Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
1.
J Vis Exp ; (203)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38284552

RESUMO

Rapid and fast magnetic resonance imaging (MRI) protocols have become increasingly popular for pediatric neurosurgical patients as they are a great way to reduce ionizing radiation and sedation. While their popularity has increased, there are hurdles to overcome when transitioning to using them clinically, such as cost, staffing training, and motion artifact. Through this paper, we developed a protocol for clinical applications where rapid MRI can be a substitute or adjuvant in diagnostic workup. Further, we outline the relevant literature for the use of RS-MRI for the spine, TBI, and hydrocephalus pathologies while expanding upon the limitations and logistical barriers when transitioning to their use, a few of which are discussed above. Through this, we conclude that RS-MRI can be used diagnostically for spinal pathologies such as syrinx and hydrocephalus. Further, its lack of sensitivity for TBI findings makes rapid sequence magnetic resonance imaging (RS-MRI) a strong adjuvant with other advanced imaging or computed tomography (CT) for traumatic brain injury (TBI) pathologies.


Assuntos
Lesões Encefálicas Traumáticas , Hidrocefalia , Criança , Humanos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/cirurgia , Hidrocefalia/patologia , Hidrocefalia/cirurgia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Artefatos , Adjuvantes Imunológicos
2.
Transl Vis Sci Technol ; 12(10): 11, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37831446

RESUMO

Purpose: To explore barriers and facilitators to completing scheduled outpatient appointments at an urban academic hospital-based ophthalmology department. Methods: Potential participants were stratified by neighborhood Social Vulnerability Index (SVI) (range, 0-1.0, higher scores indicate greater vulnerability), and semistructured interviews were conducted with individuals 18 years and older with an SVI of greater than 0.61 (n = 17) and providers delivering care in the General Eye Clinic of the University of Illinois Chicago (n = 8). Qualitative analysis informed by human-centered design methods was conducted to classify barriers and facilitators into three domains of the Consolidated Framework for Implementation Research: outer setting, inner setting, and characteristics of individuals. Results: There were four main themes-transportation, time burden, social support, and economic situation-all of which were within the outer setting of the Consolidated Framework for Implementation Research; transportation was most salient. Although providers perceived health literacy as a barrier affecting motivation, patients expressed a high motivation to attend visits and felt well-educated about their condition. Conclusions: A lack of resources outside of the health system presents significant barriers for patients from neighborhoods with high SVI. Future efforts to improve adherence should focus on resource-related interventions in the outer setting. Improving access to eye care will require community-level interventions, particularly transportation. Translational Relevance: Understanding the barriers and facilitators within the Consolidated Framework for Implementation Research provides useful guidance for future interventions, specifically to focus future efforts to improve adherence on resource-related interventions.


Assuntos
Acesso aos Serviços de Saúde , Oftalmologia , Cooperação do Paciente , Humanos , Hospitais de Ensino
3.
JMIR Cancer ; 9: e45101, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37737837

RESUMO

BACKGROUND: Young women with metastatic breast cancer (MBC) are part of a digitally connected generation yet are underserved in terms of information needs. YouTube is widely used to find and identify health information. The accessibility of health-related content on social media together with the rare and marginalized experiences of young women with MBC and the digital media practices of younger generations imply a considerable likelihood that young women with MBC will seek information and community on the internet. OBJECTIVE: This study aims to assess the content quality of MBC YouTube videos and to identify themes in the experiences of young women with MBC based on YouTube videos. METHODS: A systematic assessment of MBC YouTube videos using the search term "metastatic breast cancer young" was conducted in August 2021. The search was performed in an incognito browser and with no associated YouTube or Google account. Search results were placed in order from most to least views. Title, date uploaded, length, poster identity, number of likes, and number of comments were collected. Understandability and actionability were assessed using the Patient Education Materials Assessment Tool (PEMAT); information reliability and quality were assessed with DISCERN. Themes, sponsorships, and health care professionals' and patients' narratives were reported. RESULTS: A total of 101 videos were identified. Of these, 78.2% (n=79) included sponsorships. The mean PEMAT scores were 78.8% (SD 15.3%) and 43.1% (SD 45.2%) for understandability and actionability, respectively. The mean DISCERN score was 2.44 (SD 0.7) out of 5. Identified themes included treatment (n=67, 66.3%), family relationship (n=46, 45.5%), and motherhood (n=38, 37.6%). CONCLUSIONS: YouTube videos about young women with MBC are highly understandable but demonstrate moderate rates of actionability, with low reliability and quality scores. Many have a commercial bias. While web-based materials have limitations, their potential to provide patient support is not fully developed. By acknowledging their patients' media habits, health care professionals can further develop a trusting bond with their patients, provide a space for open and honest discussions of web-based materials, and avoid any potential instances of confusion caused by misleading, inaccurate, or false web-based materials.

