Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 79
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Surg Endosc ; 38(3): 1654-1661, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38326586

RESUMO

INTRODUCTION: There is a critical need for comprehensive surgical training in African countries given the unmet surgical burden of disease in this region. Collaborative and progressive initiatives in global surgical education will have the greatest impact on trainees. Little is known about surgical education needs from the perspective of practicing surgeons and trainees in low-middle-income countries (LMICs). Even less is known about the potential role for simulation to augment training. METHODS: A modified Delphi methodology with 2 rounds of responses was employed to survey program directors (PD) and associate program directors (APD) of Pan-African Association of Christian Surgeons (PAACS) general surgery residency programs across eight low-middle-income countries in Africa. 3 PD/APDs and 2 surgical residents participated in semi-structured interviews centered around the role of simulation in training. Descriptive analysis was performed to elicit key themes and illustrative examples. RESULTS: The survey of program directors revealed that teaching residents the psychomotor skills need to perform intracorporeal suturing was both high priority and desired in multiple training sites. Other high priority skills were laparoscopic camera driving and medial visceral rotation. The interviews revealed a specific desire to perform laparoscopic surgery and a need for a simulation curriculum to familiarize staff and trainees with laparoscopic techniques. Several barriers to laparoscopic surgery exist, such as lack of staff familiarity with the equipment, lack of public buy in, and lack of generalizable and adaptable educational modules. Trainees saw utility in the use of simulation to optimize time in the operating room and sought opportunities to improve their laparoscopic skills. CONCLUSION: Faculty and surgical trainees in LMICs have interest in learning advanced surgical techniques, such as laparoscopy. Developing a simulation curriculum tailored to the trainees' local context has the potential to fill this need.


Assuntos
Internato e Residência , Laparoscopia , Treinamento por Simulação , Cirurgiões , Humanos , Avaliação das Necessidades , Currículo , Escolaridade , Laparoscopia/educação , Competência Clínica , Simulação por Computador , Educação de Pós-Graduação em Medicina/métodos
2.
Surg Endosc ; 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39455451

RESUMO

BACKGROUND: Significant disparities exist in laparoscopic training opportunities for surgeons in low- and middle-income countries (LMICs). ALL-SAFE is an innovative, low-cost training system for LMIC surgeons' laparoscopic development. However, strategies to implement and scale ALL-SAFE are unstudied. We aimed to assess the impact of implementation science strategies on ALL-SAFE uptake in Liberia, a novel and low-resource context. METHODS: This study used implementation science approaches to evaluate ALL-SAFE uptake in three Liberian hospitals: John F. Kennedy Medical Center, Phebe, and ELWA. Five validated implementation strategies of program orientation, local champions, network weaving, feedback mechanisms, and practical supervision were piloted. All five strategies were implemented at two hospitals, while four strategies, excluding clinician supervision, were implemented at the final site as a pseudo-control, to evaluate the impact of resource-intensive supervision. Participants included surgical consultants, residents, and medical students. Engagement was assessed with mixed methods including participant number, practice hours, module completion rates, and strategy feasibility through end-user interviews. RESULTS: Across three hospitals, 33 participants used ALL-SAFE for 87.8 total training hours (5,268 min). Participant numbers varied across sites (NJFK = 20, 80%; NPhebe = 7, 88%; NELWA = 6, 86%), as did practice times (TotalJFK = 3,060 min, Median time/ParticipantJFK = 103 min; TotalPhebe = 1,434 min, Median time/ParticipantPhebe = 126 min; TotalELWA = 774 min, Median time/ParticipantELWA = 100 min). Sites with practical supervision demonstrated higher engagement than those without (P = 0.042). Interviews (n = 8) revealed positive perceptions toward program orientation, practical supervision, and network weaving. Participants recommended thirteen additional strategies for sustainability including translating ALL-SAFE skills to patient care. CONCLUSION: Our study is one of the first to evaluate implementation science strategies for laparoscopic training in sub-Saharan Africa. The implementation bundles of five validated strategies were considered feasible by Liberian surgeons in both urban and rural hospitals. Mixed methods suggested a positive association between engagement and the resource-intensive practical supervision strategy. Future studies should focus on quantifying individual strategy contributions with rigorous implementation designs and assessing sustainability strategies.

