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1.
J Rheum Dis ; 31(2): 86-96, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38559796

RESUMO

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

2.
West J Emerg Med ; 25(2): 230-236, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38596924

RESUMO

Introduction: Older adults often have multiple comorbidities; therefore, they are at high risk for adverse events after discharge. The 4Ms framework-what matters, medications, mentation, mobility-has been used in acute and ambulatory care settings to identify risk factors for adverse events in older adults, although it has not been used in the emergency department (ED). We aimed to determine whether 1) use of the 4Ms worksheet would help emergency clinicians understand older adult patients' goals of care and 2) use of the worksheet was feasible in the ED. Methods: We conducted a qualitative, descriptive study among patients aged ≥60 years and emergency clinicians from January-June 2022. Patients were asked to fill out a 4Ms worksheet; following this, semi-structured interviews were conducted with patients and clinicians separately. We analysed data to create codes, which were divided into categories and sub-categories. Results: A total of 20 older patients and 19 emergency clinicians were interviewed. We identified two categories based on our aims: understanding patient goals of care (sub-categories: clinician/ patient concordance; understanding underlying goals of care; underlying goals of care discrepancy) and use of 4Ms Worksheet (sub-categories: worksheet to discussion discrepancy; challenges using worksheet; challenge completing worksheet before discharge). Rates of concordance between patient and clinician on main concern/goal of care and underlying goals of care were 82.4% and 15.4%, respectively. Conclusion: We found that most patients and emergency clinicians agreed on the main goal of care, although clinicians often failed to elicit patients' underlying goal(s) of care. Additionally, many patients preferred to have the interviewer fill out the worksheet for them. There was often discrepancy between what was written and what was discussed with the interviewer. More research is needed to determine the best way to integrate the 4Ms framework within emergency care.


Assuntos
Alta do Paciente , Pacientes , Humanos , Idoso , Fatores de Risco , Assistência Ambulatorial , Serviço Hospitalar de Emergência , Pesquisa Qualitativa
4.
Saudi J Anaesth ; 18(1): 108-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313730

RESUMO

Spinal anesthesia usually lasts up to two hours, but an infusion of IV dexmedetomidine can prolong it to three to four hours. We report two cases where single spinal anesthesia with IV dexmedetomidine was maintained for more than six hours during tibia fracture surgery. The spinal anesthesia was maintained for 350 and 390 minutes without another medication, and the sensory level confirmed after the surgery was T10 and L1. Dexmedetomidine can very-prolong the duration of spinal anesthesia beyond what has been reported. However, longer infusion times can also result in longer recovery times.

5.
BMC Health Serv Res ; 23(1): 1334, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041081

RESUMO

BACKGROUND: The recent rising health spending intrigued efficiency and cost-based performance measures. However, mortality risk adjustment methods are still under consideration in cost estimation, though methods specific to cost estimate have been developed. Therefore, we aimed to compare the performance of diagnosis-based risk adjustment methods based on the episode-based cost to utilize in efficiency measurement. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Sample as the data source. A separate linear regression model was constructed within each Major Diagnostic Category (MDC). Individual models included explanatory (demographics, insurance type, institutional type, Adjacent Diagnosis Related Group [ADRG], diagnosis-based risk adjustment methods) and response variables (episode-based costs). The following risk adjustment methods were used: Refined Diagnosis Related Group (RDRG), Charlson Comorbidity Index (CCI), National Health Insurance Service Hierarchical Condition Categories (NHIS-HCC), and Department of Health and Human Service-HCC (HHS-HCC). The model accuracy was compared using R-squared (R2), mean absolute error, and predictive ratio. For external validity, we used the 2017 dataset. RESULTS: The model including RDRG improved the mean adjusted R2 from 40.8% to 45.8% compared to the adjacent DRG. RDRG was inferior to both HCCs (RDRG adjusted R2 45.8%, NHIS-HCC adjusted R2 46.3%, HHS-HCC adjusted R2 45.9%) but superior to CCI (adjusted R2 42.7%). Model performance varied depending on the MDC groups. While both HCCs had the highest explanatory power in 12 MDCs, including MDC P (Newborns), RDRG showed the highest adjusted R2 in 6 MDCs, such as MDC O (pregnancy, childbirth, and puerperium). The overall mean absolute errors were the lowest in the model with RDRG ($1,099). The predictive ratios showed similar patterns among the models regardless of the  subgroups according to age, sex, insurance type, institutional type, and the upper and lower 10th percentiles of actual costs. External validity also showed a similar pattern in the model performance. CONCLUSIONS: Our research showed that either NHIS-HCC or HHS-HCC can be useful in adjusting comorbidities for episode-based costs in the process of efficiency measurement.


