased range of motion, and potential for anterior knee pain. Therefore, researchers have explored other options, including the peroneus longus (PL) autograft. Indication: Anterior cruciate ligament (ACL) reconstruction (both primary and revision), as well as multiligament reconstruction, particularly in areas where access to allografts is limited. Surgical Technique: A 3-cm longitudinal skin incision is placed 2 fingerbreadths (or 3 cm) proximal to the tip of the lateral malleolus, and 3 mm posterior to the fibula. The PL and peroneus brevis tendons are identified and isolated, followed by a tenodesis at the distal limit of the incision. The PL is whipstitched proximal to the tenodesis site, and then incised between the tenodesis and whipstitched portion. A closed tendon stripper is inserted and advanced proximally until the PL graft is released. Discussion/Conclusion: PL autograft harvest has been shown to generate thicker and longer grafts relative to the semitendinosus, with demonstrated efficacy in terms of both biomechanical and clinical outcomes. Current literature points largely to a good safety profile, although there is still conflicting evidence in terms of foot and ankle morbidity and no mid- to long-term follow-up data available. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form.

Background: Genu recurvatum is a challenging disorder and can negatively affect knee biomechanics, as reflected in its role as a risk factor for knee ligament injury and poor outcomes following ligament reconstruction or arthroplasty. Indication: Pathological recurvatum should be addressed in the presence of a causative correctible structural abnormality, whether due to decreased posterior tibial slope or due to multiligament injury. We described a posterior oblique ligament (POL) advancement technique for the treatment of knee recurvatum. Technique Description: After completion of all concomitant procedures such as ligament reconstructions, the procedure is initiated with a medial approach. The POL is isolated with an inverted L-shaped dissection and mobilized. Mattress sutures are passed through the resulting POL flap, and are re-tensioned and fixed anteriorly and distally, with the knee close to extension, in order for the imbrication to restrain hyperextension. Results: Anecdotal evidence points to satisfactory control of knee recurvatum postoperatively, which can potentially avoid its deleterious effects in surgical outcomes. Discussion/Conclusion: We present a promising option in the treatment of pathological recurvatum, with favorable cost-efficacy, low morbidity relative to slope-altering osteotomy or posterolateral soft tissue procedures, and focused on the biomechanically demonstrated main restrictors to knee hyperextension. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

IntroductionScreening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency.Methods and findingsData from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with 60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test.ConclusionsThe STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

An online, amendable classifier for detecting malaria parasite country of origin from genomic data is developed using a machine learning approach.

Abstract Background The groundwork for malaria elimination does not currently consider the potential of Plasmodium zoonotic cycles that involve non-human primates (NHPs) in sylvatic environments. Since vivax malaria is less responsive to control measures, finding Plasmodium vivax infected NHPs adds even more concern. Methods Both Free-living monkeys in forest fragments inside the urban area and captive monkeys from a local zoo had blood samples tested for Plasmodium species. Results In this study, among the Neotropical monkeys tested, three (4.4%), one captive and two free-living, were found to be naturally infected by P. vivax. Conclusion This important finding indicates that it is necessary to estimate the extent to which P. vivax NHP infection contributes to the maintenance of malaria transmission to humans. Therefore, the discussion on wildlife conservation and management must be incorporated into the malaria elimination agenda.

We report an imported case of myositis caused by a rare parasite, Haycocknema perplexum, in Australia in a 37-year-old man who had progressive facial, axial, and limb weakness, dysphagia, dysphonia, increased levels of creatine kinase and hepatic aminotransferases, and peripheral eosinophilia for 8 years. He was given extended, high-dose albendazole.

Early damage detection plays an essential role in the safe and satisfactory maintenance of structures. This work investigates techniques that use only damaged structure responses. A Timoshenko beam was modeled in finite element method, and an additional mass was applied along their length. Thus, a frequency-shift curve is observed, and different damage identification techniques were used, such as the discrete wavelet transform and the derivatives of the frequency-shift curve. A new index called wavelet damage ratio (WDR) was defined as a metric to measure the damage levels. Damages were simulated like a mass discontinuity (mass damage). It was evaluated for different damage levels and positions. Numerical results showed that all proposed techniques are efficient for damage identification in Timoshenko beams with low computational cost and practical application

Multiple factors, including vaccine platform and prior vaccinations, influence vaccine responses. We compared antibody responses to CoronaVac (Sinovac) and ChAdOx1-S (AstraZeneca-Oxford) vaccination in 874 healthcare workers in Brazil. As participants were randomised to BCG vaccination or placebo in the preceding 0-6 months as part of the BCG vaccination to reduce the impact of COVID-19 in healthcare workers (BRACE) trial, we also investigated the influence of recent BCG vaccination on antibody responses to these COVID-19 vaccines. Twenty-eight days after the second dose of each vaccine, ChAdOx1-S induced a stronger anti-spike IgG response than CoronaVac vaccination. Recent BCG vaccination did not impact IgG antibody responses to ChAdOx1-S or CoronaVac.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.

