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1.
Arch Sex Behav ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956001

RESUMO

Feminist considerations have influenced how women and men view sex, affecting not only women's perspectives but also men's feelings about sexual desire with regard to gender equity. This might be especially the case among men who self-identify as feminist. However, how men should manage their sexual desire or communicate about it within relationships with women is not always clear in this evolving social climate. Thus, the current study aimed to explore the successes and/or struggles feminist heterosexual men experience while navigating their desires alongside feminist considerations. To explore this, we recruited feminist-identified heterosexual men in long-term relationships. We asked participants (N = 30) a series of questions regarding their sexual desire, considering the context of their long-term relationships and evolving gender norms, during a one-on-one interview via Zoom. Using thematic analysis, we identified 11 themes from the interview data. We found that, though the feminist men in this study were all aware of negative societal perceptions of heterosexual men's sexual desire, most men in this study did not feel conflicts between their feminist principles and their own sexual desires. This is because they reported already following feminist principles; those who felt ambivalent navigated this by communicating with their partners. Findings demonstrate the usefulness and positive impact men report feminism having on them, their sexuality, and their long-term relationships, by allowing them to better engage with their sexuality and partners.

2.
Cureus ; 16(5): e61388, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38947652

RESUMO

Blunt abdominal trauma patients who have had prior bariatric procedures may present a diagnostic and therapeutic challenge. The single anastomosis duodenal-ileal bypass with sleeve (SADI-S) is a modified duodenal switch procedure that is relatively uncommon. This case report describes a patient who previously underwent a SADI-S for the management of obesity and subsequently sustained a seat belt injury in a motor vehicle collision resulting in a laceration of the efferent loop. The patient presented with symptoms of acute abdominal pain and was diagnosed through imaging studies. Prompt surgical intervention was performed with resection and primary anastomosis of the damaged section of the jejunum, and repair of a large mesenteric laceration. We discuss the importance of early recognition and intraoperative decision-making in the case of this patient concerning her SADI-S.

3.
mBio ; 15(6): e0073624, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38695564

RESUMO

Sindbis virus (SINV) infection of mice provides a model system for studying the pathogenesis of alphaviruses that infect the central nervous system (CNS) to cause encephalomyelitis. While studies of human viral infections typically focus on accessible cells from the blood, this compartment is rarely evaluated in mice. To bridge this gap, single-cell RNA sequencing (scRNAseq) was combined with flow cytometry to characterize the transcriptional and phenotypic changes of peripheral blood mononuclear cells (PBMCs) from SINV-infected mice. Twenty-one clusters were identified by scRNAseq at 7 days after infection, with a unique cluster and overall increase in naive B cells for infected mice. Uninfected mice had fewer immature T cells and CCR9+ CD4 T cells and a unique immature T cell cluster. Gene expression was most altered in the Ki67+ CD8 T cell cluster, with chemotaxis and proliferation-related genes upregulated. Global analysis indicated metabolic changes in myeloid cells and increased expression of Ccl5 by NK cells. Phenotypes of PBMCs and cells infiltrating the CNS were analyzed by flow cytometry over 14 days after infection. In PBMCs, CD8 and Th1 CD4 T cells increased in representation, while B cells showed a transient decrease at day 5 in total, Ly6a+, and naive cells, and an increase in activated B cells. In the brain, CD8 T cells increased for the first 7 days, while Th1 CD4 T cells and naive and Ly6a+ B cells continued to accumulate for 14 days. Therefore, dynamic immune cell changes can be identified in the blood as well as the CNS during viral encephalomyelitis. IMPORTANCE: The outcome of viral encephalomyelitis is dependent on the host immune response, with clearance and resolution of infection mediated by the adaptive immune response. These processes are frequently studied in mouse models of infection, where infected tissues are examined to understand the mechanisms of clearance and recovery. However, studies of human infection typically focus on the analysis of cells from the blood, a compartment rarely examined in mice, rather than inaccessible tissue. To close this gap, we used single-cell RNA sequencing and flow cytometry to profile the transcriptomic and phenotypic changes of peripheral blood mononuclear cells (PBMCs) before and after central nervous system (CNS) infection in mice. Changes to T and B cell gene expression and cell composition occurred in PBMC and during entry into the CNS, with CCL5 being a differentially expressed chemokine. Therefore, dynamic changes occur in the blood as well as the CNS during the response of mice to virus infection, which will inform the analysis of human studies.