Assuntos
Seguro Saúde , Risco Ajustado , Feminino , Humanos , Recém-Nascido , Risco Ajustado/métodos , Comorbidade , Grupos Diagnósticos Relacionados , Modelos Lineares
6.
Int J Mol Sci ; 24(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37894839

RESUMO

Mesenchymal stem cells derived from rheumatoid arthritis patients (RA-MSCs) provide an understanding of a variety of cellular and immunological responses within the inflammatory milieu. Sustained exposure of MSCs to inflammatory cytokines is likely to exert an influence on genetic variations, including reference genes (RGs). The sensitive effect of cytokines on the reference genes of RA-SF-MSCs may be a variation factor affecting patient-derived MSCs as well as the accuracy and reliability of data. Here, we comparatively evaluated the stability levels of nine RG candidates, namely GAPDH, ACTB, B2M, EEF1A1, TBP, RPLP0, PPIA, YWHAZ, and HPRT1, to find the most stable ones. Alteration of the RG expression was evaluated in MSCs derived from the SF of healthy donors (H-SF-MSCs) and in RA-SF-MSCs using the geNorm and NormFinder software programs. The results showed that TBP, PPIA, and YWHAZ were the most stable RGs for the normalization of H-SF-MSCs and RA-SF-MSCs using RT-qPCR, whereas ACTB, the most commonly used RG, was less stable and performed poorly. Additionally, the sensitivity of RG expression upon exposure to proinflammatory cytokines (TNF-α and IL-1ß) was evaluated. RG stability was sensitive in the H-SF-MSCs exposed to TNF-α and IL-1ß but insensitive in the RA-SF-MSCs. Furthermore, the normalization of IDO expression using ACTB falsely diminished the magnitude of biological significance, which was further confirmed with a functional analysis and an IDO activity assay. In conclusion, the results suggest that TBP, PPIA, and YWHAZ can be used in SF-MSCs, regardless of their exposure to inflammatory cytokines.


Assuntos
Artrite Reumatoide , Células-Tronco Mesenquimais , Humanos , Citocinas/genética , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Líquido Sinovial , Reprodutibilidade dos Testes , Perfilação da Expressão Gênica/métodos , Células-Tronco Mesenquimais/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Padrões de Referência , Reação em Cadeia da Polimerase em Tempo Real/métodos
7.
Medicine (Baltimore) ; 102(43): e35103, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904476

