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1.
bioRxiv ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38948875

RESUMO

Kidney disease is highly heritable; however, the causal genetic variants, the cell types in which these variants function, and the molecular mechanisms underlying kidney disease remain largely unknown. To identify genetic loci affecting kidney function, we performed a GWAS using multiple kidney function biomarkers and identified 462 loci. To begin to investigate how these loci affect kidney function, we generated single-cell chromatin accessibility (scATAC-seq) maps of the human kidney and identified candidate cis -regulatory elements (cCREs) for kidney podocytes, tubule epithelial cells, and kidney endothelial, stromal, and immune cells. Kidney tubule epithelial cCREs explained 58% of kidney function SNP-heritability and kidney podocyte cCREs explained an additional 6.5% of SNP-heritability. In contrast, little kidney function heritability was explained by kidney endothelial, stromal, or immune cell-specific cCREs. Through functionally informed fine-mapping, we identified putative causal kidney function variants and their corresponding cCREs. Using kidney scATAC-seq data, we created a deep learning model (which we named ChromKid) to predict kidney cell type-specific chromatin accessibility from sequence. ChromKid and allele specific kidney scATAC-seq revealed that many fine-mapped kidney function variants locally change chromatin accessibility in tubule epithelial cells. Enhancer assays confirmed that fine-mapped kidney function variants alter tubule epithelial regulatory element function. To map the genes which these regulatory elements control, we used CRISPR interference (CRISPRi) to target these regulatory elements in tubule epithelial cells and assessed changes in gene expression. CRISPRi of enhancers harboring kidney function variants regulated NDRG1 and RBPMS expression. Thus, inherited differences in tubule epithelial NDRG1 and RBPMS expression may predispose to kidney disease in humans. We conclude that genetic variants affecting tubule epithelial regulatory element function account for most SNP-heritability of human kidney function. This work provides an experimental approach to identify the variants, regulatory elements, and genes involved in polygenic disease.

2.
Phys Rev E ; 109(5-1): 054410, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38907439

RESUMO

In this work, we used a dynamical system derived from an avian vocal production model to generate synthetic songs that mimic the Zonotrichia capensis songs. We confirmed that these synthetic renditions elicited behavioral responses similar to those evoked by real songs in wild songbirds of the same species. Specifically, we observed an increase in the singing rate of individual birds when a playback device was introduced into their territories. The success of our approach instills confidence in the hypotheses underpinning the model and provides a valuable tool for investigating a wide range of biological questions.


Assuntos
Aves Canoras , Vocalização Animal , Animais , Aves Canoras/fisiologia , Modelos Biológicos
3.
An Acad Bras Cienc ; 96(3): e20230675, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38922255

RESUMO

The presence of humans frequently modifies the behavior of animals, particularly their foraging patterns, compromising energetic demands. The fiddler crab Leptuca leptodactyla inhabits mangroves with high degrees of anthropogenic influence. Thus, we tested if populations living in highly anthropized mangroves respond differently from those living in more protected areas. We predict that individuals from touristy areas will be more tolerant to humans and will resume their activities sooner after disturbance. To do so, we conducted an experiment that consisted in the approach of an observer to the burrows, recording the response of individuals to the stimuli. The experiment took place in July 2022, in Ubatuba, São Paulo, Brazil. We analysed the duration and latency of various behaviors of a total of 80 adult males from two populations (high and low anthropogenic influence). Contrary to our predictions, individuals from the anthropized population were less tolerant, spending more time inside their burrows and taking longer to resume their activities. Therefore, fiddler crabs were not habituated to human presence. These results help us understand the learning process in invertebrates and their ability to select stimuli, contributing to understanding the impacts of human-wildlife interactions.


Assuntos
Comportamento Animal , Braquiúros , Animais , Braquiúros/fisiologia , Braquiúros/classificação , Masculino , Humanos , Brasil , Comportamento Animal/fisiologia
4.
J Immunol Res ; 2024: 6876247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939744

RESUMO

Sepsis treatment is a challenging condition due to its complexity, which involves host inflammatory responses to a severe and potentially fatal infection, associated with organ dysfunction. The aim of this study was to analyze the scientific literature on the immunomodulatory effects of glucans in a murine model of systemic infection induced by cecal ligation and puncture. This study comprises an integrative literature review based on systematic steps, with searches carried out in the PubMed, ScienceDirect, Scopus, Web of Science, and Embase databases. In most studies, the main type of glucan investigated was ß-glucan, at 50 mg/kg, and a reduction of inflammatory responses was identified, minimizing the occurrence of tissue damage leading to increased animal survival. Based on the data obtained and discussed in this review, glucans represent a promising biotechnological alternative to modulate the immune response and could potentially be used in the clinical management of septic individuals.


