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The Deepwater Horizon explosion in April 2010 and subsequent oil spill released 3.19 × 106 barrels (5.07 × 108 l) of MC252 crude oil into important foraging areas of the endangered Kemp’s ridley sea turtle Lepidochelys kempii (Lk) in the northern Gulf of Mexico (GoM). We measured δ13C and δ15N in scute biopsy samples from 33 Lk nesting in Texas during the period 2010 to 2012. Of these, 27 were equipped with satellite transmitters and were tracked to traditional foraging areas in the northern GoM after the spill. Differences in δ13C between the oldest and newest scute layers from 2010 nesters were not significant, but δ13C in the newest layers from 2011 and 2012 nesters was significantly lower compared to 2010. δ15N differences were not statistically significant. Collectively, the stable isotope and tracking data indicate that the lower δ13C values reflect the incorporation of oil rather than changes in diet or foraging area. Discriminant analysis indicated that 51.5% of the turtles sampled had isotope signatures indicating oil exposure. Growth of the Lk population slowed in the years following the spill. The involvement of oil exposure in recent population trends is unknown, but long-term effects may not be evident for many years. Our results indicate that C isotope signatures in scutes may be useful biomarkers of sea turtle exposure to oil.

We proposed to use artificial channels in laboratory assays to expose periphyton to substances released in rural environments in order to test the following hypotheses 1) a high concentration of humic substances decreases the biofilm biomass and alters its metabolism; 2) periphyton biomass and metabolism increase in response to nutrient addition in spite of the previous high nutrient concentration; 3) periphyton response to nutrient addition is smaller in the presence of humic acids. Nutrient loading associated with nonpoint pollution often occurs both during and after signiûcant precipitation events. Humic acids also increase their levels after rain. This may limit the availability of light and thus, the development of the autotrophic community. However, the influence of these pollutants on periphyton in eutrophic environments may be either modest or too difficult to detect using traditional endpoints. We found that in short exposures: 1) humic substances do not decrease the biomass of periphyton nor alter its metabolism; 2) periphyton biomass and metabolism increase in response to the addition of fertilizer but not to the addition of a single nutrient; 3) periphyton response to nutrient addition is smaller in the presence of humic acids. These finding have implications for river ecosystems as they suggest that changes produced by nutrient inputs into the eutrophic stream could be fast and clearly affect periphyton algae and other related organisms such as grazers and decomposers. In addition, the presence of humic acids decreases these responses. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development is the non-invasive therapeutic access to the motor cortex currently limited by the presence of the blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS + MB ) treatment is an emerging technology that was successfully used in ALS patients to temporarily open the cortical BBB. However, FUS + MB -mediated drug delivery across ALS patients' BBB has not yet been reported. Similarly, the effects of FUS + MB on human ALS BBB cells remain unexplored., Methods: Here we established the first FUS + MB -compatible, fully-human ALS patient-cell-derived BBB model based on induced brain endothelial-like cells (iBECs) to study anti-TDP-43 antibody delivery and FUS + MB bioeffects in vitro., Results: Generated ALS iBECs recapitulated disease-specific hallmarks of BBB pathology, including reduced BBB integrity and permeability, and TDP-43 proteinopathy. The results also identified differences between sporadic ALS and familial (C9orf72 expansion carrying) ALS iBECs reflecting patient heterogeneity associated with disease subgroups. Studies in these models revealed successful ALS iBEC monolayer opening in vitro with no adverse cellular effects of FUS + MB as reflected by lactate dehydrogenase (LDH) release viability assay and the lack of visible monolayer damage or morphology change in FUS + MB treated cells. This was accompanied by the molecular bioeffects of FUS + MB in ALS iBECs including changes in expression of tight and adherens junction markers, and drug transporter and inflammatory mediators, with sporadic and C9orf72 ALS iBECs generating transient specific responses. Additionally, we demonstrated an effective increase in the delivery of anti-TDP-43 antibody with FUS + MB in C9orf72 (2.7-fold) and sporadic (1.9-fold) ALS iBECs providing the first proof-of-concept evidence that FUS + MB can be used to enhance the permeability of large molecule therapeutics across the BBB in a human ALS in vitro model., Conclusions: Together, this study describes the first characterisation of cellular and molecular responses of ALS iBECs to FUS + MB and provides a fully-human platform for FUS + MB -mediated drug delivery screening on an ALS BBB in vitro model., (© 2024. The Author(s).)