Assuntos
Infecções por Alphavirus , Leucócitos Mononucleares , Animais , Camundongos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Infecções por Alphavirus/virologia , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/genética , Sindbis virus/genética , Sindbis virus/imunologia , Camundongos Endogâmicos C57BL , Fenótipo , Feminino , Modelos Animais de Doenças , Encefalite Viral/imunologia , Encefalite Viral/virologia , Encefalite Viral/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Análise de Célula Única
4.
Cell Death Dis ; 15(4): 246, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575601

RESUMO

Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons (DaNs) and the abnormal accumulation of α-Synuclein (α-Syn) protein. Currently, no treatment can slow nor halt the progression of PD. Multiplications and mutations of the α-Syn gene (SNCA) cause PD-associated syndromes and animal models that overexpress α-Syn replicate several features of PD. Decreasing total α-Syn levels, therefore, is an attractive approach to slow down neurodegeneration in patients with synucleinopathy. We previously performed a genetic screen for modifiers of α-Syn levels and identified CDK14, a kinase of largely unknown function as a regulator of α-Syn. To test the potential therapeutic effects of CDK14 reduction in PD, we ablated Cdk14 in the α-Syn preformed fibrils (PFF)-induced PD mouse model. We found that loss of Cdk14 mitigates the grip strength deficit of PFF-treated mice and ameliorates PFF-induced cortical α-Syn pathology, indicated by reduced numbers of pS129 α-Syn-containing cells. In primary neurons, we found that Cdk14 depletion protects against the propagation of toxic α-Syn species. We further validated these findings on pS129 α-Syn levels in PD patient neurons. Finally, we leveraged the recent discovery of a covalent inhibitor of CDK14 to determine whether this target is pharmacologically tractable in vitro and in vivo. We found that CDK14 inhibition decreases total and pathologically aggregated α-Syn in human neurons, in PFF-challenged rat neurons and in the brains of α-Syn-humanized mice. In summary, we suggest that CDK14 represents a novel therapeutic target for PD-associated synucleinopathy.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Sinucleinopatias , Animais , Humanos , Camundongos , Ratos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Neurônios Dopaminérgicos/metabolismo , Mesencéfalo/metabolismo , Doenças Neurodegenerativas/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Sinucleinopatias/metabolismo , Sinucleinopatias/patologia
5.
Cureus ; 16(3): e56626, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646226

RESUMO

Motor vehicle collisions are a leading cause of morbidity and mortality within the United States. Safety devices such as seatbelts and airbags have significantly reduced mortality rates for drivers. Some drivers personalize their vehicles with inexpensive items that may cause significant injury during vehicular collisions. We present a case of a face and neck penetrating injury from a metal aftermarket rhinestone emblem attached to the steering wheel during a motor vehicle collision. A 43-year-old female was involved in an accident where the airbag had deployed and projected two pieces of the metal emblem at her face and neck. The fragment in the neck was removed at the bedside, while that in the face required removal in the operating room. She recovered well postoperatively and was discharged the same day. This case highlights the potential for the dangers caused by aftermarket rhinestone emblems on steering wheels. We recommend that increased national advisories and legislative actions be considered to limit the use of these emblems.

