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1.
Front Neurol ; 15: 1432330, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39281409

RESUMO

Spasticity management should be provided within the context of a comprehensive person-centered rehabilitation program. Furthermore, active goal setting for specific spasticity interventions is also important, with a well-established "more is better" approach. It is critical to consider adjunctive therapy and multimodal approaches if patients are not attaining their treatment goals. Often used interchangeably, there may be confusion between the terms adjunctive and multimodal therapy. Yet it is imperative to understand the differences between these approaches to achieve treatment goals in spasticity management. Addition of a secondary pharmacologic or non-pharmacologic treatment to optimize the efficacy of the initial modality, such as adding electrical stimulation or casting to BoNT-A, is considered an adjunctive therapy. Adjunctive therapy is time-specific and requires the added therapy be initiated within a specific period to enhance the primary treatment; usually within 2 weeks. Multimodal therapy is an integrated, patient-centric program of pharmacologic and non-pharmacologic strategies utilized in a concurrent/integrated or sequential manner to enhance the overall treatment effect across a variety of spasticity-associated impairments (e.g., neural and non-neural components). Moreover, within a multimodal approach, adjunctive therapy can be used to help enhance the treatment effect of one specific modality. The objectives of this paper are to clarify the differences between adjunctive and multimodal therapies, provide a brief evidence-based review of such approaches, and highlight clinical insights on selecting multimodal and adjunctive therapies in spasticity management.

2.
ACS Omega ; 9(36): 38195-38204, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39281942

RESUMO

Cellulose nanofibril-silver (CNF-Ag) hybrid and ultralight silver-infused aerogel were produced using cotton gin trash (CGT), an abundant agro-waste material. This repurposing of CGT was achieved by exploiting its potential for CNF extraction and the in situ synthesis of silver nanoparticles (Ag NPs). CNFs were extracted from CGT through a mechanical shearing process. These CNFs served as a multifunctional nanotemplate for the controlled reduction of Ag ions, efficient nucleation, and stabilization of NPs, resulting in the production of a high concentration of Ag NPs (ca. 19 wt %) within the CNFs. Transmission electron microscopy images of cross-sectioned CNFs confirmed the uniform dispersion of NPs (ca. 18 nm diameter) inside the CNFs. Rietveld refinement analysis of X-ray diffraction patterns revealed that CNFs produced smaller Ag crystallites compared to CGT microparticles. The CNF-Ag hybrid was then fabricated into an aerogel using freeze-drying, with its weight being light enough to rest on a cotton flower's stamen. The infusion of Ag NPs led to approximately 20% reductions in the specific surface area and pore volume of the aerogel.

3.
MethodsX ; 13: 102921, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39253000

RESUMO

In this detailed procedure, we include open-source methodologies using 'solidworks' designs for creating solo or semi-group housing units for rats wearing miniscopes for long periods of time. Builds are optimized to preserve rat health and prevent hardware destruction. We include all prices and suggestions for purchasing strategies to reduce overall build-costs.•Chambers are optimized for long-term housing to protect rats wearing delicate headstages (e.g., miniscopes).•Designed to be low-cost, efficient supplement to operant chambers and provides numerous benefits to long-term miniscope imaging. The housing chambers can be augmented by installing cameras, commutators, or different types of floor grids depending on experimental conditions.•The chambers can also be secured to one another to create "rat-duplexes", allowing experimenters to control the degree of social isolation.

4.
J Travel Med ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259891

RESUMO

INTRODUCTION: Hepatitis A (hepA) vaccination is highly immunogenic in healthy individuals, however there is uncertainty about the immunogenicity in immunocompromised populations (ICPs). METHODS: In this prospective cohort study, people living with HIV (PLWH), patients on immunosuppressive mono- and combination therapy, and controls received two hepA vaccine doses at months 0 and 6-12, or three combined hepA/B vaccine doses at months 0, 1 and 6-12. Antibody levels were measured before and at different time-points post-vaccination (T2, 6, 8, 12 months). The primary endpoint was the seroconversion rate (SCR) at T8, defined as hepA antibodies ≥20 mIU/ml. To assess boostability, an additional vaccine dose was administered 1-5 years after T12 in those with antibodies < 50 mIU/ml, with antibody measurements before and seven days after the booster dose. RESULTS: We included 150 participants. At T2 SCRs ranged between 35-58% in ICPs versus 94% in controls. Among PLWH, patients on monotherapy, combination therapy and controls SCRs at T8 were 33/34 (97%), 32/34 (94%), 25/30 (83%) and 28/28 (100%) respectively. The booster dose resulted in 71% additional seroconversion (17/24), with only patients using combination therapy not responding. CONCLUSIONS: HepA vaccination is highly immunogenic in virologically suppressed PLWH and patients on immunosuppressive monotherapy, with SCRs after the complete hepA vaccination schedule similar to controls and adequate booster responses in case of waning immunity. However, patients using immunosuppressive combination therapy as well as all ICPs who did not receive the complete hepA vaccination schedule, are at risk of non-response to vaccination and post-vaccination antibody measurements are recommended.

