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1.
Analyst ; 149(7): 2180-2189, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38426542

RESUMO

New electrochemical probes offer the opportunity to investigate new systems. A dual barrel electrode can be laser pulled to produce micron-sized platinum disk electrodes. Here, we detail several important considerations for both the fabrication process and for experimental implimentation of the probe. We provide parameters for a Sutter P-2000 laser puller, methods for optical and electrochemical characterization, tips for how to successfully bevel the microelectrodes, and how salt concentrations and electrostatic discharge affect the voltammetry. This paper serves as a guide for how to successfully implement dual barrel electrodes from fabrication to experimentation.

2.
J Community Health ; 49(2): 343-354, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37985556

RESUMO

INTRODUCTION: A disproportionate share of Federally Qualified Health Center (FQHC) users have a behavioral health condition, but there exists limited research examining changes in behavioral health provision in FQHCs. The objectives of this study were to describe how the provision of behavioral health services by FQHCs to the population of people with behavioral health conditions has changed over time in the US, how these trends varied across states, and whether the proportion of total delivered services that are behavioral health services has changed within FQHCs over time. METHODS: Descriptive analysis using the Uniform Data System and Global Burden of Disease Datasets from years 2012 to 2019. RESULTS: From 2012 to 2019, FQHC behavioral health visits per 1,000 population with any behavioral health condition grew 103%, with a 26-fold difference in average rates across states during the study period. Annual behavioral health visits per patient increased from 3.2 to 2012 to 3.4 in 2019. From 2012 to 2019, the number of behavioral health visits per 1,000 FQHC patients grew by 51%, whereas the rate of asthma visits declined by 14%, heart disease visits declined by 4%, and hypertension and diabetes related visits remained stable (changing < 1% for both). DISCUSSION/CONCLUSION: Behavioral health visit growth at FQHCs outpaced national prevalence of behavioral health conditions. This growth was driven by FQHCs serving an increasing number of patients with behavioral health conditions, without sacrificing the frequency of visits for individual patients with behavioral health conditions.


Assuntos
Saúde Mental , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estados Unidos/epidemiologia , Atenção Primária à Saúde , Serviços de Saúde , Acessibilidade aos Serviços de Saúde , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia
3.
Food Microbiol ; 119: 104431, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38225041

RESUMO

Isolation of Salmonella from enrichment cultures of food or environmental samples is a complicated process. Numerous factors including fitness in various selective enrichment media, relative starting concentrations in pre-enrichment, and competition among multi-serovar populations and associated natural microflora, come together to determine which serovars are identified from a given sample. A recently developed approach for assessing the relative abundance (RA) of multi-serovar Salmonella populations (CRISPR-SeroSeq or Deep Serotyping, DST) is providing new insight into how these factors impact the serovars observed, especially when different selective enrichment methods are used to identify Salmonella from a primary enrichment sample. To illustrate this, we examined Salmonella-positive poultry pre-enrichment samples through the selective enrichment process in Tetrathionate (TT) and Rappaport Vassiliadis (RVS) broths and assessed recovery of serovars with each medium. We observed the RA of serovars detected post selective enrichment varied depending on the medium used, initial concentration, and competitive fitness factors, all which could result in minority serovars in pre-enrichment becoming dominant serovars post selective enrichment. The data presented provide a greater understanding of culture biases and lays the groundwork for investigations into robust enrichment and plating media combinations for detecting Salmonella serovars of greater concern for human health.