6.
Respir Med ; 224: 107533, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38355019

RESUMO

BACKGROUND AND OBJECTIVE: The interstitial lung diseases (ILD) are a heterogenous group of disorders with similar clinical presentation, but widely varying prognoses. The use of a pragmatic disease behaviour classification (DBC), first proposed in international guidelines in 2013, categorises diseases into five behavioural classes based on their predicted clinical course. This study aimed to determine the prognostic utility of the DBC in an ILD cohort. METHODS: Consecutive patients presented at the weekly multidisciplinary meeting (MDM) of a specialist ILD centre were included. MDM consensus was obtained for diagnosis and DBC category (1-5). Baseline and serial clinical and physiological data were collected over the study period (median 3.9 years, range 0-5.4 years). The relationship between DBC and prognostic outcomes was explored. RESULTS: 137 ILD patients, [64 (47%) female] were included with mean age 67.0 ± 1.1 years, baseline FVC% 72.7 ± 1.7, and baseline DLco% 57.8 ± 1.6%. Patients were stratified into DBC by consensus at MDM: DBC1 n = 0 (0%), DBC2 n = 16 (12%), DBC3 n = 10 (7.3%), DBC4 n = 55 (40%), and DBC5 n = 56 (41%). On univariable Cox regression, increasing DBC class was associated with poorer progression-free survival (HR 1.6, 95% CI 1.2-2.0, p < 0.001). On multivariable Cox regression, DBC remained predictive of PFS when combined with age and gender (HR 1.4, 95% CI 1.1-1.9, p = 0.011), baseline FVC% (HR 1.5, 95% CI 1.1-1.8, p = 0.003) and ILD diagnosis (HR 1.6, 95% CI 1.2-2.2, p < 0.0001). CONCLUSION: DBC as determined at ILD multidisciplinary meeting may be a useful prognostic tool for the management of ILD patients.


Assuntos
Doenças Pulmonares Intersticiais , Humanos , Feminino , Idoso , Masculino , Doenças Pulmonares Intersticiais/diagnóstico , Prognóstico , Capacidade Vital , Intervalo Livre de Progressão , Testes de Função Respiratória , Pulmão , Estudos Retrospectivos
7.
J Virol ; 97(10): e0095923, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37772825

RESUMO

IMPORTANCE: Viral encephalomyelitis outcome is dependent on host responses to neuronal infection. Interferon (IFN) is an important component of the innate response, and IFN regulatory factor (IRF) 7 is an inducible transcription factor for the synthesis of IFN-α. IRF7-deficient mice develop fatal paralysis after CNS infection with Sindbis virus, while wild-type mice recover. Irf7 -/- mice produce low levels of IFN-α but high levels of IFN-ß with induction of IFN-stimulated genes, so the reason for this difference is not understood. The current study shows that Irf7 -/- mice developed inflammation earlier but failed to clear virus from motor neuron-rich regions of the brainstem and spinal cord. Levels of IFN-γ and virus-specific antibody were comparable, indicating that IRF7 deficiency does not impair expression of these known viral clearance factors. Therefore, IRF7 is either necessary for the neuronal response to currently identified mediators of clearance or enables the production of additional antiviral factor(s) needed for clearance.


Assuntos
Infecções por Alphavirus , Encefalomielite , Fator Regulador 7 de Interferon , Sindbis virus , Animais , Camundongos , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/virologia , Tronco Encefálico/virologia , Encefalomielite/imunologia , Encefalomielite/virologia , Inflamação/virologia , Fator Regulador 7 de Interferon/deficiência , Fator Regulador 7 de Interferon/genética , Fator Regulador 7 de Interferon/metabolismo , Interferon beta/imunologia , Interferon beta/metabolismo , Neurônios Motores/virologia , Sindbis virus/imunologia , Medula Espinal/virologia
8.
Am Surg ; 89(1): 88-97, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33877932

RESUMO

INTRODUCTION: Advanced directives (ADs) provide a framework from which families may understand patient's wishes. However, end-of-life planning may not be prioritized by everyone. This analysis aimed to determine what populations have ADs and how they affected trauma outcomes. METHODS: Adult trauma patients recorded in the American College of Surgeons Trauma Quality Improvement Program (TQIP) from 2013-2015 were included. The primary outcome was presence of an AD. Secondary outcomes included mortality, length of stay (LOS), mechanical ventilation, ICU admission/LOS, withdrawal of life-sustaining measures, and discharge disposition. Multivariable logistic regression models were developed for outcomes. RESULTS: 44 705 patients were included in the analyses. Advanced directives were present in 1.79% of patients. The average age for patients with ADs was 77.8 ± 10.7. African American (odds ratio (OR) .53, confidence intervals [CI] .36-.79) and Asian (OR .22, CI .05-.91) patients were less likely to have ADs. Conversely, Medicaid (OR 1.70, CI 1.06-2.73) and Medicare (OR 1.65, CI 1.25-2.17) patients were more likely to have ADs as compared to those with private insurance. The presence of ADs was associated with increased hospital mortality (OR 2.84, CI 2.19-3.70), increased transition to comfort measures (OR 2.87, CI 2.08-3.95), and shorter LOS (CO -.74, CI -1.26-.22). Patients with ADs had an increased odds of hospice care (OR 4.24, CI 3.18-5.64). CONCLUSION: Advanced directives at admission are uncommon, particularly among African Americans and Asians. The presence of ADs was associated with increased mortality, use of mechanical ventilation, admission to the ICU, withdrawal of life-sustaining measures, and hospice. Future research should target expansion of ADs among minority populations to alleviate disparities in end-of-life treatment.


