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1.
Cell ; 185(24): 4507-4525.e18, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36356582

RESUMO

The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. tuberculosis (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. We found that the causal strain carried an ancestral full-length version of the type VII-secreted effector EsxM rather than the truncated version present in other modern Mtb lineages. The ancestral EsxM variant exacerbated dissemination through enhancement of macrophage motility, increased egress of macrophages from established granulomas, and alterations in macrophage actin dynamics. Reconstitution of the ancestral version of EsxM in an attenuated modern strain of Mtb altered the migratory mode of infected macrophages, enhancing their motility. In a zebrafish model, full-length EsxM promoted bone disease. The presence of a derived nonsense variant in EsxM throughout the major Mtb lineages 2, 3, and 4 is consistent with a role for EsxM in regulating the extent of dissemination.


Assuntos
Doenças Ósseas , Mycobacterium marinum , Mycobacterium tuberculosis , Tuberculose , Animais , Humanos , Peixe-Zebra , Tuberculose/microbiologia , Macrófagos/microbiologia , Proteínas de Bactérias/genética
2.
Immunity ; 45(4): 861-876, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27760340

RESUMO

Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures. We identified fundamental macrophage reprogramming events that parallel E-cadherin-dependent mesenchymal-epithelial transitions. Macrophage-specific disruption of E-cadherin function resulted in disordered granuloma formation, enhanced immune cell access, decreased bacterial burden, and increased host survival, suggesting that the granuloma can also serve a bacteria-protective role. Granuloma macrophages in humans with tuberculosis were similarly transformed. Thus, during mycobacterial infection, granuloma macrophages are broadly reprogrammed by epithelial modules, and this reprogramming alters the trajectory of infection and the associated immune response.


Assuntos
Epitélio/imunologia , Macrófagos/imunologia , Mycobacterium marinum/imunologia , Animais , Caderinas/imunologia , Epitélio/microbiologia , Granuloma/imunologia , Granuloma/microbiologia , Macrófagos/microbiologia , Mycobacterium tuberculosis/imunologia , Peixe-Zebra
3.
Support Care Cancer ; 32(3): 184, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393418

RESUMO

PURPOSE: This study provides an updated evaluation of the prevalence and severity of acute cancer-related symptoms and quality of life (QOL) concerns among patients treated with emetogenic chemotherapy. METHODS: Patients were recruited to a larger, multi-site observational study prior to starting chemotherapy. Participants completed sociodemographic questionnaires and clinical data were abstracted via medical record review. Symptoms and QOL were assessed 5 days after starting moderately or highly emetogenic chemotherapy. Functional Assessment of Cancer Therapy - General assessed QOL concerns. Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events evaluated symptoms. Symptoms were considered severe when participants responded "severe" or "very severe." RESULTS: Participants (N = 1174) were on average 58 ± 13 years, mostly female (73%), non-Hispanic (89%), and White (87%). Most participants were diagnosed with breast (38.1%), gynecological (20%), and gastrointestinal (17.1%) cancer. The most common QOL concerns of any severity were fatigue (94%), anhedonia (89%), dissatisfaction with QOL (86%), and sleep disturbance (86%). The most common severe QOL concerns were anhedonia (44%), fatigue (40%), and inability to work (38%). Decreased appetite (74%), pain (71%), and constipation (70%) were the most common symptoms of any severity, as well as most common severe symptoms (13%, 18%, and 18%, respectively). CONCLUSION: Herein, updates are provided in regard to QOL concerns and symptoms reported by patients in the days after chemotherapy and demonstrates that concerns and symptoms have shifted in the last decade.