Introduction: Veterinary oncology is constituted mainly by human-use drugs with hazardous agents. Occupational risks are present in all stages of handling. Many studies highlighted that veterinarians and pharmacists staff present a lack of knowledge and insufficient structure for promoting safety practices. This study investigated the professional profile and structure of veterinary antineoplastic chemotherapy in Brazilian services., Methods: A nationwide survey was carried out through digital platforms by a self-applicable from 2020 to 2021. The characteristics of the structure, facilities, professional profiles, practices related to antineoplastic chemotherapy services, and inspections provided by regulatory companies were investigated. Frequency and ranges were used to examine and describe data., Results: This study analyzed 108 respondents from all Brazilian regions where 36 participants worked in veterinary oncology. Dogs and cats comprised more than 90% of animals assisted. Vincristine, doxorubicin, carboplatin, vinblastine, and cyclophosphamide were the most commonly used drugs. Considering pharmacists-led (n = 4) vs veterinarians-led (n = 18) services, structure with safety for handling hazardous drugs (4 vs 9), correct PPE usage (3 vs 0), and occurrence of occupational accident (0 vs 5) were registered. Almost 60% were dissatisfied with the structure and the managerial unwillingness to promote facility improvements. The majority of participants reported an absence of service inspection., Conclusion: The results demonstrated worrying concerning the inadequacy of the physical structure of the facilities, human resources, and handling hazardous drugs increased occupational health risk. The lack of competent authority standards and supervision corroborates practices that expose professionals, the population, and the environment to hazardous agents., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with Hemophilia are continually monitored at treatment centers to avoid and control bleeding episodes. This study estimated the direct and indirect costs per patient with hemophilia A in Brazil and evaluated the cost variability across different age groups., Methods: A prospective observational research was conducted with retrospective data collection of patients assisted at three referral blood centers in Brazil. Time-driven Activity-based Costing method was used to analyze direct costs, while indirect costs were estimated based on interviews with family and caregivers. Cost per patient was analyzed according to age categories, stratified into 3 groups (0-11;12-18 or older than 19 years old). The non-parametric Mann-Whitney test was used to confirm the differences in costs across groups., Results: Data from 140 hemophilia A patients were analyzed; 53 were 0-11 years, 29 were 12-18 years, and the remaining were older than 19 years. The median cost per patient per year was R$450,831 (IQR R$219,842; R$785,149; $174,566), being possible to confirm age as a cost driver: older patients had higher costs than younger's (p = 0.001; median cost: 0-11 yrs R$299,320; 12-18 yrs R$521,936; ≥19 yrs R$718,969)., Conclusion: This study is innovative in providing cost information for hemophilia A using a microcosting technique. The variation in costs across patient age groups can sustain more accurate health policies driven to increase access to cutting-edge technologies and reduce the burden of the disease., (© 2024. The Author(s).)

The advancement of nanobiocomposites reinforced with 2D nano-materials plays a pivotal role in enhancing bone tissue engineering. In this study, we introduce a nanobiocomposite that reinforces bovine collagen with 2D nano-talc, a recently exfoliated nano-mineral. These nanobiocomposites were prepared by blending collagen with varying concentrations of 2D nano-talc, encompassing mono- and few-layers talc from soapstone nanomaterial. Extensive characterization techniques including AFM, XPS, nano-FTIR, s-SNOM nanoimaging, Force Spectroscopy, and PeakForce QNM® were employed. The incorporation of 2D nano-talc significantly enhanced the mechanical properties of the nanobiocomposites, resulting in increased stiffness compared to pristine collagen. In vitro studies supported the growth and proliferation of osteoblasts onto 2D nano-talc-reinforced nanobiocomposites, as well as showed the highest mineralization potential. These findings highlight the substantial potential of the developed nanobiocomposite as a scaffold material for bone tissue engineering applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1 , an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis., 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 © 2024 da Silva Costa, Ito, da Cruz, De Souza, Rios, Bertozzo, Camargo, Viturino, Lanaro, de Albuquerque, do Canto, Saad, Ospina-Prieto, Ozelo, Costa and de Melo.)

