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BACKGROUND: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. METHODS: We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. RESULTS: Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62). CONCLUSIONS: After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.
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Hepatopatias Alcoólicas , Humanos , Feminino , Masculino , Estados Unidos/epidemiologia , Estudos Retrospectivos , Hepatopatias Alcoólicas/etnologia , Pessoa de Meia-Idade , Adulto , Prevalência , Disparidades nos Níveis de Saúde , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Fatores de Risco , Hispânico ou Latino/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Idoso , Modelos LogísticosRESUMO
We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition after admission. Admissions included feeding and medication titration, interdisciplinary care, and a home parenteral nutrition team consultation.
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BACKGROUND: Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). METHODS: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. RESULTS: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. CONCLUSION: We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.
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Transplante de Fígado , Soluções para Preservação de Órgãos , Preservação de Órgãos , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Preservação de Órgãos/métodos , Perfusão/métodos , Perfusão/instrumentação , Estudo de Prova de Conceito , Oxigênio , Fígado/cirurgia , Trifosfato de Adenosina , Idoso , Adulto , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Isquemia FriaAssuntos
Tratamento Farmacológico da COVID-19 , Inibidores de Protease Viral , Adulto , Humanos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , COVID-19 , Tratamento Farmacológico da COVID-19/efeitos adversos , Tratamento Farmacológico da COVID-19/métodos , Combinação de Medicamentos , Hospitalização/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento , Inibidores de Protease Viral/administração & dosagem , Inibidores de Protease Viral/efeitos adversos , Assistência Ambulatorial/métodos , Assistência Ambulatorial/estatística & dados numéricosRESUMO
We were interested in micro-variations in an athlete's psychophysical state that separate peak exertion from physiological collapse. Thus, we measured perceptual acuity in runners using a classic psychophysical approach, the just noticeable difference (JND) on two standard stimuli runs at treadmill speed corresponding to 70%VO2max and 80%VO2max. Thirty-four male runners (M age = 35.26, SD = 7.33 years) first performed a maximal treadmill test to determine the speed of a standard exercise bout for the JND trials. The JND trials consisted of four 5-minute running bouts on a treadmill with 5-minute rests between bouts. For bouts 1 and 3, participants ran at the standard stimuli pace, but for bouts 2 and 4, they adjusted their speeds to achieve a level of exertion at a JND above/below the SS. They achieved differences in the final 30 seconds of the VO2 between each JND bout and the previous standard stimuli at just above (JND-A) and just below (JND-B) the JND perceived exertions. We used a Generalized Linear Model analysis to compare the JND-A and JND-B within and between ventilatory threshold groups (lower/higher) in absolute and relative VO2 and in terms of the total JND magnitude. The magnitude of JND-A was greater than that of JND-B at 70%VO2max and 80%VO2max in absolute units (70%VO2 Δ = 2.62; SE = 0.37; p < .001; 80%VO2 Δ = 1.67; SE = 0.44; p = .002) and in relative units (70%VO2max Δ = 4.70; SE = 0.66; p < .001; 80%VO2max Δ = 2.96; SE = 0.80; p = .002). The total magnitude was greater in the 70%VO2max trial than 80%VO2max in absolute units (70%VO2 M = 3.78, SE = 0.31 mL·kg-1·min-1; 80%VO2 M = 2.62, SE = 0.37 mL·kg-1·min-1; p = .020) and in relative units (70%VO2max M = 6.57, SE = 0.53%VO2max; 80%VO2max M = 4.71, SE = 0.64%VO2max; p = .030). The JND range narrowed when physiologic demand increased, for both physical (speed) and psychological (RPE) variables.
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Consumo de Oxigênio , Corrida , Humanos , Masculino , Corrida/fisiologia , Adulto , Consumo de Oxigênio/fisiologia , Teste de Esforço/métodos , Esforço Físico/fisiologia , Psicofísica/métodosRESUMO
Quartzite caves located on table-top mountains (tepuis) in the Guyana Shield, are ancient, remote, and pristine subterranean environments where microbes have evolved peculiar metabolic strategies to thrive in silica-rich, slightly acidic and oligotrophic conditions. In this study, we explored the culturable fraction of the microbiota inhabiting the (ortho)quartzite cave systems in Venezuelan tepui (remote table-top mountains) and we investigated their metabolic and enzymatic activities in relation with silica solubilization and extracellular hydrolytic activities as well as the capacity to produce antimicrobial compounds. Eighty microbial strains were isolated with a range of different enzymatic capabilities. More than half of the isolated strains performed at least three enzymatic activities and four bacterial strains displayed antimicrobial activities. The antimicrobial producers Paraburkholderia bryophila CMB_CA002 and Sphingomonas sp. MEM_CA187, were further analyzed by conducting chemotaxonomy, phylogenomics, and phenomics. While the isolate MEM_CA187 represents a novel species of the genus Sphingomonas, for which the name Sphingomonas imawarii sp. nov. is proposed, P. bryophila CMB_CA002 is affiliated with a few strains of the same species that are antimicrobial producers. Chemical analyses demonstrated that CMB_CA002 produces ditropolonyl sulfide that has a broad range of activity and a possibly novel siderophore. Although the antimicrobial compounds produced by MEM_CA187 could not be identified through HPLC-MS analysis due to the absence of reference compounds, it represents the first soil-associated Sphingomonas strain with the capacity to produce antimicrobials. This work provides first insights into the metabolic potential present in quartzite cave systems pointing out that these environments are a novel and still understudied source of microbial strains with biotechnological potential.