5.
ISME J ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259908

RESUMO

Many factors contribute to the ability of a microbial species to persist when encountering complexly contaminated environments including time of exposure, the nature and concentration of contaminants, availability of nutritional resources, and possession of a combination of appropriate molecular mechanisms needed for survival. Herein we sought to identify genes that are most important for survival of Gram-negative Enterobacteriaceae in contaminated groundwater environments containing high concentrations of nitrate and metals using the metal-tolerant Oak Ridge Reservation (ORR) isolate, Pantoea sp. MT58 (MT58). Survival fitness experiments in which a randomly barcoded transposon insertion (RB-TnSeq) library of MT58 was exposed directly to contaminated ORR groundwater samples from across a nitrate and mixed metal contamination plume were used to identify genes important for survival with increasing exposure times and concentrations of contaminants, and availability of a carbon source. Genes involved in controlling and using carbon, encoding transcriptional regulators, and related to Gram-negative outer membrane processes were among those found to be important for survival in contaminated ORR groundwater. A comparative genomics analysis of 75 Pantoea genus strains allowed us to further separate the survival determinants into core and non-core genes in the Pantoea pangenome, revealing insights into the survival of subsurface microorganisms during contaminant plume intrusion.

6.
Clin Dermatol ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260462

RESUMO

The new revised MPATH-Dx (Version 2.0) reporting schema for melanocytic lesions is presented herein. Principal changes include the simplification of the previous five-class Version 1.0 to a four-class hierarchy of melanocytic lesions to improve diagnostic agreement and to provide more explicit guidance in the management of patients. Version 2.0 also has clearly defined histopathological criteria for classification of Class I and II lesions now designated as low-grade (mild to moderate) atypia and high-grade (high-end moderate to severe) atypia, respectively. This new revised schema, also includes specific provisions for the less common WHO pathways to melanoma, provides guidance for classifying "intermediate" Class II tumors (melanocytomas), and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as a neoplasm falling short of fully-evolved melanoma.

7.
Fam Cancer ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261344

RESUMO

To determine the preoperative detection of signet ring cancer cells (SRC) on upper endoscopy (EGD) in patients with CDH1 pathogenic variant (PV) undergoing gastrectomy. To evaluate the development of advanced diffuse gastric cancer (DGC) in patients choosing surveillance. Guidelines recommend prophylactic total gastrectomy (pTG) in CDH1 PV carriers with family history of DGC between 18 and 40 years. Annual EGD with biopsies according to established protocols is recommended in carriers with no SRC and no family history of DGC, with consideration of pTG. Retrospective analysis of asymptomatic patients with CDH1 PVs with ≥ 1 surveillance EGD. Outcomes included pre-operative EGD detection of SRC, surgical stage, and progression to advanced DGC in those electing surveillance with EGD. 48 patients with CDH1 PVs who had ≥ 1 EGD were included. 24/ 48 (50%) underwent gastrectomy, including pTG in 7 patients. SRCC were detected on gastrectomy specimen in 21/24 (87.5%). SRCs were identified by EGD in 17/21 patients who had SRCC on gastrectomy specimens (sensitivity 81%, 17/21). All cancers were stage pT1a. The remaining 17 patients (50% with a family history of gastric cancer) continue in annual EGD surveillance with a median follow-up of 34.6 months. No SRCC or advanced DGC have been diagnosed. No CDH1 PV carriers without SRCC on random biopsies followed in an endoscopic program developed advanced DGC over a median follow up of 3 years. In the short term, EGD surveillance might be a safe alternative to immediate pTG in experienced hands in referral centers.