Assuntos
Assistência Terminal , Adulto , Humanos , Idoso , Estados Unidos , Medicare , Diretivas Antecipadas , Cobertura do Seguro , Morte
9.
JAMA Health Forum ; 3(11): e224149, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36399352

RESUMO

Importance: Buprenorphine is an approved medication for opioid use disorder (MOUD); however, prescribing buprenorphine is limited by a requirement to obtain a waiver to prescribe it (hereinafter, "DATA [Drug Abuse Treatment Act]-waiver") and a lack of knowledge of the best practices among clinicians. Objective: To examine how Project ECHO (Extension for Community Healthcare Outcomes) telementoring is associated with changes in DATA-waiver attainment and buprenorphine prescribing among primary care clinicians in Minnesota. Design, Setting, and Participants: In this retrospective matched-cohort study of 918 clinicians, ECHO-trained clinicians were enrolled on the date they first attended ECHO (January 3, 2018, to June 11, 2020); comparison clinicians were assigned an enrollment date from the distribution of the first ECHO sessions. The baseline period was 12 months preceding enrollment, with follow-up for 18 months or until June 30, 2020. The ECHO-trained clinicians were a population-based sample of primary care clinicians who treated Medicaid patients in Minnesota 12 months prior to the initiation of ECHO training. This analysis used propensity score matching to select comparison clinicians who were similar across demographic and clinical practice characteristics at baseline in a 2:1 ratio. Follow-up was available for 167 ECHO-trained clinicians (54.6%) and 330 comparison clinicians (53.9%) at 18 months. Exposures: ECHO-trained clinicians attended at least 1 weekly, hour-long ECHO session. Comparison clinicians never participated in any ECHO sessions. Main Outcomes and Measures: DATA-waiver attainment, any buprenorphine prescribing, and the percentage of patients with opioid use disorder (OUD) who were prescribed buprenorphine. Results: The final sample included 918 clinicians (ECHO-trained [306]; comparison [612]), of whom 620 (67.5%) practiced outside the metropolitan Twin Cities (Minneapolis-St Paul) region. The mean (SD) age of the ECHO-trained clinicians was 46.0 (12.1) years and that of the comparison clinicians was 45.7 (12.3) years. Relative to the changes among the matched comparison clinicians, the ECHO-trained clinicians were more likely to obtain a DATA-waiver (difference-in-differences, 22.7 percentage points; 95% CI, 15.5-29.9 percentage points; P < .001) and prescribe any buprenorphine (16.5 percentage points; 95% CI, 10.4-22.5 percentage points; P < .001) after 6 quarters of follow-up. ECHO-trained clinicians prescribed buprenorphine to a greater share of patients with OUD (a difference of 7.6 percentage points per month; 95% CI, 4.6-10.6 percentage points per month; P < .001), relative to that prescribed by the comparison clinicians. Conclusions and Relevance: According to the findings of this matched-cohort study, ECHO telementoring may be associated with greater prescribing of buprenorphine by primary care clinicians. These findings suggest that Project ECHO training could be a useful tool for expanding access to MOUD.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Estados Unidos , Pessoa de Meia-Idade , Buprenorfina/uso terapêutico , Tratamento de Substituição de Opiáceos , Minnesota/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Padrões de Prática Médica , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Atenção Primária à Saúde
10.
Artigo em Inglês | MEDLINE | ID: mdl-36318789