RESUMO

Aberrant regulation of the long non-coding RNA SRY-box transcription factor 2 overlapping transcript (SOX2OT) has been reported in various diseases including gastric cancer (GC). However, an association between the well-studied rs9839776 single nucleotide polymorphism in SOX2OT and GC susceptibility has not been reported. This study aimed to evaluate the association between the rs9839776 single nucleotide polymorphism in SOX2OT and GC risk. Genotyping of rs9839776 was conducted using TaqMan genotyping assay for 460 patients with GC and 386 controls. We found that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased GC risk (P = .046, adjusted odds ratio [AOR] = 0.72, 95% confidence interval [CI] = 0.52-1.00 and P = .044, AOR = 0.74, 95% CI = 0.56-0.99, respectively). In addition, stratified analysis revealed that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased risk of lymph node metastasis-negative (P = .039, AOR = 0.67, 95% CI = 0.46-0.98 and P = .049, AOR = 0.71, 95% CI = 0.51-1.00, respectively) and tumor stage I (A+B)/II (A+B+C) (P = .028, AOR = 0.66, 95% CI = 0.50-0.96 and P = .041, AOR = 0.71, 95% CI = 0.52-0.99, respectively) GC. Our findings suggest that the rs9839776 T allele may be a protective factor against GC susceptibility. Further research is needed to clarify whether rs9839776 affects SOX2OT expression.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Fatores de Proteção , República da Coreia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia
8.
Clin Geriatr Med ; 39(4): 535-551, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37798064

RESUMO

This article covers the epidemiology of delirium and the overlapping condition of altered mental status and encephalopathy that is relevant to those who practice in the emergency department.


Assuntos
Delírio , Humanos , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Serviço Hospitalar de Emergência
9.
Commun Biol ; 6(1): 871, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620589

RESUMO

Expectations are often dynamic: sports fans know that expectations are rapidly updated as games unfold. Yet expectations have traditionally been studied as static. Here we present behavioral and electrophysiological evidence of sub-second changes in expectations using slot machines as a case study. In Study 1, we demonstrate that EEG signal before the slot machine stops varies based on proximity to winning. Study 2 introduces a behavioral paradigm to measure dynamic expectations via betting, and shows that expectation trajectories vary as a function of winning proximity. Notably, these expectation trajectories parallel Study 1's EEG activity. Studies 3 (EEG) and 4 (behavioral) replicate these findings in the loss domain. These four studies provide compelling evidence that dynamic sub-second updates in expectations can be behaviorally and electrophysiologically measured. Our research opens promising avenues for understanding the dynamic nature of reward expectations and their impact on cognitive processes.


Assuntos
Motivação , Recompensa
10.
Am J Emerg Med ; 71: 190-194, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37423026

RESUMO

BACKGROUND: Altered mental status (including delirium) is a common presentations among older adults to the emergency department (ED). We aimed to report the association between altered mental status in older ED patients and acute abnormal findings on head computed tomogram (CT). METHODS: A systematic review was conducted using Ovid Medline, Embase, Clinicaltrials.gov, Web of Science, and Cochrane Central from conception to April 8th, 2021. We included citations if they described patients aged 65 years or older who received head imaging at the time of ED assessment, and reported whether patients had delirium, confusion, or altered mental status. Screening, data extraction, and bias assessment were performed in duplicate. We estimated the odds ratios (OR) for abnormal neuroimaging in patients with altered mental status. RESULTS: The search strategy identified 3031 unique citations, of which two studies reporting on 909 patients with delirium, confusion or altered mental status were included. No identified study formally assessed for delirium. The OR for abnormal head CT findings in patients with delirium, confusion or altered mental status was 0.35 (95% CI 0.031 to 3.97) compared to patients without delirium, confusion or altered mental status. CONCLUSION: We did not find a statistically significant association between delirium, confusion or altered mental status and abnormal head CT findings in older ED patients.


Assuntos
Delírio , Humanos , Idoso , Delírio/diagnóstico por imagem , Serviço Hospitalar de Emergência , Transtornos da Consciência , Tomografia Computadorizada por Raios X
11.
J Am Coll Emerg Physicians Open ; 4(4): e13012, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37520079

