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1.
J Immunol ; 209(5): 938-949, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35948399

RESUMO

RAG1/RAG2 (RAG) endonuclease-mediated assembly of diverse lymphocyte Ag receptor genes by V(D)J recombination is critical for the development and immune function of T and B cells. The RAG1 protein contains a ubiquitin ligase domain that stabilizes RAG1 and stimulates RAG endonuclease activity in vitro. We report in this study that mice with a mutation that inactivates the Rag1 ubiquitin ligase in vitro exhibit decreased rearrangements and altered repertoires of TCRß and TCRα genes in thymocytes and impaired thymocyte developmental transitions that require the assembly and selection of functional TCRß and/or TCRα genes. These Rag1 mutant mice present diminished positive selection and superantigen-mediated negative selection of conventional αß T cells, decreased genesis of invariant NK T lineage αß T cells, and mature CD4+ αß T cells with elevated autoimmune potential. Our findings reveal that the Rag1 ubiquitin ligase domain functions in vivo to stimulate TCRß and TCRα gene recombination and influence differentiation of αß T lineage cells, thereby establishing replete diversity of αß TCRs and populations of αß T cells while restraining generation of potentially autoreactive conventional αß T cells.


Assuntos
Proteínas de Homeodomínio , Receptores de Antígenos de Linfócitos T alfa-beta , Ubiquitina , Animais , Linhagem da Célula , Endonucleases/genética , Proteínas de Homeodomínio/genética , Ligases/genética , Camundongos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Superantígenos , Recombinação V(D)J/genética
2.
Br J Clin Psychol ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923582

RESUMO

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental condition and is characterized by inattention, hyperactivity, and impulsivity. Research suggests that some populations, such as females and individuals with high intelligence quotients may be a risk for late ADHD diagnosis and subsequent treatment. Our goal is to advance our understanding of ADHD diagnosis, by examining (1) how child sex and cognitive abilities together are related to the age of diagnosis and (2) whether symptom presentation, current internalizing and externalizing symptoms, and demographic factors are related to age of diagnosis. METHODS: Our analyses contained children who completed the required tests (N = 568) from a pre-existing dataset of 1380 children with ADHD from the Province of Ontario Neurodevelopmental Disorders (POND) Network (pond-network.ca). First, we conducted a moderation analysis with sex as the predictor, cognitive abilities as the moderator, and age of diagnosis as the outcome. Second, we conducted correlation analyses examining how symptom presentation, current internalizing and externalizing symptoms, and demographic factors are related to age of diagnosis. RESULTS: Higher IQ was related to a later age of diagnosis. Higher hyperactive-impulsive symptoms and externalizing symptoms were related to an earlier age of diagnosis. Internalizing symptoms were trend associated with a later age of diagnosis in girls. Higher socioeconomic status and non-White maternal ethnicity were related to later age of diagnosis. CONCLUSIONS: IQ, sex, ADHD symptomology, internalizing symptoms, externalizing symptoms, and socio-demographic factors affect the age of diagnosis.

3.
MMWR Morb Mortal Wkly Rep ; 72(7): 165-170, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36795611

RESUMO

Good nutrition in early childhood supports optimal growth, development, and health (1). Federal guidelines support a dietary pattern with daily fruit and vegetable consumption and limited added sugars, including limited consumption of sugar-sweetened beverages (1). Government-published dietary intake estimates for young children are outdated at the national level and unavailable at the state level. CDC analyzed data from the 2021 National Survey of Children's Health (NSCH)* to describe how frequently, according to parent report, children aged 1-5 years (18,386) consumed fruits, vegetables, and sugar-sweetened beverages, nationally and by state. During the preceding week, approximately one in three (32.1%) children did not eat a daily fruit, nearly one half (49.1%) did not eat a daily vegetable, and more than one half (57.1%) drank a sugar-sweetened beverage at least once. Estimates of consumption varied by state. In 20 states, more than one half of children did not eat a vegetable daily during the preceding week. In Vermont, 30.4% of children did not eat a daily vegetable during the preceding week, compared with 64.3% in Louisiana. In 40 states and the District of Columbia, more than one half of children drank a sugar-sweetened beverage at least once during the preceding week. The percentage of children drinking sugar-sweetened beverages at least once during the preceding week ranged from 38.6% in Maine to 79.3% in Mississippi. Many young children are not consuming fruits and vegetables daily and are regularly consuming sugar-sweetened beverages. Federal nutrition programs and state policies and programs can support improvements in diet quality by increasing access to and availability of fruits and vegetables and healthy beverages in places where young children live, learn, and play.