Background: Colorectal cancer (CRC) is the second leading cause of cancer death in US adults but can be reduced by screening. The roles of individual and contextual factors, and especially physician supply, in attaining universal CRC screening remains uncertain., Methods: We used data from adults 50-75 years old participating in the 2018 New York (NY) Behavioural Risk Factor Surveillance System linked to county-level covariates, including primary care physician (PCP) density and gastroenterologist (GI) density. Data were analysed in 2023-2024. Our analyses included (1) ecological and geospatial analyses of county-level CRC screening prevalence and (2) individual-level Poisson regression models of receipt of screening, adjusted for socioeconomic and county-level contextual variables., Results: Mean prevalence of up-to-date CRC screening was 71% (95% CI 70% to 73%) across NY's 62 counties. County-level CRC screening demonstrated significant spatial patterning (Global Moran's I=0.14, p=0.04), consistent with the existence of county-level contextual factors. In both county-level and individual-level analyses, lack of health insurance was associated with lower likelihood of up-to-date screening (ß=-1.09 (95% CI -2.00 to -0.19); adjusted prevalence ratio 0.68 (95% CI 0.60 to 0.77)), even accounting for age, race/ethnicity and education. In contrast, county-level densities of both PCPs and GIs were completely unassociated with screening at either the county or individual level. As expected, other determinants at the individual level included education status and age., Conclusion: In this state-wide representative analysis, physician density was completely unassociated with CRC screening, although health insurance status remains strongly related. In similar screening environments, broadened insurance coverage for CRC screening is likely to improve screening far more effectively than increased physician supply., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited., Aim: To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code., Methods: REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed., Results: The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients., Conclusions: Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

The objective of this study was to create injectable photo-crosslinkable biomaterials, using gelatin methacryloyl (GelMA) hydrogel, combined with a decellularized bone matrix (BMdc) and a deproteinized (BMdp) bovine bone matrix. These were intended to serve as bioactive scaffolds for dentin regeneration. The parameters for GelMA hydrogel fabrication were initially selected, followed by the incorporation of BMdc and BMdp at a 1% (w/v) ratio. Nano-hydroxyapatite (nHA) was also included as a control. A physicochemical characterization was conducted, with FTIR analysis indicating that the mineral phase was complexed with GelMA, and BMdc was chemically bonded to the amide groups of gelatin. The porous structure was preserved post-BMdc incorporation, with bone particles incorporated alongside the pores. Conversely, the mineral phase was situated inside the pore opening, affecting the degree of porosity. The mineral phase did not modify the degradability of GelMA, even under conditions of type I collagenase-mediated enzymatic challenge, allowing hydrogel injection and increased mechanical strength. Subsequently, human dental pulp cells (HDPCs) were seeded onto the hydrogels. The cells remained viable and proliferative, irrespective of the GelMA composition. All mineral phases resulted in a significant increase in alkaline phosphatase activity and mineralized matrix deposition. However, GelMA-BMdc exhibited higher cell expression values, significantly surpassing those of all other formulations. In conclusion, our results showed that GelMA-BMdc produced a porous and stable hydrogel, capable of enhancing odontoblastic differentiation and mineral deposition when in contact with HDPCs, thereby showing potential for dentin regeneration., (© 2024 Wiley Periodicals LLC.)

Human mobility has challenged malaria elimination efforts and remains difficult to routinely track. In Brazil, administrative records from the Ministry of Health allow monitoring of mobility locally and internationally. Although most imported malaria cases are between municipalities in Brazil, detailed knowledge of patterns of mobility is limited. Here, we address this gap by quantifying and describing patterns of malaria-infected individuals across the Amazon. We used network analysis, spatial clustering, and linear models to quantify and characterize the movement of malaria cases in Brazil between 2004 and 2022. We identified sources and sinks of malaria within and between states. We found that between-state movement of cases has become proportionally more important than within-state, that source clusters persisted longer than sink clusters, that movement of cases into sinks was seasonal while movement out of sources was not, and that importation is an impediment for subnational elimination in many municipalities. We elucidate the vast travel networks of malaria infected individuals that characterize the Amazon region. Uncovering patterns of malaria case mobility is vital for effective microstratification within Brazil. Our results have implications for intervention stratification across Brazil in line with the country's goal of malaria elimination by 2035., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arisco 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.)