RESUMO

Background: We sought to identify what matters to older adults (60 years and older) presenting to the emergency department (ED) and the challenges or concerns they identify related to medication, mobility, and mentation to inform how the 4Ms framework could improve care of older adults in the ED setting. Methods: A qualitative study was conducted using the 4Ms to identify what matters to older adults (≥60 years old) presenting to the ED and what challenges or concerns they identify related to medication, mobility, and mentation. We conducted semi-structured interviews with a convenience sample of patients in a single ED. Interview guide responses and interviewer field notes were entered into REDCap. Interviews were reviewed by the research team (2 coders per interview) who inductively assigned codes. A codebook was created through an iterative process and was used to group codes into themes and sub-themes within the 4Ms framework. Results: A total of 20 ED patients participated in the interviews lasting 30-60 minutes. Codes identified for "what matters" included problem-oriented expectation, coordination and continuity, staying engaged, being with family, and getting back home. Codes related to the other 4Ms (medication, mobility, and mentation) described challenges. Medication challenges included: non-adherence, side effects, polypharmacy, and knowledge. Mobility challenges included physical activity and independence. Last, mentation challenges included memory concerns, depressed mood, and stress and worry. Conclusions: Our study used the 4Ms to identify "what matters" to older adults presenting to the ED and the challenges they face regarding medication, mobility, and mentation. Understanding what matters to patients and the specific challenges they face can help shape and individualize a patient-centered approach to care to facilitate the goals of care discussion and handoff to the next care team.

12.
bioRxiv ; 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37131777

RESUMO

Expectations are often dynamic: any sports fan knows that expectations are rapidly updated as games unfold. Yet expectations have traditionally been studied as static. Here, using slot machines as a case study, we provide parallel behavioral and electrophysiological evidence of sub-second moment-to-moment changes in expectations. In Study 1, we show that the dynamics of the EEG signal before the slot machine stopped differed depending on the nature of the outcome, including not only whether the participant won or lost, but also how close they came to winning. In line with our predictions, Near Win Before outcomes (the slot machine stops one item before a match) were similar to Wins, but different than Near Win After (the machine stops one item after a match) and Full Miss (the machine stops two or three items from a match). In Study 2, we designed a novel behavioral paradigm to measure moment-to-moment changes in expectations via dynamic betting. We found that different outcomes also elicited unique expectation trajectories in the deceleration phase. Notably, these behavioral expectation trajectories paralleled Study 1's EEG activity in the last second prior to the machine's stop. In Studies 3 (EEG) and 4 (behavior) we replicated these findings in the loss domain where a match entails a loss. Again, we found a significant correlation between behavioral and EEG results. These four studies provide the first evidence that dynamic sub-second updates in expectations can be behaviorally and electrophysiologically measured. Our findings open up new avenues for studying the ongoing dynamics of reward expectations and their role in healthy and unhealthy cognition.

13.
Am J Geriatr Psychiatry ; 31(9): 704-715, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37003894

RESUMO

OBJECTIVE: Delirium is dangerous and a predictor of poor patient outcomes. We have previously reported the utility of the bispectral EEG (BSEEG) with a novel algorithm for the detection of delirium and prediction of patient outcomes including mortality. The present study employed a normalized BSEEG (nBSEEG) score to integrate the previous cohorts to combine their data to investigate the prediction of patient outcomes. We also aimed to test if the BSEEG method can be applicable regardless of age, and independent of delirium motor subtypes. METHODS: We calculated nBSEEG score from raw BSEEG data in each cohort and classified patients into BSEEG-positive and BSEEG-negative groups. We used log-rank test and Cox proportional hazards models to predict 90-day and 1-year outcomes for the BSEEG-positive and -negative groups in all subjects and motor subgroups. RESULTS: A total of 1,077 subjects, the BSEEG-positive group showed significantly higher 90-day (hazard ratio 1.33 [95% CI 1.16-1.52] and 1-year (hazard ratio 1.22 [95% CI 1.06-1.40] mortality rates than the negative group after adjustment for covariates such as age, sex, CCI, and delirium status. Among patients with different motor subtypes of delirium, the hypoactive group showed significantly higher 90-day (hazard ratio 1.41 [95% CI 1.12-1.76] and 1-year mortality rates (hazard ratio 1.32 [95% CI 1.05-1.67], which remained significant after adjustment for the same covariates. CONCLUSION: We found that the BSEEG method is capable of capturing patients at high mortality risk.