Assuntos
Frutas , Bebidas Adoçadas com Açúcar , Humanos , Criança , Pré-Escolar , Estados Unidos/epidemiologia , Verduras , Dieta , Bebidas/análise , Louisiana
4.
Pulm Pharmacol Ther ; 78: 102188, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603741

RESUMO

BACKGROUND: Remdesivir was the first antiviral to show clinical benefit in patients with moderate-to-severe COVID-19. Previous trials demonstrated a faster time to recovery in hospitalized patients treated with remdesivir vs placebo. Current guidelines recommend treatment with remdesivir based on hospitalization status, oxygen requirements, and time from symptom onset. However, other factors may be evaluated to determine disease severity and risk for progression. The 4C mortality score is a validated, eight variable score that may be used to categorize patients by mortality risk at the time of hospital admission for COVID pneumonia. The objective of this study was to determine if the 4C mortality score may be used to predict which patients with moderate to severe COVID-19 would benefit the most from remdesivir at the time of hospital admission. METHODS: This was a single-center retrospective cohort study comparing time to recovery among hospitalized patients with moderate-to-severe COVID-19 who were treated with remdesivir compared to those who were treated with standard of care (SOC). The primary outcome was time to recovery, defined as discharge from the hospital or no longer requiring supplemental oxygen, stratified by the 4C mortality score risk group. Secondary outcomes included in-hospital mortality, hospital length of stay, and time to recovery in patients who were started on remdesivir within 7 days from symptom onset vs after 7 days from symptom onset. A survival analysis was used to analyze time to recovery outcomes. RESULTS: Data was collected and analyzed for a total of 300 patients, of which 200 received remdesivir and 100 received SOC. Patients in the remdesivir group had a longer time to recovery compared to patients in the SOC group (6 days vs 4 days). This finding was driven by patients who were categorized to the intermediate risk and high risk mortality groups. Additionally, patients who received remdesivir had a longer length of hospital stay compared to those who received SOC (12 days vs 9 days). Remdesivir was not associated with an increased rate of adverse events. CONCLUSIONS: This study of patients admitted with moderate-to-severe COVID-19 found that patients who were treated with remdesivir had a longer time to recovery and a longer length of stay compared to those who received SOC. These findings add to the body of evidence questioning the benefit of remdesivir therapy among patients hospitalized with COVID-19.


Assuntos
COVID-19 , Humanos , Monofosfato de Adenosina/uso terapêutico , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Tratamento Farmacológico da COVID-19 , Oxigênio , Estudos Retrospectivos , SARS-CoV-2
5.
Transpl Int ; 36: 11641, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727386

RESUMO

The Department of Health and Social Care in England established an Organ Utilisation Group, to collate and analyse evidence regarding the organ transplantation care pathway, make recommendations on how to reduce inequity of access, make the best use of available resources, and drive innovation in organ transplantation. The group consulted with national and international experts and stakeholders, sought views from service providers across the transplant care pathway, and heard from over 600 people, including over 250 patients, carers, and donors. The group uncovered new evidence about where improvements are needed-particularly in relation to patient experience and inequities in access. The final report suggests a new direction for organ transplantation services in the United Kingdom, with action required at local, regional, and national levels. Ultimately, it is expected to increase transplant activity through increased organ utilisation and improve patient experience, outcomes, and empowerment whilst also supporting the transplant clinical community.


Assuntos
Transplante de Órgãos , Transplantes , Humanos , Apoio Social , Doadores de Tecidos , Reino Unido
6.
J Adolesc ; 95(1): 82-96, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317502

RESUMO

INTRODUCTION: Bullying is an increasing concern for education, health, and policy. Adolescence is a particularly vulnerable period for the development of depressive symptoms and suicidality following exposure to bullying. However, limited research investigating the potential impact of depressive symptoms on the bullying-suicide relationship exists. METHODS: Using national data (N = 13,677) from the most recent 2019 Youth Risk Behavior Survey, the aim of the present study was to examine the prevalence among adolescents' (school/electronic) bullying victimization, depressive symptoms (sadness; sleep), and suicide ideation as well as their associations including direct and indirect relationships including exploring differences by gender and race/ethnicity. RESULTS: Descriptive results indicated an increase in the prevalence of adolescents being bullied (both on school property and electronically), experiencing feelings of sadness, and hopelessness as well as a decrease in getting more than 8 h of sleep between 2017 and 2019. In 2019, over one-third of respondents felt sad or hopeless almost every day for 2 weeks or more in a row, which stopped them from doing some usual activities. Structural equation modeling indicated that (school/electronic) bullying was directly associated with feelings of sadness/hopelessness and suicide ideation, with sadness mediating the link between bullying and suicide ideation. CONCLUSION: Now more than ever, it is critical to promote the collaboration between educators, mental health specialists, policymakers, and researchers to develop and implement evidence-based strategies and approaches to preventing and reducing both bullying victimization and the associated psychological distress and mental health outcomes.