3.
World J Surg ; 48(10): 2421-2432, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39297811

RESUMO

BACKGROUND: Laparoscopy training remains inaccessible in many low- and middle-income countries, including Liberia. We assessed the availability of laparoscopy and feasibility of implementing a laparoscopic program among Liberian surgeons and trainees. METHODS: This mixed-methods study utilized a 32-item survey and semi-structured interviews on laparoscopic experience, knowledge, desires, barriers, patient perceptions, and training opportunities among surgeons and trainees at Liberia's two main teaching hospitals in March 2023. Data analysis utilized summed knowledge and desirability scores, descriptive statistics, and qualitative content analysis. RESULTS: 31 interns, residents, and consultants participated, comprising 60% of Liberia's surgeons. Laparoscopic training (32%) and experience (16%) was low, with exposure limited to those training outside Liberia (p = 0.001). While laparoscopy knowledge varied (29% low, 55% medium, 16% high), participants expressed high interest in training (100%) and willingness to pay (52%). Interviews revealed four themes: desires for training, patient acceptability, feasibility of technology-based training, and barriers including limited equipment and expert trainers. At the time of survey, the only minimally invasive surgeries ever performed in Liberia were two diagnostic laparoscopies. CONCLUSIONS: This is the first mixed-methods study assessing laparoscopy in Liberia. Our sample, though small, comprised approximately 60% of Liberian surgeons in both rural and urban hospitals. Findings demonstrated limited experience, variable knowledge, and high desires for training, showing feasibility for laparoscopy implementation in Liberia.


Assuntos
Laparoscopia , Libéria , Laparoscopia/educação , Humanos , Masculino , Feminino , Adulto , Cirurgiões/educação , Pessoa de Meia-Idade , Competência Clínica , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários
4.
Surg Endosc ; 37(9): 7170-7177, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37336843

RESUMO

BACKGROUND: Laparoscopic training remains inaccessible for surgeons in low- and middle-income countries, limiting its widespread adoption. We developed a novel tool for assessment of laparoscopic appendectomy skills through ALL-SAFE, a low-cost laparoscopy training system. METHODS: This pilot study in Ethiopia, Cameroon, and the USA assessed appendectomy skills using the ALL-SAFE training system. Performance measures were captured using the ALL-SAFE verification of proficiency tool (APPY-VOP), consisting of a checklist, modified Objective Structured Assessment of Technical Skills (m-OSATS), and final rating. Twenty participants, including novice (n = 11), intermediate (n = 8), and expert (n = 1), completed an online module covering appendicitis management and psychomotor skills in laparoscopic appendectomy. After viewing an expert skills demonstration video, participants recorded their performance within ALL-SAFE. Using the APPY-VOP, participants rated their own and three peer videos. We used the Kruskal-Wallis test and a Many-Facet Rasch Model to evaluate (i) capacity of APPY-VOP to differentiate performance levels, (ii) correlation among three APPY-VOP components, and (iii) rating differences across groups. RESULTS: Checklist scores increased from novice (M = 21.02) to intermediate (M = 23.64) and expert (M = 28.25), with differentiation between experts and novices, P = 0.005. All five m-OSATS domains and global summed, total summed, and final rating discriminated across all performance levels (P < 0.001). APPY-VOP final ratings adequately discriminated Competent (M = 2.0), Borderline (N = 1.8), and Not Competent (M = 1.4) performances, Χ2 (2,85) = 32.3, P = 0.001. There was a positive correlation between ALL-SAFE checklist and m-OSATS summed scores, r(83) = 0.63, P < 0.001. Comparison of ratings suggested no differences across expertise levels (P = 0.69) or location (P = 0.66). CONCLUSION: APPY-VOP effectively discriminated between novice and expert performance in laparoscopic appendectomy skills in a simulated setting. Scoring alignment across raters suggests consistent evaluation, independent of expertise. These results support the use of APPY-VOP among all skill levels inside a peer rating system. Future studies will focus on correlating proficiency to clinical practice and scaling ALL-SAFE to other settings.


Assuntos
Laparoscopia , Cirurgiões , Humanos , Projetos Piloto , Apendicectomia , Laparoscopia/educação , Cirurgiões/educação , Competência Clínica
5.
World J Surg ; 47(11): 2617-2625, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37689597

RESUMO

BACKGROUND: The SIMPL operative feedback tool is used in many U.S. surgical residency programs. However, the challenges of implementation and benefits of the web-based platform in low- and middle-income countries are unknown. The aim of this study was to evaluate implementation of SIMPL in a general surgery residency training program in Kenya. METHODS: SIMPL was pilot tested at Tenwek Hospital from January through December 2021. Participant perspectives of SIMPL were elicited through a survey and semi-structured interviews. Descriptive statistics were used to analyze survey data. Inductive qualitative content analysis of interview responses was performed by two independent researchers. RESULTS: Fourteen residents and six faculty (100% response rate) were included in the study and completed over 600 operative assessments. All respondents reported numerical evaluations and dictated feedback were useful. Respondents felt that SIMPL was easy to use, improved quality and frequency of feedback, helped refine surgical skills, and increased resident autonomy. Barriers to use included participants forgetting to complete evaluations, junior residents not submitting evaluations when minimally involved in cases, and technological challenges. Suggestions for improvement included expansion of SIMPL to surgical subspecialties and allowing senior residents to provide feedback to juniors. All respondents wanted to continue using SIMPL, and 90% recommended use at other programs. CONCLUSION: Residents and faculty at Tenwek Hospital believed SIMPL were a positive addition to their training program. There were a few barriers to use and suggestions for improvement specific to the training environment in Kenya, but this study demonstrates it is feasible to use SIMPL in settings outside the U.S. with the appropriate resources.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Smartphone , Retroalimentação , Quênia , Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Hospitais , Cirurgia Geral/educação
6.
Arch Phys Med Rehabil ; 103(9): 1874-1882, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533736