Assuntos
Modelos Animais de Doenças , Sepse , Animais , Sepse/tratamento farmacológico , Sepse/imunologia , Sepse/terapia , Humanos , Camundongos , Glucanos/uso terapêutico , Glucanos/farmacologia , beta-Glucanas/uso terapêutico , Imunomodulação/efeitos dos fármacos
5.
Health Aff Sch ; 2(4): qxae015, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38756174

RESUMO

COVID-19 created acute demands on health resources in jails and prisons, burdening health care providers and straining capacity. However, little is known about how carceral decision-makers balanced the allocation of scarce resources to optimize access to and quality of care for incarcerated individuals. This study analyzes a national sample of semi-structured interviews with health care and custody officials (n = 32) with decision-making authority in 1 or more carceral facilities during the COVID-19 pandemic. Interviews took place between May and October 2021. We coded transcripts using a directed content analysis approach and analyzed data for emergent themes. Participants reported that facilities distributed personal protective equipment to staff before incarcerated populations due to staff's unique role as potential vectors of COVID-19. The use of testing reflected not only an initial imperative to preserve limited supplies but also more complex decision-making about the value of test results to facility operations. Participants also emphasized the difficulties caused by limited physical space, insufficient staff, and stress from modifying job roles. The rapid onset of COVID-19 confronted decision-makers with unprecedented resource allocation decisions, often with life-or-death consequences. Planning for future resource allocation decisions now may promote more equitable decisions when confronted with a future pandemic event.

6.
Int J Circumpolar Health ; 83(1): 2343144, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38626421

RESUMO

The overincarceration of Indigenous peoples and its impacts on individual and community health is a growing concern across Canada and the United States. Federally run Healing Lodges in Canada are an example of support services for incarcerated and previously incarcerated Indigenous peoples to reintegrate into community and support their healing journey. However, there is a need to synthesise research which investigates these programmes. We report a protocol for a scoping review that is guided by the following research question: What is known about culturally informed programmes and services available to incarcerated and previously incarcerated Indigenous peoples in Canada and the US? This scoping review will follow guidelines published by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. This review will only identify programmes that are guided by Indigenous ways of being and knowing in order to best serve Indigenous communities and our community partners. The results of this review will support the development of programmes that are necessary for understanding and addressing the diverse needs of incarcerated and previously incarcerated Indigenous peoples.


Assuntos
Povos Indígenas , Prisioneiros , Humanos , Estados Unidos , Canadá , Saúde Pública , Revisões Sistemáticas como Assunto , Literatura de Revisão como Assunto
7.
Biosci Rep ; 44(4)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38563086

RESUMO

The objective of this work was to evaluate the combination of synthetic peptides based on the γ-core motif of defensin PvD1 with amphotericin B (AmB) at different concentrations against Candida albicans. We applied the checkerboard assay using different concentrations of the commercial drug AmB and the synthetic peptides γ31-45PvD1++ and γ33-41PvD1++ against C. albicans, aiming to find combinations with synergistic interactions. Between these two interactions involving γ31-45PvD1++ and AmB, an additive effect was observed. One such interaction occurred at concentrations of 0.009 µM of peptide γ31-45PvD1++ and 13.23 µM of AmB and another condition of 0.019 µM of peptide γ31-45PvD1++ and 6.61 µM of AmB. The other two concentrations of the interaction showed a synergistic effect in the combination of synthetic peptide γ31-45PvD1++ and AmB, where the concentrations were 1.40 µM peptide γ31-45PvD1++ and 0.004 µM AmB and 0.70 µM γ31-45PvD1++ peptide and 0.002 µM AmB. We proceeded with analysis of the mechanism of action involving synergistic effects. This examination unveiled a range of impactful outcomes, including the impairment of mitochondrial functionality, compromise of cell wall integrity, DNA degradation, and a consequential decline in cell viability. We also observed that both synergistic combinations were capable of causing damage to the plasma membrane and cell wall, causing leakage of intracellular components. This discovery demonstrates for the first time that the synergistic combinations found between the synthetic peptide γ31-45PvD1++ and AmB have an antifungal effect against C. albicans, acting on the integrity of the plasma membrane and cell wall.