8.
Curr Heart Fail Rep ; 21(5): 498-503, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39242479

RESUMO

PURPOSE OF REVIEW: The development and progression of heart failure is characterized by metabolic and physiologic adaptations allowing patients to cope with cardiac insufficiency. This review explores the changes in metabolism in heart failure and the potential role of biomarkers, particularly ketone bodies, in staging and prognosticating heart failure progression. RECENT FINDINGS: Recent insights into myocardial metabolism shed light on the heart's response to stress, highlighting the shift towards reliance on ketone bodies as an alternative fuel source. Elevated blood ketone levels have been shown to correlate with the severity of cardiac dysfunction, emphasizing their potential as prognostic indicators. Furthermore, studies exploring therapeutic interventions targeting specific metabolic pathways offer promise for improving outcomes in heart failure. Ketones have prognostic utility in heart failure, and potentially, an avenue for therapeutic intervention. Challenges remain in deciphering the optimal balance between metabolic support and exacerbating cardiac remodeling. Future research endeavors must address these complexities to advance personalized approaches in managing heart failure.

9.
PLoS Comput Biol ; 20(9): e1012435, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39255272

RESUMO

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. We show that the persistence of bacilli in aquatic ecosystems is driven by a seasonal upstream supply, and that the attachment and development of cells to aquatic living forms is essential for such pathogen persistence and population dynamics. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

10.
Am J Obstet Gynecol MFM ; : 101488, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293588

RESUMO

BACKGROUND: Perinatal depression has been suggested to adversely impact child neurodevelopment. However, the complexity of the early childhood environment challenges conclusive findings. OBJECTIVE: To evaluate whether there is an association between perinatal depressive symptoms and child intelligence quotient (IQ) at 5 years of age. STUDY DESIGN: Secondary analysis of an ancillary study to a multicenter randomized trial of thyroxine therapy for pregnant individuals with subclinical hypothyroidism. Dyads of infants and birthing parent, with completed Center for Epidemiological Studies-Depression (CES-D) screens during pregnancy and postpartum and child neurodevelopment testing completed at five years of age (n=209) were included. CES-D screening was performed at 11-20 weeks, 34-38 weeks, and one-year postpartum. Depressive symptoms were categorized as antenatal (i.e., a positive screen at any point during pregnancy) or postpartum. The primary outcome was child IQ score < 85 at 5 years of age using the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) Full Scale test. Secondary outcomes included other assessments of childhood neurodevelopment. Bivariable analyses and multivariable logistic regressions were utilized. RESULTS: Of the 209 birthing people included, 72 (34%) screened positive for depression during pregnancy and 32 (15%) screened positive one year postpartum. Children born to individuals with a positive antenatal depression screen had a higher odds of IQ <85 at 5 years of age compared with children born to individuals with a CES-D <16 (35% vs. 18 %, OR 2.4, 95% CI 1.2-4.7). Similar findings were seen for children born to individuals with a positive postpartum depression screen (47% vs. 21%, OR 3.3, 95% CI 1.5-7.3). These associations did not persist in multivariable analyses that controlled for social determinants of health and clinical characteristics (adjusted odd ratio (aOR) 1.4, 95% CI 0.7-3.1; aOR 2.1, 95% CI 0.9-5.1, for antenatal and postpartum depressive symptoms, respectively). Similar findings were observed for other adverse neurodevelopmental outcomes. CONCLUSIONS: Having a positive perinatal depression screen was not associated with child cognitive outcomes after controlling for covariates including social determinants of health.