Assuntos
Salmonella enterica , Animais , Humanos , Salmonella enterica/genética , Sorogrupo , Aves Domésticas , Salmonella/genética , Sorotipagem/métodos , Meios de Cultura
4.
J Nurs Adm ; 54(4): 227-234, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38512084

RESUMO

OBJECTIVE: This quality improvement project targeted an enculturation gap among new nurses by assembling and piloting an Enculturation Toolkit. BACKGROUND: Enculturation of new nurses contributes to engagement, performance, sense of belonging, and retention. During the COVID-19 pandemic, orientation was shortened, virtual, and asynchronous, creating a gap in enculturation. METHODS: New nurses and their preceptors were surveyed at baseline, 2 to 3 months, and 4 to 5 months to measure engagement and enculturation using the Meaning and Joy in Work Questionnaire (MJWQ) and questions about the history and values of the organization. RESULTS: Initial MJWQ responses were high and sustained throughout the study period. Participants demonstrated increased knowledge of the organization's mission statement and logo. New nurses rated the toolkit activities favorably, with an average score of 4.6 out of 5. CONCLUSIONS: An Enculturation Toolkit was effective in improving knowledge about the organization and sustaining engagement and belonging.


Assuntos
COVID-19 , Pandemias , Humanos , Felicidade , Melhoria de Qualidade
5.
Curr Opin Anaesthesiol ; 37(3): 279-284, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573179

RESUMO

PURPOSE OF REVIEW: The opioid epidemic remains a constant and increasing threat to our society with overdoses and overdose deaths rising significantly during the COVID-19 pandemic. Growing evidence suggests a link between perioperative opioid use, postoperative opioid prescribing, and the development of opioid use disorder (OUD). As a result, strategies to better optimize pain management during the perioperative period are urgently needed. The purpose of this review is to summarize the most recent multimodal analgesia (MMA) recommendations, summarize evidence for efficacy surrounding the increased utilization of Enhanced Recovery After Surgery (ERAS) protocols, and discuss the implications for rising use of buprenorphine for OUD patients who present for surgery. In addition, this review will explore opportunities to expand our treatment of complex patients via transitional pain services. RECENT FINDINGS: There is ample evidence to support the benefits of MMA. However, optimal drug combinations remain understudied, presenting a target area for future research. ERAS protocols provide a more systematic and targeted approach for implementing MMA. ERAS protocols also allow for a more comprehensive approach to perioperative pain management by necessitating the involvement of surgical specialists. Increasingly, OUD patients taking buprenorphine are presenting for surgery. Recent guidance from a multisociety OUD working group recommends that buprenorphine not be routinely discontinued or tapered perioperatively. Lastly, there is emerging evidence to justify the use of transitional pain services for more comprehensive treatment of complex patients, like those with chronic pain, preoperative opioid tolerance, or substance use disorder. SUMMARY: Perioperative physicians must be aware of the impact of the opioid epidemic and explore methods like MMA techniques, ERAS protocols, and transitional pain services to improve the perioperative pain experience and decrease the risks of opioid-related harm.


Assuntos
Analgésicos Opioides , COVID-19 , Epidemia de Opioides , Transtornos Relacionados ao Uso de Opioides , Manejo da Dor , Dor Pós-Operatória , Assistência Perioperatória , Humanos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/etiologia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/diagnóstico , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Epidemia de Opioides/prevenção & controle , Manejo da Dor/métodos , Manejo da Dor/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Buprenorfina/uso terapêutico , Buprenorfina/efeitos adversos , Recuperação Pós-Cirúrgica Melhorada
6.
Gerontol Geriatr Educ ; : 1-16, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832640

RESUMO

Interprofessional education (IPE) and research enhances learning, team-based communication, and cross-disciplinary collaborations, which can result in higher quality care for older adults. Despite the importance of IPE, it remains underutilized in higher education, demonstrating the need for extracurricular IPE opportunities. This study describes an interprofessional research project that brought together faculty, undergraduate, and graduate students from several health and social science disciplines to design and deliver a 15-week healthy aging program for older adults living in the urban Circumpolar North. Five faculty and one graduate research assistant led the project while eight students team-taught weekly, 1-hour sessions in the community focusing on healthy lifestyles within a framework of Persuasive Hope Theory. This paper describes the project, the student training procedures, and reports the results of the student satisfaction survey regarding their involvement with the research. Using a student self-assessment survey, students report gains in thinking like a scientist, increased confidence conducting research tasks, benefits from teamwork, and greater consideration of the needs of older adults in their field of study. Despite a small sample size, this study also suggests that students may be more likely to consider a career working with older adults if given hands-on experiences.