Competing Interests: CR is CEO and founder of Scottish Brain Sciences and has been a paid consultant on advisory boards for Actinogen, Biogen, CogState, Eisai, Eli Lilly, Janssen Cilag, Merck, Novo Nordisk, Roche Diagnostics, and Signant Health. KB has served as a consultant at advisory boards or data monitoring committees for Acumen, Alzpath, BioArctic, Biogen, Eisai, Julius Clinical, Lilly, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions (BBS) in Gothenburg AB, which is part of the GU Ventures Incubator Program, outside of the present work. JDG has received research support from GE Healthcare, F. Hoffmann-La Roche, and Roche Diagnostics, and speaker or consultant fees from Biogen, Philips Nederlands, and Roche Diagnostics. SJ has served as a consultant for Alzpath, Merck, and Roche Diagnostics, and has also received equipment grants from Roche Diagnostics. IvM has served as a consultant for Roche Diagnostics, received grants from ZonMW, and received PPP allowance from Health~Holland (Top Sector Life Sciences & Health). LV has served as a consultant for Roche Diagnostics and has received research support from Alzheimer Nederland, OLINK, and ZonMw; all payments were made to her institution. MS-C has served as a consultant and attended advisory boards for, and received project grants from, Roche Diagnostics, and has given lectures in symposia sponsored by Roche Diagnostics, S.L.U., Roche Farma, S.A., and Roche Sistemas de Diagnósticos, Sociedade Unipessoal, Lda; all payments for consultancy, advisory boards, and project grants were made to his institution; payments for giving lectures in symposia were made to MS-C directly and his institution. CPM and MHSC are employees of Gates Ventures LLC and volunteer for the Alzheimer's Disease Data Initiative. CAL is an employee and shareholder of Roche Diagnostics GmbH. F-CQ is a former employee and shareholder (during employment) of Roche Diagnostics International Ltd, and Altoida Inc. MCD and MC are employees and shareholders of Roche Diagnostics International Ltd. AA, ER, and OC are employees of Nagarro. The authors declare that this work received funding from Roche Diagnostics International Ltd. The funder had the following involvement: provided support and resources for the Hackathon event; and funded medical writing support for publication of this article.

Rural workers are disproportionally exposed to pesticides and might be at an increased risk of developing chronic diseases. Here, we investigated the impact of pesticide exposure on breast cancer (BC) risk and disease profile in rural female workers. This is a case-control study that prospectively included 758 individuals. The study was conducted in the Southwest region of Paraná state in Brazil, a region characterized by family-based agriculture and intensive use of pesticides. We found that this region has a 41% higher BC diagnosis rate and 14% higher BC mortality rate than the mean rates in Brazil, as well as a pesticide trade volume about 6 times higher than the national average. We showed substantial exposure in this population and found that even women who did not work in the fields but performed equipment decontamination and clothes washing of male partners who worked in the fields had urine samples positive for glyphosate, atrazine, and/or 2,4-D. The crude association showed a significantly higher risk of BC among women exposed to pesticides (OR: 1.58, 95% CI 1.18-2.13). Adjusted analyses showed a lower and nonstatistically significant association (OR: 1.30, 95% CI 41 0.87-1.95). Stratification on disease profile showed a significantly higher risk of lymph node metastasis (adjusted OR: 2.19, 95% CI 1.31-3.72) in women exposed to pesticides. Our findings suggest that female populations exposed to pesticides are at a higher risk of developing BC with a more aggressive profile and draw attention to the need to monitor rural populations potentially exposed to pesticides in the field or at home.

Komagataella phaffii (formerly Pichia pastoris ) is a methylotrophic yeast widely used in laboratories around the world to produce recombinant proteins. Given its advantageous features, it has also gained much interest in the context of modern biotechnology. In this review, we present the utilization of K. phaffii as a platform to produce several products of economic interest such as biopharmaceuticals, renewable chemicals, fuels, biomaterials, and food/feed products. Finally, we present synthetic biology approaches currently used for strain engineering, aiming at the production of new bioproducts.

This study presents the initial results of a pilot project using the Elucis Virtual Reality (VR) platform for fetal heart segmentation. Twelve fetal heart cases, ranging in gestational age from 24 to 30 weeks, including various cardiac conditions, were reconstructed using 3D models facilitated by the Elucis platform's integration of automated algorithms and manual adjustments. The models, which were evaluated by four experts in virtual and 3D printed formats, were of high quality and offered improved visuospatial visualization and detailed anatomical insights. This research highlights the potential of VR technology to improve prenatal diagnosis and planning for complex cardiac conditions, suggesting significant implications for continuing medical education and clinical practice in fetal cardiology., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Competing Interests: The Author declares no conflicts of interest.

Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies., (© 2024. The Author(s).)