RESUMO

Introduction: Secondhand and thirdhand tobacco smoke exposure most often occur at home, but little is known about occurrences of in-home cannabis smoking. We ascertained in-home cannabis smoking reported by all cannabis-using (i.e., used in the last 12 months) respondents to the Global Drug Survey (GDS; international-GDS sample), and among U.S. cannabis-using respondents (US-GDS sample). Materials and Methods: We used data collected November 2019-January 2020 for the 2020 GDS, an annual anonymous, cross-sectional survey; respondents were 16+ years old, from 191 countries. We estimated any and daily in-home cannabis smoking in the last 30 days among international-GDS respondents (n=63,797), using mixed effects logistic regression. US-GDS respondents (n=6,580) were weighted to the covariate distribution of the nationally representative 2018 National Survey on Drug Use and Health cannabis-using sample, using inverse odds probability weighting, to make estimates more generalizable to the U.S. cannabis-using population. Results: For the international-GDS cannabis-using respondents, any in-home cannabis smoking was reported by 63.9% of men, 61.9% of women, and 68.6% of nonbinary people; and by age (<25 years old=62.7%, 25-34 years old=65.0%, and 35+ years old=62.8%). Daily in-home cannabis smoking was highest among nonbinary (28.7%) and respondents 35+ years of age (28.0%). For the weighted US-GDS cannabis-using respondents, any in-home cannabis smoking was reported by 49.8% of males and 61.2% of females; and by age (<25 years old=62.6%, 25-34 years old=41.8%, 35+ years old=57.9%). Weighted daily in-home smoking was 23.2% among males and 37.1% among females; by age (<25 years old=34.8%, 25-34 years old=27.8%, and 35+ years old=21.6%). Conclusions: There was high daily cannabis smoking in homes of international-GDS and US-GDS respondents who used cannabis in the last 12 months. In part, due to cannabis legalization, the number of users worldwide has increased over the past decade. Criminal stigma historically associated with cannabis continues to drive those users indoors. In this context, our findings support further investigation of cannabis use behavior to understand how often people are exposed to secondhand and thirdhand cannabis smoke and the consequences of that exposure.

11.
PLoS Pathog ; 18(5): e1010556, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35576231

RESUMO

Antibiotic tolerance is typically associated with a phenotypic change within a bacterial population, resulting in a transient decrease in antibiotic susceptibility that can contribute to treatment failure and recurrent infections. Although tolerant cells may emerge prior to treatment, the stress of prolonged antibiotic exposure can also promote tolerance. Here, we sought to determine how Yersinia pseudotuberculosis responds to doxycycline exposure, to then verify if these gene expression changes could promote doxycycline tolerance in culture and in our mouse model of infection. Only four genes were differentially regulated in response to a physiologically-relevant dose of doxycycline: osmB and ompF were upregulated, tusB and cnfy were downregulated; differential expression also occurred during doxycycline treatment in the mouse. ompF, tusB and cnfy were also differentially regulated in response to chloramphenicol, indicating these could be general responses to ribosomal inhibition. cnfy has previously been associated with persistence and was not a major focus here. We found deletion of the OmpF porin resulted in increased antibiotic accumulation, suggesting expression may promote diffusion of doxycycline out of the cell, while OsmB lipoprotein had a minor impact on antibiotic permeability. Overexpression of tusB significantly impaired bacterial survival in culture and in the mouse, suggesting that tRNA modification by tusB, and the resulting impacts on translational machinery, promotes survival during treatment with an antibiotic classically viewed as bacteriostatic. We believe this may be the first observation of bactericidal activity of doxycycline under physiological conditions, which was revealed by reversing tusB downregulation.


Assuntos
Yersinia pseudotuberculosis , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Doxiciclina/metabolismo , Doxiciclina/farmacologia , Camundongos , Permeabilidade , RNA de Transferência/metabolismo , Yersinia pseudotuberculosis/genética , Yersinia pseudotuberculosis/metabolismo
13.
J Digit Imaging ; 35(3): 534-537, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35169963

RESUMO

We are among the many that believe that artificial intelligence will not replace practitioners and is most valuable as an adjunct in diagnostic radiology. We suggest a different approach to utilizing the technology, which may help even radiologists who may be averse to adopting AI. A novel method of leveraging AI combines computer vision and natural language processing to ambiently function in the background, monitoring for critical care gaps. This AI Quality workflow uses a visual classifier to predict the likelihood of a finding of interest, such as a lung nodule, and then leverages natural language processing to review a radiologist's report, identifying discrepancies between imaging and documentation. Comparing artificial intelligence predictions with natural language processing report extractions with artificial intelligence in the background of computer-aided detection decisions may offer numerous potential benefits, including streamlined workflow, improved detection quality, an alternative approach to thinking of AI, and possibly even indemnity against malpractice. Here we consider early indications of the potential of artificial intelligence as the ultimate quality assurance for radiologists.