4.
Pediatrics ; 152(1)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37278207

RESUMO

Neonatal herpes simplex virus (HSV) infections are serious infections that usually occur in the first few weeks of life. Infants generally present with mucocutaneous lesions, central nervous system infection, and/or systemic disease. In this case report, we describe a set of twins that had unexpected presentations of neonatal HSV. Twin A was diagnosed incidentally on routine eye exam, and Twin B was diagnosed only because his twin was found to be infected; both infants were still hospitalized and were beyond 1 month of age. These twins exhibited atypical manifestations that diverge from the 3 main categories of neonatal HSV and expand our understanding of the spectrum of disease.


Assuntos
Herpes Simples , Complicações Infecciosas na Gravidez , Gravidez , Recém-Nascido , Feminino , Humanos , Lactente , Herpes Simples/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico
5.
JMIR Form Res ; 7: e39857, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140959

RESUMO

BACKGROUND: Patients increasingly use web-based evaluation tools to assess their physicians, health care teams, and overall medical experience. OBJECTIVE: This study aimed to evaluate the extent to which the standardized physician competencies of the CanMEDS Framework are present in web-based patient reviews (WPRs) and to identify patients' perception of important physician qualities in the context of quality cancer care. METHODS: The WPRs of all university-affiliated medical oncologists in midsized cities with medical schools in the province of Ontario (Canada) were collected. Two reviewers (1 communication studies researcher and 1 health care professional) independently assessed the WPRs according to the CanMEDS Framework and identified common themes. Comment scores were then evaluated to identify κ agreement rates between the reviewers, and a descriptive quantitative analysis of the cohort was completed. Following the quantitative analysis, an inductive thematic analysis was performed. RESULTS: This study identified 49 actively practicing university-affiliated medical oncologists in midsized urban areas in Ontario. A total of 473 WPRs reviewing these 49 physicians were identified. Among the CanMEDS competencies, those defining the roles of medical experts, communicators, and professionals were the most prevalent (303/473, 64%; 182/473, 38%; and 129/473, 27%, respectively). Common themes in WPRs include medical skill and knowledge, interpersonal skills, and answering questions (from the patient to the physician). Detailed WPRs tend to include the following elements: experience and connection; discussion and evaluation of the physician's knowledge, professionalism, interpersonal skills, and punctuality; in positive reviews, the expression of feelings of gratitude and a recommendation; and in negative reviews, discouragement from seeking the physician's care. Patients' perception of medical skills is less specific than their perception of interpersonal qualities, although medical skills are the most commented-on element of care in WPRs. Patients' perception of interpersonal skills (listening, compassion, and overall caring demeanor) and other experiential phenomena, such as feeling rushed during appointments, is often specific and detailed. Details about a physician's interpersonal skills or "bedside manner" are highly perceived, valued, and shareable in an WPR context. A small number of WPRs reflected a distinction between the value of medical skills and that of interpersonal skills. The authors of these WPRs claimed that for them, a physician's medical skills and competence are more important than their interpersonal skills. CONCLUSIONS: CanMEDS roles and competencies that are explicitly patient facing (ie, those directly experienced by patients in their interactions with physicians and through the care that physicians provide) are the most likely to be present and reported on in WPRs. The findings demonstrate the opportunity to learn from WPRs, not simply to discern physicians' popularity but to grasp what patients may expect from their physicians. In this context, WPRs can represent a method for the measurement and assessment of patient-facing physician competency.