Assuntos
Delírio , Humanos , Delírio/diagnóstico , Estudos Prospectivos , Eletroencefalografia , Modelos de Riscos Proporcionais , Algoritmos
14.
J Am Coll Emerg Physicians Open ; 4(2): e12941, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37090953

RESUMO

Objectives: Little is known about current practices in consulting physical therapy (PT) in the emergency department (ED) for older adults with falls, a practice that can reduce fall-related ED revisits. This qualitative study aimed to understand perspectives of ED staff about ED PT consultation for older adults with falls and fall-related complaints, specifically regarding perceived value and associated challenges and strategies. Methods: We performed focus groups and key informant interviews with emergency physicians, advanced practice clinicians, nurses, physical therapists, occupational therapists, and technicians who perform ED geriatric screenings. We used rapid qualitative analysis to identify common themes related to decisions to consult PT from the ED, perceived value of PT, and common challenges and strategies in ED PT consultation. Results: Twenty-five participants in 4 focus groups and 3 interviews represented 22 distinct institutions with ED PT consultation available for older adults with falls. About two thirds of EDs represented relied on clinician gestalt to request PT consultation (n = 15, 68%), whereas one third used formal consultation pathways (n = 7, 32%). Participants valued physical therapists' expertise, time, and facilitation of hospital throughput by developing safe discharge plans and contact with patients to improve outpatient follow-up. Common challenges included limited ED PT staffing and space for PT evaluations; strategies to promote ED PT consultation included advocating for leadership buy-in and using ED observation units to monitor patients and avoid admission until PT consultation was available. Conclusion: ED PT consultation for older adults with falls may benefit patients, ED staff, and hospital throughput. Uncertainty remains over whether geriatric screening-triggered consultation versus emergency clinician gestalt successfully identifies patients likeliest to benefit from ED PT evaluation. Leadership buy-in, designated consultation space, and formalized consultation pathways are strategies to address current challenges in ED PT consultation.

15.
Acta Psychiatr Scand ; 147(5): 493-505, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36999191

RESUMO

INTRODUCTION: Delirium is a cerebral dysfunction seen commonly in the acute care setting. It is associated with increased mortality and morbidity and is frequently missed in the emergency department (ED) and inpatient care by clinical gestalt alone. Identifying those at risk of delirium may help prioritize screening and interventions in the hospital setting. OBJECTIVE: Our objective was to leverage electronic health records to identify a clinically valuable risk estimation model for prevalent delirium in patients being transferred from the ED to inpatient units. METHODS: This was a retrospective cohort study to develop and validate a risk model to detect delirium using patient data available from prior visits and ED encounter. Electronic health records were extracted for patients hospitalized from the ED between January 1, 2014, and December 31, 2020. Eligible patients were aged 65 or older, admitted to an inpatient unit from the emergency department, and had at least one DOSS assessment or CAM-ICU recorded within 72 h of hospitalization. Six machine learning models were developed to estimate the risk of delirium using clinical variables including demographic features, physiological measurements, medications administered, lab results, and diagnoses. RESULTS: A total of 28,531 patients met the inclusion criteria with 8057 (28.4%) having a positive delirium screening within the outcome observation period. Machine learning models were compared using the area under the receiver operating curve (AUC). The gradient boosted machine achieved the best performance with an AUC of 0.839 (95% CI, 0.837-0.841). At a 90% sensitivity threshold, this model achieved a specificity of 53.5% (95% CI 53.0%-54.0%) a positive predictive value of 43.5% (95% CI 43.2%-43.9%), and a negative predictive value of 93.1% (95% CI 93.1%-93.2%). A random forest model and L1-penalized logistic regression also demonstrated notable performance with AUCs of 0.837 (95% CI, 0.835-0.838) and 0.831 (95% CI, 0.830-0.833) respectively. CONCLUSION: This study demonstrated the use of machine learning algorithms to identify a combination of variables that enables an estimation of risk of positive delirium screens early in hospitalization to develop prevention or management protocols.