Assuntos
Neoplasias , Qualidade de Vida , Feminino , Humanos , Masculino , Anedonia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Pessoa de Meia-Idade , Idoso
4.
Nutr Neurosci ; 27(5): 451-459, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37183583

RESUMO

OBJECTIVES: To investigate the gut-brain axis, we explored the relationships among mood disturbance (MD), diet quality (DQ), and fecal microbiota in free-living adults. METHODS: A cross-sectional analysis was conducted with data from 75 healthy adults enrolled in two studies. Anthropometrics, 16s rRNA gene sequencing of fecal microbes, DQ as assessed by Healthy Eating Index-2015 (HEI), and MD determined by Profile of Mood States (POMS) were included. Alpha-diversity and DQ differences were explored between low (n = 37) and high MD (n = 38) groups. Spearman correlations were used to investigate relationships between alpha-diversity, DQ, and POMS subscales. Moderation analysis explored the effect of HEI score on the relationship between MD and alpha-diversity. RESULTS: Participants were mostly white (67%), 54.5 years old (±11.8), and overweight (28.5 ± 6.5 kg/m2). Shannon and Simpson indices indicate higher alpha-diversity in participants with low MD compared to high MD (p = 0.004 and p = 0.008, respectively). Simpson and Shannon indices were correlated with subscale of anger (rho = -0.303, p = 0.011; rho = -0.265, p = 0.027, respectively)and total MD (rho = -0.404, p = 0.001; rho = -0.357, p = 0.002, respectively). Refined grains were associated with fatigue and tension subscales (rho = 0.428, p < 0.001; rho = 0.302, p = 0.014, respectively). DQ did not significantly moderate the relationship between alpha-diversity and mood disturbance (F(7, 53) = 2.00, p = 0.072, R2 = 0.209). Shannon index was a significant predictor of MD (b = -4.39, t(53) = -2.55, p = 0.014), but total HEI score and the interaction (Shannon index*HEI score) were not significant. DISCUSSION: Greater bacterial diversity was associated with lower MD, and DQ was associated with various mood state subscales in this sample of adults.


Assuntos
Dieta , Microbiota , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Transversais , RNA Ribossômico 16S/genética , Sobrepeso
5.
Neonatal Netw ; 43(4): 224-233, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39164095

RESUMO

The controversial topic of oral feeding while on noninvasive ventilation remains at the forefront of preterm intensive care management. The intersection of pulmonary, neurologic, and gastrointestinal maturation coalesces at a postmenstrual age that requires changes in practices compared with those used in older infants. Various animal models in the past decades aimed to gain physiological knowledge of noninvasive ventilation effects on the suck-swallow-breathe coordination sequence. However, the preterm infant poses nuanced anatomic challenges. Although concerns for oral feeding while on noninvasive ventilation include aspiration risks and potential inpatient obstacles, there is evidence to support the feasibility, initiation, and progression of oral feedings while an infant is supported on high-flow nasal cannula and continuous positive airway pressure. There is evidence to support that this may accelerate attainment of oral feeding milestones and, thus, eventual hospital discharge. More recent multidisciplinary institutional protocols may provide cautious guidance on evaluation and algorithms to assess infants who may benefit from initiation and advancement of oral feeding versus awaiting further maturation.


Assuntos
Alimentação com Mamadeira , Recém-Nascido Prematuro , Ventilação não Invasiva , Humanos , Recém-Nascido , Ventilação não Invasiva/métodos , Alimentação com Mamadeira/métodos
6.
Crit Care Med ; 51(11): 1492-1501, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37246919