6.
J Adolesc ; 95(6): 1220-1231, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37211871

RESUMO

BACKGROUND: Prior research findings are mixed regarding whether prosocial behavior is positively or negatively related to socioeconomic status and its correlates, such as economic pressure. This may be due to the lack of considerations for the type of prosocial behavior. AIMS: In this study, we aimed to examine how six types of prosocial behavior (i.e., public, anonymous, compliant, emotional, dire, and altruistic) are related to economic pressure among early adolescents. We hypothesized that family economic pressure would be associated with each type of prosocial behavior in differing ways. MATERIALS & METHODS: Participants were 11-14 years old (N = 143, Mage = 12.2 years, SDage = 0.87, 63 boys, 1 trans-identified boy, 55 girls), early adolescents and their parents. Among them, 54.6% were non-Hispanic/Latinx (NH/L) White, 23.8% were NH/L Black, 11.2% were NH/L Asian, 2.1% were NH/L Multiracial, and 8.4% were Hispanic/Latinx. Parents reported family economic pressure and adolescents' six types of prosocial behavior. RESULTS: Path analysis revealed that economic pressure was negatively associated with emotional and dire prosocial behavior over and above age, gender, and race/ethnicity. Family economic pressure was unrelated to public, anonymous, compliant, and altruistic prosocial behavior. DISCUSSION: These findings show some support for the Family Stress Model, such that economic stress might hinder youth's prosocial development. At the same time, youth may have similar levels of certain types of prosocial behavior regardless of their family's economic pressure. CONCLUSION: This research provided insight into the complex relation between economic pressure and youth's prosocial behavior which varies depending on the type of behavior.


Assuntos
Comportamento do Adolescente , Altruísmo , Adolescente , Criança , Feminino , Humanos , Masculino , Comportamento do Adolescente/etnologia , Comportamento do Adolescente/psicologia , Asiático , Negro ou Afro-Americano , Estresse Financeiro/economia , Estresse Financeiro/psicologia , Hispânico ou Latino , Pais , Comportamento Social , Classe Social , Fatores Socioeconômicos , Brancos , Pessoas Transgênero
7.
Nature ; 615(7953): 697-704, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36890230

RESUMO

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1-14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.


Assuntos
Antígenos de Neoplasias , Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico , Imunoterapia , Melanoma , Humanos , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Antígenos HLA/imunologia , Metástase Neoplásica , Medicina de Precisão , Edição de Genes , Sistemas CRISPR-Cas , Mutação
8.
Am J Perinatol ; 40(5): 525-531, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-33975363

RESUMO

OBJECTIVE: This study aimed to determine if prolonged antibiotic use at birth in neonates with a negative blood culture increases the total cost of hospital stay. STUDY DESIGN: This was a retrospective study performed at a 60-bed level IV neonatal intensive care unit. Neonates born <30 weeks of gestation or <1,500 g between 2016 and 2018 who received antibiotics were included. A multivariate linear regression analysis was conducted to determine if clinical factors contributed to increased hospital cost or length of stay. RESULTS: In total, 190 patients met inclusion criteria with 94 infants in the prolonged antibiotic group and 96 in the control group. Prolonged antibiotic use was associated with an increase length of hospital stay of approximately 31.87 days, resulting in a $69,946 increase in total cost of hospitalization. CONCLUSION: Prolonged antibiotics in neonates with negative blood culture were associated with significantly longer hospital length of stay and increased total cost of hospitalization. KEY POINTS: · Prolonged antibiotic use at birth is associated with prolonged hospital stay.. · Prolonged antibiotic use at birth is associated with increased cost of hospitalization.. · Prolonged antibiotic use at birth is associated with increased days on total parenteral nutrition.. · Prolonged antibiotic use at birth is associated with increased subsequent courses of antibiotics..