Assuntos
Delírio , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Hospitalização , Aprendizado de Máquina , Delírio/diagnóstico , Delírio/epidemiologia
16.
Mol Cells ; 46(5): 298-308, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36896596

RESUMO

Gastric cancer (GC) is a complex disease influenced by multiple genetic and epigenetic factors. Chronic inflammation caused by Helicobacter pylori infection and dietary risk factors can result in the accumulation of aberrant DNA methylation in gastric mucosa, which promotes GC development. Tensin 4 (TNS4), a member of the Tensin family of proteins, is localized to focal adhesion sites, which connect the extracellular matrix and cytoskeletal network. We identified upregulation of TNS4 in GC using quantitative reverse transcription PCR with 174 paired samples of GC tumors and adjacent normal tissues. Transcriptional activation of TNS4 occurred even during the early stage of tumor development. TNS4 depletion in GC cell lines that expressed high to moderate levels of TNS4, i.e., SNU-601, KATO III, and MKN74, reduced cell proliferation and migration, whereas ectopic expression of TNS4 in those lines that expressed lower levels of TNS4, i.e., SNU-638, MKN1, and MKN45 increased colony formation and cell migration. The promoter region of TNS4 was hypomethylated in GC cell lines that showed upregulation of TNS4. We also found a significant negative correlation between TNS4 expression and CpG methylation in 250 GC tumors based on The Cancer Genome Atlas (TCGA) data. This study elucidates the epigenetic mechanism of TNS4 activation and functional roles of TNS4 in GC development and progression and suggests a possible approach for future GC treatments.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/genética , Helicobacter pylori/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Tensinas/genética , Tensinas/metabolismo
17.
Plant Physiol Biochem ; 196: 393-401, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36753825

RESUMO

Soybean (Glycine max), a significant oilseed and protein source for humans and livestock feed, needs short day photoperiod for floral induction. Further, soybean has a paleopolyploid genome with multiple copies of flowering genes adding to the complexity of genetic regulation of flowering, and seed set, especially in investigating the role of the noncoding genome. microRNAs, a class of noncoding RNA, play a regulatory role in plant development. miR156 and miR172 are major components of the essential regulatory hub controlling juvenile and vegetative developments and initiation of reproductive phase change leading to flowering. These microRNAs have been originally isolated and studied from model plant, Arabidopsis. However, a study on soybean microRNAs is lacking. We investigated the temporal expression patterns of gma-miR156a and gma-miR172a and found inversely related - gma-miR156a expression was higher in the vegetative stage, and gma-miR172a expression was elevated under inductive flowering conditions. The functions of gma-miR156a and gma-miR172a were evaluated via heterologous expressions in transgenic tobacco plants (Nicotiana tabacum L.). The analysis of overexpression transgenic lines highlighted that gma-miR156a plays a role in juvenile development via repression of the SPL transcription factor family. In contrast, gma-miR172a plays a pivotal role in the reproductive development phase by down-regulating its target genes, AP2. In addition, ectopic expression of gma-miR156a and gma-miR172a affected plant morphology and physiology during plant growth. Collectively, our results suggest that gma-miR156a and gma-miR172a regulate multiple morpho-physiological traits that could be used to enhance crop yield under changing climate conditions.