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

Background: Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for individuals who were formerly incarcerated in Brazil., Methods: Using published evidence for Brazil, we constructed a Markov state transition model estimating tuberculosis-related health outcomes and costs among individuals who were formerly incarcerated, by simulating transitions between health states over time. The analysis compared tuberculosis infection screening and TPT, to no screening, considering a combination of M tuberculosis infection tests and TPT regimens. We quantified health effects as reductions in tuberculosis cases, tuberculosis deaths, and disability-adjusted life-years (DALYs). We assessed costs from a tuberculosis programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population., Findings: Compared with no intervention, an intervention incorporating tuberculin skin testing and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-56) lifetime tuberculosis cases and 4·1 (1·4-5·8) lifetime tuberculosis deaths per 1000 individuals, and cost US$242 per DALY averted. All test and regimen combinations were cost-effective compared with no screening. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favourable cost-effectiveness ratios, although the intervention was cost-effective for all subgroups examined., Interpretation: M tuberculosis infection screening and TPT for individuals who were formerly incarcerated appears cost-effective, and would provide valuable health gains., Funding: National Institutes of Health., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil., Methods: We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment., Results: Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT)., Conclusion: The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil., (© 2024. The Author(s).)

The aim of this study was to evaluate the convergence between the domains of the Autoquestionnaire Qualité de Vie Enfant image (AUQUEI) and the Child Perceptions Questionnaire (CPQ8-10) in the mixed dentition. A sample of 676 children aged 8 to 10 years responded to the health-related quality of life (HRQoL) and oral health-related quality of life (OHRQoL) questionnaires using the AUQUEI and the CPQ8-10, respectively. Clinical (dental caries and malocclusion) and socioeconomic variables were assessed. The validity of convergence between scores (total and per domain) of the two instruments was assessed by Spearman correlation analysis, considering that non-zero coefficient values represented a correlation between scores. The median was calculated to compare the scores of each questionnaire relative to the variables, and the nonparametric Mann-Whitney test was applied to determine statistically significant differences between the categories. A weak significant correlation (between 0.30 and 0.50) was observed between the domains and the total scores of instruments (p < 0.05), except for the leisure domain (p > 0.05). Participants with a lower family income had worse HRQoL (p < 0.05), and those with caries and malocclusion experience had worse OHRQoL (p < 0.05). In conclusion, the AUQUEI and CPQ8-10 instruments showed a weak correlation. Income and clinical variables had a negative impact on the AUQUEI and CPQ8-10, respectively.

Poor TB treatment outcomes are observed in patients with type 2 diabetes mellitus (DM) comorbidity and glycemic control throughout treatment may play a role. The objective of this study was to investigate glycemic control longitudinally among Filipino adults undergoing TB treatment using mixed-effects linear and logistic regression. Analyses were conducted in 188 DM-TB patients out of 901 enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, with a median baseline glycosylated hemoglobin (HbA1c) of 8.2% (range 4.5-13.3%). Previous versus new DM diagnosis was associated with higher mean HbA1c (worse glycemic control) during treatment, with a smaller effect amongst those with central obesity (coefficient 0.80, 95% confidence interval [CI] 0.26, 1.57, P = 0.043) than amongst those without central obesity (coefficient 3.48, 95% CI 2.16, 4.80, P<0.001). In those with a new DM diagnosis, central obesity was associated with higher blood glucose (coefficient 1.62, 95% CI 0.72, 2.53, P = 0.009). Of 177 participants with ≥2 HbA1c results, 40% had uncontrolled glycemia (≥2 HbA1c results ≥8%). Of 165 participants with ≥3 HbA1c results, 29.9% had consistently-controlled glycemia, 15.3% had initially-uncontrolled glycemia, and 18.6% had consistently-uncontrolled glycemia. Previous versus new DM diagnosis and glucose-lowering medication use versus no use were associated with having uncontrolled versus controlled glycemia (adjusted odds ratio [aOR] 2.50 95%CI 1.61, 6.05, P = 0.042; aOR 4.78 95% CI 1.61,14.23, P<0.001) and more likely to have consistently-uncontrolled versus consistently-controlled glycemia (adjusted relative risk ratio [aRRR] 5.14 95% CI 1.37, 19.20, P = 0.015; aRRR 10.24 95% CI 0.07, 0.95, P = 0.003). Relapse cases of TB were less likely than new cases to have uncontrolled (aOR 0.20 95%CI 0.06, 0.63, P = 0.031) or consistently-uncontrolled (aRRR 0.25 95%CI 0.07, 0.95, P = 0.042) versus controlled glycemia. Those with long-term DM, suggested by previous diagnosis, glucose-lowering medication use and possibly central obesity, may require additional support to manage blood glucose during TB treatment., 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.)