Assuntos
Antibacterianos , Custos Hospitalares , Recém-Nascido , Humanos , Lactente , Tempo de Internação , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Hospitalização
9.
Gels ; 8(9)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36135257

RESUMO

Glioma cells produce an increased amount of collagen compared with normal astrocytes. The increasing amount of collagen in the extracellular matrix (ECM) modulates the matrix structure and the mechanical properties of the microenvironment, thereby regulating tumor cell invasion. Although the regulation of tumor cell invasion mainly relies on cell-ECM interaction, the electrotaxis of tumor cells has attracted great research interest. The growth of glioma cells in a three-dimensional (3D) collagen hydrogel creates a relevant tumor physiological condition for the study of tumor cell invasion. In this study, we tested the migration of human glioma cells, fetal astrocytes, and adult astrocytes in a 3D collagen matrix with different collagen concentrations. We report that all three types of cells demonstrated higher motility in a low concentration of collagen hydrogel (3 mg/mL and 5 mg/mL) than in a high concentration of collagen hydrogel (10 mg/mL). We further show that human glioma cells grown in collagen hydrogels responded to direct current electric field (dcEF) stimulation and migrated to the anodal pole. The tumor cells altered their morphology in the gels to adapt to the anodal migration. The directedness of anodal migration shows a field strength-dependent response. EF stimulation increased the migration speed of tumor cells. This study implicates the potential role of an dcEF in glioma invasion and as a target of treatment.

10.
Front Sociol ; 7: 790397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35586263

RESUMO

This article explores the unique and understudied experiences of Indigenous women living in Toronto, Canada during the first year of the COVID-19 pandemic. The purpose of this study is to better document the impacts of COVID-19 on the mental health and wellbeing of Indigenous women in Toronto, Canada to better understand unmet needs, as well as lay the groundwork for more targeted research and potential interventions based on these needs. Using in-depth semi-structured interviews with thirteen Indigenous women, we shed light on the negative effects this pandemic has had on this population. We find that COVID-19 has negatively affected people's mental health, substance use and access to health services. This research speaks to the growing body of work that discusses the harmful effects of COVID-19 generally and how this pandemic has specifically affected Indigenous peoples.

11.
Am J Emerg Med ; 55: 64-71, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35279578

RESUMO

OBJECTIVES: We investigated whether continuous remote patient monitoring (RPM) could significantly reduce return Emergency Department (ED) revisits among coronavirus disease 2019 (COVID-19) patients discharged from the emergency Department. MATERIALS AND METHODS: A prospective observational study was conducted from a total of 2833 COVID-19 diagnosed patients who presented to the Montefiore Medical Center ED between September 2020-March 2021. Study patients were remotely monitored through a digital platform that was supervised 24/7 by licensed healthcare professionals. Age and time-period matched controls were randomly sampled through retrospective review. The primary outcome was ED revisit rates among the two groups. RESULTS: In our study, 150 patients enrolled in the RPM program and 150 controls were sampled for a total of 300 patients. Overall, 59.1% of the patients identified as Hispanic/Latino. The RPM group had higher body mass index (BMI) (29 (25-35) vs. 27 (25-31) p-value 0.020) and rates of hypertension (50.7% (76) vs. 35.8% (54) p-value 0.009). There were no statistically significant differences in rates of ED revisit between the RPM group (8% (12)) and control group (9.3% (14)) (OR: 0.863; 95% CI:0.413-1. 803; p- 0.695). DISCUSSION AND CONCLUSION: Our study explored the impact of continuous monitoring versus intermittent monitoring for reducing ED revisits in a largely underrepresented population of the Bronx. Our study demonstrated that continuous remote patient monitoring showed no significant difference in preventing ED revisits compared to non-standardized intermittent monitoring. However, potential other acute care settings where RPM may be useful for identifying high-risk patients for early interventions warrant further study.