Assuntos
Inteligência Artificial , Radiologia , Diagnóstico por Imagem , Humanos , Radiografia , Radiologistas , Radiologia/métodos
14.
Addict Behav ; 125: 107130, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34674905

RESUMO

PURPOSE OF THE RESEARCH: Early evidence from studies of home smoking policies suggests that in-home cannabis smoking is more often allowed than in-home tobacco smoking, but there are not yet data on whether cannabis is more often smoked in the home compared to tobacco, or whether in-home cannabis and tobacco smoking differs by usage status. Using cross-sectional data from over 100,000 sentinel drug users from 17 countries, we compared cannabis and tobacco smoking in the homes of Global Drug Survey 2019 respondents who currently used cannabis only, tobacco only, both tobacco and cannabis, or neither. PRINCIPAL RESULTS: Complete data on cannabis and tobacco use and in-home smoking were available for 107,272 adults (average age = 30 ± 12, 34% women, countries with the three highest response rates; Germany = 32%, USA = 10%, New Zealand = 9%). In total, 53.6% and 50.6% of respondents reported past-year cannabis and tobacco smoking in their home respectively. Stratifying respondents into current cannabis-only users, tobacco-only users, dual users, and non-users, past-year in-home cannabis smoking was more prevalent (78.8%) among cannabis-only users than was in-home tobacco smoking (67.9%) among tobacco-only users. Among dual users, past-year in-home cannabis smoking (82.8%; 95%CI = 80%-86%) was higher than in-home tobacco smoking (75.9%; 95%CI = 69%-81%; p < 0.001). In-home cannabis and tobacco smoking was similar among non-users (20.2% and 20.5%, respectively). MAJOR CONCLUSIONS: Past-year in-home cannabis smoking was more prevalent than tobacco smoking in the homes of participants who used cannabis and/or tobacco, supporting our speculation that in-home cannabis smoking might be more socially acceptable than in-home tobacco smoking.


Assuntos
Fumar Maconha , Preparações Farmacêuticas , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Fumar Maconha/epidemiologia , Inquéritos e Questionários , Fumar Tabaco , Adulto Jovem
15.
Mol Neurodegener ; 16(1): 81, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876200

RESUMO

BACKGROUND: Neurodegenerative disorders are a group of age-associated diseases characterized by progressive degeneration of the structure and function of the CNS. Two key pathological features of these disorders are blood-brain barrier (BBB) breakdown and protein aggregation. MAIN BODY: The BBB is composed of various cell types and a non-cellular component---the basal lamina (BL). Although how different cells affect the BBB is well studied, the roles of the BL in BBB maintenance and function remain largely unknown. In addition, located in the perivascular space, the BL is also speculated to regulate protein clearance via the meningeal lymphatic/glymphatic system. Recent studies from our laboratory and others have shown that the BL actively regulates BBB integrity and meningeal lymphatic/glymphatic function in both physiological and pathological conditions, suggesting that it may play an important role in the pathogenesis and/or progression of neurodegenerative disorders. In this review, we focus on changes of the BL and its major components during aging and in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). First, we introduce the vascular and lymphatic systems in the CNS. Next, we discuss the BL and its major components under homeostatic conditions, and summarize their changes during aging and in AD, PD, and ALS in both rodents and humans. The functional significance of these alterations and potential therapeutic targets are also reviewed. Finally, key challenges in the field and future directions are discussed. CONCLUSIONS: Understanding BL changes and the functional significance of these changes in neurodegenerative disorders will fill the gap of knowledge in the field. Our goal is to provide a clear and concise review of the complex relationship between the BL and neurodegenerative disorders to stimulate new hypotheses and further research in this field.