RESUMO

Health care delivery shifted and adapted with the COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2. Stroke care was negatively affected across the care continuum and may lead to poor community living outcomes in those who survived a stroke during the ongoing pandemic. For instance, delays in seeking care, changes in length of stays, and shifts in discharge patterns were observed during the pandemic. Those seeking care were younger and had more severe neurologic effects from stroke. Increased strain was placed on caregivers and public health efforts, and community-wide lockdowns, albeit necessary to reduce the spread of COVID-19, had detrimental effects on treatment and recommendations to support community living outcomes. The American Congress of Rehabilitation Medicine Stroke Interdisciplinary Special Interest Group Health and Wellness Task Force convened to (1) discuss international experiences in stroke care and rehabilitation and (2) review recently published literature on stroke care and outcomes during the pandemic. Based on the findings in the literature, the task force proposes recommendations and interdisciplinary approaches at the (1) institutional and societal level; (2) health care delivery level; and (3) individual and interpersonal level spanning across the care continuum and into the community.


Assuntos
COVID-19 , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Pandemias , Acidente Vascular Cerebral/epidemiologia
7.
Pediatr Radiol ; 52(7): 1314-1325, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35366073

RESUMO

BACKGROUND: Magnetic resonance (MR) elastography of the liver measures hepatic stiffness, which correlates with the histopathological staging of liver fibrosis. Conventional Cartesian gradient-echo (GRE) MR elastography requires breath-holding, which is challenging for children. Non-Cartesian radial free-breathing MR elastography is a potential solution to this problem. OBJECTIVE: To investigate radial free-breathing MR elastography for measuring hepatic stiffness in children. MATERIALS AND METHODS: In this prospective pilot study, 14 healthy children and 9 children with liver disease were scanned at 3 T using 2-D Cartesian GRE breath-hold MR elastography (22 s/slice) and 2-D radial GRE free-breathing MR elastography (163 s/slice). Each sequence was acquired twice. Agreement in the stiffness measurements was evaluated using Lin's concordance correlation coefficient (CCC) and within-subject mean difference. The repeatability was assessed using the within-subject coefficient of variation and intraclass correlation coefficient (ICC). RESULTS: Fourteen healthy children and seven children with liver disease completed the study. Median (±interquartile range) normalized measurable liver areas were 62.6% (±26.4%) and 44.1% (±39.6%) for scan 1, and 60.3% (±21.8%) and 43.9% (±44.2%) for scan 2, for Cartesian and radial techniques, respectively. Hepatic stiffness from the Cartesian and radial techniques had close agreement with CCC of 0.89 and 0.94, and mean difference of 0.03 kPa and -0.01 kPa, for scans 1 and 2. Cartesian and radial techniques achieved similar repeatability with within-subject coefficient of variation=1.9% and 3.4%, and ICC=0.93 and 0.92, respectively. CONCLUSION: In this pilot study, radial free-breathing MR elastography was repeatable and in agreement with Cartesian breath-hold MR elastography in children.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatias , Criança , Técnicas de Imagem por Elasticidade/métodos , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatias/patologia , Imageamento por Ressonância Magnética/métodos , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos Testes
8.
Hum Mol Genet ; 28(15): 2486-2500, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009944

RESUMO

Mutations in LMNA encoding lamin A/C and EMD encoding emerin cause cardiomyopathy and muscular dystrophy. Lmna null mice develop these disorders and have a lifespan of 7-8 weeks. Emd null mice show no overt pathology and have normal skeletal muscle but with regeneration defects. We generated mice with germline deletions of both Lmna and Emd to determine the effects of combined loss of the encoded proteins. Mice without lamin A/C and emerin are born at the expected Mendelian ratio, are grossly normal at birth but have shorter lifespans than those lacking only lamin A/C. However, there are no major differences between these mice with regards to left ventricular function, heart ultrastructure or electrocardiographic parameters except for slower heart rates in the mice lacking both lamin A/C and emerin. Skeletal muscle is similarly affected in both of these mice. Lmna+/- mice also lacking emerin live to at least 1 year and have no significant differences in growth, heart or skeletal muscle compared to Lmna+/- mice. Deletion of the mouse gene encoding lamina-associated protein 1 leads to prenatal death; however, mice with heterozygous deletion of this gene lacking both lamin A/C and emerin are born at the expected Mendelian ratio but had a shorter lifespan than those only lacking lamin A/C and emerin. These results show that mice with combined deficiencies of three interacting nuclear envelope proteins have normal embryonic development and that early postnatal defects are primarily driven by loss of lamin A/C or lamina-associated polypeptide 1 rather than emerin.