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Bactérias , Cavernas , Filogenia , RNA Ribossômico 16S , Cavernas/microbiologia , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética , Dióxido de Silício/química , Microbiota , Venezuela , Sphingomonas/metabolismo , Sphingomonas/isolamento & purificação , Sphingomonas/classificação , Sphingomonas/genética , Biotecnologia/métodos , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Microbiologia do Solo , DNA Bacteriano/genéticaRESUMO
Species of Pterygodermatites are spirurid nematodes that have expanded their geographic distribution worldwide. They infect a variety of mammalian definitive hosts with few reports of potential paratenic infections in amphibian and reptile hosts. In this study, we report Pterygodermatites sp. larvae identified in free-ranging, invasive Cuban treefrogs (Osteopilus septentrionalis), from central Florida, United States. Encysted larvae were recovered from the skeletal muscle and/or the coelomic cavity of three frogs; molecular characterization of the small subunit (18S) ribosomal RNA and cytochrome oxidase I genes of the parasites matched reported sequences of Pterygodermatites (Mesopectines) whartoni (Tubangui, 1931). This is a parasite native to Southeastern Asia and to the best of the authors' knowledge, it is the first report of the species in the New World. The recovery of invasive Pterygodermatites from invasive Cuban treefrogs in North America highlights the growing concern regarding the potential impact non-native parasites and invasive species may have on native wildlife populations.
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BACKGROUND: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. METHODS: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17ß-estradiol, and cortisol. We used general linear models to assess linear (ß = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (ß2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. RESULTS: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (ßboys = 5.88% [1.21%, 10.78%], ßgirls = 4.10% [-0.02%, 8.39%]), and cortisol (ßboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (ß2boys = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (ß2boys = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (ßboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (ßboys = 3.90% [1.28%, 6.58%]) were positively associated with 17ß-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. CONCLUSIONS: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17ß-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.
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Biomarcadores , Inseticidas , Humanos , Adolescente , Feminino , Masculino , Equador , Inseticidas/urina , Inseticidas/sangue , Biomarcadores/urina , Biomarcadores/sangue , Criança , Hidrocortisona/urina , Desidroepiandrosterona/urina , Desidroepiandrosterona/sangue , Estradiol/sangue , Estradiol/urina , Agricultura , Acetilcolinesterase/sangue , Acetilcolinesterase/metabolismo , Testosterona/sangue , Testosterona/urina , Saliva/química , Malation/urinaRESUMO
OBJECTIVE: We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide's effects on glycemic control, body weight (BW), and cardiometabolic markers. RESEARCH DESIGN AND METHODS: This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1] and A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. RESULTS: At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P < 0.001) higher glycemic levels (8.5% vs. 8.2%, P < 0.001), higher BW (97 vs. 93 kg, P < 0.001) and BMI (35 vs. 34 kg/m2, P < 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (-2.6% vs. -2.4%), BW (-14 vs. -13 kg), WC (-10 vs. -10 cm), triglycerides (-26% vs. -24%), HDL (7% vs. 7%), and systolic BP (-6 vs. -7 mmHg) were observed in both subgroups with tirzepatide. CONCLUSIONS: Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.
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Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Adulto , Hemoglobinas Glicadas/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 2 , Polipeptídeo Inibidor GástricoRESUMO
Investigation of the secondary metabolites of Streptomyces virginiae CMB-CA091 isolated from the quartz-rich (tepui) soil of a cave in Venezuela yielded two new dimeric phenazine glycosides, tepuazines A and B (1 and 2); three new monomeric phenazine glycosides, tepuazines C-E (3-5); and a series of known analogues, baraphenazine G (6), phenazinolin D (7), izumiphenazine C (8), 4-methylaminobenzoyl-l-rhamnopyranoside (9), and 2-acetamidophenol (10). Structures were assigned to 1-10 on the basis of detailed spectroscopic analysis and biosynthetic considerations, with 1 and 2 featuring a rare 2-oxabicyclo[3.3.1]nonane-like ring C/D bridge shared with only a handful of known Streptomyces natural products. We propose a plausible convergent biosynthetic relationship linking all known members of this structure class that provides a rationale for the observed ring C/D configuration.