Assuntos
Bullying , Vítimas de Crime , Humanos , Adolescente , Tristeza , Ideação Suicida , Vítimas de Crime/psicologia , Instituições Acadêmicas , Sono , Bullying/psicologia
7.
Foodborne Pathog Dis ; 20(4): 123-131, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37015074

RESUMO

Vibrio parahaemolyticus is the leading cause of seafood-related foodborne illness globally. In 2018, the U.S. federal, state, and local public health and regulatory partners investigated a multistate outbreak of V. parahaemolyticus infections linked to crabmeat that resulted in 26 ill people and nine hospitalizations. State and U.S. Food and Drug Administration (FDA) laboratories recovered V. parahaemolyticus, Salmonella spp., and Listeria monocytogenes isolates from crabmeat samples collected from various points of distribution and conducted phylogenetic analyses of whole-genome sequencing data. Federal, state, and local partners conducted traceback investigations to determine the source of crabmeat. Multiple Venezuelan processors that supplied various brands of crabmeat were identified, but a sole firm was not confirmed as the source of the outbreak. Travel restrictions between the United States and Venezuela prevented FDA officials from conducting on-site inspections of cooked crabmeat processors. Based on investigation findings, partners developed public communications advising consumers not to eat crabmeat imported from Venezuela and placed potentially implicated firms on import alerts. While some challenges limited the scope of the investigation, epidemiologic, traceback, and laboratory evidence identified the contaminated food and country of origin, and contributed to public health and regulatory actions, preventing additional illnesses. This multistate outbreak illustrates the importance of adhering to appropriate food safety practices and regulations for imported seafood.


Assuntos
Doenças Transmitidas por Alimentos , Vibrioses , Vibrio parahaemolyticus , Humanos , Estados Unidos/epidemiologia , Filogenia , Venezuela/epidemiologia , Doenças Transmitidas por Alimentos/epidemiologia , Vibrioses/epidemiologia , Surtos de Doenças
8.
J Cancer Educ ; 38(5): 1509-1521, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37002507

RESUMO

The Project ECHO model of telementoring has been used for the past 10 years to expand access to specialized cancer care. This scoping review identifies evidence for the model's ability to improve provider outcomes, synthesizing findings from existing studies within Moore et al.'s (2009) framework for continuing medical education outcomes. We search two large research databases and a collection maintained by Project ECHO staff for articles that focus on cancer ECHO programs, involve primary data collection, and were published between December 1, 2016, and November 30, 2021. We identified 25 articles for inclusion in our scoping review. Most articles reported results for outcomes related to program participation: attendance, satisfaction, and learning. Yet, just under half reported changes in provider practices. Results demonstrate widespread participation and improved learning resulting from ECHO programs focused on cancer care. There is also evidence of improved practices related to HCV vaccination and palliative care. We highlight examples of best practices as well as opportunities to improve provider outcome evaluations for cancer ECHO programs.


Assuntos
Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Humanos , Educação Médica Continuada , Coleta de Dados , Neoplasias/diagnóstico por imagem , Neoplasias/terapia
9.
J Aging Soc Policy ; 35(3): 360-373, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34016014

RESUMO

Federal and state governments provide a plethora of benefits programs intended to help older Americans, but take-up rates for the programs is low. BenefitsCheckUp® is an online tool intended to increase enrollment in these programs. To evaluate the impact of this national online screening tool providing individualized benefit information, we conducted a web survey of individuals who screened potentially eligible for programs including Supplemental Security Income, Medicaid, Medicare Savings Programs, Supplemental Nutrition Assistance Program, and energy assistance. Thirty-six percent of those surveyed applied for at least one benefit at an annualized, estimated average value of $2,865, and 20.5% enrolled, representing about 7% of the approximately 2 million site visitors age 60+. These results indicate that an online screening tool is a promising strategy for increasing benefit take-up rates among older adults with the value of benefits received far exceeding investments.