Assuntos
Proteínas de Transporte/genética , Coração/fisiopatologia , Lamina Tipo A/genética , Proteínas de Membrana/genética , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/genética , Mutação , Proteínas Nucleares/genética , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Haploinsuficiência , Masculino , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia
9.
Proc Natl Acad Sci U S A ; 115(25): 6494-6499, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29769331

RESUMO

This study exploits time, the relatively unexplored fourth dimension of gene regulatory networks (GRNs), to learn the temporal transcriptional logic underlying dynamic nitrogen (N) signaling in plants. Our "just-in-time" analysis of time-series transcriptome data uncovered a temporal cascade of cis elements underlying dynamic N signaling. To infer transcription factor (TF)-target edges in a GRN, we applied a time-based machine learning method to 2,174 dynamic N-responsive genes. We experimentally determined a network precision cutoff, using TF-regulated genome-wide targets of three TF hubs (CRF4, SNZ, and CDF1), used to "prune" the network to 155 TFs and 608 targets. This network precision was reconfirmed using genome-wide TF-target regulation data for four additional TFs (TGA1, HHO5/6, and PHL1) not used in network pruning. These higher-confidence edges in the GRN were further filtered by independent TF-target binding data, used to calculate a TF "N-specificity" index. This refined GRN identifies the temporal relationship of known/validated regulators of N signaling (NLP7/8, TGA1/4, NAC4, HRS1, and LBD37/38/39) and 146 additional regulators. Six TFs-CRF4, SNZ, CDF1, HHO5/6, and PHL1-validated herein regulate a significant number of genes in the dynamic N response, targeting 54% of N-uptake/assimilation pathway genes. Phenotypically, inducible overexpression of CRF4 in planta regulates genes resulting in altered biomass, root development, and 15NO3- uptake, specifically under low-N conditions. This dynamic N-signaling GRN now provides the temporal "transcriptional logic" for 155 candidate TFs to improve nitrogen use efficiency with potential agricultural applications. Broadly, these time-based approaches can uncover the temporal transcriptional logic for any biological response system in biology, agriculture, or medicine.


Assuntos
Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Redes Reguladoras de Genes/genética , Nitrogênio/metabolismo , Transcrição Gênica/genética , Proteínas de Arabidopsis/genética , Perfilação da Expressão Gênica/métodos , Lógica , Ligação Proteica/genética , Transdução de Sinais/genética , Fatores de Transcrição/genética
10.
Pediatr Emerg Care ; 37(5): e230-e235, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30095596

RESUMO

OBJECTIVES: The objectives of this study were to assess the ability of pediatric health care providers and social workers to recognize sentinel injuries in infants under 6 months of age and to determine what factors influence their decision to evaluate for physical abuse. METHODS: A statewide collaborative focused on sentinel injuries administered a survey to pediatric health care providers and social workers in the emergency department, urgent care, and primary care. The survey contained 8 case scenarios of infants under 6 months of age with an injury, and respondents were asked if they would consider the injury to be a sentinel injury requiring a physical abuse evaluation. Respondents were then presented with several factors and asked how much each influences the decision to perform a physical abuse evaluation. RESULTS: A total of 565 providers completed the survey. Providers had moderate interrater reliability on their classification of the cases as sentinel injuries or not (κ = 0.57). Nearly all respondents (97%) recognized genital bruising as a sentinel injury, whereas 77% of respondents recognized intraoral injuries. Agreement was highest among social workers (κ = 0.76) and physicians with categorical pediatrics training and pediatric emergency medicine fellowship (κ = 0.63) and lowest among nurse practitioners (κ = 0.48) and residents (κ = 0.51). Concern over missing the diagnosis of abuse had the greatest influence on the decision to perform a physical abuse evaluation. CONCLUSIONS: Sentinel injuries are not uniformly recognized as potential signs of child abuse requiring further evaluation by pediatric health care providers. Additional evidence and education are needed regarding sentinel injuries.