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Glicosídeos , Fenazinas , Microbiologia do Solo , Streptomyces , Streptomyces/química , Fenazinas/química , Glicosídeos/química , Glicosídeos/isolamento & purificação , Estrutura Molecular , Venezuela , Cavernas , Quartzo/químicaRESUMO
BACKGROUNDNovel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections.METHODSWe applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. Bioinformatic analysis using linear modeling and network correlation analyses identified 118 differentially expressed proteins, significant through 3 complementary analytical pipelines. Candidate biomarkers were subsequently analyzed in 2 validation cohorts of differing ethnicity using antibody-based proximity extension assays.RESULTSTB-specific host biomarkers were confirmed. A 6-protein diagnostic panel, comprising FETUB, FCGR3B, LRG1, SELL, CD14, and ADA2, differentiated patients with pulmonary TB from healthy controls and patients with other respiratory infections with high sensitivity and specificity in both cohorts.CONCLUSIONThis biomarker panel exceeds the World Health Organization Target Product Profile specificity criteria for a triage test for TB. The new biomarkers have potential for further development as near-patient TB screening assays, thereby helping to close the case-detection gap that fuels the global pandemic.FUNDINGMedical Research Council (MRC) (MR/R001065/1, MR/S024220/1, MR/P023754/1, and MR/W025728/1); the MRC and the UK Foreign Commonwealth and Development Office; the UK National Institute for Health Research (NIHR); the Wellcome Trust (094000, 203135, and CC2112); Starter Grant for Clinical Lecturers (Academy of Medical Sciences UK); the British Infection Association; the Program for Advanced Research Capacities for AIDS in Peru at Universidad Peruana Cayetano Heredia (D43TW00976301) from the Fogarty International Center at the US NIH; the UK Technology Strategy Board/Innovate UK (101556); the Francis Crick Institute, which receives funding from UKRI-MRC (CC2112); Cancer Research UK (CC2112); and the NIHR Biomedical Research Centre of Imperial College NHS.
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Biomarcadores , Proteômica , Tuberculose Pulmonar , Humanos , Biomarcadores/sangue , Proteômica/métodos , Masculino , Feminino , Adulto , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/sangue , Mycobacterium tuberculosis , Pessoa de Meia-Idade , Peru/epidemiologia , África do Sul/epidemiologia , Estudos de Casos e Controles , Sensibilidade e EspecificidadeRESUMO
Proximal interphalangeal (PIP) joint contracture is a common, difficult clinical problem that can arise from minor trauma. Management is difficult because outcomes are unpredictable and often poor, due to residual flexion deformities postoperatively. The dorsal approach for flexion contracture of the PIP joint is not discussed in present literature. In this technique guide, we wish to describe and explain the rationale for a dorsal approach. In our experience, a dorsal approach allows for ease of access to all pathologic structures, with simple positioning of the digit to allow access to volar structures, as well as when addressing more than one digits with a PIP contracture. Finally, similar to the midaxial approach, the dorsal approach also eliminates any volar soft tissue concerns and need for supplemental coverage.
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BACKGROUND: A progressive decrease in spontaneous locomotion with repeated exposure to a novel environment has been assessed using both within and between-session measures. While both are well-established and reliable measurements, neither are useful alone as methods to concurrently assess treatment effects on acquisition and retention of habituation. NEW METHOD: We report a behavioral method that measures habituation by combining the within and between measurements of locomotion. We used a 30 min session divided into 6 five min blocks. In the first novel environment session activity was maximal in the first 5 min block but was reduced to a low level by the sixth block, indicative of within-session habituation. Using 8 daily sessions, we showed that this terminal block low level of activity progressed incrementally to the first block to achieve complete habituation. RESULTS/COMPARISON WITH EXISTING METHODS: Within-session activity across sessions was used to identify different stages of between session habituation. It was then possible to assess drug treatment effects from partial to complete habituation, so that treatment effects on retention of the previously acquired partial habituation, expressed as a reversion to an earlier within session habituation pattern (retrograde amnesia assessment), as well as the effects on new learning by the failure in subsequent sessions to acquire complete between-session habituation (anterograde amnesia assessment). CONCLUSIONS: The use of spontaneous motor activity to assess learning and memory effects provides the opportunity to assess direct treatment effects on behavior and motor activity in contrast to many learning and memory models.