Assuntos
Anfotericina B , Candida albicans , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Peptídeos/farmacologia , Membrana Celular , Parede Celular , Testes de Sensibilidade Microbiana
8.
Chaos ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558050

RESUMO

During sleep, sporadically, it is possible to find neural patterns of activity in areas of the avian brain that are activated during the generation of the song. It has recently been found that in the vocal muscles of a sleeping bird, it is possible to detect activity patterns during these silent replays. In this work, we employ a dynamical systems model for song production in suboscine birds in order to translate the vocal muscles activity during sleep into synthetic songs. Besides allowing us to translate muscle activity into behavior, we argue that this approach poses the biomechanics as a unique window into the avian brain, with biophysical models as its probe.


Assuntos
Aves , Vocalização Animal , Animais , Vocalização Animal/fisiologia , Aves/fisiologia , Encéfalo/fisiologia
9.
Pharmaceuticals (Basel) ; 17(4)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38675446

RESUMO

Diabetes mellitus (DM) complications are a burden to health care systems due to the associated consequences of poor glycemic control and the side effects of insulin therapy. Recently. adjuvant therapies, such as vanadium compounds, have gained attention due to their potential to improve glucose homeostasis in patients with diabetes. In order to determine the anti-diabetic and antioxidant effects of the oxidovanadium(IV) complex (Et3NH)2[{VO(OH}2)(ox)2(µ-ox)] or Vox2), rats with streptozotocin (STZ)-induced diabetes were treated with 30 and 100 mg/kg of Vox2, orally administered for 12 days. Vox2 at 100 mg/kg in association with insulin caused a 3.4 times decrease in blood glucose in STZ rats (424 mg/dL), reaching concentrations similar to those in the normoglycemic animals (126 mg/dL). Compared to insulin alone, the association with Vox2 caused an additional decrease in blood glucose of 39% and 65% at 30 and 100 mg/kg, respectively, and an increased pancreatic GSH levels 2.5 times. Vox2 alone did not cause gastrointestinal discomfort, diarrhea, and hepatic or renal toxicity and was not associated with changes in blood glucose level, lipid profile, or kidney or liver function. Our results highlight the potential of Vox2 in association with insulin in treating diabetes.

10.
BMC Infect Dis ; 24(1): 287, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448806

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is a major global concern, with Indigenous Peoples bearing the highest burden. Previous studies exploring HCV prevalence within Indigenous populations have predominantly used a pan-Indigenous approach, consequently resulting in limited availability of Métis-specific HCV data. The Métis are one of the three recognized groups of Indigenous Peoples in Canada with a distinct history and language. The Métis Nation of Ontario (MNO) is the only recognized Métis government in Ontario. This study aims to examine the prevalence of self-reported HCV testing and positive results among citizens of the MNO, as well as to explore the association between sociodemographic variables and HCV testing and positive results. METHODS: A population-based online survey was implemented by the MNO using their citizenship registry between May 6 and June 13, 2022. The survey included questions about hepatitis C testing and results, socio-demographics, and other health related outcomes. Census sampling was used, and 3,206 MNO citizens responded to the hepatitis C-related questions. Descriptive statistics and bivariate analysis were used to analyze the survey data. RESULTS: Among the respondents, 827 (25.8%, CI: 24.3-27.3) reported having undergone HCV testing and 58 indicated testing positive, resulting in a prevalence of 1.8% (CI: 1.3-2.3). Respondents with a strong sense of community belonging, higher education levels, and lower household income were more likely to report having undergone HCV testing. Among those who had undergone testing, older age groups, individuals with lower education levels, and retired individuals were more likely to test positive for HCV. CONCLUSION: This study is the first Métis-led and Métis-specific study to report on HCV prevalence among Métis citizens. This research contributes to the knowledge base for Métis health and will support the MNO's health promotion program and resources for HCV. Future research will examine the actual HCV incidence and prevalence among MNO citizens.