11.
Reprod Domest Anim ; 59(9): e14722, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39295165

RESUMO

The objective of the study was to characterise the expression patterns of the two key components of cortisol action namely HSD11B1 (11-beta-hydroxysteroid dehydrogenase type 1) and NR3C1 (nuclear receptor subfamily 3, group C, member 1, also known as the glucocorticoid receptor) in superovulation induced bovine follicles during the periovulation and subsequent corpus luteum (CL) formation. Bovine ovaries containing preovulatory follicles or CL were timely defined during induced ovulation as follows: 0 h before GnRH (Gonadotropin-releasing hormone) application, and 4, 10, 20, 25 (follicles) and 60 h (early CL) after GnRH. The low mRNA expression of HSD11B1 and NR3C1 in the follicle group before the GnRH application increased significantly in the follicle group 20 h after GnRH and remained high afterward also in the early CL group. In contrast, the high NR3C1 mRNA decreased in follicles 25 h after GnRH (close to ovulation) and significantly increased again after ovulation (early CL). Our results indicated the involvement of HSD11B1 and NR3C1 as the two key components of cortisol action in the local mechanisms coordinating final follicle maturation, ovulation, follicular-luteal transition and CL development in the cow.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1 , Corpo Lúteo , Hormônio Liberador de Gonadotropina , Folículo Ovariano , Receptores de Glucocorticoides , Animais , Feminino , Bovinos/fisiologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Hormônio Liberador de Gonadotropina/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Indução da Ovulação/veterinária , Ovulação/fisiologia , Regulação da Expressão Gênica
12.
Am J Cardiol ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39243877

RESUMO

In modern clinical practice, less than half of new-onset heart failure (HF) patients undergo ischemic evaluation, and only a minority undergo revascularization. We aimed to assess the proportion of the effect of hypertension (antihypertensive treatment) on incident HF to be eliminated by prevention of CHD event treated with or without revascularization, considering possible treatment-mediator interaction. Causal mediation analysis of ALLHAT included 42,418 participants (age 66.9±7.7; 35.6% black, 53.2% men). A new CHD event (myocardial infarction or angina) that occurred after randomization but before the incident HF outcome was the mediator. Incident symptomatic congestive HF (CHF) and hospitalized/fatal HF (HHF) were the primary and secondary outcomes. Logistic regression (for mediator) and Cox proportional hazards regression (for outcome) were adjusted for demographics, cardiovascular disease history, and risk factors. During a median 4.5-year follow-up, 2,785 patients developed CHF, including 2,216 HHF events. Participants who developed CHD events had twice the higher incidence rate of CHF than CHD-free (28.5 vs 13.9 events/ 1,000 person-years). The proportion of reference interaction indicating direct harm due to CHD event for lisinopril (234% for CHF; 355% for HHF) and amlodipine (244% for CHF; 468% for HHF) was greater than for chlorthalidone (143% for CHF; 269% for HHF). In patients with revascularized CHD events, chlorthalidone and amlodipine eliminated 21-24%, and lisinopril - 45% of HHF. Antihypertensive treatment was not able to eliminate harm from CHD events treated without revascularization. In conclusion, the antihypertensive drugs (chlorthalidone, lisinopril, amlodipine) prevent HF not principally by preventing CHD events but via other pathways. HF is moderated but not mediated by CHD events. Revascularization of CHD events is paramount for HF prevention.

13.
Dis Esophagus ; 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39245808

RESUMO

The rapid uptake of minimally invasive antireflux surgery has led to interest in learning curves for this procedure. This study ascertains the learning curve in laparoscopic and robotic-assisted antireflux surgery. A systematic review of the literature pertaining to learning curves in minimally invasive fundoplication with or without hiatal hernia repair was performed using PubMed, Medline, Embase, Web of Science, and Cochrane Library databases. A meta-regression analysis was undertaken to identify the number of cases to achieve surgical proficiency, and a meta-analysis was performed to compare outcomes between cases that were undertaken during a surgeon's learning phase and experienced phase. Twenty-five studies met the eligibility criteria. A meta-regression analysis was performed to quantitatively investigate the trend of number of cases required to achieve surgical proficiency from 1996 to present day. Using a mixed-effects negative binomial regression model, the predicted learning curve for laparoscopic and robotic-assisted antireflux surgery was found to be 24.7 and 31.1 cases, respectively. The meta-analysis determined that surgeons in their learning phase may experience a moderately increased rate of conversion to open procedure (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.28, 4.64), as well as a slightly increased rate of intraoperative complications (OR 1.60; 95% CI 1.08, 2.38), postoperative complications (OR 1.98; 95% CI 1.36, 2.87), and needing reintervention (OR 1.64; 95% CI 1.16, 2.34). This study provides an insight into the expected caseload to be competent in performing antireflux surgery. The discrepancy between outcomes during and after the learning curve for antireflux surgery suggests a need for close proctorship for learning surgeons.