Diagnostic reference levels (DRLs) are a pivotal strategy to be implemented since pediatric interventional cardiology procedures are increasing. This work aimed to propose an initial set of Brazilian DRLs for pediatric interventional diagnostic and therapeutic (D&T) procedures. A retrospective study was carried out in four Brazilian states, distributed across the three regions of the country. Data were collected from pediatric patients undergoing cardiac interventional procedures (CIPs), including their age and anthropometric characteristics, and at least four parameters (number of images, exposure time, air kerma–area product—PKA, and cumulative air kerma). Data from 279 patients undergoing CIPs were gathered (147 diagnostic and 132 therapeutic procedures). There were no significant differences in exposure time and the number of images between the D&T procedures. A wide range of PKA was observed when the therapeutic procedures were compared to diagnostics for all age groups. There were significant differences between the D&T procedures, whether grouping data by patient weight or age. In terms of cumulative air kerma, it was noted that no value exceeded the level to trigger a monitoring process for patients. This study shows that it is possible to adopt them as the first proposal to establish national DRLs considering pediatric patient groups.

Abstract The exact path leading to cognitive impairment that goes beyond malaria is unclear, but it appears to be the result of interactive factors. Time of exposure to disease and recurrences are potentially major determinant variables. Cognitive impairment is described mainly in children, rarely in adults. The disease in high endemic areas usually does not affect elderlies, because of acquired immunity over time. However, this population is relatively more frequently sick in lower endemic areas, such as in the Amazon. This study assessed the effect of Plasmodium vivax malaria on the executive and cognitive functions of elderlies, in the Brazilian Amazon. A cohort study was conducted to evaluate executive and cognitive functions one week (T0), two months (T2) and eight months (T8) after the malaria episode. Mini-Mental State Examination (MMSE), Beck Depression Inventory II (BDI-II), Clock Drawing Test (CDT), Wechsler adult intelligence scale (WAIS-III), and Wisconsin Card Sorting Test (WCST) were used to assess executive and cognitive functions. One hundred-forty elderlies were enrolled (70 with P. vivax malaria and 70 without malaria). P. vivax malaria was associated with impairment of the executive and cognitive functions in elderlies for up to 8 months after acute P. vivax malaria. Prior history of malaria, recurrences and higher parasitemia were independently associated with various surrogates of executive and cognitive impairment. With the increase in life expectancy, elderlies living in malaria endemic areas will deserve more attention from health authorities, to guarantee improvement of their quality of life in the tropics.

Abstract Queens of Atta sexdens Forel (Hymenoptera: Formicidae) face biotic and abiotic environmental factors in the environment while establishing their nests. Biotic factors such as predation, microbial pathogens, successful symbiotic fungus regurgitation, excavation effort and abiotic factors such as radiant sunlight, temperature, density, and soil moisture exert selection pressures on ant queens. Biotic factors such as temperature and solar irradiation affect the survival of the initial colony differently, in different environments in the field. Queens of the leaf-cutting ant A. sexdens, were installed in sunny and shaded conditions to test this hypothesis. Two hundred A. sexdens queens were collected and individualized in two experimental areas (sunny and shaded), each in an experimental area (25 m2) in the center of a square (50 × 50 cm). Temperature, irradiance, nest depth, rainfall and queen mortality were evaluated. Atta sexdens colony development was better in the shaded environment, and the depth and volume of the initial chamber, fungus garden biomass and number of eggs, larvae, pupae and workers were greater. The queen masses were similar in both environments but mortality was higher in the sunny environment. The worse parameter values for A. sexdens nests in the sunny environment are due to the greater solar irradiance, increasing the variation range of the internal temperature of the initial chamber of the nest. On the other hand, the more stable internal temperature of this chamber in the shaded environment, is due to the lower incidence of solar irradiance, which is also more advantageous for queen survival and the formation and development of A. sexdens colonies. Shaded environments are a better micro habitat for nesting A. sexdens than sunny ones.

