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1.
Immunity ; 49(3): 464-476.e4, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30193847

RESUMO

According to the established model of murine innate lymphoid cell (ILC) development, helper ILCs develop separately from natural killer (NK) cells. However, it is unclear how helper ILCs and NK cells develop in humans. Here we elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils using ex vivo molecular and functional profiling and lineage differentiation assays. We demonstrated that while tonsillar NK cells, ILC2s, and ILC3s originated from a common CD34-CD117+ ILC precursor pool, final steps of ILC2 development deviated independently and became mutually exclusive from those of NK cells and ILC3s, whose developmental pathways overlapped. Moreover, we identified a CD34-CD117+ ILC precursor population that expressed CD56 and gave rise to NK cells and ILC3s but not to ILC2s. These data support a model of human ILC development distinct from the mouse, whereby human NK cells and ILC3s share a common developmental pathway separate from ILC2s.


Assuntos
Células Matadoras Naturais/imunologia , Linfócitos/imunologia , Tonsila Palatina/imunologia , Animais , Antígenos CD34/metabolismo , Antígeno CD56/metabolismo , Diferenciação Celular , Linhagem da Célula , Células Cultivadas , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Ativação Linfocitária , Camundongos , Proteínas Proto-Oncogênicas c-kit/metabolismo
2.
J Bacteriol ; 206(2): e0033723, 2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38299858

RESUMO

Genome sequencing has demonstrated that Staphylococcus aureus encodes arginine biosynthetic genes argDCJBFGH synthesizing proteins that mediate arginine biosynthesis using glutamate as a substrate. Paradoxically, however, S. aureus does not grow in a defined, glutamate-replete medium lacking arginine and glucose (CDM-R). Studies from our laboratory have found that specific mutations are selected by S. aureus that facilitate growth in CDM-R. However, these selected mutants synthesize arginine utilizing proline as a substrate rather than glutamate. In this study, we demonstrate that the ectopic expression of the argDCJB operon supports the growth of S. aureus in CDM-R, thus documenting the functionality of this pathway. Furthermore, suppressor mutants of S. aureus JE2 putA::Tn, which is defective in synthesizing arginine from proline, were selected on CDM-R agar. Genome sequencing revealed that these mutants had compensatory mutations within both spoVG, encoding an ortholog of the Bacillus subtilis stage V sporulation protein, and sarA, encoding the staphylococcal accessory regulator. Transcriptional studies document that argD expression is significantly increased when JE2 spoVG sarA was grown in CDM-R. Lastly, we found that a mutation in ahrC was required to induce argD expression in JE2 spoVG sarA when grown in an arginine-replete medium (CDM), suggesting that AhrC also functions to repress argDCJB in an arginine-dependent manner. In conclusion, these data indicate that the argDCJB operon is functional when transcribed in vitro and that SNPs within potential putative regulatory proteins are required to alleviate the repression.IMPORTANCEAlthough Staphylococcus aureus has the capability to synthesize all 20 amino acids, it is phenotypically auxotrophic for several amino acids including arginine. This work identifies putative regulatory proteins, including SpoVG, SarA, and AhrC, that function to inhibit the arginine biosynthetic pathways using glutamate as a substrate. Understanding the ultimate mechanisms of why S. aureus is selected to repress arginine biosynthetic pathways even in the absence of arginine will add to the growing body of work assessing the interactions between metabolism and S. aureus pathogenesis.