Assuntos
Medicaid , Medicare , Humanos , Estados Unidos , Idoso , Renda , Inquéritos e Questionários , Internet
10.
Appl Environ Microbiol ; 87(3)2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33187991

RESUMO

Vibrio parahaemolyticus is the most common cause of seafood-borne illness reported in the United States. The draft genomes of 132 North American clinical and oyster V. parahaemolyticus isolates were sequenced to investigate their phylogenetic and biogeographic relationships. The majority of oyster isolate sequence types (STs) were from a single harvest location; however, four were identified from multiple locations. There was population structure along the Gulf and Atlantic Coasts of North America, with what seemed to be a hub of genetic variability along the Gulf Coast, with some of the same STs occurring along the Atlantic Coast and one shared between the coastal waters of the Gulf and those of Washington State. Phylogenetic analyses found nine well-supported clades. Two clades were composed of isolates from both clinical and oyster sources. Four were composed of isolates entirely from clinical sources, and three were entirely from oyster sources. Each single-source clade consisted of one ST. Some human isolates lack tdh, trh, and some type III secretion system (T3SS) genes, which are established virulence genes of V. parahaemolyticus Thus, these genes are not essential for pathogenicity. However, isolates in the monophyletic groups from clinical sources were enriched in several categories of genes compared to those from monophyletic groups of oyster isolates. These functional categories include cell signaling, transport, and metabolism. The identification of genes in these functional categories provides a basis for future in-depth pathogenicity investigations of V. parahaemolyticusIMPORTANCEVibrio parahaemolyticus is the most common cause of seafood-borne illness reported in the United States and is frequently associated with shellfish consumption. This study contributes to our knowledge of the biogeography and functional genomics of this species around North America. STs shared between the Gulf Coast and the Atlantic seaboard as well as Pacific waters suggest possible transport via oceanic currents or large shipping vessels. STs frequently isolated from humans but rarely, if ever, isolated from the environment are likely more competitive in the human gut than other STs. This could be due to additional functional capabilities in areas such as cell signaling, transport, and metabolism, which may give these isolates an advantage in novel nutrient-replete environments such as the human gut.


Assuntos
Vibrio parahaemolyticus/genética , Animais , Monitoramento Biológico , Genes Bacterianos , Genoma Bacteriano , Humanos , América do Norte , Ostreidae/microbiologia , Filogenia , Vibrioses/microbiologia , Vibrio parahaemolyticus/isolamento & purificação , Virulência/genética , Sequenciamento Completo do Genoma
11.
Diabet Med ; 38(5): e14528, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33496979

RESUMO

CONTEXT AND AIM: Continuous glucose monitoring (CGM) is becoming widely accepted as an adjunct to diabetes management. Compared to standard care, CGM can provide detailed information about glycaemic variability in an internationally standardised ambulatory glucose profile, enabling more informed user and clinician decision making. We aimed to review the evidence, user experience and cost-effectiveness of CGM. METHODS: A literature search was conducted by combining subject headings 'CGM' and 'flash glucose monitoring', with key words 'type 1 diabetes' and 'type 2 diabetes', limited to '1999 to current'. Further evidence was obtained from relevant references of retrieved articles. RESULTS: There is a strong evidence for CGM use in people with type 1 diabetes, with benefits of reduced glycated haemoglobin and hypoglycaemia, and increased time in range. While the evidence for CGM use in type 2 diabetes is less robust, similar benefits have been demonstrated. CGM can improve diabetes-related satisfaction in people with diabetes (PWD) and parents of children with diabetes, as well as the clinician experience. However, CGM does have limitations including cost, accuracy and perceived inconvenience. Cost-effectiveness analyses have indicated that CGM is a cost-effective adjunct to type 1 diabetes management that is associated with reduced diabetes-related complications and hospitalisation. CONCLUSIONS: Continuous glucose monitoring is revolutionising diabetes management. It is a cost-effective adjunct to diabetes management that has the potential to improve glycaemic outcomes and quality of life in PWD, especially type 1 diabetes.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Automonitorização da Glicemia/economia , Automonitorização da Glicemia/instrumentação , Análise Custo-Benefício/estatística & dados numéricos , Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 1/economia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas/análise , Controle Glicêmico/economia , Controle Glicêmico/instrumentação , Controle Glicêmico/estatística & dados numéricos , História do Século XX , História do Século XXI , Hospitalização/estatística & dados numéricos , Humanos , Satisfação do Paciente/estatística & dados numéricos , Qualidade de Vida
12.
J Am Pharm Assoc (2003) ; 61(3): 233-239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33414014