Assuntos
Doença de Alzheimer , Sistema Glinfático , Doenças Neurodegenerativas , Doença de Alzheimer/metabolismo , Membrana Basal/metabolismo , Membrana Basal/patologia , Barreira Hematoencefálica/metabolismo , Sistema Glinfático/metabolismo , Sistema Glinfático/patologia , Humanos , Doenças Neurodegenerativas/metabolismo
16.
Brain Res ; 1768: 147578, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284021

RESUMO

While the notion of the brain as a prediction machine has been extremely influential and productive in cognitive science, there are competing accounts of how best to model and understand the predictive capabilities of brains. One prominent framework is of a "Bayesian brain" that explicitly generates predictions and uses resultant errors to guide adaptation. We suggest that the prediction-generation component of this framework may involve little more than a pattern completion process. We first describe pattern completion in the domain of visual perception, highlighting its temporal extension, and show how this can entail a form of prediction in time. Next, we describe the forward momentum of entrained dynamical systems as a model for the emergence of predictive processing in non-predictive systems. Then, we apply this reasoning to the domain of language, where explicitly predictive models are perhaps most popular. Here, we demonstrate how a connectionist model, TRACE, exhibits hallmarks of predictive processing without any representations of predictions or errors. Finally, we present a novel neural network model, inspired by reservoir computing models, that is entirely unsupervised and memoryless, but nonetheless exhibits prediction-like behavior in its pursuit of homeostasis. These explorations demonstrate that brain-like systems can get prediction "for free," without the need to posit formal logical representations with Bayesian probabilities or an inference machine that holds them in working memory.


Assuntos
Cognição/fisiologia , Reconhecimento Fisiológico de Modelo/fisiologia , Resolução de Problemas/fisiologia , Teorema de Bayes , Encéfalo/fisiologia , Humanos , Memória de Curto Prazo/fisiologia , Modelos Neurológicos , Probabilidade , Percepção Visual/fisiologia
17.
Intern Med J ; 51(5): 660-665, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34047037

RESUMO

BACKGROUND: Oxygen is commonly used in the acute care setting. However, used inappropriately, oxygen therapy can result in adverse consequences, including progressive respiratory failure and death. AIM: To investigate the effectiveness of a targeted intervention to improve prescribing practice and therapeutic application of supplemental oxygen. METHODS: Respiratory, Oncology and Surgery wards were targeted for the intervention. Nursing and junior medical staff from these wards undertook an education programme about safe use of oxygen. Cross-sectional data about oxygen prescribing, administration and monitoring were collected on inpatients in these wards at baseline, and at 3 and 6 months post-intervention, using a modified version of the British Thoracic Society Oxygen Audit Tool. RESULTS: At baseline, there was a written prescription for oxygen in 56% of patients (n = 43) using oxygen and this increased to 75% (n = 44) at 3 months, and remained at 65% (n = 48) at 6 months. However, the increased prescription rates were not statistically significant when compared to baseline (χ2 = 3.54, df = 1, P = 0.06 and χ2 = 0.73, df = 1, P = 0.40, respectively). The observed increase in oxygen prescriptions was driven by the medical wards: Oncology ward at 3 months (χ2 = 8.24, df = 1, P = 0.004); and Respiratory ward at 3 months (χ2 = 3.31, df = 1, P = 0.069) and 6 months (χ2 = 4.98, df = 1, P = 0.026). CONCLUSION: The education programme intervention to improve oxygen prescription showed promise in the medical wards but did not impact outcomes in the surgical ward setting, where different strategies may be needed.