RESUMO

OBJECTIVES: Effective interventions to prevent diagnostic error among critically ill children should be informed by diagnostic error prevalence and etiologies. We aimed to determine the prevalence and characteristics of diagnostic errors and identify factors associated with error in patients admitted to the PICU. DESIGN: Multicenter retrospective cohort study using structured medical record review by trained clinicians using the Revised Safer Dx instrument to identify diagnostic error (defined as missed opportunities in diagnosis). Cases with potential errors were further reviewed by four pediatric intensivists who made final consensus determinations of diagnostic error occurrence. Demographic, clinical, clinician, and encounter data were also collected. SETTING: Four academic tertiary-referral PICUs. PATIENTS: Eight hundred eighty-two randomly selected patients 0-18 years old who were nonelectively admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 882 patient admissions, 13 (1.5%) had a diagnostic error up to 7 days after PICU admission. Infections (46%) and respiratory conditions (23%) were the most common missed diagnoses. One diagnostic error caused harm with a prolonged hospital stay. Common missed diagnostic opportunities included failure to consider the diagnosis despite a suggestive history (69%) and failure to broaden diagnostic testing (69%). Unadjusted analysis identified more diagnostic errors in patients with atypical presentations (23.1% vs 3.6%, p = 0.011), neurologic chief complaints (46.2% vs 18.8%, p = 0.024), admitting intensivists greater than or equal to 45 years old (92.3% vs 65.1%, p = 0.042), admitting intensivists with more service weeks/year (mean 12.8 vs 10.9 wk, p = 0.031), and diagnostic uncertainty on admission (77% vs 25.1%, p < 0.001). Generalized linear mixed models determined that atypical presentation (odds ratio [OR] 4.58; 95% CI, 0.94-17.1) and diagnostic uncertainty on admission (OR 9.67; 95% CI, 2.86-44.0) were significantly associated with diagnostic error. CONCLUSIONS: Among critically ill children, 1.5% had a diagnostic error up to 7 days after PICU admission. Diagnostic errors were associated with atypical presentations and diagnostic uncertainty on admission, suggesting possible targets for intervention.


Assuntos
Estado Terminal , Unidades de Terapia Intensiva Pediátrica , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Cuidados Críticos , Estado Terminal/epidemiologia , Erros de Diagnóstico , Prevalência , Estudos Retrospectivos
7.
Psychosom Med ; 85(9): 813-819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37678326

RESUMO

OBJECTIVE: Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic hematopoietic cell transplant (HCT). METHODS: Blood was collected from patients and their donors before HCT. Patients completed self-report measures of depression and fatigue before HCT (T1), 90 days post-HCT (T2), and 1 year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate-adjusted p value of <.05. RESULTS: The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time ( p values of > .41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 ( p = 3.0 × 10 -4 ) and rs6311 ( p = 2.0 × 10 -4 ) in HTR2A . Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 ( p = 6.0 × 10 -5 ) and a patient-donor interaction at rs1885884 in HTR2A ( p < 1.0 × 10 -4 ). CONCLUSIONS: Data suggest that variants in genes regulating the serotonergic system ( HTR2A ) and lipid metabolism ( SORL1 ) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients' own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Depressão/genética , Projetos Piloto , Transplante Homólogo , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Fadiga/genética , Células Germinativas , Proteínas Relacionadas a Receptor de LDL , Proteínas de Membrana Transportadoras
8.
Vet Res ; 53(1): 77, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195961

RESUMO

Bovine respiratory disease (BRD) dramatically affects young calves, especially in fattening facilities, and is difficult to understand, anticipate and control due to the multiplicity of factors involved in the onset and impact of this disease. In this study we aimed to compare the impact of farming practices on BRD severity and on antimicrobial usage. We designed a stochastic individual-based mechanistic BRD model which incorporates not only the infectious process, but also clinical signs, detection methods and treatment protocols. We investigated twelve contrasted scenarios which reflect farming practices in various fattening systems, based on pen sizes, risk level, and individual treatment vs. collective treatment (metaphylaxis) before or during fattening. We calibrated model parameters from existing observation data or literature and compared scenario outputs regarding disease dynamics, severity and mortality. The comparison of the trade-off between cumulative BRD duration and number of antimicrobial doses highlighted the added value of risk reduction at pen formation even in small pens, and acknowledges the interest of collective treatments for high-risk pens, with a better efficacy of treatments triggered during fattening based on the number of detected cases.