Mites of the genus Thyreophagus (Acari: Acaridae) are distributed worldwide; they inhabit concealed habitats and include several beneficial and economically important species. However, species identification is difficult because many species are poorly described or delimited and their phoretic stages are unknown or uncorrelated. Furthermore, Thyreophagus is interesting because it includes entirely asexual (parthenogenetic) species. However, among the 34 described species of Thyreophagus, the asexual status is confirmed through laboratory rearing for only two species. Here, we provide detailed descriptions of five new species from North America (four) and Europe (one) based on adults and phoretic heteromorphic deutonymphs. Four of these species were asexual, while one was sexual. For most of these mites, the asexual status was confirmed and phoretic deutonymphs were obtained through rearing in the lab. We show that asexual mites retain seemingly functional copulatory and sperm storage systems, indicating that these lineages have relatively short evolutionary lifespans. One North American species, Thyreophagus ojibwe, was found in association with the native American chestnut Castanea dentata, suggesting a possibility that this mite can be used to control chestnut blight in North America. We also provide a diagnostic key to females, males, and heteromorphic deutonymphs of the Thyreophagus species in the world.

A lack of control over blood loss can have catastrophic implications, including death. Although several hemostatic medications have been employed to reduce bleeding, a vast majority of them are ineffective, expensive, or pose health risks to the patient. To overcome these constraints, chitosan-polyethylene glycol (CS-PEG) hemostatic gels loaded with ethanolic extract of Jatropha mollissima sap (EES) were prepared and their hemostatic, physicochemical, and cytotoxic properties were evaluated. The gels were produced by mixing CS with PEG (an external plasticizer) and EES. The phytochemical analysis revealed a significant concentration of total polyphenols and tannins content in the extract and catechin was identified as one of the key compounds of EES. Infrared spectroscopy analysis revealed the presence of EES in the gels, as well as the chemical interaction between CS and PEG. The gels were thermally stable between 25 and 37 °C (ambient and human body temperature range), had pseudoplastic deformation behavior (rheological properties preserved after shearing), were simple to inject (compression force 30 N), and were biocompatible. In vivo experiments showed that both CS-PEG-EES gels exhibited greater hemostatic action in preventing tail hemorrhage in Wistar rats, with decreased bleeding time and blood weight compared with unloaded CS-PEG gels (control groups) and Hemostank, a commercial product. However, the gel prepared with acetic acid was more efficient in controlling bleeding. These findings reveal that CS-PEG-EES gels can reduce hemorrhages and are a potent, simple, and safe hemostatic agent.

Type IV pilus (TFP) is a multifunctional bacterial structure involved in twitching motility, adhesion, biofilm formation, as well as natural competence. Here, by site-directed mutagenesis and functional analysis, we determined the phenotype conferred by each of the 38 genes known to be required for TFP biosynthesis and regulation in the reemergent plant pathogenic fastidious prokaryote Xylella fastidiosa. This pathogen infects > 650 plant species and causes devastating diseases worldwide in olives, grapes, blueberries, and almonds, among others. This xylem-limited, insect-transmitted pathogen lives constantly under flow conditions and therefore is highly dependent on TFP for host colonization. In addition, TFP-mediated natural transformation is a process that impacts genomic diversity and environmental fitness. Phenotypic characterization of the mutants showed that ten genes were essential for both movement and natural competence. Interestingly, seven sets of paralogs exist, and mutations showed opposing phenotypes, indicating evolutionary neofunctionalization of subunits within TFP. The minor pilin FimT3 was the only protein exclusively required for natural competence. By combining approaches of molecular microbiology, structural biology, and biochemistry, we determined that the minor pilin FimT3 (but not the other two FimT paralogs) is the DNA receptor in TFP of X. fastidiosa and constitutes an example of neofunctionalization. FimT3 is conserved among X. fastidiosa strains and binds DNA non-specifically via an electropositive surface identified by homolog modeling. This protein surface includes two arginine residues that were exchanged with alanine and shown to be involved in DNA binding. Among plant pathogens, fimT3 was found in ~ 10% of the available genomes of the plant associated Xanthomonadaceae family, which are yet to be assessed for natural competence (besides X. fastidiosa). Overall, we highlight here the complex regulation of TFP in X. fastidiosa, providing a blueprint to understand TFP in other bacteria living under flow conditions.

Abstract Aims To evaluate a telemonitoring strategy based on automated text messaging and telephone support after heart failure (HF) hospitalization. Methods and results The MESSAGE‐HF study is a prospective multicentre, randomized, nationwide trial enrolling patients from 30 clinics in all regions of Brazil. HF patients with reduced left ventricular ejection fraction (