RESUMO

OBJECTIVE: To examine the measured contents of over-the-counter (OTC) and prescription (Rx) prenatal multivitamins and minerals (PMVMs) and compare the findings with the amounts reported on the nutrition labels. The findings were subsequently examined on the basis of cost and ability to adequately supplement dietary intake during pregnancy on the basis of The National Academies' dietary reference intakes (DRIs) and tolerable upper intake levels. METHODS: This was an observational convenience sample of OTC and Rx PMVMs available through online retailers and retail pharmacies. The amounts of folic acid, vitamin B6, vitamin C, and choline were measured in triplicate using mass spectrometry. RESULTS: Twenty OTC and 16 Rx PMVMs were evaluated. The average measured quantities of the vitamins were not statistically different from the mean reported quantities for OTC and Rx PMVMs. When a standard diet was combined with the labeled nutrition information, 95% of the OTC PMVMs and 88% of the Rx PMVMs met the DRIs for folic acid and vitamins B6 and C. When a standard diet was combined with the actual measured PMVM quantities, 79% of the OTC PMVMs and 82% of the Rx PMVMs met the DRIs for folic acid and vitamins B6 and C. The measured choline content, with and without diet considerations, did not meet the DRIs. No statistically significant difference was found for the adequacy of supplementation between the OTC and Rx PMVMs on the basis of cost. CONCLUSION: On the basis of a comparison of the measured and reported values for folic acid, vitamin C, vitamin B6, and choline, it seems that either OTC or Rx PMVMs at low or high cost can be recommended to supplement diets and meet the DRIs during pregnancy for these vitamins.


Assuntos
Suplementos Nutricionais , Vitaminas , Dieta , Feminino , Humanos , Minerais , Gravidez , Prescrições
13.
J Appl Res Intellect Disabil ; 34(3): 805-817, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33599087

RESUMO

INTRODUCTION: Preliminary evidence suggests dialectical behaviour therapy (DBT) may be beneficial for persons with intellectual disabilities. This pilot randomized controlled trial aimed to determine the feasibility of adapted DBT for adults with intellectual disabilities and co-morbid psychiatric disorders in the community. METHODS: An adapted DBT programme (aDBT-ID) was delivered to adults with mild-to-moderate intellectual disability (n = 20) and their caregivers (n = 20). A single-blind, mixed-methods design was employed with treatment (n = 10) and control (n = 10). In addition to feasibility, pre-post-measures of emotional regulation, anger and mental health were taken from clients and caregivers. RESULTS: Results suggest it was feasible and beneficial to deliver adapted DBT in the community. Qualitative findings found both participants and caregivers were satisfied with the treatment delivery. No differences between conditions were found. CONCLUSION: This pilot study highlights the feasibility of adapted DBT for individuals with intellectual disabilities and the practicalities of delivering community-based inclusive research.


Assuntos
Terapia do Comportamento Dialético , Deficiência Intelectual , Adulto , Criança , Deficiências do Desenvolvimento , Estudos de Viabilidade , Humanos , Deficiência Intelectual/terapia , Projetos Piloto , Método Simples-Cego , Resultado do Tratamento
14.
Transfusion ; 60(9): 2067-2078, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32729161

RESUMO

BACKGROUND: The microparticle content (MP%) of apheresis platelets-a marker of platelet activation-is influenced by donor factors and by external stressors during collection and storage. This study assessed the impact of apheresis technology and other factors on the activation status (MP%) of single-donor apheresis platelets. STUDY DESIGN AND METHODS: Data from six US hospitals that screened platelets by measuring MP% through dynamic light scattering (ThromboLUX) were retrospectively analyzed. Relative risks (RRs) were derived from univariate and multivariable regression models, with activation rate (MP% ≥15% for plasma-stored platelets; ≥10% for platelet additive solution [PAS]-stored platelets) and MP% as outcomes. Apheresis platform (Trima Accel vs Amicus), storage medium (plasma vs PAS), pathogen reduction, storage time, and testing location were used as predictors. RESULTS: Data were obtained from 7511 platelet units collected using Trima (from 16 suppliers, all stored in plasma, 20.0% were pathogen-reduced) and 2456 collected using Amicus (from four different collection facilities of one supplier, 65.0% plasma-stored, 35.0% PAS-stored, none pathogen-reduced). Overall, 30.0% of Trima platelets were activated compared to 45.6% of Amicus platelets (P < .0001). Multivariable analysis identified apheresis platform as significantly associated with platelet activation, with a lower activation rate for Trima than Amicus (RR: 0.641, 95% confidence interval [CI]: 0.578; 0.711, P < .0001) and a 6.901% (95% CI: 5.926; 7.876, P < .0001) absolute reduction in MP%, when adjusting for the other variables. CONCLUSION: Trima-collected platelets were significantly less likely to be activated than Amicus-collected platelets, irrespective of the storage medium, the use of pathogen reduction, storage time, and testing site.