Assuntos
Anti-Infecciosos , Complexo Respiratório Bovino , Doenças Respiratórias , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Complexo Respiratório Bovino/diagnóstico , Complexo Respiratório Bovino/tratamento farmacológico , Complexo Respiratório Bovino/prevenção & controle , Bovinos , Fazendas , Doenças Respiratórias/veterinária
9.
BMC Gastroenterol ; 22(1): 184, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413837

RESUMO

BACKGROUND: Zonulin is observed in animal models to regulate intestinal permeability and influenced by dietary intake, gut microbiota, and inflammation. We conducted a secondary analysis of a randomized controlled crossover trial (NCT03582306) in individuals with a BMI greater than 30 kg/m2 and high habitual red meat intake and low habitual green leafy vegetable (GLV) intake. METHODS: Participants were provided with frozen GLV during the first or last four weeks (immediate or delayed intervention) of the twelve-week trial. Biological and anthropometric measures were taken at the beginning and at each four-week interval. A subset of 20 participants was selected for this secondary analysis of the intestinal permeability and inflammation-related biomarkers: serum and fecal zonulin; serum lipopolysaccharide binding protein (LBP), Alpha-1-acid glycoprotein 1 (ORM-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and C-reactive protein; 8-hydroxy-2'-deoxyguanosine (8OHdG) and plasma Vitamin K1 as a marker of protocol adherence. Nutrient and food group intake from two-24-h dietary recalls collected at each time point were assessed. Fecal microbiota was measured by 16 s rRNA PCR sequencing. Changes in biological markers, dietary factors, and microbial taxa were assessed with Wilcoxon Sign Ranks Tests. Exploratory analyses of the relationship between changes in outcome variables were conducted with Spearman correlations. RESULTS: No changes in serum and fecal zonulin and serum LBP were observed. Plasma Vitamin K (p = 0.005) increased, while plasma 8OHdG (p = 0.023) decreased during the intervention compared to the control. The only dietary factors that changed significantly were increases during intervention in Vitamin K and Dark GLV (p < 0.001 for both) compared to control. Fecal microbiota did not change significantly across all times points; however, change in serum zonulin was associated with change in Proteobacteria (ρ = - 0.867, p = 0.001) in females and Bifidobacterium (ρ = - 0.838, p = 0.009) and Bacteroidaceae (ρ = 0.871, p = 0.005) in men. CONCLUSIONS: A high GLV dietary intervention increased serum zonulin levels and had no effect on fecal zonulin. Lack of concordance between several inflammation-associated biomarkers and zonulin corroborate recent reports of limited utility of zonulin in obese adults free of lower gastrointestinal disease. Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT03582306 (NCT03582306) registered on 07/11/2018.


Assuntos
Haptoglobinas , Inflamação , Obesidade , Precursores de Proteínas , Verduras , 8-Hidroxi-2'-Desoxiguanosina/sangue , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos Cross-Over , Fezes , Feminino , Haptoglobinas/metabolismo , Humanos , Obesidade/sangue , Obesidade/dietoterapia , Obesidade/metabolismo , Precursores de Proteínas/sangue , Precursores de Proteínas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina K
10.
Support Care Cancer ; 31(1): 10, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36512109