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Habituação Psicofisiológica , Receptores de N-Metil-D-Aspartato , Humanos , Aprendizagem , Amnésia RetrógradaRESUMO
Manual outdoor work is essential in many agricultural systems. Climate change will make such work more stressful in many regions due to heat exposure. The physical work capacity metric (PWC) is a physiologically based approach that estimates an individual's work capacity relative to an environment without any heat stress. We computed PWC under recent past and potential future climate conditions. Daily values were computed from five earth system models for three emission scenarios (SSP1-2.6, SSP3-7.0, and SSP5-8.5) and three time periods: 1991-2010 (recent past), 2041-2060 (mid-century) and 2081-2100 (end-century). Average daily PWC values were aggregated for the entire year, the growing season, and the warmest 90-day period of the year. Under recent past climate conditions, the growing season PWC was below 0.86 (86% of full work capacity) on half the current global cropland. With end-century/SSP5-8.5 thermal conditions this value was reduced to 0.7, with most affected crop-growing regions in Southeast and South Asia, West and Central Africa, and northern South America. Average growing season PWC could falls below 0.4 in some important food production regions such as the Indo-Gangetic plains in Pakistan and India. End-century PWC reductions were substantially greater than mid-century reductions. This paper assesses two potential adaptions-reducing direct solar radiation impacts with shade or working at night and reducing the need for hard physical labor with increased mechanization. Removing the effect of direct solar radiation impacts improved PWC values by 0.05 to 0.10 in the hottest periods and regions. Adding mechanization to increase horsepower (HP) per hectare to levels similar to those in some higher income countries would require a 22% increase in global HP availability with Sub-Saharan Africa needing the most. There may be scope for shifting to less labor-intensive crops or those with labor peaks in cooler periods or shift work to early morning.
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Agricultura , Mudança Climática , Temperatura Alta , Produtos Agrícolas , América do SulRESUMO
Multiple sclerosis, and its murine model experimental autoimmune encephalomyelitis (EAE), is a neurodegenerative autoimmune disease of the CNS characterized by T cell influx and demyelination. Similar to other autoimmune diseases, therapies can alleviate symptoms but often come with side effects, necessitating the exploration of new treatments. We recently demonstrated that the Cullin-RING E3 ubiquitin ligase 4b (CRL4b) aided in maintaining genome stability in proliferating T cells. In this study, we examined whether CRL4b was required for T cells to expand and drive EAE. Mice lacking Cul4b (Cullin 4b) in T cells had reduced EAE symptoms and decreased inflammation during the peak of the disease. Significantly fewer CD4+ and CD8+ T cells were found in the CNS, particularly among the CD4+ T cell population producing IL-17A, IFN-γ, GM-CSF, and TNF-α. Additionally, Cul4b-deficient CD4+ T cells cultured in vitro with their wild-type counterparts were less likely to expand and differentiate into IL-17A- or IFN-γ-producing effector cells. When wild-type CD4+ T cells were activated in vitro in the presence of the recently developed CRL4 inhibitor KH-4-43, they exhibited increased apoptosis and DNA damage. Treatment of mice with KH-4-43 following EAE induction resulted in stabilized clinical scores and significantly reduced numbers of T cells and innate immune cells in the CNS compared with control mice. Furthermore, KH-4-43 treatment resulted in elevated expression of p21 and cyclin E2 in T cells. These studies support that therapeutic inhibition of CRL4 and/or CRL4-related pathways could be used to treat autoimmune disease.
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Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Interleucina-17/metabolismo , Proteínas Culina/metabolismo , Linfócitos T CD4-Positivos , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: Translate, investigate reliability, and construct validity of the Brazilian Early Activity Scale for Endurance (EASE). MATERIALS AND METHODS: Translation followed the international guidelines. Test-retest reliability was tested by 100 parents of children with cerebral palsy (CP): 18 months-5 years and 6-11 years. To determine construct validity, 94 parents of typically children completed the EASE. Statistical analysis included Bland-Altman, Intraclass Correlation Coefficient (ICC), Internal Consistency, and Floor and Ceiling Effect. RESULTS: The majority of the sample consisted of children with CP in GMFCS (IV-V). EASE showed good test-retest reliability for younger (ICC = 0.8) and excellent test-retest reliability for older children with CP (ICC = 0.9), and good internal consistency of 0.7 and 0.8 for the young and older group, respectively. Bland-Altman showed the bias close to zero, with no ceiling or floor effect. Regarding construct validity, younger children showed lower scores when compared to the older children. Endurance differed significantly between children with CP who were walking and those who were not walking and also for age groups. Children with CP showed lower endurance compared to typically participants in the same age group. CONCLUSIONS: Brazilian EASE is reliable and valid to estimate endurance in children with CP. Results provide evidence of construct validity.