Assuntos
Ácido Glutâmico , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Ácido Glutâmico/metabolismo , Arginina/metabolismo , Proteínas de Bactérias/metabolismo , Fatores de Transcrição/metabolismo , Aminoácidos/metabolismo , Prolina/genética , Prolina/metabolismo , Regulação Bacteriana da Expressão Gênica
3.
Psychol Sci ; 35(4): 376-389, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38446868

RESUMO

Inhibitory control is central to many theories of cognitive and brain development, and impairments in inhibitory control are posited to underlie developmental psychopathology. In this study, we tested the possibility of shared versus unique associations between inhibitory control and three common symptom dimensions in youth psychopathology: attention-deficit/hyperactivity disorder (ADHD), anxiety, and irritability. We quantified inhibitory control using four different experimental tasks to estimate a latent variable in 246 youth (8-18 years old) with varying symptom types and levels. Participants were recruited from the Washington, D.C., metro region. Results of structural equation modeling integrating a bifactor model of psychopathology revealed that inhibitory control predicted a shared or general psychopathology dimension, but not ADHD-specific, anxiety-specific, or irritability-specific dimensions. Inhibitory control also showed a significant, selective association with global efficiency in a frontoparietal control network delineated during resting-state functional magnetic resonance imaging. These results support performance-based inhibitory control linked to resting-state brain function as an important predictor of comorbidity in youth psychopathology.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Psicopatologia , Humanos , Adolescente , Criança , Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
4.
Inj Prev ; 30(4): 272-276, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029927

RESUMO

BACKGROUND: The older adult (65+) population in the USA is increasing and with it the number of medically treated falls. In 2015, healthcare spending attributable to older adult falls was approximately US$50 billion. We aim to update the estimated medical expenditures attributable to older adult non-fatal falls. METHODS: Generalised linear models using 2017, 2019 and 2021 Medicare Current Beneficiary Survey and cost supplement files were used to estimate the association of falls with healthcare expenditures while adjusting for demographic characteristics and health conditions in the model. To portion out the share of total healthcare spending attributable to falls versus not, we adjusted for demographic characteristics and health conditions, including self-reported health status and certain comorbidities associated with increased risk of falling or higher healthcare expenditure. We calculated a fall-attributable fraction of expenditure as total expenditures minus total expenditures with no falls divided by total expenditures. We applied the fall-attributable fraction of expenditure from the regression model to the 2020 total expenditures from the National Health Expenditure Data to calculate total healthcare spending attributable to older adult falls. RESULTS: In 2020, healthcare expenditure for non-fatal falls was US$80.0 billion, with the majority paid by Medicare. CONCLUSION: Healthcare spending for non-fatal older adult falls was substantially higher than previously reported estimates. This highlights the growing economic burden attributable to older adult falls and these findings can be used to inform policies on fall prevention efforts in the USA.


Assuntos
Acidentes por Quedas , Gastos em Saúde , Medicare , Humanos , Acidentes por Quedas/economia , Acidentes por Quedas/estatística & dados numéricos , Acidentes por Quedas/prevenção & controle , Estados Unidos/epidemiologia , Idoso , Gastos em Saúde/estatística & dados numéricos , Masculino , Feminino , Medicare/economia , Idoso de 80 Anos ou mais
5.
Inj Prev ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227146

RESUMO

BACKGROUND: Firearm suicides constitute a major public health issue. Policies that enhance economic security and decrease community-level poverty may be effective strategies for reducing risk of firearm suicide. This study examined the association between state minimum wage and firearm suicide. METHODS: State minimum wage, obtained from Temple's Law Atlas and augmented by legal research, was conceptualised using the modified Kaitz Index and a continuous variable centred on the federal minimum wage. State-level suicide counts were obtained from 2000 to 2020 multiple-cause-of-death mortality data from the National Vital Statistics System. Log-linear regressions were conducted to model the associations between state minimum wage and firearm suicides, stratifying by demographic groups. Analyses were conducted in 2023. RESULTS: A one percentage point increase in a state's modified Kaitz Index was associated with a 0.3% (95% CI -0.6% to -0.0%) decrease in firearm suicides within a state. A US$1.00 increase in a state's minimum wage above the federal minimum wage was associated with a 1.4% (95% CI -2.1% to -0.6%) decrease in firearm suicides. When stratified by quartile of firearm ownership, the modified Kaitz Index was associated with decreases in firearm suicides most consistently in the two lowest quartiles. CONCLUSION: Increasing a state's minimum wage may be a policy option to consider as part of a comprehensive approach to reducing firearm suicides. These findings expand the evidence base for how economic policies may be leveraged to reduce firearm suicides.