Assuntos
Doadores de Sangue , Plaquetas/metabolismo , Preservação de Sangue , Ativação Plaquetária , Plaquetoferese , Plaquetas/citologia , Feminino , Humanos , Masculino , Estudos Retrospectivos
15.
J Immunol ; 200(4): 1347-1359, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29305434

RESUMO

In obesity, IL-13 overcomes insulin resistance by promoting anti-inflammatory macrophage differentiation in adipose tissue. Endogenous IL-13 levels can be modulated by the IL-13 decoy receptor, IL-13Rα2, which inactivates and depletes the cytokine. In this study, we show that IL-13Rα2 is markedly elevated in adipose tissues of obese mice. Mice deficient in IL-13Rα2 had high expression of IL-13 response markers in adipose tissue, consistent with increased IL-13 activity at baseline. Moreover, exposure to the type 2 cytokine-inducing alarmin, IL-33, enhanced serum and tissue IL-13 concentrations and elevated tissue eosinophils, macrophages, and type 2 innate lymphoid cells. IL-33 also reduced body weight, fat mass, and fasting blood glucose levels. Strikingly, however, the IL-33-induced protection was greater in IL-13Rα2-deficient mice compared with wild-type littermates, and these changes were largely attenuated in mice lacking IL-13. Although IL-33 administration improved the metabolic profile in the context of a high fat diet, it also resulted in diarrhea and perianal irritation, which was enhanced in the IL-13Rα2-deficient mice. Weight loss in this group was associated with reduced food intake, which was likely related to the gastrointestinal effects. These findings outline both potentially advantageous and deleterious effects of a type 2-skewed immune response under conditions of metabolic stress, and identify IL-13Rα2 as a critical checkpoint in adipose tissues that limits the protective effects of the IL-33/IL-13 axis in obesity.


Assuntos
Subunidade alfa2 de Receptor de Interleucina-13/metabolismo , Interleucina-13/metabolismo , Interleucina-33/metabolismo , Obesidade/imunologia , Obesidade/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Humanos , Interleucina-13/imunologia , Subunidade alfa2 de Receptor de Interleucina-13/imunologia , Interleucina-33/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
Mol Biol Rep ; 47(9): 7297-7303, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32804305

RESUMO

Physical inactivity and unhealthy food intake are strongly associated with the growing prevalence of type 2 diabetes (T2D). Dyslipidemia, a characteristic of T2D patient, contributes to an increase in intra-myocellular lipid accumulation and mitochondria dysfunction, in skeletal muscle cells and further to insulin resistance. The aim of this study was to evaluate the effect of aerobic exercise on dyslipidemia, mitochondrial homeostasis and mitochondrial DNA (mtDNA) transcription in T2D- induced animals. Wistar rats (8 weeks old) were fed a diet containing 60% fat over 9 weeks, at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced). At week 3 of the experiment half of the animals started on an aerobic exercise 5-days/week. Blood and soleus muscle were collected at 9th experimental week. Abdominal fat, blood glucose, triglyceride, low-density-lipoprotein and high-density lipoprotein (HDL), and cellular mtDNA copy number, cytochrome b (cytb) mRNA and 8-isoprostane were measured. T2D-induced animals exhibited changes in blood glucose, weight gain, abdominal fat, LDL and muscular 8-isoprostane, mtDNA copy number and cytb mRNA. Aerobic exercise attenuated the increase in weight gain and abdominal fat and the decreased cytb mRNA, and increased HDL. Our results suggest that aerobic exercise might not affect all characteristics related to the development of T2D in the same way. However, since T2D is a multifactorial disease, improvement in parameters such as HDL levels, abdominal fat and weight gain induced by aerobic exercise might delay or inhibit the onset of T2D.