Assuntos
COVID-19 , COVID-19/epidemiologia , Serviço Hospitalar de Emergência , Humanos , Monitorização Fisiológica , Alta do Paciente , Readmissão do Paciente , Estudos Retrospectivos
12.
Psychopharmacology (Berl) ; 239(1): 253-266, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34982171

RESUMO

RATIONALE: The voltage-insensitive, small-conductance calcium-activated potassium (SK) channel is a key regulator of neuronal depolarization and is implicated in the pathophysiology of depressive disorders. OBJECTIVE: We ascertained whether the SK channel is impaired in the chronic unpredictable stress (CUS) model and whether it can serve as a molecular target of antidepressant action. METHODS: We assessed the depressive-like behavioral phenotype of CUS-exposed rats and performed post-mortem SK channel binding and activity-dependent zif268 mRNA analyses on their brains. To begin an assessment of SK channel subtypes involved, we examined the effects of genetic and pharmacological inhibition of the SK3 channel using conditional knockout mice and selective SK3 channel negative allosteric modulators (NAMs). RESULTS: We found that [125I]apamin binding to SK channels is increased in the prefrontal cortex and decreased in the hippocampus, an effect that was associated with reciprocal levels of zif268 mRNA transcripts indicating abnormal regional cell activity in this model. We found that genetic and pharmacological manipulations significantly decreased immobility in the forced swim test without altering general locomotor activity, a hallmark of antidepressant-like activity. CONCLUSIONS: Taken together, these findings link depression-related neural and behavioral pathophysiology with abnormal SK channel functioning and suggest that this can be reversed by the selective inhibition of SK3 channels.


Assuntos
Neurônios , Canais de Potássio Ativados por Cálcio de Condutância Baixa , Animais , Antidepressivos/farmacologia , Apamina , Cálcio/metabolismo , Camundongos , Neurônios/metabolismo , Ratos , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética
13.
Parasitologia ; 2(2): 147-159, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36872919

RESUMO

The human parasite Entamoeba histolytica, which causes approximately 100 million cases of amoebic dysentery each year, relies on glycolysis as the major source of ATP production from glucose as it lacks a citric acid cycle and oxidative phosphorylation. Ethanol and acetate, the two major glycolytic end products for E. histolytica, are produced at a ratio of 2:1 under anaerobic conditions, creating an imbalance between NADH production and utilization. In this study we investigated the role of acetate kinase (ACK) in acetate production during glycolysis in E. histolytica metabolism. Analysis of intracellular and extracellular metabolites demonstrated that acetate levels were unaffected in an ACK RNAi cell line, but acetyl-CoA levels and the NAD+/NADH ratio were significantly elevated. Moreover, we demonstrated that glyceraldehyde 3-phosphate dehydrogenase catalyzes the ACK-dependent conversion of acetaldehyde to acetyl phosphate in E. histolytica. We propose that ACK is not a major contributor to acetate production, but instead provides a mechanism for maintaining the NAD+/NADH balance during ethanol production in the extended glycolytic pathway.