Assuntos
Maus-Tratos Infantis , Contusões , Criança , Maus-Tratos Infantis/diagnóstico , Serviço Hospitalar de Emergência , Humanos , Lactente , Abuso Físico , Reprodutibilidade dos Testes
11.
J Virol ; 93(9)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30787156

RESUMO

Reactivation of herpes simplex virus 2 (HSV-2) from latency causes viral shedding that develops into recurrent genital lesions. The immune mechanisms of protection against recurrent genital herpes remain to be fully elucidated. In this preclinical study, we investigated the protective therapeutic efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed HSV-2 envelope and tegument proteins. These viral protein antigens (Ags) were rationally selected for their ability to recall strong CD4+ and CD8+ T-cell responses from naturally "protected" asymptomatic individuals, who, despite being infected, never develop any recurrent herpetic disease. Out of the eight HSV-2 proteins, the envelope glycoprotein D (gD), the tegument protein VP22 (encoded by the UL49 gene), and ribonucleotide reductase subunit 2 protein (RR2; encoded by the UL40 gene) produced significant protection against recurrent genital herpes. The RR2 protein, delivered either intramuscularly or intravaginally with CpG and alum adjuvants, (i) boosted the highest neutralizing antibodies, which appear to cross-react with both gB and gD, and (ii) enhanced the numbers of functional gamma interferon (IFN-γ)-producing CRTAM+ CFSE+ CD4+ and CRTAM+ CFSE+ CD8+ TRM cells, which express low levels of PD-1 and TIM-3 exhaustion markers and were localized to healed sites of the vaginal mucocutaneous (VM) tissues. The strong B- and T-cell immunogenicity of the RR2 protein was associated with a significant decrease in virus shedding and a reduction in both the severity and frequency of recurrent genital herpes lesions. In vivo depletion of either CD4+ or CD8+ T cells significantly abrogated the protection. Taken together, these preclinical results provide new insights into the immune mechanisms of protection against recurrent genital herpes and promote the tegument RR2 protein as a viable candidate Ag to be incorporated in future genital herpes therapeutic mucosal vaccines.IMPORTANCE Recurrent genital herpes is one of the most common sexually transmitted diseases, with a global prevalence of HSV-2 infection predicted to be over 536 million worldwide. Despite the availability of many intervention strategies, such as sexual behavior education, barrier methods, and the costly antiviral drug treatments, eliminating or at least reducing recurrent genital herpes remains a challenge. Currently, no FDA-approved therapeutic vaccines are available. In this preclinical study, we investigated the immunogenicity and protective efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed herpes envelope and tegument proteins. We discovered that similar to the dl5-29 vaccine, based on a replication-defective HSV-2 mutant virus, which has been recently tested in clinical trials, the RR2 protein-based subunit vaccine elicited a significant reduction in virus shedding and a decrease in both the severity and frequency of recurrent genital herpes sores. This protection correlated with an increase in numbers of functional tissue-resident IFN-γ+ CRTAM+ CFSE+ CD4+ and IFN-γ+ CRTAM+ CFSE+ CD8+ TRM cells that infiltrate healed sites of the vaginal tissues. Our study sheds new light on the role of TRM cells in protection against recurrent genital herpes and promotes the RR2-based subunit therapeutic vaccine to be tested in the clinic.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Herpes Genital/prevenção & controle , Herpesvirus Humano 2/imunologia , Vacinas contra Herpesvirus/farmacologia , Imunização Secundária , Ribonucleotídeo Redutases/farmacologia , Adulto , Idoso , Animais , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Feminino , Cobaias , Herpes Genital/imunologia , Herpes Genital/patologia , Vacinas contra Herpesvirus/imunologia , Humanos , Imunidade nas Mucosas/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Ribonucleotídeo Redutases/imunologia
12.
J Immunol ; 200(8): 2915-2926, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29549178

RESUMO

Circulating conventional memory CD8+ T cells (i.e., the CD8+ effector memory T [TEM] cell and CD8+ central memory T [TCM] cell subsets) and the noncirculating CD8+ tissue-resident memory T (TRM) cell subset play a critical role in mucosal immunity. Mucosal chemokines, including the recently discovered CXCL17, are also important in mucosal immunity because they are homeostatically expressed in mucosal tissues. However, whether the CXCL17 chemokine contributes to the mobilization of memory CD8+ T cell subsets to access infected mucosal tissues remains to be elucidated. In this study, we report that after intravaginal HSV type 1 infection of B6 mice, we detected high expression levels of CXCL17 and increased numbers of CD44highCD62LlowCD8+ TEM and CD103highCD8+ TRM cells expressing CXCR8, the cognate receptor of CXCL17, in the vaginal mucosa (VM) of mice with reduced genital herpes infection and disease. In contrast to wild-type B6 mice, the CXCL17-/- mice developed 1) fewer CXCR8+CD8+ TEM and TRM cells associated with more virus replication in the VM and more latency established in dorsal root ganglia, and 2) reduced numbers and frequencies of functional CD8+ T cells in the VM. These findings suggest that the CXCL17/CXCR8 chemokine pathway plays a crucial role in mucosal vaginal immunity by promoting the mobilization of functional protective CD8+ TEM and CD8+ TRM cells, within this site of acute and recurrent herpes infection.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Quimiocinas CXC/imunologia , Herpes Genital/imunologia , Imunidade nas Mucosas/imunologia , Vagina/imunologia , Animais , Quimiotaxia de Leucócito/imunologia , Feminino , Memória Imunológica/imunologia , Camundongos , Subpopulações de Linfócitos T/imunologia
13.
J Virol ; 92(16)2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29899087