Assuntos
Hepacivirus , Hepatite C , Humanos , Idoso , Ontário/epidemiologia , Prevalência , Hepatite C/epidemiologia , Grupos Raciais
11.
Sensors (Basel) ; 24(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38475076

RESUMO

The proposed novel algorithm named decision-making algorithm with geographic mobility (DMAGM) includes detailed analysis of decision-making for cognitive radio (CR) that considers a multivariable algorithm with geographic mobility (GM). Scarce research work considers the analysis of GM in depth, even though it plays a crucial role to improve communication performance. The DMAGM considerably reduces latency in order to accurately determine the best communication channels and includes GM analysis, which is not addressed in other algorithms found in the literature. The DMAGM was evaluated and validated by simulating a cognitive radio network that comprises a base station (BS), primary users (PUs), and CRs considering random arrivals and disappearance of mobile devices. The proposed algorithm exhibits better performance, through the reduction in latency and computational complexity, than other algorithms used for comparison using 200 channel tests per simulation. The DMAGM significantly reduces the decision-making process from 12.77% to 94.27% compared with ATDDiM, FAHP, AHP, and Dijkstra algorithms in terms of latency reduction. An improved version of the DMAGM is also proposed where feedback of the output is incorporated. This version is named feedback-decision-making algorithm with geographic mobility (FDMAGM), and it shows that a feedback system has the advantage of being able to continually adjust and adapt based on the feedback received. In addition, the feedback version helps to identify and correct problems, which can be beneficial in situations where the quality of communication is critical. Despite the fact that the FDMAGM may take longer than the DMAGM to calculate the best communication channel, constant feedback improves efficiency and effectiveness over time. Both the DMAGM and the FDMAGM improve performance in practical scenarios, the former in terms of latency and the latter in terms of accuracy and stability.

12.
Injury ; 55(5): 111490, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38523031

RESUMO

BACKGROUND: Damage control surgery aims to control hemorrhage and contamination in the operating room (OR) with definitive management of injuries delayed until normal physiology is restored in the intensive care unit (ICU). There are limited studies evaluating the use of damage control thoracotomy (DCT) in trauma, and the best method of temporary closure is unclear. METHODS: A retrospective review of trauma patients at two level I trauma centers who underwent a thoracotomy operation was performed. Subjects who underwent a thoracotomy after 24 h, age less than 16, expired in the trauma bay, or in the OR prior to ICU admission were excluded. One-way ANOVA and Kruskal-Wallis test were used to compare continuous and categorical variables between DCT and definitive thoracotomy (DT) patients. RESULTS: 207 trauma patients underwent thoracotomy, 76 met our inclusion criteria. DCT was performed in 30 patients (39%), 46 (61 %) underwent DT operation. Techniques for temporizing the chest varied from skin closure with suture (8), adhesive dressing (5), towel clamps (2), or negative pressure devices (12). Compared to definitive closure, DCT had more derangements in HR, pH, (110 vs. 95, p = 0.04; 7.05 vs 7.24, p < 0.001), and injury severity score (41 vs 25, p < 0.001), and required more blood transfusions (40 vs 6, p < 0.001). Eleven (36.7 %) DCT patients survived to discharge compared to 38 patients (95.0 %) in the DT group. DCT showed significantly higher differences in cardiac arrest and unplanned returns to the OR rates. No differences were observed in ventilator days, or ICU length of stay. CONCLUSIONS: DCT is a viable option for management of patients in extremis following thoracic trauma. DCT was associated with higher mortality rates, likely due to differences in injury and physiologic derangement. Despite this, DCT was associated with similar rates of complications, ICU stay, and ventilator days.