14.
BMC Nutr ; 7(1): 82, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34886909

RESUMO

BACKGROUND: Patients undergoing hepatopancreatobiliary (HPB) surgery, such patients with pancreatic, periampullary, and liver cancer, are at high risk for malnutrition. Malnutrition increases surgical complications and reduces overall survival. Despite its severity, there are limited interventions addressing malnutrition after HPB surgery. The aim of this pilot trial was to examine feasibility, acceptability, usability, and preliminary efficacy of a remote nutrition monitoring intervention after HPB surgery. METHODS: Participants received tailored nutritional counseling before and after surgery at 2 and 4 weeks after hospital discharge. Participants also recorded nutritional intake daily for 30 days, and these data were reviewed remotely by registered dietitians before nutritional counseling visits. Descriptive statistics were used to describe study outcomes. RESULTS: All 26 patients approached to participate consented to the trial before HPB surgery. Seven were excluded after consent for failing to meet eligibility criteria (e.g., did not receive surgery). Nineteen participants (52.6% female, median age = 65 years) remained eligible for remote monitoring post-surgery. Nineteen used the mobile app food diary, 79% of participants recorded food intake for greater than 80% of study days, 95% met with the dietitian for all visits, and 89% were highly satisfied with the intervention. Among participants with complete data, the average percent caloric goal obtained was 82.4% (IQR: 21.7). CONCLUSIONS: This intervention was feasible and acceptable to patients undergoing HPB surgery. Preliminary efficacy data showed most participants were able to meet calorie intake goals. Future studies should examine intervention efficacy in a larger, randomized controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov. Registered 16 September 2019, https://clinicaltrials.gov/ct2/show/NCT04091165 .

17.
Am J Pharm Educ ; 84(2): 7571, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32226073

RESUMO

Objective. To assess burnout and engagement in first- and second-year Doctor of Pharmacy (PharmD) students and to investigate their relationships to students' perception of their academic ability. Methods. An online survey that included three validated scales was administered in May 2017 to first- and second-year pharmacy students enrolled in didactic coursework at Touro University California College of Pharmacy. The Maslach Burnout Inventory was used to assess burnout and the Utrecht Work Engagement Scale was used to measure student engagement. To characterize academic ability, Academic Self-Perception, a subscale of the School Attitude Assessment Survey-Revised, was used. Regression analysis was performed using statistical software. Results. One hundred sixty-two students (81.4% response rate) completed the survey. Emotional exhaustion and professional inefficacy were negatively correlated with students' academic self-perception. Dedication was positively correlated with academic self-perception. Conclusion. In pharmacy students completing the didactic portion of the PharmD curriculum, various engagement and burnout parameters correlated with academic self-perception.


Assuntos
Esgotamento Profissional/psicologia , Autoimagem , Estudantes de Farmácia/psicologia , Estudantes de Farmácia/estatística & dados numéricos , Desempenho Acadêmico/psicologia , Currículo , Educação em Farmácia , Humanos , Angústia Psicológica , Inquéritos e Questionários , Universidades , Engajamento no Trabalho
18.
Hum Mol Genet ; 29(9): 1547-1567, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32338760

RESUMO

Dominant mutations in the mitochondrial paralogs coiled-helix-coiled-helix (CHCHD) domain 2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia/myopathy, respectively. The mechanism by which they disrupt mitochondrial cristae, however, has been uncertain. Using the first C2/C10 double knockout (DKO) mice, we report that C10 pathogenesis and the normal function of C2/C10 are intimately linked. Similar to patients with C10 mutations, we found that C2/C10 DKO mice have disrupted mitochondrial cristae, because of cleavage of the mitochondrial-shaping protein long form of OPA1 (L-OPA1) by the stress-induced peptidase OMA1. OMA1 was found to be activated similarly in affected tissues of mutant C10 knock-in (KI) mice, demonstrating that L-OPA1 cleavage is a novel mechanism for cristae abnormalities because of both C10 mutation and C2/C10 loss. Using OMA1 activation as a functional assay, we found that C2 and C10 are partially functionally redundant, and some but not all disease-causing mutations have retained activity. Finally, C2/C10 DKO mice partially phenocopied mutant C10 KI mice with the development of cardiomyopathy and activation of the integrated mitochondrial integrated stress response in affected tissues, tying mutant C10 pathogenesis to C2/C10 function.