Purpose of Review: To discuss the recent discoveries and limitations of the available literature on emerging circulating biomarkers of cancer cachexia., Recent Findings: Studies on circulating factors in cancer cachexia show promising alternatives for diagnosing the syndrome in a minimally invasive manner in the clinic setting, as well as potential targets for cancer cachexia treatment. Factors secreted by the tumor and the adipose tissue, such as extracellular vesicles and soluble proteins, respectively, have been shown to either directly induce wasting in vitro and in vivo or to be altered in the cachectic phenotype. The detection and characterization of circulating cells allows detection of the precachectic stage and the levels of the soluble immune checkpoint protein programmed death ligand-1 (PD-L1) are correlated with the presence of the hallmarks of cancer cachexia., Summary: Structural, molecular, and metabolic alterations have been observed in various tissues, revealing the occurrence of sustained inter-compartment crosstalk in cachectic patients. Early diagnosis of cancer cachexia becomes crucial to avoid the establishment of refractory cachexia through the implementation of interventions that may attenuate systemic inflammation and muscle loss. More studies on human cancer cachexia are required in order to address the recently discovered cachexia-associated circulating factors' value as biomarkers of the syndrome., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Nitric Oxide (NO) photocleavable donors are useful tools for interrogating nitric oxide signalling and have potential use in photopharmacological applications. There is currently intensive research into newer methods to improve NO release and kinetic profiles. Herein, we report the design and synthesis of a solid-supported photocleavable NO donor synthesized by ligating an N -nitroso photocleavable nitric oxide derivative to a TentaGel ® polymer resin bead. Illumination with 365 nm light released nitric oxide that could be tracked via a turn-on fluorescence response (λ ex = 450 nm, λ em = 545 nm) and measured using the Griess assay and diaminorhodamine derivatives. These beads were further shown to be compatible with living A549 cells and had the ability to deliver greater concentrations of nitric oxide to cells proximal to a bead versus cells at more distal locations within the same well., Competing Interests: 5.Conflicts of interest A.R.L. declares a financial stake in BioLum Sciences, LLC. This work was funded as a subaward of the NIH grant 1R41GM140575-01 awarded to BioLum Sciences, LLC.

Objective: To longitudinally assess domestic violence (DV) during the postpartum period, identifying types, patterns and determinants of DV, according to mothers' reports in Fortaleza, Brazil., Methods: Data from the Iracema-COVID cohort study interviewed at home mothers who gave birth in the first wave of COVID-19, at 18 and 24 months after birth. Patterns of reported DV were classified as follows: no DV, interrupted DV, started DV and persistent DV. Adjusted multinomial logistic regressions were used to assess factors associated with persistent DV., Results: DV was reported by 19 and 24% of the mothers at 18 and 24 months postpartum, respectively, a 5 percentage points increase. Persistent DV was present in 11% of the households in the period. The most frequent forms of DV were verbal aggression, reported by 17-20% of the mothers at 18 and 24 months, respectively; drunkenness or use of drugs at home, present in 3-5% of the households; physical aggression, reported by 1.2-1.6% of the mothers. Households with two or more forms of DV increased from 2 to 12% in the period. Adjusted factors associated with persistent DV were maternal common mental disorder, family headed by the mother and head of family's poor schooling. Food insecurity was associated with starting DV., Conclusion: Prevalence of DV was considerably high in the postpartum period. DV prevention policies should rely on improving care to women's mental health; preventing food insecurity; and fostering the educational level of young people of both sexes.