RESUMO

PURPOSE: To investigate relationships between body size, gut microbiome, and health-related quality of life (QOL) in breast cancer survivors (BCS) in a clinical trial. METHODS: A cross-sectional substudy was conducted using baseline data from 70 BCS participating in a randomized controlled trial of a lifestyle intervention. Measures included anthropometrics, QOL (Short Form Health-related QOL Survey-36 [SF-36]), and 16S rRNA gene sequencing of fecal microbes. Participants were categorized by body mass index (BMI) into without obesity (≤ 29.9 kg/m2; n = 38) and with obesity (≥ 30.0 kg/m2; n = 32) groups. Differences in bacterial taxa between groups were assessed using Kruskal-Wallis one-way analysis of variance. Spearman and partial correlations explored associations between taxa and SF-36 subscales. Mediation analysis explored the relationship between BMI and SF-36 mental health summary score with alpha diversity as a mediator. RESULTS: Most BCS (72.9%) were non-Hispanic White with average age of 61.6 (± 8.7) years. No differences were observed for SF-36 subscales between groups. Physical functioning, vitality, and mental health subscales were negatively associated with Ruminococcus (ρ = - 0.304, p = 0.036; ρ = - 0.361, p = 0.012; ρ = - 0.495, p < 0.001) and Dorea (ρ = - 0.378, p = 0.028; ρ = - 0.33, p = 0.022; ρ = - 0.388, p = 0.006) abundance controlling for BMI. BCS without obesity had a significantly higher relative abundance of Ruminococcus (p = 0.003), Streptococcus (p = 0.049), Roseburia (p = 0.035), and Dorea (p = 0.003). CONCLUSIONS: Fecal microbial composition differed between BCS with and without obesity, with associations between QOL and several microbial taxa. Several of these genera, previously identified as potentially beneficial, may also influence QOL in BCS. These results support further studies to determine the role of individual microbiota in QOL and obesity in cancer survivors.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Pessoa de Meia-Idade , Feminino , Qualidade de Vida/psicologia , Neoplasias da Mama/psicologia , Estudos Transversais , RNA Ribossômico 16S , Obesidade/complicações
11.
J Am Pharm Assoc (2003) ; 62(3): 740-749.e3, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35012893

RESUMO

BACKGROUND: Lean methodology, specifically value stream mapping, can be used to identify and reduce inefficiencies in the medication synchronization process. OBJECTIVES: The objectives of this study were to (1) evaluate potential medication synchronization process improvements to reduce nonvalue-added actions, (2) assess fidelity to the medication synchronization core components, and (3) identify the best process for medication synchronization for an independent community pharmacy with multiple locations. METHODS: This study used an observational, cross-sectional design. A value stream map was created to provide a detailed illustration of each step in the medication synchronization process. Time for each step of the medication synchronization process was observed on site on different days and times as well as the time required to process, package, and verify prescription medications. These steps were conducted before interventions were made to the process and after to compare the difference. The organizational readiness for change tool was administered to employees of the independent pharmacy before interventions to determine their perspective of the medication synchronization process and assess their readiness for change. RESULTS: Owing to various interventions made to the medication synchronization process, 2 steps in the process were eliminated. This resulted in a decrease in adherence packaging time workflow by 69.4%. Staff (n = 9) rated the medication synchronization process on 4 components: acceptability of the current process (13.8 ± 3.6), intervention appropriateness (13.7 ± 3.7), feasibility of a new medication synchronization process (17.1 ± 2.3), and organizational level of support (21.8 ± 4.1). CONCLUSION: Value stream mapping proved to be a valuable tool in identifying inefficiencies in the medication synchronization process and reducing nonvalue-added waste. The result was a decrease in time required for adherence packaging workflow and a more standardized medication synchronization process across multiple independent pharmacy locations. This more standardized process can play a key role in improving the continuity of patient care, increasing medication adherence, and in turn decreasing the number of hospital admissions.


Assuntos
Serviços Comunitários de Farmácia , Farmácias , Farmácia , Estudos Transversais , Humanos , Adesão à Medicação
12.
Aust J Soc Issues ; 57(2): 252-273, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35910416

RESUMO

Reducing the rate of over-representation of Aboriginal and Torres Strait Islander children in out-of-home care (OOHC) is a key Closing the Gap target committed to by all Australian governments. Current strategies are failing. The "gap" is widening, with the rate of Aboriginal and Torres Strait Islander children in OOHC at 30 June 2020 being 11 times that of non-Indigenous children. Approximately, one in five Aboriginal and Torres Strait Islander children entering OOHC each year are younger than one year. These figures represent compounding intergenerational trauma and institutional harm to Aboriginal and Torres Strait Islander families and communities. This article outlines systemic failures to address the needs of Aboriginal and Torres Strait Islander parents during pregnancy and following birth, causing cumulative harm and trauma to families, communities and cultures. Major reform to child and family notification and service systems, and significant investment to address this crisis, is urgently needed. The Family Matters Building Blocks and five elements of the Aboriginal and Torres Strait Islander Child Placement Principle (Prevention, Participation, Partnership, Placement and Connection) provide a transformative foundation to address historical, institutional, well-being and socioeconomic drivers of current catastrophic trajectories. The time for action is now.