Assuntos
Esclerose Amiotrófica Lateral/genética , Proteínas de Ligação a DNA/genética , Demência Frontotemporal/genética , Metaloproteases/genética , Proteínas Mitocondriais/genética , Doença de Parkinson/genética , Fatores de Transcrição/genética , Esclerose Amiotrófica Lateral/patologia , Animais , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/genética , Cardiomiopatias/patologia , Modelos Animais de Doenças , Demência Frontotemporal/patologia , Predisposição Genética para Doença , Células HeLa , Humanos , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/patologia , Mutação/genética , Doença de Parkinson/patologia
19.
Pediatr Emerg Care ; 36(8): e438-e446, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28885390

RESUMO

BACKGROUND AND OBJECTIVES: Febrile infants younger than 90 days are often subjected to invasive diagnostic evaluation and hospitalization to monitor for serious bacterial infection (SBI) despite recent changes in SBI risk and advances in diagnostics. Nationwide provider practices, over time, are unknown for this group. Our objective was to determine the likelihood of admission and associated complications of care for such infants, particularly those at lowest risk for SBI. METHODS: This is a retrospective cohort study including multisite emergency department (ED) visits using administrative data from the Pediatric Emergency Care Applied Research Network Core Data Project. We examined uncomplicated febrile infants younger than 90 days seen in the ED from 2002 to 2012 who did not have an explicit infectious diagnosis, critical illness, or chronic condition. RESULTS: We identified 38,224 infants, among whom, 11,600 (31%) were admitted. We observed a 3% increase in ED admission every year during the study period (P < 0.05). Age less than 30 days and black race were independent predictors of admission (P < 0.01). We identified 227 complications of care in the ED. Among those with a specified cause, 49% were attributed to antibiotic use or procedures related to the diagnosis and empiric treatment of suspected infection. CONCLUSIONS: Despite the decreasing risk of SBI and diagnostic advances during the study period, the odds of hospital admission increased for febrile infants at low risk for sepsis. We also provide first data on therapeutic and diagnostic test-related adverse events in this setting. These data provide further justification for a consensus guideline on management of such infants.


Assuntos
Febre/epidemiologia , Hospitalização/estatística & dados numéricos , Infecções Bacterianas/diagnóstico , Serviço Hospitalar de Emergência , Feminino , Febre/etnologia , Febre/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia
20.
Psychopharmacology (Berl) ; 236(12): 3541-3556, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31302721

RESUMO

RATIONALE: Ethanol-induced behavioural sensitization (EBS) does not occur uniformly in mice exposed to the sensitization paradigm. This suggests innate differential responses to ethanol (EtOH) in the reward circuitry of individual animals. OBJECTIVES: To better characterize the adaptive differences between low-sensitized (LS) and high-sensitized (HS) mice, we examined excitatory amino acid (EAA) and inhibitory amino acid (IAA) neurotransmitter levels in the nucleus accumbens (NAc) during EBS expression. METHODS: Male DBA/2J mice received five ethanol (EtOH) (2.2 g/kg) or saline injections, and locomotor activity (LMA) was assessed during EBS induction. EtOH mice were classified as LS or HS on the basis of final LMA scores. Following an EtOH challenge (1.8 g/kg) 2 weeks later, LMA was re-evaluated and in vivo microdialysis samples were collected from the NAc. RESULTS: Most differences in amino acid levels were observed within the first 20 min after EtOH challenge. LS mice exhibited similar glutamate levels compared with acutely treated (previously EtOH naïve) mice, and generally increased levels of the IAAs GABA, glycine, and taurine. By contrast, HS mice exhibited increased glutamate and attenuated levels of GABA, glycine, and taurine. CONCLUSION: These data suggest that the profile of amino acid neurotransmitters in the NAc of LS and HS mice significantly differs. Elucidating these adaptive differences contributes to our understanding of factors that confer susceptibility/resilience to alcohol use disorder.


Assuntos
Etanol/administração & dosagem , Rede Nervosa/metabolismo , Neurotransmissores/metabolismo , Núcleo Accumbens/metabolismo , Sinapses/metabolismo , Aminoácidos/metabolismo , Animais , Aminoácidos Excitatórios/metabolismo , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Microdiálise/métodos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Rede Nervosa/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Sinapses/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...