Background: Malarial infections are often missed by microscopy, and most parasite carriers are asymptomatic in low-endemicity settings. Whether parasite detectability and its ability to elicit symptoms change as transmission declines remains unclear., Methods: We performed a prospective panel survey with repeated measurements on the same participants over 12 months to investigate whether Plasmodium vivax detectability by microscopy and risk of symptoms upon infection varied during a community-wide larviciding intervention in the Amazon basin of Brazil that markedly reduced vector density. We screened 1096 to 1400 residents in the intervention site for malaria by microscopy and quantitative TaqMan assays at baseline and twice during intervention., Results: We found that more P vivax infections than expected from their parasite densities measured by TaqMan assays were missed by microscopy as transmission decreased. At lower transmission, study participants appeared to tolerate higher P vivax loads without developing symptoms. We hypothesize that changes in the ratio between circulating parasites and those that accumulate in the bone marrow and spleen, by avoiding peripheral blood microscopy detection, account for decreased parasite detectability and lower risk of symptoms under low transmission., Conclusions: P vivax infections are more likely to be subpatent and remain asymptomatic as malaria transmission decreases., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The study of the emergence and stability of bimanual and interlimb coordination patterns in children with Developmental Coordination Disorder (DCD) has shown that they encounter greater difficulties in coupling their limbs compared to typically developing (TD) children. Verbal cues have been identified as strategies to direct children's attention to more relevant task information, thus potentially improving motor performance. Consequently, this study investigated the effect of providing verbal cues on the execution of bimanual tasks in children with and without probable DCD. Twenty-eight children aged 9-10, matched by age and gender, were divided into two groups: pDCD [n = 14] and TD. The children performed bilateral trajectory movements with both hands (horizontal back-and-forth), holding a pen on a tablet, in anti-phase (180°) coordination pattern, in two conditions: No cues and Verbal cues. In the last condition, children received verbal cues to maintain the anti-phase pattern even with an increase in hand oscillation frequency. Relative phase and variability of relative phase between the hands were calculated for analysis of pattern coupling and stability. Hand cycles, movement amplitude, and tablet pressure force were calculated to analyze pattern control parameters. All these variables were compared between groups and conditions. The results indicated that despite the pDCD group showing greater variability in the anti-phase coordination pattern compared to the TD group, both groups performed better in the Verbal cues than the No cues condition. Furthermore, the pDCD group exhibited more hand movement cycles and applied greater pressure force compared to the TD group, suggesting different motor control strategies during the bimanual task. It is suggested that the use of verbal cues during bimanual task execution improves children's performance, potentially by promoting interaction between attention, as a cognitive function, and intrinsic coordination dynamics, thereby reducing variability in the perceptual-motor system., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Gun violence is the leading cause of death for youth. This study examined an academic-community partnership to address gun violence through a strength-based approach called Asset-Based Community Development., Methods: We used a case study design. Participants were Black youth who encounter frequent gun violence (average age = 16.7 years; 72% male). Our partnership involved survey development/completion and semistructured discussions. We also interviewed community stakeholders to collect data on local assets. We interpreted data through a communitywide forum to guide social action to address gun violence., Results: The majority of youth (76%) witnessed neighborhood violence in the last year. The top youth concerns related to gun violence included poverty, guns, and gangs. Community stakeholders saw local people and local organizations as primary community assets. A community forum to interpret these data led to social action in the form of an environmental strategy-cleaning up an unused commercial building for the development of a youth tech center. The majority of youth participants (89.5%) agreed or strongly agreed that they had a voice in the research process., Conclusion: Participatory research that takes an asset-based approach can enable relevant inquiry that engages youth and guides social action to address gun violence., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: During the COVID-19 pandemic, the literature highlighted an increased risk of child abuse and the use of negative parenting practices. Furthermore, pregnancy during this time may have been challenging and generated different feelings regarding the pandemic and motherhood. Many pregnant women had other young children, underscoring the need to understand this scenario better. Therefore, the present study examined the predictive effect of indicators of mental health disorders, emotional discomfort with motherhood, and negative perceptions of COVID-19 on negative parenting practices., Methods: The study used a cross-sectional design. Pregnant women (n = 303) who had other children younger than six years answered an online questionnaire during the physical distancing period due to COVID-19 in Fortaleza. A partially latent structural equation model (SEM) was used to test direct and indirect relations between the variables., Results: The results revealed a direct positive relation between maternal mental health and the variables COVID-19 feelings, emotional discomfort with motherhood, and negative parenting practices. The stronger relationship was between maternal mental health and emotional discomfort with motherhood. The COVID-19 negative feelings also showed a direct positive relation to emotional discomfort with motherhood. Additionally, older mothers and those with fewer children tended to have less mental health disorders. Furthermore, being in a later trimester of pregnancy was linked to more negative feelings about motherhood., Discussion: The study suggests that mothers experiencing mental health challenges are more likely to feel discomfort with motherhood and use negative parenting practices, highlighting a need for intervention., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)