6.
J Acoust Soc Am ; 155(1): 145-155, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180155

RESUMO

The call characteristics and vocal behaviour of sei whales (Balaenoptera borealis) off eastern Canada, including potential spatiotemporal variation, is poorly understood. Such information can improve the performance of automated detector-classifiers, enhancing the accuracy and efficiency of identifying sei whales in large acoustic datasets. Ultimately, these data can be used to understand the occurrence, distribution, and population structure of sei whales in Atlantic Canada. We measured sei whale downsweep characteristics recorded from six locations off Nova Scotia (NS) and Newfoundland and Labrador (NFLD), Canada over a two-year period (2015-2017), and examined variation between call subtypes (singlets, doublets, triplets+), and seasons (Spring, Summer, Fall, Winter). We found that downsweeps had a mean duration of 1.58 s, sweeping from 75.66 to 34.22 Hz, with a peak frequency of 43.89 Hz and an intra-call interval of 2.22 s. Most call characteristics did not vary between location, subtype, or season; however, significantly longer downsweeps occurred off NS, within doublet calls, and in fall months. We also found that NFLD had a higher proportion of doublets (70%) than NS (52%). This variation may be evidence of acoustically diverging sei whale populations, as well as useful for improving detector-classifiers of sei whales in the region.


Assuntos
Acústica , Balaenoptera , Animais , Canadá , Citoesqueleto , Estações do Ano
7.
J Transl Med ; 21(1): 410, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353797

RESUMO

BACKGROUND: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. METHODS: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. RESULTS: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. CONCLUSION: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.


Assuntos
Doenças Raras , Doenças não Diagnosticadas , Estados Unidos , Humanos , Doenças Raras/diagnóstico , Doenças Raras/genética , Doenças Raras/terapia , Atenção Terciária à Saúde , Medicina Genômica , Testes Genéticos , Aconselhamento Genético
8.
Inj Prev ; 29(1): 91-100, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36600522

RESUMO

CONTEXT: Costs related to criminal justice are an important component of the economic burden of injuries; such costs could include police involvement, judicial and corrections costs, among others. If the literature has sufficient information on the criminal justice costs related to injury, it could be added to existing estimates of the economic burden of injury. OBJECTIVE: To examine research on injury-related criminal justice costs, and what extent cost information is available by type of injury. DATA SOURCES: Medline, PsycINFO, Sociological Abstracts ProQuest, EconLit and National Criminal Justice Reference Service were searched from 1998 to 2021. DATA EXTRACTION: Preferred Reporting Items for Systematic reviews and Meta-Analyses was followed for data reporting. RESULTS: Overall, 29 studies reported criminal justice costs and the costs of crime vary considerably. CONCLUSIONS: This study illustrates possible touchpoints for cost inputs and outputs in the criminal justice pathway, providing a useful conceptualisation for better estimating criminal justice costs of injury in the future. However, better understanding of all criminal justice costs for injury-related crimes may provide justification for prevention efforts and potentially for groups who are disproportionately affected. Future research may focus on criminal justice cost estimates from injuries by demographics to better understand the impact these costs have on particular populations.


Assuntos
Crime , Direito Penal , Humanos , Polícia
9.
Inj Prev ; 29(3): 246-252, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36600521

RESUMO

INTRODUCTION: Negative outcomes, including suicidal ideation/attempts, are a major public health concern, particularly among individuals who sustain a traumatic brain injury (TBI). TBI is associated with high rates of postinjury substance use, psychiatric disorders, post-traumatic stress disorder and sleep disturbances. This study examines the mediation effects of substance use, psychiatric disorder and sleep disorder on the associations between TBI and suicidal ideation/attempts. METHODS: A matched case-control study using data from MarketScan databases for private health insurance and Medicaid from October 2015 to December 2018 estimated the association between TBI and suicidal ideation/attempts using a mediation approach. Individuals less than 65 years of age were included. RESULTS: In the Medicaid sample, psychiatric disorders mediated 22.4% of the total effect between TBI and suicidal ideation/attempt, while substance use disorders other than opioid use disorder mediated 7.47%. In the private health insurance sample, psychiatric disorders mediated 3.97% of the total effect, opioid use disorders mediated 2.08% of the total effect and sleep disorder mediated 1.25% of the total effect. CONCLUSIONS: Mediators explained less than 30% of the relationship between TBI and suicidal ideation/attempt. Findings reinforce the importance of primary prevention of TBI and monitoring patients with a TBI for risk of suicide in the first 6-12 months following injury.


Assuntos
Lesões Encefálicas Traumáticas , Transtornos do Sono-Vigília , Transtornos Relacionados ao Uso de Substâncias , Suicídio , Humanos , Ideação Suicida , Suicídio/psicologia , Tentativa de Suicídio/psicologia , Estudos de Casos e Controles , Lesões Encefálicas Traumáticas/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Fatores de Risco
10.
Pediatr Radiol ; 53(6): 1163-1170, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36859687

RESUMO

BACKGROUND: Current guidelines recommend healthcare professionals avoid routine use of neuroimaging for diagnosing mild traumatic brain injury (mTBI). OBJECTIVE: This study aimed to examine current use of CT and MRI among children and young adult patients with mTBI and factors that increase likelihood of neuroimaging in this population. MATERIALS AND METHODS: Data were analyzed using the 2019 MarketScan commercial claims and encounters database for the commercially insured population for both inpatient and outpatient claims. Descriptive statistics and logistic regression models for patients ≤24 years of age who received an ICD-10-CM code indicative of a possible mTBI were analyzed. RESULTS: Neuroimaging was performed in 16.9% (CT; 95% CI=16.7-17.1) and 0.9% (MRI; 95% CI=0.8-0.9) of mTBI outpatient visits (including emergency department visits) among children (≤18 years old). Neuroimaging was performed in a higher percentage of outpatient visits for patients 19-24 years old (CT=47.1% [95% CI=46.5-47.6] and MRI=1.7% [95% CI=1.5-1.8]), and children aged 15-18 years old (CT=20.9% [95% CI=20.5-21.2] and MRI=1.4% [95% CI=1.3-1.5]). Outpatient visits for males were 1.22 (95% CI=1.10-1.25) times more likely to include CT compared to females, while there were no differences by sex for MRI or among inpatient stays. Urban residents, as compared to rural, were less likely to get CT in outpatient settings (adjusted odds ratio [aOR]=0.55, 95% CI=0.53-0.57). Rural residents demonstrated a larger proportion of inpatient admissions that had a CT. CONCLUSIONS: Despite recommendations to avoid routine use of neuroimaging for mTBI, neuroimaging remained common practice in 2019.


Assuntos
Concussão Encefálica , Masculino , Feminino , Adulto Jovem , Humanos , Criança , Adulto , Adolescente , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/epidemiologia , Estudos Transversais , Neuroimagem , Imageamento por Ressonância Magnética , Serviço Hospitalar de Emergência
11.
J Hum Nutr Diet ; 36(1): 191-202, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35722666

RESUMO

BACKGROUND: Few studies have assessed dietary patterns (DPs) and the changes in these patterns over time in adults. The present study aimed to investigate whether possible changes in DPs in two assessments are associated with obesity and excess body fat. METHODS: A prospective study was conducted in which data were collected from 1082 adults of a Brazilian birth cohort during two periods 15 years apart (T1: 2002-2004; T2: 2016-2017). Food consumption was assessed in both periods using validated food frequency questionnaires. Three similar DPs were found in the two assessments, and adherence to these patterns was classified as prudent, risk or mixed. Nine DPs changes were defined. At T2, subjects with a body mass index ≥ 30.0 kg m- ² were classified as obese, and men and women with a body fat (BF) percentage ≥ 25.0 and ≥ 35.0, respectively, were classified as having excess BF. A directed acyclic graph was built to adjust the association for confounding variables. RESULTS: At T2, 34.4% of the subjects were obese and 61.4% had excess BF. In the adjusted analysis, the changes associated with obesity and excess BF were prudent-mixed (prevalence ratio [PR] 1.55; 95% confidence interval [CI] = 1.04-2.29 and PR = 1.35; 95% CI = 1.10-1.65), risk-risk (PR = 1.49; 95% CI = 1.03-2.13 and PR = 1.27; 95% CI = 1.04-1.53), risk-mixed (PR = 1.56; 95% CI = 1.05-2.31 and PR = 1.33; 95% CI = 1.07-1.63) and mixed-risk (PR = 1.61; 95% CI = 1.10-2.35 and PR = 1.29; 95% CI = 1.04-1.58). CONCLUSIONS: A decline in food quality over time or stagnation in an unhealthy DP can lead to obesity and excess BF.


Assuntos
Coorte de Nascimento , Dieta , Masculino , Adulto , Humanos , Feminino , Dieta/efeitos adversos , Estudos Prospectivos , Brasil/epidemiologia , Obesidade/epidemiologia , Obesidade/etiologia , Índice de Massa Corporal , Tecido Adiposo
12.
J Bacteriol ; 204(10): e0026922, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36106854

RESUMO

Staphylococcus aureus chronically colonizes up to 30% of the human population on the skin or mucous membranes, including the nasal tract or vaginal canal. While colonization is often benign, this bacterium also has the capability to cause serious infections. Menstrual toxic shock syndrome (mTSS) is a serious toxinosis associated with improper use of tampons, which can induce an environment that is favorable to the production of the superantigen known as toxic shock syndrome toxin-1 (TSST-1). To better understand environmental signaling that influences TSST-1 production, we analyzed expression in the prototype mTSS strain S. aureus MN8. Using transcriptional and protein-based analysis in two niche-related media, we observed that TSST-1 expression was significantly higher in synthetic nasal medium (SNM) than in vaginally defined medium (VDM). One major divergence in medium composition was high glucose concentration in VDM. The glucose-dependent virulence regulator gene ccpA was deleted in MN8, and, compared with wild-type MN8, we observed increased TSST-1 expression in the ΔccpA mutant when grown in VDM, suggesting that TSST-1 is repressed by catabolite control protein A (CcpA) in the vaginal environment. We were able to relieve CcpA-mediated repression by modifying the glucose level in vaginal conditions, confirming that changes in nutritional conditions contribute to the overexpression of TSST-1 that can lead to mTSS. We also compared CcpA-mediated repression to other key regulators of tst, finding that CcpA regulation is dominant compared to other characterized regulatory mechanisms. This study underlines the importance of environmental signaling for S. aureus pathogenesis in the context of mTSS. IMPORTANCE Menstrual toxic shock syndrome (mTSS) is caused by strains of Staphylococcus aureus that overproduce a toxin known as toxic shock syndrome toxin-1 (TSST-1). This work studied how glucose levels in a model vaginal environment could influence the amount of TSST-1 that is produced by S. aureus. We found that high levels of glucose repress TSST-1 production, and this is done by a regulatory protein called catabolite control protein A (CcpA). The research also demonstrated that, compared with other regulatory proteins, the CcpA regulator appears to be the most important for maintaining low levels of TSST-1 in the vaginal environment, and this information helps to understand how changes in the vaginal environmental can lead to mTSS.


Assuntos
Choque Séptico , Infecções Estafilocócicas , Feminino , Humanos , Staphylococcus aureus/metabolismo , Proteína Estafilocócica A/metabolismo , Choque Séptico/microbiologia , Glucose/metabolismo , Superantígenos/genética , Superantígenos/metabolismo , Enterotoxinas/genética , Enterotoxinas/metabolismo , Infecções Estafilocócicas/microbiologia , Meios de Cultura
13.
Hum Brain Mapp ; 43(1): 83-112, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618421

RESUMO

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.


Assuntos
Transtornos de Ansiedade , Sistema Límbico , Neuroimagem , Córtex Pré-Frontal , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/patologia , Transtornos de Ansiedade/fisiopatologia , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/patologia , Sistema Límbico/fisiopatologia , Estudos Multicêntricos como Assunto , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia
14.
Hum Brain Mapp ; 43(1): 255-277, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.


Assuntos
Transtornos de Ansiedade/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Interpretação Estatística de Dados , Metanálise como Assunto , Estudos Multicêntricos como Assunto , Neuroimagem , Humanos , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/normas , Neuroimagem/métodos , Neuroimagem/normas
15.
Brain Behav Immun ; 104: 18-28, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35580792

RESUMO

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which results in deleterious changes to psychological and physical health. Patients with PTSD are especially susceptible to life-threatening co-morbid inflammation-driven pathologies, such as autoimmunity, while also demonstrating increased T-helper 17 (TH17) lymphocyte-driven inflammation. While the exact mechanism of this increased inflammation is unknown, overactivity of the sympathetic nervous system is a hallmark of PTSD. Neurotransmitters of the sympathetic nervous system (i.e., catecholamines) can alter T-lymphocyte function, which we have previously demonstrated to be partially mitochondrial redox-mediated. Furthermore, we have previously elucidated that T-lymphocytes generate their own catecholamines, and strong associations exist between tyrosine hydroxylase (TH; the rate-limiting enzyme in the synthesis of catecholamines) and pro-inflammatory interleukin 17A (IL-17A) expression within purified T-lymphocytes in a rodent model of psychological trauma. Therefore, we hypothesized that T-lymphocyte-generated catecholamines drive TH17 T-lymphocyte polarization through a mitochondrial superoxide-dependent mechanism during psychological trauma. To test this, T-lymphocyte-specific TH knockout mice (THT-KO) were subjected to psychological trauma utilizing repeated social defeat stress (RSDS). RSDS characteristically increased tumor necrosis factor-α (TNFα), IL-6, IL-17A, and IL-22, however, IL-17A and IL-22 (TH17 produced cytokines) were selectively attenuated in circulation and in T-lymphocytes of THT-KO animals. When activated ex vivo, secretion of IL-17A and IL-22 by THT-KO T-lymphocytes was also found to be reduced, but could be partially rescued with supplementation of norepinephrine specifically. Interestingly, THT-KO T-lymphocytes were still able to polarize to TH17 under exogenous polarizing conditions. Last, contrary to our hypothesis, we found RSDS-exposed THT-KO T-lymphocytes still displayed elevated mitochondrial superoxide, suggesting increased mitochondrial superoxide is upstream of T-lymphocyte TH induction, activity, and TH17 regulation. Overall, these data demonstrate TH in T-lymphocytes plays a critical role in RSDS-induced TH17 T-lymphocytes and offer a previously undescribed regulator of inflammation in RSDS.


Assuntos
Interleucina-17 , Tirosina 3-Mono-Oxigenase , Animais , Camundongos , Humanos , Interleucina-17/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Derrota Social , Superóxidos/metabolismo , Células Th17/metabolismo , Catecolaminas/metabolismo , Inflamação/metabolismo
16.
AIDS Care ; 34(6): 679-688, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33625927

RESUMO

Chronic pain commonly occurs in people living with HIV (PLWH). Many PLWH in the United States obtain opioids for chronic pain management. Whether insomnia severity and depressive symptoms are exacerbated by chronic pain and opioid use in PLWH remains to be determined. This study examined insomnia severity and depressive symptoms in 85 PLWH with chronic pain and 35 PLWH without chronic pain. Among PLWH with chronic pain, reported opioid use was examined in relation to insomnia severity and depressive symptoms. PLWH with chronic pain reported significantly greater insomnia severity (p = .033) and depressive symptoms (p = .025) than PLWH without chronic pain. Among PLWH with chronic pain who reported opioid use (n = 36), insomnia severity was greater compared to those who denied opioid use (n = 49), even after controlling for pain severity and number of comorbidities (p = .026). Greater pain severity was significantly associated with greater insomnia severity (p < .001) and depressive symptoms (p = .048) among PLWH with chronic pain who reported opioid use. These associations were not significant among those PLWH with chronic pain who denied opioid use. Findings suggest that PLWH with chronic pain are likely to experience poor sleep and depressed mood. Furthermore, poor sleep was associated with opioid use among PLWH with chronic pain.


Assuntos
Dor Crônica , Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Distúrbios do Início e da Manutenção do Sono , Analgésicos Opioides/uso terapêutico , Dor Crônica/complicações , Dor Crônica/tratamento farmacológico , Depressão , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estados Unidos/epidemiologia
17.
Inj Prev ; 28(5): 405-409, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35296543

RESUMO

BACKGROUND: Quality-adjusted life years (QALYs) provide a means to compare injuries using a common measurement which allows quality of life and duration of life from an injury to be considered. A more comprehensive picture of the economic losses associated with injuries can be found when QALY estimates are combined with medical and work loss costs. This study provides estimates of QALY loss. METHODS: QALY loss estimates were assigned to records in the 2018 National Electronic Injury Surveillance System - All Injury Program. QALY estimates by body region and nature of injury were assigned using a combination of previous research methods. Injuries were rated on six dimensions, which identify a set of discrete qualitative impairments. Additionally, a seventh dimension, work-related disability, was included. QALY loss estimates were produced by intent and mechanism, for all emergency department-treated cases, by two disposition groups. RESULTS: Lifetime QALY losses ranged from 0.0004 to 0.388 for treated and released injuries, and from 0.031 to 3.905 for hospitalised injuries. The 1-year monetary value of QALY losses ranged from $136 to $437 000 among both treated and released and hospitalised injuries. The lifetime monetary value of QALY losses for hospitalised injuries ranged from $16 000 to $2.1 million. CONCLUSIONS: These estimates provide information to improve knowledge about the comprehensive economic burden of injuries; direct cost elements that can be measured through financial transactions do not capture the full cost of an injury. Comprehensive assessment of the long-term cost of injuries, including quality of life losses, is critical to accurately estimate the economic burden of injuries.


Assuntos
Serviço Hospitalar de Emergência , Qualidade de Vida , Análise Custo-Benefício , Humanos , Intenção , Anos de Vida Ajustados por Qualidade de Vida
18.
J Exp Child Psychol ; 214: 105274, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34507183

RESUMO

This research examined how mothers' goal orientation and exposure to misinformation can shape how mothers engage their children in conversation about past experiences and consequently affect the accuracy of children's memory reports. To investigate this question, 169 mothers were asked to talk with their preschool-age children (Mage = 55 months, SD = 6.15; 90 female) about an earlier nonshared event. Some mothers were instructed to focus on eliciting an accurate account, whereas others were told to talk naturally as in everyday life. Before this conversation, some mothers in each goal condition were exposed to misleading information about what their children experienced. Mothers focused on accuracy exhibited more bias in their conversations than those centered on talking naturally. When later interviewed, children with accuracy-focused mothers made more false reports and recalled less correct details than those with natural-focused mothers. These trends were found even when mothers were not misinformed. The implications of these results for children's eyewitness memory and suggestibility are discussed.