RESUMO

Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea, causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull vaccine was tested in a human leukocyte antigen (HLA) transgenic rabbit model of ocular herpes (HLA Tg rabbits). Three peptide epitopes were selected, from the HSV-1 membrane glycoprotein C (UL44400-408), the DNA replication binding helicase (UL9196-204), and the tegument protein (UL25572-580), all preferentially recognized by CD8+ T cells from "naturally protected" HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were immunized with a mixture of these three ASYMP CD8+ T cell peptide epitopes (UL44400-408, UL9196-204, and UL25572-580), which were delivered subcutaneously with CpG2007 adjuvant (prime). Fifteen days later, half of the rabbits received a topical ocular treatment with a recombinant neurotropic adeno-associated virus type 8 (AAV8) vector expressing the T cell-attracting CXCL10 chemokine (pull). The frequency and function of HSV-specific CD8+ T cells induced by the prime/pull vaccine were assessed in the peripheral blood, cornea, and trigeminal ganglion (TG). Compared to the cells generated in response to peptide immunization alone, the peptide/CXCL10 prime/pull vaccine generated frequent polyfunctional gamma interferon-positive (IFN-γ+) CD107+ CD8+ T cells that infiltrated both the cornea and TG. CD8+ T cell mobilization into the cornea and TG of prime/pull-vaccinated rabbits was associated with a significant reduction in corneal herpesvirus infection and disease following an ocular HSV-1 (strain McKrae) challenge. These findings draw attention to the novel prime/pull vaccine strategy for mobilizing antiviral CD8+ T cells into tissues to protect against herpesvirus infection and disease.IMPORTANCE There is an urgent need for a vaccine against widespread herpes simplex virus infections. The present study demonstrates that immunization of HLA transgenic rabbits with a peptide/CXCL10 prime/pull vaccine triggered mobilization of HSV-specific CD8+ T cells locally into the cornea and TG, the sites of acute and latent herpesvirus infections, respectively. Mobilization of antiviral CD8+ T cells into the cornea and TG of rabbits that received the prime/pull vaccine was associated with protection against ocular herpesvirus infection and disease following an ocular HSV-1 challenge. These results highlight the importance of the prime/pull vaccine strategy to bolster the number and function of protective CD8+ T cells within infected tissues.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Quimiocina CXCL10/metabolismo , Córnea/imunologia , Vacinas contra o Vírus do Herpes Simples/imunologia , Ceratite Herpética/prevenção & controle , Subpopulações de Linfócitos T/imunologia , Gânglio Trigeminal/imunologia , Animais , Animais Geneticamente Modificados , Quimiocina CXCL10/administração & dosagem , Modelos Animais de Doenças , Epitopos/imunologia , Antígenos HLA/genética , Antígenos HLA/metabolismo , Vacinas contra o Vírus do Herpes Simples/administração & dosagem , Humanos , Interferon gama/análise , Ceratite Herpética/patologia , Ceratite Herpética/virologia , Proteína 1 de Membrana Associada ao Lisossomo/análise , Coelhos , Simplexvirus/imunologia , Simplexvirus/isolamento & purificação , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Carga Viral
14.
Am J Occup Ther ; 73(4): 7304345040p1-7304345040p9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31318681