7.
N Engl J Med ; 383(20): 1907-1919, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33017106

RESUMO

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).


Assuntos
Antibacterianos/uso terapêutico , Apendicectomia , Apendicite/tratamento farmacológico , Apendicite/cirurgia , Apêndice/cirurgia , Absenteísmo , Administração Intravenosa , Adulto , Antibacterianos/efeitos adversos , Apendicectomia/estatística & dados numéricos , Apendicite/complicações , Apêndice/patologia , Impacção Fecal , Feminino , Nível de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento
8.
Med Care ; 61(11): 779-786, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37712715

RESUMO

OBJECTIVE: To determine the extent to which counting observation stays changes hospital performance on 30-day readmission measures. METHODS: This was a retrospective study of inpatient admissions and observation stays among fee-for-service Medicare enrollees in 2017. We generated 3 specifications of 30-day risk-standardized readmissions measures: the hospital-wide readmission (HWR) measure utilized by the Centers for Medicare and Medicaid Services, which captures inpatient readmissions within 30 days of inpatient discharge; an expanded HWR measure, which captures any unplanned hospitalization (inpatient admission or observation stay) within 30 days of inpatient discharge; an all-hospitalization readmission (AHR) measure, which captures any unplanned hospitalization following any hospital discharge (observation stays are included in both the numerator and denominator of the measure). Estimated excess readmissions for hospitals were compared across the 3 measures. High performers were defined as those with a lower-than-expected number of readmissions whereas low performers had higher-than-expected or excess readmissions. Multivariable logistic regression identified hospital characteristics associated with worse performance under the measures that included observation stays. RESULTS: Our sample had 2586 hospitals with 5,749,779 hospitalizations. Observation stays ranged from 0% to 41.7% of total hospitalizations. Mean (SD) readmission rates were 16.6% (5.4) for the HWR, 18.5% (5.7) for the expanded HWR, and 17.9% (5.7) in the all-hospitalization readmission measure. Approximately 1 in 7 hospitals (14.9%) would switch from being classified as a high performer to a low performer or vice-versa if observation stays were fully included in the calculation of readmission rates. Safety-net hospitals and those with a higher propensity to use observation would perform significantly worse. CONCLUSIONS: Fully incorporating observation stays in readmission measures would substantially change performance in value-based programs for safety-net hospitals and hospitals with high rates of observation stays.

9.
Ann Emerg Med ; 81(1): 47-56, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36257864

RESUMO

The emergency department serves as a vital source of health care for residents in the United States, including as a safety net. However, patients from minoritized racial and ethnic groups have historically experienced disproportionate barriers to accessing health care services and lower quality of services than White patients. Quality measures and their application to quality improvement initiatives represent a critical opportunity to incentivize health care systems to advance health equity and reduce health disparities. Currently, there are no nationally recognized quality measures that track the quality of emergency care delivery by race and ethnicity and no published frameworks to guide the development and prioritization of quality measures to reduce health disparities in emergency care. To address these gaps, the American College of Emergency Physicians (ACEP) convened a working group of experts in quality measurement, health disparities, and health equity to develop guidance on establishing quality measures to address racial and ethnic disparities in the provision of emergency care. Based on iterative discussion over 3 working group meetings, we present a summary of existing emergency medicine quality measures that should be adapted to track racial and ethnic disparities, as well as a framework for developing new measures that focus on disparities in access to emergency care, care delivery, and transitions of care.