Endurance to physical activity is an important construct to be evaluated and that directly interferes with the health and quality of life of children with Cerebral Palsy (CP).The Brazilian-Portuguese version of the 4-item Early Activity Scale for Endurance (EASE) is a valid and reliable scale to assess endurance to physical activity in children with CP.
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Paralisia Cerebral , Caminhada , Criança , Humanos , Adolescente , Reprodutibilidade dos Testes , Brasil , Portugal , Paralisia Cerebral/diagnóstico , Inquéritos e Questionários , Psicometria/métodosRESUMO
BACKGROUND: The current fungal meningitis outbreak caused by contaminated epidural anesthesia with Fusarium solani among patients who underwent surgical procedures in Matamoros, Mexico remains a cause of concern. Its association with an increased susceptibility for cerebrovascular complications (CVC) has not been reported. This single-center study describes 3 patients with a unique pattern of CVC attributed to fungal meningitis. METHODS: A retrospective case series of patients diagnosed with fungal meningitis following surgical procedures under contaminated epidural anesthesia who developed a unique pattern of CVC during their hospitalization. RESULTS: Three female patients (mean age, 35 years) with CVC due to iatrogenic fungal meningitis were included. Positive Fungitell ß-D-glucan assay in cerebrospinal fluid was documented in all cases, and F. solani was confirmed by polymerase chain reaction in case 3. All cases were complicated by severe vertebrobasilar circulation vasculopathy and arterial dissections with resultant subarachnoid hemorrhage and intraventricular hemorrhage, ultimately leading to patients' death. CONCLUSIONS: The death toll from the ongoing fungal meningitis outbreak keeps rising, underscoring the need for early recognition and aggressive treatment. We highlight the risk for vertebrobasilar circulation CVC among these patients. The angioinvasive nature of F. solani is yet to be clarified; however, a clear pattern has been observed. Public health awareness should be raised and a strong response should be pursued.
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Meningite Fúngica , Metilprednisolona , Humanos , Feminino , Adulto , Estudos Retrospectivos , México/epidemiologia , Meningite Fúngica/epidemiologia , Meningite Fúngica/etiologia , Meningite Fúngica/diagnóstico , Doença Iatrogênica/epidemiologiaRESUMO
OBJECTIVE: The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). BACKGROUND: The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. METHODS: Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. RESULTS: In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. CONCLUSIONS: The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.
Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Terapia Neoadjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Quimioterapia Adjuvante , Pancreatectomia , Estudos RetrospectivosRESUMO
In recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients.
Nas últimas décadas, houve avanços significativos no diagnóstico de gliomas difusos, impulsionados pela integração de novas tecnologias. Esses avanços aprofundaram nossa compreensão da oncogênese tumoral, permitindo uma estratificação mais refinada do comportamento biológico dessas neoplasias. Esse progresso culminou na quinta edição da classificação da OMS de tumores do sistema nervoso central (SNC) em 2021. Esta revisão abrangente tem como objetivo elucidar esses avanços de forma multidisciplinar, no contexto da nova classificação. Este artigo irá explorar a patologia morfológica e as técnicas moleculares/genéticas (imuno-histoquímica, sequenciamento genético e perfil de metilação), que são fundamentais no diagnóstico, além da correlação dos radiofenótipos da neuroimagem estrutural com a patologia e a genética. Aborda sucintamente a utilidade da tractografia e da neuroimagem funcional no planejamento cirúrgico. Destacaremos o valor de outras técnicas de imagem funcional, como ressonância magnética de perfusão, espectroscopia e medicina nuclear, na distinção entre a progressão do tumor e as alterações relacionadas ao tratamento. Discutiremos as vantagens das diferentes técnicas de diagnóstico na classificação desses tumores, bem como suas limitações em termos de disponibilidade e utilização. Além disso, os crescentes avanços no processamento de dados, inteligência artificial, radiômica e radiogenômica têm grande potencial e podem em breve exercer uma influência substancial no diagnóstico de gliomas. Essas tecnologias inovadoras têm o potencial de revolucionar nossa abordagem a esses tumores. Em última análise, esta revisão destaca a importância fundamental da colaboração multidisciplinar na utilização dos recentes avanços diagnósticos, com a esperança de traduzi-los em uma melhor qualidade de vida e uma maior sobrevida.