RESUMO

IMPORTANCE: Effective treatment of the affected hand after stroke is crucial for improved functional independence and recovery. OBJECTIVE: To determine the feasibility and clinical utility of an electromyography-triggered hand robot. DESIGN: Single-group repeated-measures design. Participants completed training 3×/wk for 6 wk. Feasibility data included participant feedback, adverse events, and compliance rates. Upper extremity outcomes were collected at baseline, discharge, and 6-wk follow-up. SETTING: Outpatient clinic. PARTICIPANTS: Twelve stroke survivors at least 6 mo poststroke living in the community. INTERVENTION: Eighteen sessions of intensive robotic hand therapy over 6 wk. Each 60-min treatment session was personalized to match the participant's ability. OUTCOMES AND MEASURES: Arm Motor Ability Test (AMAT), Stroke Impact Scale Hand subscale (SIS-H), Stroke Upper Limb Capacity Scale (SULCS), Fugl-Meyer Assessment, Box and Block Test, and dynamometer. RESULTS: All participants completed the training phase. Mild skin pinching or rubbing at dorsal proximal interphalangeal joint and proximal arm fatigue were the most common adverse events. Improvements in raw scores were achieved from baseline to discharge for all outcome measures, except the SULCS. Participants significantly improved from baseline to discharge on the AMAT and the SIS-H, and improvements were maintained at 6-wk follow-up. CONCLUSION AND RELEVANCE: Robotic hand training was feasible, safe, and well tolerated. Participants reported and demonstrated improvements in functional use of the affected arm. Thirty percent of participants achieved clinically significant improvements on the AMAT. We recommend further study of the device in a larger study using the AMAT as a primary outcome measure. WHAT THIS ARTICLE ADDS: It is feasible and safe to implement a robotic hand training protocol for people with moderate to severe arm impairment in an outpatient setting. Robotic training may provide a viable option for this group to actively participate in intensive training of the distal hand.


Assuntos
Eletromiografia/métodos , Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estudos de Viabilidade , Humanos , Resultado do Tratamento , Extremidade Superior
15.
J Infect Dis ; 215(7): 1117-1123, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28498996

RESUMO

Background: Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI after engraftment. Methods: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed from each sample. Bacterial taxa with protective effects against development of CDI were identified by means of linear discriminant analysis effect size analysis and then further assessed with clinical predictors of CDI using survival analysis. Results: A total of 234 allo-HSCT recipients were studied; postengraftment CDI developed in 53 (22.6%). Within the composition of the microbiota, the presence of 3 distinct bacterial taxa was correlated with protection against CDI: Bacteroidetes, Lachnospiraceae, and Ruminococcaceae. Colonization with these groups at engraftment was associated with a 60% lower risk of CDI, independent of clinical factors. Conclusions: Colonization with these 3 bacterial groups is associated with a lower risk of CDI. These groups have been shown to be vital components of the intestinal microbiota. Targeted efforts to maintain them may help minimize the risk of CDI in this at-risk population.


Assuntos
Infecções por Clostridium/microbiologia , Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Bacteroidetes/classificação , Bacteroidetes/isolamento & purificação , Clostridiales/classificação , Clostridiales/isolamento & purificação , Clostridioides difficile , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , RNA Ribossômico 16S/genética , Transplante Homólogo
16.
PLoS Pathog ; 11(9): e1005132, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26334306

RESUMO

Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.


Assuntos
Enterite/microbiologia , Enterococcus faecium/fisiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Mucosa Intestinal/microbiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/fisiologia , Enterococos Resistentes à Vancomicina/fisiologia , Ampicilina/efeitos adversos , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Contagem de Colônia Microbiana , Farmacorresistência Bacteriana , Enterite/patologia , Enterite/prevenção & controle , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/crescimento & desenvolvimento , Enterococcus faecium/isolamento & purificação , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/patologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Interações Hospedeiro-Patógeno , Hibridização in Situ Fluorescente , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Infecções por Klebsiella/patologia , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento , Klebsiella pneumoniae/isolamento & purificação , Camundongos Endogâmicos C57BL , Interações Microbianas , Organismos Livres de Patógenos Específicos , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/crescimento & desenvolvimento , Enterococos Resistentes à Vancomicina/isolamento & purificação
17.
Arch Phys Med Rehabil ; 98(10): 1924-1931, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28652064

RESUMO

OBJECTIVE: To compare the long-term effects of external focus (EF) and internal focus (IF) of attention after 4 weeks of arm training. DESIGN: Randomized, repeated-measures, mixed analysis of variance. SETTING: Outpatient clinic. PARTICIPANTS: Individuals with stroke and moderate-to-severe arm impairment living in the community (N=33; withdrawals: n=3). INTERVENTIONS: Four-week arm training protocol on a robotic device (12 sessions). MAIN OUTCOME MEASURES: Joint independence, Fugl-Meyer Assessment, and Wolf Motor Function Test measured at baseline, discharge, and 4-week follow-up. RESULTS: There were no between-group effects for attentional focus. Participants in both groups improved significantly on all outcome measures from baseline to discharge and maintained those changes at 4-week follow-up regardless of group assignment (joint independence EF condition: F1.6,45.4=17.74; P<.0005; partial η2=.39; joint independence IF condition: F2,56=18.66; P<.0005; partial η2=.40; Fugl-Meyer Assessment: F2,56=27.83; P<.0005; partial η2=.50; Wolf Motor Function Test: F2,56=14.05; P<.0005; partial η2=.35). CONCLUSIONS: There were no differences in retention of motor skills between EF and IF participants 4 weeks after arm training, suggesting that individuals with moderate-to-severe arm impairment may not experience the advantages of an EF found in healthy individuals. Attentional focus is most likely not an active ingredient for retention of trained motor skills for individuals with moderate-to-severe arm impairment, whereas dosage and intensity of practice appear to be pivotal. Future studies should investigate the long-term effects of attentional focus for individuals with mild arm impairment.