Assuntos
Serviços Médicos de Emergência , Equidade em Saúde , Humanos , Estados Unidos , Acessibilidade aos Serviços de Saúde , Etnicidade , Serviço Hospitalar de Emergência , Disparidades em Assistência à Saúde
10.
J Med Internet Res ; 25: e47933, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37310782

RESUMO

Abundant disparities for women in medicine contribute to many women physicians considering leaving medicine. There is a strong financial and ethical case for leaders in academic medicine to focus on strategies to improve retention. This article focuses on five immediate actions that leaders can take to enhance gender equity and improve career satisfaction for all members of the workplace.


Assuntos
Equidade de Gênero , Medicina , Humanos , Feminino , Organizações , Local de Trabalho
11.
Dev Dyn ; 251(9): 1524-1534, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-33728725

RESUMO

BACKGROUND: Genetic tools to study gene function and the fate of cells in the anterior limb bud are very limited. RESULTS: We describe a transgenic mouse line expressing CreERT2 from the Aristaless-like 4 (Alx4) promoter that induces recombination in the anterior limb. Cre induction at embryonic day 8.5 revealed that Alx4-CreERT2 labeled cells using the mTmG Cre reporter contributed to anterior digits I to III as well as the radius of the forelimb. Cre activity is expanded further along the AP axis in the hindlimb than in the forelimb resulting in some Cre reporter cells contributing to digit IV. Induction at later time points labeled cells that become progressively restricted to more anterior digits and proximal structures. Comparison of Cre expression from the Alx4 promoter transgene with endogenous Alx4 expression reveals Cre expression is slightly expanded posteriorly relative to the endogenous Alx4 expression. Using Alx4-CreERT2 to induce loss of intraflagellar transport 88 (Ift88), a gene required for ciliogenesis, hedgehog signaling, and limb patterning, did not cause overt skeletal malformations. However, the efficiency of deletion, time needed for Ift88 protein turnover, and for cilia to regress may hinder using this approach to analyze cilia in the limb. Alx4-CreERT2 is also active in the mesonephros and nephric duct that contribute to the collecting tubules and ducts of the adult nephron. Embryonic activation of the Alx4-CreERT2 in the Ift88 conditional line results in cyst formation in the collecting tubules/ducts. CONCLUSION: Overall, the Alx4-CreERT2 line will be a new tool to assess cell fates and analyze gene function in the anterior limb, mesonephros, and nephric duct.


Assuntos
Proteínas Hedgehog , Fatores de Transcrição , Animais , Extremidades , Proteínas Hedgehog/genética , Proteínas de Homeodomínio , Integrases/genética , Integrases/metabolismo , Camundongos , Camundongos Transgênicos , Fatores de Transcrição/genética , Transgenes
12.
Antimicrob Agents Chemother ; 66(4): e0194121, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35293780

RESUMO

Combination antiretroviral therapy (cART) dramatically changed the face of the HIV/AIDS pandemic, making it one of the most prominent medical breakthroughs of the past 3 decades. However, as the life span of persons living with HIV (PLWH) continues to approach that of the general population, the same cannot be said regarding their quality of life. PLWH are affected by comorbid conditions such as high blood pressure, diabetes, and neurocognitive impairment at a higher rate and increased severity than their age-matched counterparts. PLWH also have higher levels of inflammation, the drivers of which are not entirely clear. As cART treatment is lifelong, we assessed here the effects of cART, independent of HIV, on primary human monocyte-derived macrophages (MDMs). MDMs were unskewed or skewed to an alternative phenotype and treated with Atripla or Triumeq, two first-line cART treatments. We report that Triumeq skewed alternative MDMs toward an inflammatory nonsenescent phenotype. Both Atripla and Triumeq caused mitochondrial dysfunction, specifically efavirenz and abacavir. Additionally, transcriptome sequencing (RNA-seq) demonstrated that both Atripla and Triumeq caused differential regulation of genes involved in immune regulation and cell cycle and DNA repair. Collectively, our data demonstrate that cART, independent of HIV, alters the MDM phenotype. This suggests that cART may contribute to cell dysregulation in PLWH that subsequently results in increased susceptibility to comorbidities.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/metabolismo , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/farmacologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Humanos , Macrófagos , Mitocôndrias , Qualidade de Vida
13.
J Appl Microbiol ; 132(3): 2410-2420, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34821433