Assuntos
Oxigênio , Insuficiência Respiratória , Estudos Transversais , Humanos , Oxigenoterapia , Estudos Prospectivos , Insuficiência Respiratória/terapia
18.
Transl Behav Med ; 11(8): 1558-1566, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-33823045

RESUMO

Few studies have examined the relative effectiveness of reinforcing versus aversive consequences at changing behavior in real-world environments. Real-time sensing devices makes it easier to investigate such questions, offering the potential to improve both intervention outcomes and theory. This research aims to describe the development of a real-time, operant theory-based secondhand smoke (SHS) intervention and compare the efficacy of aversive versus aversive plus reinforcement contingency systems. Indoor air particle monitors were placed in the households of 253 smokers for approximately three months. Participants were assigned to a measurement-only control group (N = 129) or one of the following groups: 1.) aversive only (AO, N = 71), with aversive audio/visual consequences triggered by the detection of elevated air particle measurements, or 2.) aversive plus reinforcement (AP, N = 53), with reinforcing consequences contingent on the absence of SHS added to the AO intervention. Residualized change ANCOVA analysis compared particle concentrations over time and across groups. Post-hoc pairwise comparisons were also performed. After controlling for Baseline, Post-Baseline daily particle counts (F = 6.42, p = 0.002), % of time >15,000 counts (F = 7.72, p < 0.001), and daily particle events (F = 4.04, p = 0.02) significantly differed by study group. Nearly all control versus AO/AP pair-wise comparisons were statistically significant. No significant differences were found for AO versus AP groups. The aversive feedback system reduced SHS, but adding reinforcing consequences did not further improve outcomes. The complexity of real-world environments requires the nuances of these two contingency systems continue to be explored, with this study demonstrating that real-time sensing technology can serve as a platform for such research.


Assuntos
Poluição do Ar em Ambientes Fechados , Poluição por Fumaça de Tabaco , Afeto , Características da Família , Humanos , Fumantes
20.
Clin Nutr ; 40(3): 1367-1375, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32938549

RESUMO

BACKGROUND: Malnutrition remains a critical public health issue in the US, particularly in surgery where perioperative malnutrition is commonly underdiagnosed and undertreated. In 2016, the Global Leadership Initiative on Malnutrition (GLIM) proposed a set of consensus criteria for the diagnosis of malnutrition. Our project aims to assess the post-operative outcomes of patients meeting a modified GLIM-defined (mGLIM) malnutrition criteria undergoing emergent gastrointestinal surgery (EGS) in the NSQIP database. Current GLIM-criteria were modified with addition of admission albumin (a NSQIP-defined malnutrition variable). METHODS: Adapting NSQIP data, mGLIM criteria are (1) BMI of ≤20 for age ≤ 70 and BMI ≤22 for age ≥ 71, (2) weight loss > 10% within the past 6 months, (3) admission albumin ≤ 3.5, and (4) emergent bowel surgery as etiologic criteria of acute disease/injury. All patients undergoing emergent small bowel, colon, and rectal procedures were extracted from the NSQIP database and included in the study. Multivariate linear and logistic regression models controlling for relevant covariates were developed to evaluate mGLIM criteria on length of stay (LOS), mortality, and overall complication rates. RESULTS: We included 31,029 patients who underwent emergent bowel surgeries from years 2011-2016. Demographically, 53.6% (n = 16,622) were female, 13.0% (n = 4023) were African American, and 78.3% (n = 24,292) were Caucasian. Case composition included 71.5% colon operations, 28.0% small bowel, and 0.5% rectal cases. Overall, 1.7% (n = 517) had data necessary to qualify as malnourished as per mGLIM. Controlling for covariates, multivariate linear and logistic regression analyses show that these patients have significantly higher mortality for both colon (p < 0.001, CI 1.55 | 2.61) and small bowel (p = 0.022, CI 1.08 | 2.67) procedures, longer LOS for colon (p < 0.001, CI 1.93 | 4.33) operations, and higher post-operative complications for both colon (p < 0.001, CI 1.61 | 2.62) and small bowel (p < 0.001, CI 1.57 | 3.37) cases. CONCLUSION: This analysis shows that mGLIM criteria malnutrition is associated with poor clinical outcomes following EGS affecting LOS and mortality. Our data indicates the new mGLIM criteria can be a powerful and simple predictive score for malnutrition that can be used to predict malnutrition-related risk of poor outcomes after EGS.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Tratamento de Emergência , Desnutrição/complicações , Desnutrição/diagnóstico , Avaliação Nutricional , Complicações Pós-Operatórias/epidemiologia , Estudos de Coortes , Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Tratamento de Emergência/mortalidade , Feminino , Humanos , Intestino Delgado/cirurgia , Tempo de Internação , Masculino , Estudos Retrospectivos
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