Assuntos
Atenção , Paresia/reabilitação , Robótica , Reabilitação do Acidente Vascular Cerebral/métodos , Extremidade Superior/fisiopatologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/fisiopatologia , Retenção Psicológica
18.
Arch Phys Med Rehabil ; 96(12): 2243-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26189202

RESUMO

OBJECTIVE: To investigate the feasibility of a combined clinic-home intervention using a robotic elbow brace and, secondarily, to collect preliminary data on the efficacy of this clinic-home intervention. DESIGN: Nonrandomized pre-/postinterventional study. SETTING: Outpatient clinic and participants' homes. PARTICIPANTS: Individuals at least 6 months after stroke (N=11; 5 women and 6 men; mean age, 51.7y; mean time since stroke, 7.6y; mean Fugl-Meyer Assessment of the Upper Extremity [FMA-UE] score, 22 of 66) were enrolled from the community. INTERVENTIONS: Participants received training in an outpatient clinic from an experienced occupational therapist to gain independence with use of the device (3-9 sessions) followed by a 6-week home program using the device at home. MAIN OUTCOME MEASURES: Five instruments were administered before and after the study intervention: Modified Ashworth Scale, Box and Blocks test, FMA-UE, Arm Motor Ability Test, and Motor Activity Log-Amount of Use and Motor Activity Log-How Well subscales (MAL-AOU, MAL-HW). RESULTS: Nine participants completed the study. Participants used the device on average 42.9min/d, 5.3d/wk. The FMA-UE (t=3.32; P=.01), MAL-AOU (t=4.40; P=.002), and MAL-HW (t=4.02; P=.004) scores showed statistically significant improvement from baseline to discharge; the MAL-AOU (t=2.61; P=.035) and MAL-HW (t=2.47; P=.043) scores were also significantly improved from baseline to 3-month follow-up. CONCLUSIONS: This combined clinic-home intervention was feasible and effective. Participants demonstrated improvements in arm impairment and self-reported use of the arm from baseline to discharge; they continued to report significant improvement in actual use of the arm at 3-month follow-up.


Assuntos
Terapia Ocupacional/métodos , Aparelhos Ortopédicos , Paresia/reabilitação , Robótica , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Recuperação de Função Fisiológica
19.
Am J Surg ; : 115946, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39289129

RESUMO

Though a key component of the surgical training paradigm envisioned by Halstead and critical for the generation of future surgeons, teaching surgery is increasingly challenging. The qualities and practices of effective educators have been published and can be acquired through practice. Teaching allows us to connect with our learners and the larger surgical community.

20.
Am Surg ; 90(3): 350-355, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37681457

RESUMO

BACKGROUND: Necessitated by the COVID-19 pandemic, virtual care is now a fixture in health care delivery. Literature describes the pivot to virtual clinical education; however, less is known about the learner experience. Understanding perspectives of medical students and residents provides insight to optimize the educational experience in virtual care. METHODS: Third-year medical students and general surgery residents at an academic teaching institution rated their experience of virtual clinic compared to in-person clinic through an anonymous 20-question survey. Questions were on a 5-point Likert scale with narrative opportunities and queried 4 learner objectives: patient care, systems-based practice, education, and faculty engagement. Medical student and resident responses were compared using a t-test. RESULTS: Lowest rated items included the ability to perform an accurate physical exam, engage with faculty, promote efficiency, and learn clinical skills. Residents gave lower ratings than medical students on all questions. There were significant differences between medical students and residents (P < .05) in actively participating in patient care, obtaining patient history, having adequate time for patient history, and facilitating efficiency. Narrative themes included faculty variability, virtual visits as additive but insufficient to replace in-person visits, and the importance of being in the same physical space or Zoom Room as faculty. DISCUSSION: Learners perceive the ability to perform a physical exam, promote efficiency, and engage with faculty to be compromised in the virtual clinic setting. Residents had less favorable perceptions of virtual clinic compared to medical students. Faculty should consider these varying learner perceptions to optimize the educational environment in virtual care.


Assuntos
Educação Médica , Internato e Residência , Estudantes de Medicina , Humanos , Pandemias , Exame Físico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA