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1.
Artigo em Inglês | MEDLINE | ID: mdl-38748362

RESUMO

PURPOSE: This study examines correlates of experiences of hunger among adolescents in the United States (U.S) by the intersectionality of race/ethnicity with sociodemographic characteristics (gender, sexual identity, and adolescent/parent job loss) with the aim of identifying subgroups most at risk for hunger during the COVID-19 pandemic. METHODS: This cross-sectional study uses nationally representative data from the Adolescent Behaviors and Experiences Survey (ABES) collected from January to June 2021. The analytic sample was high school students aged 14-17 with complete data (n = 6023). Descriptive statistics, bivariate, and multivariate logistic regression models were used to examine associations between sociodemographic factors and hunger (1-item measure) among adolescents during the pandemic for the analytic sample and stratified by race/ethnicity. RESULTS: The prevalence of hunger was 24.1% for the analytic sample and was highest among American Indian/Alaskan Native/Other Pacific Islander youth (37.2%), followed by non-Hispanic Black (31.8%) and Hispanic (28.4%) youth, and lowest among Non-Hispanic White youth (18.6%). In the analytic sample, there were significant differences in experiences of hunger by race/ethnicity, sexual identity, and adolescent/parent job loss during the pandemic (p < 0.05). When stratified by race/ethnicity, there were differential associations of hunger with sexual identity, and adolescent/parent job loss. CONCLUSIONS: These findings provide evidence of differential experiences of hunger during the pandemic among adolescents by sociodemographic factors. Results highlight the need for taking an intersectional approach when examining issues such as hunger. Future policies and programs should be mindful of factors associated with hunger and should prioritize using an equity-informed approach when engaging with multiply-marginalized adolescents.

2.
J Neuroophthalmol ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38706093

RESUMO

BACKGROUND: Administrative claims have been used to study the incidence and outcomes of nonarteritic ischemic optic neuropathy (NAION), but the validity of International Classification of Diseases (ICD)-10 codes for identifying NAION has not been examined. METHODS: We identified patients at 3 academic centers who received ≥1 ICD-10 code for NAION in 2018. We abstracted the final diagnosis from clinical documentation and recorded the number of visits with an NAION diagnosis code. We calculated positive predictive value (PPV) for the overall sample and stratified by subspecialty and the number of diagnosis codes. For patients with ophthalmology or neuro-ophthalmology visit data, we recorded presenting symptoms, examination findings, and laboratory data and calculated PPV relative to case definitions of NAION that incorporated sudden onset of symptoms, optic disc edema, afferent pupillary defect, and other characteristics. RESULTS: Among 161 patients, PPV for ≥1 ICD-10 code was 74.5% (95% CI: 67.2%-80.7%). PPV was similar when restricted to patients who had visited an ophthalmologist (75.8%, 95% CI: 68.4%-82.0%) but increased to 86.8% when restricted to those who had visited neuro-ophthalmologists (95% CI: 79.2%-91.9%). Of 113 patients with >1 ICD-10 code and complete examination data, 37 (32.7%) had documented sudden onset, optic disc swelling, and an afferent pupillary defect (95% CI: 24.7%-42.0%). Of the 76 patients who did not meet these criteria, 54 (71.0%) still received a final clinical diagnosis of NAION; for most (41/54, 75.9%), this discrepancy was due to lack of documented optic disc edema. CONCLUSIONS: The validity of ICD-10 codes for NAION in administrative claims data is high, particularly when combined with provider specialty.

3.
J Hip Preserv Surg ; 11(1): 59-66, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38606328

RESUMO

Slipped capital femoral epiphysis (SCFE) is a common adolescent hip disorder that can lead to complex proximal femur deformities and devastating consequences such as avascular necrosis, femoroacetabular impingement syndrome and early-onset osteoarthritis. Existing surgical techniques are often insufficient to fully address the constellation of multiplanar deformities in patients with severe SCFE. Therefore, the McMaster Osteotomy, a novel intertrochanteric proximal femur osteotomy, was developed to improve anatomic correction and hip mechanics in patients with chronic SCFE. The McMaster Osteotomy was implemented in two patients (A: 16-year-old male, B: 17-year-old female) with proximal femur deformities due to chronic SCFE. Surgical planning was facilitated with a 3D-printed pelvic model generated from a CT scan of a patient with the SCFE deformity. Patient B also underwent concurrent arthroscopic osteochondroplasty and labral repair. Pre- and post-operative function and radiographic measurements were recorded. Post-operatively, patient A's neck-shaft angle improved from 125° to 136°, Southwick angle from 52° to 33°, neck length from 66 mm to 80 mm and hip internal rotation from 5° to 25°. Patient B's post-operative neck-shaft angle improved from 122° to 136°, Southwick angle from 25° to 15°, neck length from 76 mm to 84 mm, hip internal rotation from 5° to 20° and alpha angle from 87.6° to 44.3°. Both patients are pain-free and have obtained full union of their osteotomies. The McMaster Osteotomy is a versatile technique that can produce a more anatomic reconstruction of hip anatomy and restoration of abductor mechanics. As an extracapsular technique, the risk of femoral head avascular necrosis is minimized.

5.
bioRxiv ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38464292

RESUMO

Introduction: The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition. Methods: Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects. Perivascular AP burden among cognitive states was correlated with neuroimaging and cognitive measures. Results: Peri-arteriolar exceeded peri-venular AP count (p<0.0001). Secondary branch AP count was significantly higher in cognitively impaired (p<0.01). Secondary small and tertiary peri-venular AP count strongly correlated with clinical dementia rating, hippocampal volumes, and white matter hyperintensity count. Discussion: Our topographic analysis indicates greater retinal amyloid accumulation in the retinal peri-arteriolar regions overall, and distal peri-venular regions in cognitively impaired individuals. Larger longitudinal studies are warranted to understand the temporal-spatial relationship between vascular dysfunction and perivascular amyloid deposition in AD. Highlights: Retinal peri-arteriolar region exhibits more amyloid compared with peri-venular regions.Secondary retinal vascular branches have significantly higher perivascular amyloid burden in subjects with impaired cognition, consistent across sexes.Cognitively impaired individuals have significantly greater retinal peri-venular amyloid deposits in the distal small branches, that correlate with CDR and hippocampal volumes.

6.
Obes Surg ; 34(5): 1639-1652, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38483742

RESUMO

BACKGROUND: Physical activity (PA) can play an important role in optimizing metabolic/bariatric surgery (MBS) outcomes. However, many MBS patients have difficulty increasing PA, necessitating the development of theory-driven counseling interventions. This study aimed to (1) assess the feasibility and acceptability of the TELEhealth BARIatric behavioral intervention (TELE-BariACTIV) trial protocol/methods and intervention, which was designed to increase moderate-to-vigorous intensity physical activity (MVPA) in adults awaiting MBS and (2) estimate the effect of the intervention on MVPA. METHODS: This trial used a repeated single-case experimental design. Twelve insufficiently active adults awaiting MBS received 6 weekly 45-min PA videoconferencing counseling sessions. Feasibility and acceptability data (i.e., refusal, recruitment, retention, attendance, and attrition rates) were tracked and collected via online surveys, and interviews. MVPA was assessed via accelerometry pre-, during, and post-intervention. RESULTS: Among the 24 patients referred to the research team; five declined to participate (refusal rate = 20.8%) and seven were ineligible or unreachable. The recruitment rate was 1.2 participants per month between 2021-09 and 2022-07. One participant withdrew during the baseline phase, and one after the intervention (retention rate = 83.3%). No participant dropouts occurred during the intervention and 98.6% of sessions were completed. Participants' anticipated and retrospective acceptability of the intervention was 3.2/4 (IQR, 0.5) and 3.0/4 (IQR, 0.2), respectively. There was a statistically significant increase in MVPA [Tau-U = 0.32(0.11; 0.51)] from pre- to post-intervention. CONCLUSION: Despite a low recruitment rate, which could be explained by circumstances (COVID-19 pandemic), results support feasibility, acceptability, and preliminary efficacy of the TELE-Bari-ACTIV intervention for increasing MVPA in patients awaiting MBS.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Telemedicina , Adulto , Humanos , Estudos de Viabilidade , Pandemias , Estudos Retrospectivos , Obesidade Mórbida/cirurgia , Exercício Físico/psicologia
7.
Prev Med ; 181: 107924, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432307

RESUMO

OBJECTIVE: To determine the time to first report of signs of nicotine dependence among youth exclusive e-cigarette users and compare this time to that for exclusive cigarette users. METHODS: Secondary analysis of data (Waves 1-5; 2013-2019) from the Population Assessment of Tobacco and Health was conducted. Youth never tobacco users in the United States who reported exclusive past-30-day (P30D) e-cigarette or cigarette use (n = 2940, N = 5,391,642) in at least one wave were included in the current analysis. Survival analysis was used to estimate the time to the first report of three nicotine dependence indicators (i.e., "use within 30 minutes of waking"; "cravings" and "really needing to use") following the first report of P30D use. Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). RESULTS: There were no significant differences in the time to first report of "use within 30 minutes of waking" (aHR = 1.1, 95% CI = 0.87-1.40) and "cravings" (aHR = 1.09, 95% CI = 0.81-1.47) between exclusive P30D e-cigarette use and exclusive P30D cigarette use. However, compared to exclusive P30D e-cigarette use, the hazard of first reporting "really needing to use" tobacco was 39% (aHR 1.39; 95% CI: 1.05-1.84) times higher for those who reported exclusive P30D cigarette use after controlling for covariates. CONCLUSION: Compared to exclusive P30D cigarette use, no differences in the time to first report of signs of nicotine dependence ("use within 30 minutes" and "cravings") were observed among exclusive P30D e-cigarette users. Policymakers and regulatory agencies should consider this evidence when assessing the abuse liability of e-cigarette products.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Tabagismo , Humanos , Adolescente , Estados Unidos/epidemiologia , Tabagismo/epidemiologia , Estudos de Coortes , Uso de Tabaco/epidemiologia
8.
BMJ Open ; 14(2): e070749, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38413149

RESUMO

OBJECTIVES: To describe the prevalence of school-based tobacco prevention programme exposure among adolescents in low-income and middle-income countries (LMICs) and its association with psychosocial predictors of smoking. DESIGN: Analysis of pooled cross-sectional data. SETTING: Global Youth Tobacco Survey (GYTS), conducted in 38 LMICs. PARTICIPANTS: This was a pooled analysis of data involving a total of 132 755 adolescent respondents to GYTS in 38 LMICs across Africa, Europe and Central/South America between 2014 and 2017. EXPOSURE AND OUTCOME MEASURES: The primary independent variable for this study was self-reported exposure to school-based tobacco prevention programmes in the past year. Five psychosocial determinants of smoking were explored as outcomes: perceived addictiveness of nicotine, perceived harm of secondhand smoke exposure, support for restricting cigarette smoking at public indoor locations, support for restricting cigarette smoking at public outdoor areas and self-reported prediction of enjoying cigarette smoking. Multivariable logistic regression models were used to examine the relationship between exposure to school-based tobacco prevention programmes and study outcomes, controlling for sociodemographic and smoking-related characteristics of respondents. RESULTS: Overall, 59.1% of adolescents in LMICs self-reported exposure to school-based tobacco prevention programmes. The country-specific prevalence of adolescent exposure to school-based tobacco interventions ranged from 24.9% in the Comoros to 99.3% in Turkmenistan. Exposure to school-based tobacco interventions was significantly associated with greater secondhand smoke harm perceptions (adjusted OR (AOR): 1.69; 95% CI: 1.69 to 1.70), perceptions of addictiveness (AOR: 1.37; 95% CI: 1.36 to 1.37) and supporting tobacco use restrictions indoors (AOR: 1.70; 95% CI: 1.69 to 1.70) and outdoors (AOR: 1.59; 95% CI: 1.59 to 1.60). Exposure to school-based tobacco interventions was associated with lower odds of anticipating enjoying cigarette smoking (AOR: 0.76; 95% CI: 0.76 to 0.76). CONCLUSION: Exposure to tobacco prevention programmes in schools is suboptimal in LMICs. Given the protective associations described in this study from school-based tobacco prevention programme exposure, it is imperative that national governments implement school-based programmes into ongoing tobacco control measures.


Assuntos
Fumar Cigarros , Poluição por Fumaça de Tabaco , Humanos , Adolescente , Estudos Transversais , Países em Desenvolvimento , Poluição por Fumaça de Tabaco/prevenção & controle , Inquéritos e Questionários , Fumar Cigarros/epidemiologia , Produtos do Tabaco
9.
Artigo em Inglês | MEDLINE | ID: mdl-38347309

RESUMO

BACKGROUND: Differences in symptoms of depression and anxiety by race/ethnicity and socioeconomic status (SES) among a diverse cohort of young adults during the COVID-19 pandemic (Spring 2020-Fall 2021) have not been examined. METHOD: We analyzed four waves of biannual, panel data from n = 2629 emerging adults (16-25 years old) from the Texas Adolescent Tobacco and Marketing Surveillance study (TATAMS). We conducted a series of mixed effects ordinal logistic regression models to compare the independent and joint effects of race/ethnicity and SES on symptoms of (a) depression and (b) anxiety, adjusting for sex, cohort, and time. RESULTS: Symptoms of depression (aOR range: 1.54 - 2.19; 95% CI: 1.02 - 3.08) and anxiety (aOR range: 1.64 - 2.19; 95% CI: 1.22 - 2.79) were elevated among low SES young adults, across all racial/ethnic groups. Across SES groups, symptoms of depression were lower among non-Hispanic Blacks compared to non-Hispanic Whites (aOR range: 0.33 - 0.41; 95% CI: 0.18 - 0.62) and Hispanics /Latinos (aOR range: 0.33 - 0.38; 95% CI: 0.20 - 0.57); similarly, symptoms of anxiety were lower among non-Hispanic Blacks compared to non-Hispanic Whites (aOR range: 0.44; 95% CI: 25 - 0.77) and Hispanics/Latinos (aOR range: 0.47 - 0.56; 95% CI: 0.29 - 0.83). No significant interaction (joint effect) was observed between SES and race/ethnicity during this period. CONCLUSION: Low SES was persistently related to poor mental health. Lower odds of symptoms of anxiety and depression among non-Hispanic Black young adults may reflect the 'mental health paradox'. Overall, mental health policies should prioritize lower SES young adults regardless of race and ethnicity.

10.
Am J Physiol Endocrinol Metab ; 326(4): E428-E442, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324258

RESUMO

Glucagon rapidly and profoundly stimulates hepatic glucose production (HGP), but for reasons that are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course of glucagon-mediated molecular events and their relevance to metabolic flux in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a sixfold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group, glucose remained at basal, whereas in the other, glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) and largely sustained increase in hepatic cAMP over 4 h, a continued elevation in glucose-6-phosphate (G6P), and activation and deactivation of glycogen phosphorylase and synthase activities, respectively. Net hepatic glycogenolysis increased rapidly, peaking at 15 min due to activation of the cAMP/PKA pathway, then slowly returned to baseline over the next 3 h in line with allosteric inhibition by glucose and G6P. Glucagon's stimulatory effect on HGP was sustained relative to the hyperglycemic control group due to continued PKA activation. Hepatic gluconeogenic flux did not increase due to the lack of glucagon's effect on substrate supply to the liver. Global gene expression profiling highlighted glucagon-regulated activation of genes involved in cellular respiration, metabolic processes, and signaling, as well as downregulation of genes involved in extracellular matrix assembly and development.NEW & NOTEWORTHY Glucagon rapidly stimulates hepatic glucose production, but these effects are transient. This study links the molecular and metabolic flux changes that occur in the liver over time in response to a rise in glucagon, demonstrating the strength of the dog as a translational model to couple findings in small animals and humans. In addition, this study clarifies why the rapid effects of glucagon on liver glycogen metabolism are not sustained.


Assuntos
Glucagon , Insulina , Humanos , Cães , Animais , Glucagon/metabolismo , Insulina/metabolismo , Transcriptoma , Glucose/metabolismo , Fígado/metabolismo , Gluconeogênese/genética , Glicemia/metabolismo
11.
Nicotine Tob Res ; 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181207

RESUMO

INTRODUCTION: We quantified the linear trend in combustible tobacco smoking among adolescents in the United States from 2014 to 2020, then compared these trends across racial and ethnic category. We also tested the effect of e-cigarette use on these trends for all youth and across racial and ethnic categories. METHODS: We pooled and analyzed seven years of National Youth Tobacco Survey (NYTS) data for n=124,151 middle and high school students from 2014 to 2020. Weighted logistic regression analyses calculated the annual change in combustible tobacco smoking (i.e., cigarettes, cigars, and hookah) from 2014 to 2020. Stratified analyses examined linear trends for non-Hispanic White (NHW), NH-Black (NHB), Hispanic/Latino, and NH-Other (NHO) youth. All models controlled for sex, grade level, and past 30-day e-cigarette use. RESULTS: Combustible tobacco smoking from 2014 to 2020 dropped by more than 50% for NHW youth, more than 40% for Latino and NHO youth, compared to just 16% among NHB youth. From 2014 to 2020, odds of combustible tobacco smoking declined by 21.5% per year for NHWs, which was significantly greater than Hispanic/Latinos (17% per year; p=0.025), NHOs (15.4% per year; p=0.01), and NHBs (5.1% per year; p<0.001), adjusting for sex, grade, and e-cigarette use. Trends and disparities in trends by race and ethnicity were observed independent of e-cigarette use. CONCLUSIONS: Combustible tobacco smoking declined for all youth but at significantly different rates across races and ethnicity. Notably, declines in combustible tobacco smoking are lagging among NHB youth. Interventions are critically needed to address this disparity. IMPLICATIONS: A direct, evidence-based intervention to reduce combustible tobacco smoking among NHB youth is critically needed. Such tobacco control initiatives should follow the Best Practices for Comprehensive Tobacco Control Framework, incorporating sustainable funding for school-based intervention, public health education, and adult cessation.

12.
Surg Obes Relat Dis ; 20(1): 98-108, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38238107

RESUMO

BACKGROUND: Physical activity (PA) is important for the long-term health and weight management of patients who undergo metabolic and bariatric surgery (MBS). However, the roles of exercise professionals in MBS settings have not been systematically determined. OBJECTIVES: To investigate: (1) who are the professionals implementing PA programming in MBS clinical settings; and (2) what patient-centric tasks do they perform? SETTING: Clinical and academic exercise settings worldwide. METHODS: This multimethod study included a scoping review of PA programs in MBS described in the research literature. Data about job tasks were extracted and provided to 10 experts to sort into categories. Cluster analysis was utilized to find the hierarchical structure of tasks. A Delphi process was used to agree on a final model. RESULTS: The majority of PA professionals were exercise physiologists in the USA and physiotherapists or other types of exercise professionals elsewhere. Forty-three tasks were identified, the most reported being supervision of exercise, fitness testing, and exercise prescription. Seven higher-order categories were determined: (1) Exercise-related health assessment, (2) Body composition and physical fitness assessment, (3) Lifestyle physical activity and sedentary behavior assessment, (4) Education, instruction, and prescription, (5) Exercise monitoring, (6) Behavioral counseling and psychosocial support, and (7) Dietary support. The following statements were rated an average of 9.0, classifying them as "imperative": 1) "Pre- and postoperative PA/exercise guidelines for MBS patients are needed", 2) "MBS programs need to include PA/exercise as part of multidisciplinary care". CONCLUSIONS: The expert group reached a consensus on 7 major classifications of job tasks for the exercise professional. It is important for governing medical associations across the world to formally recognize experienced exercise professionals as playing pivotal roles in continuing, multidisciplinary care for MBS patients. These findings also provide evidence-based information in the effort to solidify these positions within the greater context of healthcare.


Assuntos
Cirurgia Bariátrica , Exercício Físico , Humanos , Exercício Físico/psicologia , Cirurgia Bariátrica/métodos , Terapia por Exercício , Estilo de Vida , Aptidão Física
13.
Obes Sci Pract ; 10(1): e717, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38263993

RESUMO

Objective: Greater perceived social support (PSS) is associated with more favorable changes in weight loss, activity behaviors, and eating regulation after metabolic and bariatric surgery (MBS). However, studies have relied on generic, retrospective PSS measures, and stability of PSS levels and relations with weight loss and weight-related behaviors over time is unknown. Using smartphone-based Ecological Momentary Assessment, this study evaluated pre-to 1-year post-MBS changes in daily weight management-focused PSS and associations with weight loss, device-measured activity behaviors, and eating regulation before and during the initial year after MBS. Method: Adult MBS patients (n = 71) received (1) an accelerometer to measure daily moderate-to-vigorous intensity physical activity (MVPA) and sedentary time (ST) minutes/day, and (2) a smartphone to complete morning weight-focused PSS ratings and eating regulation (dietary restraint/disinhibition) ratings at four semi-random times daily for 10 days at pre- and 3, 6, and 12-month postoperative. Generalized linear mixed models analyzed the associations of PSS with total weight loss (%TWL) and activity/eating outcomes. Results: Participants on average reported relatively stable moderate-to-high PSS (3.98 on one to five scale) across assessments. Perceived social support was not related to %TWL, MVPA, or ST. Participants with higher PSS reported lower disinhibition and higher restraint than those with lower PSS (ps < 0.05); however, participants reported higher restraint on days that PSS was lower than their usual levels (p = 0.009). Conclusions: MBS patients on average had stable PSS levels across time. Higher PSS levels were associated with greater resistance to overeating cues (disinhibition) and cognitive control to restrict food intake (restraint) over time. Additionally, participants reported higher restraint when PSS levels were lower than usual. Overall, weight-focused PSS appeared to hold greater importance in relation to regulating eating behavior than engaging in activity behaviors or weight loss among MBS patients during the initial postoperative year. Clinical Trial Registration: NCT02777177.

14.
J Mol Biol ; 436(4): 168409, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38128824

RESUMO

Human immunodeficiency virus type 1 (HIV-1) stimulates innate immune responses upon infection, including cyclic GMP-AMP synthase (cGAS) signaling that results in type I interferon production. HIV-1-induced activation of cGAS requires the host cell factor polyglutamine binding protein 1 (PQBP1), an intrinsically disordered protein that bridges capsid recognition and cGAS recruitment. However, the molecular details of PQBP1 interactions with the HIV-1 capsid and their functional implications remain poorly understood. Here, we show that PQBP1 binds to HIV-1 capsids through charge complementing contacts between acidic residues in the N-terminal region of PQBP1 and an arginine ring in the central channel of the HIV-1 CA hexamer that makes up the viral capsid. These studies reveal the molecular details of PQBP1's primary interaction with the HIV-1 capsid and suggest that additional elements are likely to contribute to stable capsid binding.


Assuntos
Capsídeo , Proteínas de Ligação a DNA , HIV-1 , Humanos , Capsídeo/química , Proteínas do Capsídeo/química , Proteínas de Ligação a DNA/química , HIV-1/química , Imunidade Inata , Nucleotidiltransferases/química , Ligação Proteica , Conformação Proteica
15.
Pain ; 165(5): 1154-1168, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38147415

RESUMO

ABSTRACT: Painful diabetic neuropathy (PDN) is one of the most common and intractable complications of diabetes. Painful diabetic neuropathy is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, axonal degeneration, and changes in cutaneous innervation. However, the complete molecular profile underlying the hyperexcitable cellular phenotype of DRG nociceptors in PDN has not been elucidated. This gap in our knowledge is a critical barrier to developing effective, mechanism-based, and disease-modifying therapeutic approaches that are urgently needed to relieve the symptoms of PDN. Using single-cell RNA sequencing of DRGs, we demonstrated an increased expression of the Mas-related G protein-coupled receptor d (Mrgprd) in a subpopulation of DRG neurons in the well-established high-fat diet (HFD) mouse model of PDN. Importantly, limiting Mrgprd signaling reversed mechanical allodynia in the HFD mouse model of PDN. Furthermore, in vivo calcium imaging allowed us to demonstrate that activation of Mrgprd-positive cutaneous afferents that persist in diabetic mice skin resulted in an increased intracellular calcium influx into DRG nociceptors that we assess in vivo as a readout of nociceptors hyperexcitability. Taken together, our data highlight a key role of Mrgprd-mediated DRG neuron excitability in the generation and maintenance of neuropathic pain in a mouse model of PDN. Hence, we propose Mrgprd as a promising and accessible target for developing effective therapeutics currently unavailable for treating neuropathic pain in PDN.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Hiperalgesia , Neuralgia , Receptores Acoplados a Proteínas G , Animais , Camundongos , Cálcio/metabolismo , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Hipersensibilidade/genética , Neuralgia/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Hiperalgesia/genética , Hiperalgesia/fisiopatologia
16.
Drug Alcohol Depend ; 255: 111059, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38150895

RESUMO

BACKGROUND: Many modern e-cigarette brands contain equivalent or higher nicotine levels than traditional cigarettes. OBJECTIVE: To examine differences in four nicotine dependence indicators (i.e., use within 30minutes of waking, cravings, needing to use, and frequent use) among adolescents (aged 12-17 years) with past 30-day (P30D) exclusive use of e-cigarettes, cigarettes, or dual use of both. METHODS: Data were from Wave 5 (2018-2019) of the Population Assessment of Tobacco and Health (PATH) study (n=1060; N=2053,659). Multivariable logistic regression was performed to determine differences in indicators by P30D e-cigarette and cigarette use behavior (exclusive vs. dual use) and brand (e-cigarette use: JUUL vs. non-JUUL vs. Unknown). RESULTS: The odds of frequent use among adolescents with JUUL (AOR: 2.11; 95% CI=1.02-4.37) and non-JUUL (AOR: 2.12; 95% CI=0.95-4.77) use were similar and paralleled that for dual use (AOR: 3.50; 95% CI=1.46-8.43) but were stronger (JUUL only) than exclusive cigarette use. The odds of using within 30minutes of waking for adolescents with JUUL (AOR: 2.23; 95% CI=0.80-6.25) and non-JUUL (AOR:1.42; 95% CI=0.47-4.32) use were similar and paralleled that for both dual (AOR=3.00; 95% CI=1.01-8.88) and exclusive cigarette use. For adolescents who used unknown brands, the odds of all indicators paralleled exclusive cigarette use but were lower than JUUL, non-JUUL, and dual use. CONCLUSION: Compared to exclusive cigarette use, symptoms of nicotine dependence are similar for adolescents with exclusive e-cigarette use, irrespective of brand. Symptoms of nicotine dependence for JUUL and non-JUUL use parallel dual use. Tobacco regulation should consider these findings when assessing the abuse liability of e-cigarettes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Tabagismo , Vaping , Adolescente , Humanos , Tabagismo/epidemiologia , Estudos Transversais , Vaping/epidemiologia , Projetos de Pesquisa
17.
Surg Obes Relat Dis ; 20(4): 383-390, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38160134

RESUMO

BACKGROUND: Little is known about longer-term adherence to recommended physical activity (PA) and dietary behaviors after metabolic and bariatric surgery (MBS) and whether adherence is associated with weight recurrence. OBJECTIVES: To explore (1) changes in and associations between adherence to PA and general dietary recommendations after MBS and (2) whether PA and dietary behaviors interact to predict weight recurrence. SETTING: University hospital; public practice. METHODS: Participants completed ActiGraph PA monitoring, dietary questionnaire, and weighing 1 and 5 years after surgery. Parametric and non-parametric tests evaluated changes in and associations between adherence to PA and dietary recommendations. Multiple linear regression explored associations of adherence and weight recurrence 5 years post-surgery. RESULTS: A total of 73 participants (66% loss to follow-up, 80.8% females) were included. From 1 to 5 years after surgery, adherence to PA recommendations did not change (23.5% versus 20.5%, P = .824), whereas adherence to dietary recommendations decreased (P = <.001). Adherence to PA recommendations is positively associated with eating fruits and vegetables and limiting intake of sugar and fat at 1 year (P < .05) and negatively associated with choosing meat with less fat at 5 years (P = .018). Adherence to PA and dietary behaviors did not independently contribute or interact to predict weight recurrence. CONCLUSIONS: Adherence to recommendations was poor. Dietary adherence decreased from 1 to 5 years post-surgery, whereas PA adherence remained stable. PA adherence was positively associated with adherence to some dietary recommendations at 1 year but not at 5 years. Neither behavioral adherences were associated with weight recurrence. Additional research is needed to understand how to improve adherence and its relationship with other health outcomes after MBS.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Feminino , Humanos , Masculino , Obesidade Mórbida/cirurgia , Redução de Peso , Dieta , Exercício Físico
18.
Artigo em Inglês | MEDLINE | ID: mdl-38107165

RESUMO

Introduction/Purpose: Observational research suggests that consistent exercise timing could be leveraged to promote moderate-to-vigorous physical activity (MVPA) among adults with obesity. However, the feasibility and acceptability of prescribed consistent exercise timing in a free-living setting is unknown. The purpose of this study was to assess the feasibility and acceptability of prescribed consistent exercise timing in a free-living setting among inactive adults with obesity (primary) and to compare MVPA timing prescriptions and characterize exercise barriers/facilitators (secondary). Methods: Using a within-subjects design, inactive adults with obesity (n=15) were randomized in counterbalanced order to three 3-wk exercise timing conditions separated by 2-wk washout periods: 1) consistent morning, 2) consistent evening, and 3) choice timing (control). Feasibility was assessed using prespecified benchmarks. Acceptability and preferred timing were assessed with questionnaires post-intervention. Secondarily, exercise timing and MVPA were assessed via accelerometry and nightly surveys and barriers/facilitators were assessed with nightly surveys. Results: All feasibility benchmarks were achieved (e.g., timing adherence = 69.9% via accelerometry and 87.4% via self-report (target: ≥60%)). Consistent exercise timing was acceptable (mean rating = 3.7 of 5 (target: ≥3.5)). Choice was the most popular prescription. There were medium- to large-sized effects (partial η2 of 0.09-0.16) of condition on MVPA; MVPA was higher during the morning and evening conditions versus choice condition. Facilitators were similar across conditions, while some barriers were time specific. Conclusion: Prescribed exercise timing in a free-living setting appears feasible and acceptable. While choice timing was most preferred, consistent timing appeared most effective for increasing MVPA. Data warrant larger trials to test the efficacy and mechanisms of consistent exercise timing as a translational strategy for promoting MVPA. Pending findings from a fully powered randomized trial, practitioners interested in promoting MVPA among their patients or clients could consider encouraging exercise at a consistent time day-to-day.

19.
medRxiv ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38106156

RESUMO

Background: It is unknown whether the impact of high diet-quality and physical activity (PA) depends on the level of polygenic risk score (PRS) in different ancestries. Objective: Determine the associations and interactions between high-risk PRSs, dietary patterns, and high PA with atherosclerotic cardiovascular disease (ASCVD) in European Americans (EAs) and African Americans (AAs). Another aim determined the molecular pathways of PRS-mapped genes and their relationships with dietary intake. Methods: Cross-sectional analyses utilized de-identified data from 1987-2010 from 7-National Heart, Lung, and Blood Institute Candidate Gene Association Resource studies from the Database of Genotypes and Phenotypes studies for EAs (n=6,575) and AAs (n=1,606). Results: The high-risk PRS increased ASCVD risk by 59% (Risk Ratio=1.59;95% Confidence Interval:1.16-2.17) in the highest tertile for AAs and by 15% (RR=1.15;1.13-1.30) and 18% (RR=1.18;1.04-1.35) in the second and highest tertiles compared to the lowest tertile in EAs. Within the highest PRS tertiles, high PA-diet combinations (Dietary Approaches to Stop High Blood Pressure (DASH), or Mediterranean, or Southern) reduced ASCVD risks by 9% (RR=0.91;0.85-0.96) to 15% (RR=0.85;0.80-0.90) in EAs; and by 13% (RR=0.87;0.78-0.97) and 18% (RR=0.82;0.72-0.95) for the DASH and Mediterranean diets, respectively in AAs. Top molecular pathways included fructose metabolism and catabolism linked to obesity, insulin resistance, and type 2 diabetes in both ancestries. Additional molecular pathways for AAs were Vitamin D linked to depression and aging acceleration; and death signaling associated with cancer. Conclusions: Effects of high diet-quality and high PA can counterbalance the influences of genetically high-risk PRSs on ASCVD risk, especially in AAs.

20.
PLoS One ; 18(12): e0296400, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38134122

RESUMO

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and ß-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the ß-cell's capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Resistência à Insulina , Humanos , Cães , Animais , Frutose , Insulina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glicemia/metabolismo
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