Assuntos
Traumatismos Torácicos , Humanos , Traumatismos Torácicos/cirurgia , Toracotomia/métodos , Hospitalização , Escala de Gravidade do Ferimento , Estudos Retrospectivos , Bandagens
13.
Front Cell Infect Microbiol ; 14: 1327241, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371299

RESUMO

Plasmid-encoded toxin (Pet) is an autotransporter protein of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, important in the pathogenicity of Escherichia coli. The pet gene was initially found in the enteroaggregative E. coli (EAEC) virulence plasmid, pAA2. Although this virulence factor was initially described in EAEC, an intestinal E. coli pathotype, pet may also be present in other pathotypes, including extraintestinal pathogenic strains (ExPEC). The complement system is an important defense mechanism of the immune system that can be activated by invading pathogens. Proteases produced by pathogenic bacteria, such as SPATEs, have proteolytic activity and can cleave components of the complement system, promoting bacterial resistance to human serum. Considering these factors, the proteolytic activity of Pet and its role in evading the complement system were investigated. Proteolytic assays were performed by incubating purified components of the complement system with Pet and Pet S260I (a catalytic site mutant) proteins. Pet, but not Pet S260I, could cleave C3, C5 and C9 components, and also inhibited the natural formation of C9 polymers. Furthermore, a dose-dependent inhibition of ZnCl2-induced C9 polymerization in vitro was observed. E. coli DH5α survived incubation with human serum pre-treated with Pet. Therefore, Pet can potentially interfere with the alternative and the terminal pathways of the complement system. In addition, by cleaving C9, Pet may inhibit membrane attack complex (MAC) formation on the bacterial outer membrane. Thus, our data are suggestive of a role of Pet in resistance of E. coli to human serum.


Assuntos
Toxinas Bacterianas , Infecções por Escherichia coli , Proteínas de Escherichia coli , Humanos , Escherichia coli/metabolismo , Toxinas Bacterianas/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas do Sistema Complemento/metabolismo , Serina Proteases/metabolismo , Infecções por Escherichia coli/microbiologia , Plasmídeos/genética
14.
Am J Obstet Gynecol ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38367758

RESUMO

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

15.
Nature ; 628(8006): 57-61, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354833

RESUMO

Early JWST observations have uncovered a population of red sources that might represent a previously overlooked phase of supermassive black hole growth1-3. One of the most intriguing examples is an extremely red, point-like object that was found to be triply imaged by the strong lensing cluster Abell 2744 (ref. 4). Here we present deep JWST/NIRSpec observations of this object, Abell2744-QSO1. The spectroscopy confirms that the three images are of the same object, and that it is a highly reddened (AV ≃ 3) broad emission line active galactic nucleus at a redshift of zspec = 7.0451 ± 0.0005. From the width of Hß (full width at half-maximum = 2,800 ± 250 km s-1), we derive a black hole mass of M BH = 4 - 1 + 2 × 1 0 7 M ⊙ . We infer a very high ratio of black-hole-to-galaxy mass of at least 3%, an order of magnitude more than that seen in local galaxies5 and possibly as high as 100%. The lack of strong metal lines in the spectrum together with the high bolometric luminosity (Lbol = (1.1 ± 0.3) × 1045 erg s-1) indicate that we are seeing the black hole in a phase of rapid growth, accreting at 30% of the Eddington limit. The rapid growth and high black-hole-to-galaxy mass ratio of Abell2744-QSO1 suggest that it may represent the missing link between black hole seeds6 and one of the first luminous quasars7.

16.
Reprod Biol ; 24(1): 100856, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295721

RESUMO

Calorie restriction (CR) is an intervention that promotes longevity and preserves the ovarian reserve. Some studies have observed that the positive impacts of CR can be linked to restriction of protein (PR) and branched-chain amino acids (BCAAs) independent of calorie intake. The aim of this study was to compare the effects of protein and BCAA restriction to 30% CR on the ovarian reserve of female mice. For this, 3 month-old C57BL/6 female mice (n = 35) were randomized into four groups for four months dietary interventions including: control group (CTL; n = 8), 30% CR (CR; n = 9), protein restriction (PR; n = 9) and BCAA restriction (BCAAR; n = 9). Body mass gain, body composition, food intake, serum levels of BCAAs, ovarian reserve and estrous cyclicity were evaluated. We observed that CR, protein and BCAA restriction prevented weight gain and changed body composition compared to the CTL group. The BCAA restriction did not affect the ovarian reserve, while both PR and CR prevented activation of primordial follicles. This prevention occurred in PR group despite the lack of reduction of calorie intake compared to CTL group, and CR did not reduce protein intake in levels similar to the PR group. BCAA restriction resulted in increased calorie intake compared to CTL and PR mice, but only PR reduced serum BCAA levels compared to the CTL group. Our data indicates that PR has similar effects to CR on the ovarian reserve, whereas BCAA restriction alone did not affect it.