RESUMO

AIMS: Salmonella is extremely diverse, with >2500 serovars that are genetically and phenotypically diverse. The aim of this study was to build a collection of Salmonella isolates that are genetically diverse and to evaluate their ability to form biofilm under different conditions relevant to a processing environment. METHODS AND RESULTS: Twenty Salmonella isolates representative of 10 serovars were subtyped using Clustered regularly interspaced short palindromic repeats (CRISPR)-typing to assess the genetic diversity between isolates of each serovar. Biofilm formation of the isolates on both plastic and stainless-steel surfaces at 25 and 15°C was assessed. At 25°C, 8/20 isolates each produced strong and moderate biofilm on plastic surface compared to stainless-steel (3/20 and 13/20 respectively). At 15°C, 5/20 produced strong biofilm on plastic surface and none on stainless-steel. Several isolates produced weak biofilm on plastic (11/20) and stainless-steel (16/20) surfaces. Serovar Schwarzengrund consistently produced strong biofilm while serovars Heidelberg and Newport produced weak biofilm. CONCLUSION: These results suggest that Salmonellae differ in their attachment depending on the surface and temperature conditions encountered, which may influence persistence in the processing environment. SIGNIFICANCE AND IMPACT OF STUDY: These differences in biofilm formation could provide useful information for mitigation of Salmonella in processing environments.


Assuntos
Aderência Bacteriana , Salmonella , Biofilmes , Salmonella/genética , Sorogrupo , Aço Inoxidável , Temperatura
14.
Pain Med ; 23(2): 288-294, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34601612

RESUMO

The Liaison Committee on Medical Education (LCME) require medical schools to teach their students how to recognize and work toward eliminating health disparities. However, time constraints and a dearth of guidance for educators in teaching pain disparities curricula pose significant challenges. Herein we describe successes and lessons learned after designing, implementing, and evaluating an innovative pain disparities curriculum that was embedded in a longitudinal health equity curriculum for third year medical school students at an academic institution. Although the curriculum was developed for medical school students, the concepts may be broadly applicable to other training settings such as residency and fellowship programs.


Assuntos
Educação Médica , Internato e Residência , Currículo , Humanos , Dor , Faculdades de Medicina
15.
Am J Emerg Med ; 55: 51-56, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35279577

RESUMO

BACKGROUND: Patients with mental illness have been shown to receive lower quality of care and experience worse cardiovascular (CV) outcomes compared to those without mental illness. This present study examined mental health-related disparities in CV outcomes after an Emergency Department (ED) visit for chest pain. METHODS: This retrospective cohort included adult Medicaid beneficiaries in Washington state discharged from the ED with a primary diagnosis of unspecified chest pain in 2010-2017. Outcomes for patients with any mental illness (any mental health diagnosis or mental-health specific service use within 1 year of an index ED visit) and serious mental illness (at least two claims (on different dates of service) within 1 year of an index ED visit with a diagnosis of schizophrenia, other psychotic disorder, or major mood disorder) were compared to those of patients without mental illness. Our outcomes of interest were the incidence of major adverse cardiac events (MACE) within 30 days and 6 months of discharge of their ED visit, defined as a composite of death, acute myocardial infarction (AMI), CV rehospitalization, or revascularization. Secondary outcomes included cardiovascular diagnostic testing (diagnostic angiography, stress testing, echocardiography, and coronary computed tomography (CT) angiography) rates within 30 days of ED discharge. Only treat-and-release visits were included for outcomes assessment. Hierarchical logistic random effects regression models assessed the association between mental illness and the outcomes of interest, controlling for age, gender, race, ethnicity, Elixhauser comorbidities, and health care use in the past year, as well as fixed year effects. RESULTS: There were 98,812 treat-and-release ED visits in our dataset. At 30 days, enrollees with any mental illness had no differences in rates of MACE (AOR 0.96; 95% CI, 0.72-1.27) or any of the individual components. At 6 months, enrollees with any mental illness (AOR 1.86; 95% CI, 1.11-3.09) and serious mental illness (AOR 2.60; 95% CI 1.33-5.13) were significantly more likely to be hospitalized for a CV condition compared to those without mental illness. Individuals with any mental illness had higher rates of testing at 30 days (AOR 1.16; 95% CI 1.07-1.27). CONCLUSION: Patients with mental illness have similar rates of MACE, but higher rates of certain CV outcomes, such as CV hospitalization and diagnostic testing, after an ED visit for chest pain.