14.
Nat Commun ; 15(1): 7737, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231939

RESUMO

Semiconductor nanoplatelets are atomically flat nanocrystals which emit light with high spectral purity at wavelengths controlled by their thickness. Despite their technological potential, efforts to further sharpen the emission lines of nanoplatelets have generally failed for unknown reasons. Here, we demonstrate theoretically that the linewidth is controlled by surface chemistry-specifically, inhomogeneities in the ligand layer on the nanoplatelet surface lead to a spatially fluctuating potential that localizes excitons. This localization leads to increased scattering and optical broadening. Importantly, localization also reduces the rate of radiative emission. Our model explains the observed linewidth and predicts that a more uniform ligand layer will sharpen the lines and increase the emission rates. These findings demonstrate that light emission from nanoplatelets can be controlled by optimizing their surface chemistry, an important advantage for their eventual use in optical technologies.

15.
Alzheimers Dement ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39234647

RESUMO

INTRODUCTION: Speech-based testing shows promise for sensitive and scalable objective screening for Alzheimer's disease (AD), but research to date offers limited evidence of generalizability. METHODS: Data were taken from the AMYPRED (Amyloid Prediction in Early Stage Alzheimer's Disease from Acoustic and Linguistic Patterns of Speech) studies (N = 101, N = 46 mild cognitive impairment [MCI]) and Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4) remote digital (N = 426, N = 58 self-reported MCI, mild AD or dementia) and in-clinic (N = 57, N = 13 MCI) cohorts, in which participants provided audio-recorded responses to automated remote story recall tasks in the Storyteller test battery. Text similarity, lexical, temporal, and acoustic speech feature sets were extracted. Models predicting early AD were developed in AMYPRED and tested out of sample in the demographically more diverse cohorts in ADNI4 (> 33% from historically underrepresented populations). RESULTS: Speech models generalized well to unseen data in ADNI4 remote and in-clinic cohorts. The best-performing models evaluated text-based metrics (text similarity, lexical features: area under the curve 0.71-0.84 across cohorts). DISCUSSION: Speech-based predictions of early AD from Storyteller generalize across diverse samples. HIGHLIGHTS: The Storyteller speech-based test is an objective digital prescreener for Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4). Speech-based models predictive of Alzheimer's disease (AD) were developed in the AMYPRED (Amyloid Prediction in Early Stage Alzheimer's Disease from Acoustic and Linguistic Patterns of Speech) sample (N = 101). Models were tested out of sample in ADNI4 in-clinic (N = 57) and remote (N = 426) cohorts. Models showed good generalization out of sample. Models evaluating text matching and lexical features were most predictive of early AD.

16.
Cornea ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231632

RESUMO

PURPOSE: The purpose of this study was to evaluate and compare the anatomic characteristics of eyes with Fuchs endothelial corneal dystrophy (FECD) with eyes without FECD. METHODS: This study was a retrospective chart review performed at an academic medical center. Patients with FECD were identified through a search of the electronic medical records. Eligible patients underwent Scheimpflug imaging and optical biometry and were compared with age and sex-matched control subjects who underwent similar testing in preparation for cataract surgery. Several measurements of the cornea, anterior chamber, and eyes were evaluated using multivariable linear regression models and multivariable logistic regression models. RESULTS: A total of 404 eyes (202 eyes with FECD and 202 control eyes) were included in this study. Compared with controls, eyes with FECD had shallower AC depths, lower AC volumes, and narrower angles. Conversely, the spherical equivalent before cataract surgery, corneal pachymetry, and corneal volume were higher in eyes with FECD. On Scheimpflug imaging analysis, these anatomical differences were present in FECD eyes with and without corneal edema. After adjusting for sex, these differences remained statistically significant. Shorter axial length was found to be statistically significant in male eyes but not in female eyes with FECD. CONCLUSIONS: This study reports new ocular characteristics in FECD eyes with and without edema. Optical biometry and Scheimpflug imaging established that the anatomic findings in eyes with FECD were not simply due to the larger volume of an edematous cornea but rather unique to eyes with FECD. These findings will provide reliable, normative data for future studies examining surgical, medical, and anatomical factors in FECD.