Assuntos
Arabidopsis , MicroRNAs , Humanos , /metabolismo , /metabolismo , Arabidopsis/genética , Fatores de Transcrição/genética , Plantas Geneticamente Modificadas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação da Expressão Gênica de Plantas , Flores/fisiologia
18.
J Neurosci ; 43(9): 1600-1613, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36657973

RESUMO

Individual differences in delay discounting-how much we discount future compared to immediate rewards-are associated with general life outcomes, psychopathology, and obesity. Here, we use machine learning on fMRI activity during an intertemporal choice task to develop a functional brain marker of these individual differences in human adults. Training and cross-validating the marker in one dataset (Study 1, N = 110 male adults) resulted in a significant prediction-outcome correlation (r = 0.49), generalized to predict individual differences in a completely independent dataset (Study 2: N = 145 male and female adults, r = 0.45), and predicted discounting several weeks later. Out-of-sample responses of the functional brain marker, but not discounting behavior itself, differed significantly between overweight and lean individuals in both studies, and predicted fasting-state blood levels of insulin, c-peptide, and leptin in Study 1. Significant predictive weights of the marker were found in cingulate, insula, and frontoparietal areas, among others, suggesting an interplay among regions associated with valuation, conflict processing, and cognitive control. This new functional brain marker is a step toward a generalizable brain model of individual differences in delay discounting. Future studies can evaluate it as a potential transdiagnostic marker of altered decision-making in different clinical and developmental populations.SIGNIFICANCE STATEMENT People differ substantially in how much they prefer smaller sooner rewards or larger later rewards such as spending money now versus saving it for retirement. These individual differences are generally stable over time and have been related to differences in mental and bodily health. What is their neurobiological basis? We applied machine learning to brain-imaging data to identify a novel brain activity pattern that accurately predicts how much people prefer sooner versus later rewards, and which can be used as a new brain-based measure of intertemporal decision-making in future studies. The resulting functional brain marker also predicts overweight and metabolism-related blood markers, providing new insight into the possible links between metabolism and the cognitive and brain processes involved in intertemporal decision-making.


Assuntos
Desvalorização pelo Atraso , Adulto , Humanos , Masculino , Feminino , Desvalorização pelo Atraso/fisiologia , Imageamento por Ressonância Magnética/métodos , Individualidade , Sobrepeso , Encéfalo/fisiologia , Recompensa
20.
Mil Med ; 188(11-12): 3599-3605, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-35713331

RESUMO

INTRODUCTION: African Americans (AAs) experience disparities in chronic pain care. This study aimed to identify the rates of emergency department (ED) utilization for visits associated with chronic pain diagnoses among AAs compared to Whites and to determine variables that accounted for any differences. METHODS: This retrospective observational study used national Veterans Affairs (Veteran's Health Administration) administrative data to identify Veterans with chronic pain diagnoses in 2018. Race/ethnicity was self-reported and assessed to examine if differences exist in ED utilization. Differences between AAs and Whites were examined using negative binomial regression models, controlling for ethnicity. Multivariable models (including demographics, pain characteristics, psychiatric comorbidities, medical comorbidities, pain-related health care utilization, and medication utilization) were examined to determine factors that contributed to these disparities. RESULTS: Among the 2,261,030 patients, 22% (n = 492,138) were AA. The incidence rate ratio of ED utilization for AAs, relative to Whites, was 1.58 (95% CI: 1.56-1.59). The only independent variable that produced a clinically meaningful reduction in the race effect on ED use was rurality, which was associated with reduced ED use. Post hoc model including all variables reduced the race effect to 1.37 (95% CI: 1.36-1.38). CONCLUSION: AA Veterans had a 58% greater risk of ED utilization for visits associated with chronic pain diagnoses relative to White Veterans, which remained meaningfully elevated after adjustment for observable confounders (37%). This observation may reflect disparities in outpatient chronic pain care for AAs. Future research could focus on enhancing therapeutic alliance in primary care to improve chronic pain treatment for AAs.


Assuntos
Dor Crônica , Veteranos , Estados Unidos/epidemiologia , Humanos , Dor Crônica/epidemiologia , Dor Crônica/tratamento farmacológico , Fatores Raciais , Etnicidade , Serviço Hospitalar de Emergência , Estudos Retrospectivos , United States Department of Veterans Affairs
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