Assuntos
Restrição Calórica , Ingestão de Energia , Camundongos , Feminino , Animais , Camundongos Endogâmicos C57BL , Envelhecimento , Aminoácidos de Cadeia Ramificada/metabolismo
18.
Arch Pathol Lab Med ; 148(1): 74-77, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37014976

RESUMO

CONTEXT.­: End-stage kidney disease (ESKD) is defined as renal impairment requiring renal replacement therapy to sustain life. With a 1-year mortality of ∼20% to 30%, many die of complications related to this disease. OBJECTIVE.­: To determine the percentage of autopsy cases of decedents with ESKD in which the contribution of ESKD to death is accurately reflected in the final report. DESIGN.­: Autopsy case records were retrospectively reviewed at 4 institutions (Yale New Haven Hospital, University of Chicago Medical Center, University of Illinois at Chicago Hospital, University of Iowa Hospital). Clinical, macroscopic, and microscopic autopsy findings were reviewed, with attention to renal disease findings. RESULTS.­: One hundred sixty decedents with documented ESKD and premortem dialysis who underwent autopsy assessment were identified. ESKD was implicated as a cause of death (CoD) or significant contributing factor in 44 cases (28%), but not in the remaining 116 cases (72%). Cardiovascular disease was the most common CoD in ESKD. There was significant interpathologist variation in the inclusion of ESKD as a CoD across institutions. These rates ranged from 85% correlation (23 of 27 cases), to 13% (4 of 31 and 8 of 62 cases at 2 institutions), and 22.5% (9 of 40 cases) across the 4 participating institutions. CONCLUSIONS.­: The recognition at autopsy of ESKD as a CoD or contributing CoD at autopsy in patients undergoing dialysis remains low (28%). The detrimental impact of ESKD is not reflected in hospital autopsy reports, which carries implications for collection of vital statistics and allocation of research funding for kidney diseases.


Assuntos
Nefropatias , Falência Renal Crônica , Humanos , Estudos Retrospectivos , Falência Renal Crônica/terapia , Causas de Morte , Diálise Renal , Autopsia
19.
Hip Int ; 34(2): 194-200, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37728010

RESUMO

BACKGROUND: The primary purpose of this retrospective case series was to describe the prevalence and outcomes of single-stage hip arthroplasty in patients who were previously treated for septic arthritis of the native hip at our institution over a 20-year period. This study also examined rates of persistent or recurrent infection, reoperation, and mortality for septic arthritis of the native hip. METHODS: Adult patients treated for septic arthritis of the native hip at our institution from 1995 to 2015 were retrospectively identified. Exclusion criteria included age <18 years, missing or incomplete medical records, treatment at an outside institution, and prior surgery of the hip. RESULTS: 97 patients were included in this study. 3 patients (3.1%) who were previously treated for septic arthritis of the native hip underwent single-stage hip arthroplasty an average of 40 ± 25 months from the date of infection. 3 of the 18 (16.7%) patients who were treated with resection arthroplasty underwent second-stage joint reconstruction. There were no cases of periprosthetic joint infection (PJI). 1 patient who underwent single-stage arthroplasty experienced implant-induced metallosis, necessitating removal of the implant. There were no other cases of revision arthroplasty. CONCLUSIONS: The prevalence of single-stage hip arthroplasty in patients with a history of septic arthritis of the native hip joint was 3.1%, which is higher than the prevalence of hip arthroplasty in the United States general population, suggesting that a history of septic arthritis may increase the risk of requiring hip arthroplasty. In the small number of patients who went on to receive a hip replacement, there were no reported cases of PJI. This study suggests that hip arthroplasty is a viable option for patients with symptomatic osteoarthritis and a history of septic arthritis of their hip.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Adulto , Humanos , Adolescente , Estudos Retrospectivos , Artroplastia de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Articulação do Quadril/cirurgia , Artrite Infecciosa/epidemiologia , Artrite Infecciosa/cirurgia , Artrite Infecciosa/etiologia , Reoperação
20.
Nature ; 626(8000): 737-741, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37879361

RESUMO

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs)1, sources of high-frequency gravitational waves (GWs)2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process)3. Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers4-6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs. 7-12). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe.

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