17.
Mol Biol Rep ; 51(1): 959, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230620

RESUMO

Cancer remains a global health burden, shaped by both genetic mutations and epigenetic dysregulation. Epigenetic alteration plays a pivotal role in tumorigenesis, immune response modulation, and the emergence of treatment resistance. This review emphasizes the intricate interplay between epigenetically reprogrammed cancer cells and the tumor microenvironment (TME), a relationship central to the immunoediting concept, which encompasses elimination, equilibrium, and escape phases. This review highlights the significance of CD8+ T cells as potent anticancer agents and discusses the mechanisms by which tumor cells evade immune surveillance and evolve resistance to immunotherapy. Such evasion entails the regulation of inhibitory molecules, antigen presentation machinery, and cytokine milieu. Furthermore, this review explores the complex dynamics culminating in CD8+ T cell dysfunction within the TME. In summary, this work offers insights into the indispensable role of epigenetic mechanisms in bolstering cancer cell survival amidst immunological challenges within the TME.


Assuntos
Linfócitos T CD8-Positivos , Epigênese Genética , Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Neoplasias/imunologia , Neoplasias/genética , Linfócitos T CD8-Positivos/imunologia , Imunoterapia/métodos , Evasão Tumoral/genética , Animais
18.
JAMA Surg ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230929
19.
Artigo em Inglês | MEDLINE | ID: mdl-39301965

RESUMO

BACKGROUND: We have developed a mouse model of Parenteral Nutrition Associated Liver Disease in which PN infusion results in cholestatic liver injury. In the liver, the master circadian genes Arntl/Bmal drive rhythmic gene expression and regulate circadian expression of hepatic functions including bile acid synthesis. The aim of this study was to examine the effect of continuous PN on ileal and hepatic expression of circadian regulatory (CR) genes, FXR signaling and bile acid synthesis in mice. METHODS: WT mice were exposed to continuous soy oil lipid emulsion-based PN infusion through a central venous catheter for 4 days (PN). Water was provided ad libitum, but no nutrients were provided enterally. On d4, mice were sacrificed every 6 hours (7AM, 1PM, 7PM and 1AM), and ileal, hepatic tissue and serum harvested. From tissue samples, the relative expression of circadian transcription factors and FXR signaling was assessed. RESULTS: Administration of 4d PN increased hepatic injury, inflammatory cytokine expression and gut permeability. In the ileum, PN activated FXR and induced expression of Fgf15 and Nr0b2. In the liver, expression of FXR-downstream targets was dysregulated. PN administrations impacted hepatic and ileal circadian transcription factor mRNA expression which was discordant between the two organs. CONCLUSIONS: Dysregulation of circadian regulatory machinery is in part due to discordance of the gut-liver axis during PN. Pharmacologic targeting of CR as a therapeutic strategy for PNALD thus deserves further investigation.

20.
Artigo em Inglês | MEDLINE | ID: mdl-39302564

RESUMO

OBJECTIVE: The objective of this study was to characterize and compare national estimates of mental healthcare use among White and Asian American groups to provide an update using post Affordable Care Act data. METHODS: We analyzed yearly cross-sectional data from the 2013-2019 Medical Expenditure Panel Survey, including White (n = 112,590) and Asian American (n = 10,210) individuals, and examined rates of mental healthcare use for Asian (overall), Asian Indian, Chinese, Filipino, and Other Asian individuals relative to White individuals. Using multivariable logistic regression models and predictive margin methods, we estimated overall Asian disparities and Asian subgroup disparities compared to White group rates in mental health care (outpatient, specialty, psychotropic medication) among adults with and without elevated risk for mental illness. Regression models were adjusted for variables related to need for treatment, demographic, and socioeconomic status variables. RESULTS: Asian individuals had lower rates of mental healthcare use than White individuals. Unadjusted results and adjusted regression model predictions are consistent in identifying wide disparities in mental health care treatment across risk for mental illness, Asian subgroups, and types of treatment. CONCLUSIONS: Asian Americans have significantly lower rates of mental healthcare use than White Americans, even among those with elevated risk for mental illness. There is small variation by Asian subgroups but disparities persist across subgroups and types of treatment. Our results imply interventions are needed to improve linguistically, culturally, and ethnically tailored outreach and engagement in treatment services, as well as examining treatment and its effectiveness for Asian American individuals living with psychological distress.

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