Assuntos
Dor no Peito , Transtornos Mentais , Adulto , Dor no Peito/diagnóstico , Dor no Peito/epidemiologia , Dor no Peito/etiologia , Angiografia Coronária/métodos , Serviço Hospitalar de Emergência , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
16.
J Neurochem ; 159(1): 145-155, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34129687

RESUMO

Mutations in ubiquilin-2 (UBQLN2), a ubiquitin-binding shuttle protein involved in several protein quality control processes, can lead to amyotrophic lateral sclerosis (ALS). We previously found that wild-type UBQLN2 forms dynamic, membraneless biomolecular condensates upon cellular stress, and undergoes liquid-liquid phase separation in vitro. However, the impact of ALS-linked mutations on UBQLN2 condensate formation in cells remains unknown. Here, we overexpress mCherry-fused UBQLN2 with five patient-derived ALS-linked mutations and employ live-cell imaging and photokinetic analysis to investigate how each of these mutations impact stress-induced UBQLN2 condensate assembly and condensate material properties. Unlike endogenous UBQLN2, exogenously introduced UBQLN2 forms condensates distinct from stress granules. Both wild-type and mutant UBQLN2 condensates are generally cytoplasmic and liquid-like. However, mutant UBQLN2 forms fewer stress-induced UBQLN2 condensates than wild-type UBQLN2. Exogenously expressed P506T UBQLN2 forms the lowest number of stress-induced condensates of all UBQLN2 mutants, and these condensates are significantly smaller than those of wild-type UBQLN2. Fluorescence recovery after photobleaching (FRAP) analysis of UBQLN2 condensates revealed higher immobile fractions for UBQLN2 mutants, especially P506T. P497S and P497H mutations differentially impact condensate properties, demonstrating that the effects of ALS-linked mutations are both position- and amino acid-dependent. Collectively, our data show that disease mutations hinder assembly and alter viscoelastic properties of stress-induced UBQLN2 condensates, potentially leading to aggregates commonly observed in ALS.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Mutação/fisiologia , Estresse Oxidativo/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/análise , Esclerose Lateral Amiotrófica/patologia , Proteínas Relacionadas à Autofagia/análise , Linhagem Celular , Humanos , Imagem Óptica/métodos
17.
MMWR Morb Mortal Wkly Rep ; 70(29): 1013-1019, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34292924

RESUMO

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.


Assuntos
COVID-19/epidemiologia , Influenza Humana/epidemiologia , Pandemias , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Humanos , Estados Unidos/epidemiologia
18.
Pain Med ; 22(8): 1743-1752, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-33690845