Assuntos
DNA Mitocondrial/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/metabolismo , Mitocôndrias Musculares/metabolismo , Condicionamento Físico Animal , Transcrição Gênica , Animais , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Dislipidemias/terapia , Masculino , Ratos , Ratos Wistar
17.
J Lipid Res ; 60(4): 856-868, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30782959

RESUMO

Treatment with PPARγ agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences in responsiveness to their effects are poorly understood. To examine the ex vivo metabolic effects of rosiglitazone (Rosi), we cultured explants of human visceral (omental) and abdominal subcutaneous adipose tissues for 7 days. Rosi increased mRNA levels of transcriptional regulators of brite/beige adipocytes (PGC1α, PRDM16), triglyceride synthesis (GPAT3, DGAT1), and lipolysis (ATGL) similarly in adipose tissues from both depots. In parallel, Rosi increased key modulators of FA oxidation (UCP1, FABP3, PLIN5 protein), rates of FA oxidation, and protein levels of electron transport complexes, suggesting an enhanced respiratory capacity as confirmed in newly differentiated adipocytes. Rosi led to the formation of small lipid droplets (SLDs) around the adipocyte central lipid droplet; each SLD was decorated with redistributed mitochondria that colocalized with PLIN5. SLD maintenance required lipolysis and FA reesterification. Rosi thus coordinated a structural and metabolic remodeling in adipocytes from both visceral and subcutaneous depots that enhanced oxidative capacity. Selective targeting of these cellular mechanisms to improve adipocyte FA handling may provide a new approach to treat metabolic complications of obesity and diabetes.


Assuntos
Adipócitos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Gotículas Lipídicas/efeitos dos fármacos , Rosiglitazona/farmacologia , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adulto , Idoso , Feminino , Humanos , Gotículas Lipídicas/metabolismo , Masculino , Pessoa de Meia-Idade , Oxirredução , Fenótipo
18.
Anesth Analg ; 129(4): 1137-1143, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31219915

RESUMO

BACKGROUND: It is unknown whether the implementation of an information video on spinal anesthesia for cesarean delivery, narrated in a patient's first language, reduces anxiety, increases satisfaction, and improves doctor-patient communication if there is a language barrier. In South Africa, most doctors speak English, and patients speak Xhosa, with educational and cultural disparities existing in many doctor-patient interactions. METHODS: One hundred seventy-five Xhosa patients scheduled for elective cesarean delivery were enrolled in the study. The first 92 patients received "usual care" verbal explanations of the spinal anesthesia procedure (control group); the next 83 patients watched a spinal anesthesia information video (intervention group), narrated in Xhosa. Videos were displayed using smartphones. Maternal anxiety was assessed before and after spinal explanation, using a Numerical Visual Analog Anxiety Scale (NVAAS). A difference in postexplanation NVAAS score of 1.5 points between intervention and control groups was regarded as clinically significant. Patient satisfaction was assessed using the Maternal Satisfaction Scale for Cesarean Section (MSSCS). RESULTS: The mean (standard deviation [SD]) age (31.5 years [5.2 years] and 32.1 years [5.4 years]) and preexplanation NVAAS score (4.2 [3.2] and 4.0 [3.0]) of the intervention and control groups, respectively, showed no difference at baseline. The mean (SD) postexplanation decrease in NVAAS score was greater in the intervention than in the control group (1.6 [3.5] vs 0.7 [2.3]; P = .046; unadjusted mean difference, 0.9 points [95% confidence interval {CI}, 0.02-1.8]). A linear regression model for the postexplanation NVAAS score showed that the intervention effect was significantly associated with the preexplanation score (P = .002), adjusted for age and English fluency. Patients with preexplanation NVAAS scores ≥5 showed a statistically significant intervention effect. There was no significant difference in patient satisfaction between the intervention and control groups. The smartphone was an accessible and convenient display medium for the video. Ninety-nine percent of patients exposed to the intervention would recommend watching the video before the procedure. CONCLUSIONS: In this pilot study, lower NVAAS scores were observed in anxious patients, when a Xhosa information video was used to ameliorate challenges posed by a doctor-patient language barrier. It is easily implemented and demonstrates a novel use of mobile health technology. The study provides baseline data to inform sample size calculations for future studies. A high level of patient recommendation for the video suggests that this is an agreeable practice.