Assuntos
Memória , Mães , Criança , Pré-Escolar , Comunicação , Feminino , Humanos , Rememoração Mental
19.
J Public Health Manag Pract ; 28(1): E194-E197, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32956289

RESUMO

BACKGROUND: Beginning in 2009, there was an increase in the number of states with laws addressing 3 different components of youth sports-related concussion prevention and management: concussion education, removal from play, and medical clearance requirements before allowing an athlete to return to play. Schools are an important setting to implement policies and practices related to concussions, as many youth participate in organized sports through school venues. OBJECTIVE: To examine whether the prevalence of concussion-related policies and practices adopted by school districts changed from 2012 to 2016. METHODS: This study used nationally representative data from the 2012 and 2016 School Health Policies and Practices Study to examine whether the prevalence of 4 concussion-related policies and practices changed during 2012 and 2016 and whether comprehensive policies changed during the same time frame. Comprehensive policies were defined as those that address removal from play after injury, medical clearance before returning to play, and concussion-related educational materials and sessions for parents and student athletes. RESULTS: Among school districts nationwide, the prevalence of each of the 4 concussion-related policies and practices significantly increased during 2012 and 2016. The prevalence of comprehensive policies significantly increased from 51.6% in 2012 to 66.7% in 2016. While these findings are promising, it is important to note that one-third of districts still lacked comprehensive policies in 2016 and only 71% of districts provided educational sessions in 2016. CONCLUSIONS: The findings in this study highlight improvements in school districts nationwide in adopting concussion-related policies and practices. Policies such as requiring educational sessions allow parents and student athletes to learn about concussions and understand the importance of reporting a concussion or concussion symptoms.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Adolescente , Atletas , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/prevenção & controle , Concussão Encefálica/diagnóstico , Concussão Encefálica/epidemiologia , Concussão Encefálica/prevenção & controle , Política de Saúde , Humanos , Prevalência , Instituições Acadêmicas , Estados Unidos/epidemiologia
20.
J Public Health Manag Pract ; 28(1): 25-35, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33938487

RESUMO

BACKGROUND: Schools are an integral part of the community; however, congregate settings facilitate transmission of SARS-CoV-2, presenting a challenge to school administrators to provide a safe, in-school environment for students and staff. METHODS: We adapted the Centers for Disease Control and Prevention's COVIDTracer Advanced tool to model the transmission of SARS-CoV-2 in a school of 596 individuals. We estimate possible reductions in cases and hospitalizations among this population using a scenario-based analysis that accounts for (a) the risk of importation of infection from the community; (b) adherence to key Centers for Disease Control and Prevention-recommended mitigation strategies: mask wearing, cleaning and disinfection, hand hygiene, and social distancing; and (c) the effectiveness of contact tracing interventions at limiting onward transmission. RESULTS: Low impact and effectiveness of mitigation strategies (net effectiveness: 27%) result in approximately 40% of exposed staff and students becoming COVID-19 cases. When the net effectiveness of mitigation strategies was 69% or greater, in-school transmission was mostly prevented, yet importation of cases from the surrounding community could result in nearly 20% of the school's population becoming infected within 180 days. The combined effects of mitigation strategies and contact tracing were able to prevent most onward transmission. Hospitalizations were low among children and adults (<0.5% of the school population) across all scenarios examined. CONCLUSIONS: Based on our model, layering mitigation strategies and contact tracing can limit the number of cases that may occur from transmission in schools. Schools in communities with substantial levels of community spread will need to be more vigilant to ensure adherence of mitigation strategies to minimize transmission. Our results show that for school administrators, teachers, and parents to provide the safest environment, it is important to utilize multiple mitigation strategies and contract tracing that reduce SARS CoV-2 transmission by at least 69%. This will require training, reinforcement, and vigilance to ensure that the highest level of adherence is maintained over the entire school term.


Assuntos
COVID-19 , Adulto , Criança , Busca de Comunicante , Humanos , SARS-CoV-2 , Instituições Acadêmicas , Estudantes , Estados Unidos
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