RESUMO

OBJECTIVE: Patients with sickle cell disease (SCD) face inconsistent effective analgesic management, leading to high inpatient healthcare utilization and significant financial burden for healthcare institutions. Current evidence does not provide guidance for inpatient management of acute pain in adults with sickle cell disease. We conducted a retrospective analysis of a longitudinal cohort quality improvement project to characterize the role of individualized care plans on improving patient care and reducing financial burden in high healthcare-utilizing patients with SCD-related pain. METHODS: Individualized care plans were developed for patients with hospital admissions resulting from pain associated with sickle cell disease. A 2-year prospective longitudinal cohort quality improvement project was performed and retrospectively analyzed. Primary outcome measure was duration of hospitalization. Secondary outcome measures included: pain intensity; 7, 30, and 90-day readmission rates; cost per day; total admissions; total cost per year; analgesic regimen at index admission; and discharge disposition. RESULTS: Duration of hospitalization, the primary outcome, significantly decreased by 1.23 days with no worsening of pain intensity scores. Seven-day readmission decreased by 34%. Use of intravenous hydromorphone significantly decreased by 25%. The potential cost saving was $1,398,827 as a result of this quality initiative. CONCLUSIONS: Implementation of individualized care plans reduced both admission rate and financial burden of high utilizing patients. Importantly, pain outcomes were not diminished. Results suggest that individualized care plans are a promising strategy for managing acute pain crisis in adult sickle cell patients from both care-focused and utilization outcomes.


Assuntos
Dor Aguda , Anemia Falciforme , Adulto , Anemia Falciforme/complicações , Hospitais , Humanos , Tempo de Internação , Estudos Prospectivos , Estudos Retrospectivos
19.
Mol Cell Proteomics ; 17(7): 1426-1431, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29118029

RESUMO

Here we present a free interactive web tool to process and visualize proteomics data sets with a single click. GiaPronto can process all proteomics quantification methods, i.e. label-free, SILAC and isobaric labeling, and analyze post-translational modifications (PTMs). The software performs normalization and statistics, assists determination of regulated proteins, biomarkers and Gene Ontology (GO) enrichment, and provides high resolution images and tables for further data analysis. We foresee that GiaPronto will become the most rapid and simple tool for assessing data quality and determining most relevant features of proteomic data sets. GiaPronto is available at giapronto.diskinlab.org.


Assuntos
Bases de Dados de Proteínas , Ontologia Genética , Proteômica/métodos , Software , Animais , Biomarcadores/metabolismo , Humanos , Controle de Qualidade , Estatística como Assunto , Interface Usuário-Computador
20.
Clin Exp Dermatol ; 45(5): 565-571, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31989656

RESUMO

BACKGROUND: Coexistence of hidradenitis suppurativa (HS) and amyloidosis has been anecdotally described, but the association between these conditions is yet to be firmly established. AIM: To study the association between HS and amyloidosis using a large-scale computerized database, and to perform a literature review to characterize all reported patients with coexistent HS and amyloidosis. METHODS: A cross-sectional study was conducted comparing the prevalence of amyloidosis among patients with HS and age-, sex- and ethnicity-matched healthy controls (HCs). Additionally, a review of literature was performed to summarize all reported cases with a dual diagnosis of both conditions. RESULTS: In total, 4417 patients with HS and 22 085 controls were included in the study. The prevalence of amyloidosis was increased in patients with HS compared with the HC group [n = 7 (0.2%) vs. n = 2 (0.0%), respectively; OR = 17.5; 95% CI 3.6-84.4; P < 0.001]. In a multivariate analysis, HS was still associated with amyloidosis (OR = 11.2; 95% CI 1.3-94.5; P = 0.03). The literature review identified nine patients who developed amyloidosis during the course of HS, with 44.4% eventually having renal failure. ‬Favourable outcomes were reported in patients managed by tumour necrosis factor (TNF)-α inhibitors. CONCLUSION: This study establishes the association between HS and amyloidosis. Screening for amyloidosis may be considered in patients with HS with a relevant clinical picture, mainly proteinuria. TNF-α inhibitors may be preferred in patients with a dual diagnosis of these conditions.


Assuntos
Amiloidose/complicações , Hidradenite Supurativa/complicações , Adulto , Idoso , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência
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