Assuntos
Anestesia Obstétrica , Raquianestesia , Ansiedade/prevenção & controle , Cesárea , Barreiras de Comunicação , Idioma , Mães/psicologia , Educação de Pacientes como Assunto/métodos , Telemedicina/métodos , Gravação em Vídeo , Adulto , Anestesia Obstétrica/efeitos adversos , Anestesia Obstétrica/psicologia , Raquianestesia/efeitos adversos , Raquianestesia/psicologia , Ansiedade/diagnóstico , Ansiedade/psicologia , Cesárea/efeitos adversos , Cesárea/psicologia , Compreensão , Feminino , Humanos , Relações Médico-Paciente , Projetos Piloto , Gravidez , Fatores de Risco , Smartphone , África do Sul , Telemedicina/instrumentação
19.
J Pediatr Orthop ; 39(9): e718-e721, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31503233

RESUMO

BACKGROUND: Accessory ossicles off the talus (os trigonum) are a common radiographic finding seen within the foot with variable symptomatology in adult and pediatric patients. Although most studies have examined the incidence of these anatomic variants in a retrospective manner, few have longitudinally followed the behavior of os trigonum over time. The aim of this study was to investigate the incidence, mean age of appearance and fusion, and fusion rate of os trigonum in a large cohort of asymptomatic pediatric patients. METHODS: A total of 2620 serial digitized unilateral foot and ankle radiographs from 261 healthy white children (age range, 0.25 to 7 y at enrollment) were retrospectively reviewed. Radiographs were examined to determine the incidence of os trigonum, noting age of appearance and if present, the age of fusion. Skeletal maturity was graded based on ossification pattern of the calcaneal apophysis. RESULTS: Radiographic evidence of os trigonum was present in 18% of patients (n=16 females, n=15 males) with radiographs extending 1 SD beyond the average age of os trigonum appearance. There was no difference in incidence between females and males (P=0.27), and os trigonum was found to appear at a significantly younger age in females (9.1±1.8 y) than males (10.4±2.0 y, P=0.04). Overall, 70% (n=26) of subjects with os trigonum achieved fusion by age 17 (mean, 9.5±1.6 y in females, 11.2±1.6 in males) with no significant difference between sexes (P=0.61). Grading of skeletal maturity at the time of fusion showed that both male and female subjects underwent fusion on average between calcaneal stages 2 and 3 (P=0.5). CONCLUSIONS: This study confirms a relatively large prevalence of os trigonum in a random pediatric population, and clarifies both the average age of onset and high rate of fusion at a relatively narrow range of skeletal maturity. LEVEL OF EVIDENCE: Prognostic level II-retrospective study.


Assuntos
Osso e Ossos/anormalidades , Anormalidades Congênitas/epidemiologia , Tálus/anormalidades , Adolescente , Fatores Etários , Osso e Ossos/diagnóstico por imagem , Criança , Pré-Escolar , Anormalidades Congênitas/diagnóstico por imagem , Feminino , Humanos , Incidência , Lactente , Masculino , Prevalência , Radiografia , Estudos Retrospectivos , Fatores Sexuais
20.
Matern Child Health J ; 22(8): 1093-1102, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29744710

RESUMO

Introduction Since 2001, the Health Resources and Services Administration's Maternal and Child Health Bureau (HRSA MCHB) has funded and directed the National Survey of Children's Health (NSCH) and the National Survey of Children with Special Health Care Needs (NS-CSHCN), unique sources of national and state-level data on child health and health care. Between 2012 and 2015, HRSA MCHB redesigned the surveys, combining content into a single survey, and shifting from a periodic interviewer-assisted telephone survey to an annual self-administered web/paper-based survey utilizing an address-based sampling frame. Methods The U.S. Census Bureau fielded the redesigned NSCH using a random sample of addresses drawn from the Census Master Address File, supplemented with a unique administrative flag to identify households most likely to include children. Data were collected June 2016-February 2017 using a multi-mode design, encouraging web-based responses while allowing for paper mail-in responses. A parent/caregiver knowledgeable about the child's health completed an age-appropriate questionnaire. Experiments on incentives, branding, and contact strategies were conducted. Results Data were released in September 2017. The final sample size was 50,212 children; the overall weighted response rate was 40.7%. Comparison of 2016 estimates to those from previous survey iterations are not appropriate due to sampling and mode changes. Discussion The NSCH remains an invaluable data source for key measures of child health and attendant health care system, family, and community factors. The redesigned survey extended the utility of this resource while seeking a balance between previous strengths and innovations now possible.


Assuntos
Serviços de Saúde da Criança , Saúde da Criança , Inquéritos Epidemiológicos , Adolescente , Criança , Pré-Escolar , Crianças com Deficiência , Características da Família , Feminino , Inquéritos Epidemiológicos/métodos , Inquéritos Epidemiológicos/normas , Humanos , Masculino , Projetos de Pesquisa
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