Background Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models.Methods We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models.Results Analyzing human CRC samples revealed that MCs can be active or inactive in this disease. An activated MC population decreased the number of tumor-residing CD8 T cells. In mice, MC deficiency decreased the development of CA-CRC lesions, while it increased the density of tumor-based CD8 infiltration. Furthermore, co-culture experiments revealed that tumor-primed MCs promote apoptosis in CRC cells. In MC-deficient mice, we found that MCs inhibited the development of sCRC lesions. Further exploration of this with several GEM models confirmed that different immune responses alter and are altered by MC activity, which directly alters colon tumorigenesis. Since rescuing MC activity with bone marrow transplantation in MC-deficient mice or pharmacologically inhibiting MC effects impacts the development of sCRC lesions, we explored its therapeutic potential against CRC. MC activity promoted CRC cell engraftment by inhibiting CD8+ cell infiltration in tumors, pharmacologically blocking it inhibits the ability of allograft tumors to develop. This therapeutic strategy potentiated the cytotoxic activity of fluorouracil chemotherapy.Conclusion Therefore, we suggest that MCs have a dual role throughout CRC development and are potential druggable targets against this disease.

Este ensaio contempla, em perspectiva comparada, três grandes romances da Literatura Mundial: Grande Sertão: Veredas (1956), A Montanha Mágica (1924) e Os Anos de Aprendizado de Wilhelm Meister (1795/6). Após breve consideração introdutória sobre o motivo astrológico, a argumentação crítica se concentra nos procedimentos mobilizados pelo eu-narrador rosiano, a fim de exprimir sua complexa vivência do decurso temporal. Sob esse enfoque, a análise se estende ao romance de Thomas Mann, paradigma da reflexão romanesca sobre o fenômeno “tempo”. Em seguida, se procede, também em visada comparativa, à investigação de outros tópicos, voltados à simbologia do número sete, ao motivo do pacto e, ainda, ao significado do dinheiro e da propriedade privada na economia romanesca. Deste último ponto desprendeu-se a necessidade de incorporar à discussão o romance goethiano, fundador do Bildungsroman. Uma breve consideração de cunho ecocrítico se constitui como fecho do ensaio.

This paper presents a detailed derivation of the small-signal model and components design considerations for the Quasi-Y-Source inverter. The design methodology is based on the converter steady-state operation, considering the impedance network inductor and capacitor voltage and charge balances, respectively. Moreover, the additional design criteria for component selection, considering control constraints and performance compromise, are given by parametric variation analysis based on converter dynamic response. The small-signal model and transfer functions are obtained using a state-space averaged model, including converter non-ideal characteristics given by equivalent-series resistances (ESR), which makes possible the proposition of different control strategies, using both single or multi-loop schemes. To demonstrate the usefulness of the proposed small-signal model, a DSP-based single-loop type-II PI control strategy is used in which the peak DC-link voltage is indirectly controlled through the measurement of the impedance network capacitor voltage. The controller and converter performances are verified with simulation and experimental results and successfully confirm the validity of the proposed dynamic model. Finally, the obtained results are validated with a built small-scale three-phase/three-wire inverter prototype.

Abstract We calculate the small-momentum expansion of vector, axial-vector, scalar, and pseudo-scalar heavy-quark current correlators in the large-β 0 limit of QCD, extending the analysis of Grozin and Sturm beyond the vector current. Our results are used to study the higher-order behaviour of dimensionless ratios of vector and pseudo-scalar moments used for the precise extraction of the strong coupling, α s , from relativistic quarkonium sum rules and lattice data, respectively. We show that these ratios benefit from a partial cancellation of the leading renormalon singularities. Our results can guide the design of combinations of moments with improved perturbative behaviour.

ABSTRACT Background: Increasing numbers of mutations causing monogenic forms of Parkinson's disease (PD) have been described, mostly among patients in Europe and North America. Since genetic architecture varies between different populations, studying the specific genetic profile of Brazilian patients is essential for improving genetic counseling and for selecting patients for clinical trials. Objective: We conducted a systematic review to identify genetic studies on Brazilian patients and to set a background for future studies on monogenic forms of PD in Brazil. Methods: We searched MEDLINE, EMBASE and Web of Science from inception to December 2019 using terms for "Parkinson's disease", "genetics" and "Brazil". Two independent reviewers extracted the data. For the genes LRRK2 and PRKN, the estimated prevalence was calculated for each study, and a meta-analysis was performed. Results: A total of 32 studies were included, comprising 94 Brazilian patients with PD with a causative mutation, identified from among 2,872 screened patients (3.2%). PRKN mutations were causative of PD in 48 patients out of 576 (8.3%). LRRK2 mutations were identified in 40 out of 1,556 patients (2.5%), and p.G2019S was the most common mutation (2.2%). Conclusions: PRKN is the most common autosomal recessive cause of PD, and LRRK2 is the most common autosomal dominant form. We observed that there was a lack of robust epidemiological studies on PD genetics in Brazil and, especially, that the diversity of Brazil’s population had not been considered.