13.
Nutr Neurosci ; 24(12): 963-977, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858898

RESUMO

Objective: Altering the gut microflora may produce health benefits in individuals suffering from mood disorders. The purpose of this review was to evaluate the efficacy of probiotics, prebiotics, or synbiotics as a potential treatment for symptoms of depression, anxiety, and stress (as psychobiotics).Methods: Google Scholar, PubMed, PsychINFO, and Web of Science were utilized to identify and evaluate studies through October 31, 2019. Studies were included if subjects were evaluated for altered mood or stress levels at start of the study and consumed probiotics, prebiotics, and/or synbiotics for intervention.Results: Search results yielded 142 articles, while only 12 studies met all inclusion criteria. Nine of the 12 studies identified evaluated the efficacy of various probiotic strains, while only two evaluated synbiotics and one evaluated prebiotics. Six out of 12 studies found probiotics to reduce depression, while two studies found probiotics to reduce anxiety.Discussion: Translational research in this field is limited and further investigation of the efficacy of psychobiotics in mood disorders is warranted.


Assuntos
Ansiedade/terapia , Depressão/terapia , Microbioma Gastrointestinal/fisiologia , Prebióticos/administração & dosagem , Probióticos/uso terapêutico , Simbióticos/administração & dosagem , Ansiedade/microbiologia , Depressão/microbiologia , Humanos , Estresse Psicológico/microbiologia , Estresse Psicológico/terapia
14.
Postgrad Med J ; 97(1149): 423-426, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34039692

RESUMO

Little has been published regarding postgraduate assessments during the COVID-19 pandemic. There is an urgent need to graduate well-trained specialists including family physicians who play a key role in patient care. The successes and challenges encountered in mounting qualifying 2020 Family Medicine examinations during the COVID-19 pandemic at the University of the West Indies are described in this paper. Human resource, planning, use of technology and virtual environments are discussed, which enabled successful examinations at this multicampus regional site.


Assuntos
COVID-19 , Certificação , Educação de Pós-Graduação em Medicina/organização & administração , Avaliação Educacional , Medicina de Família e Comunidade/educação , Médicos de Família/normas , Desempenho Acadêmico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Certificação/métodos , Certificação/normas , Avaliação Educacional/métodos , Avaliação Educacional/estatística & dados numéricos , Escolaridade , Tecnologia Educacional/métodos , Humanos , Avaliação das Necessidades , SARS-CoV-2 , Ensino/normas , Ensino/tendências , Índias Ocidentais
15.
Infect Immun ; 88(12)2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-32989037

RESUMO

The interaction of host cells with mycobacteria is complex and can lead to multiple outcomes ranging from bacterial clearance to progressive or latent infection. Autophagy is recognized as one component of host cell responses that has an essential role in innate and adaptive immunity to intracellular bacteria. Many microbes, including Mycobacterium tuberculosis, have evolved to evade or exploit autophagy, but the precise mechanisms and virulence factors are mostly unknown. Through a loss-of-function screening of an M. tuberculosis transposon mutant library, we identified 16 genes that contribute to autophagy inhibition, six of which encoded the PE/PPE protein family. Their expression in Mycobacterium smegmatis confirmed that these PE/PPE proteins inhibit autophagy and increase intracellular bacterial persistence or replication in infected cells. These effects were associated with increased mammalian target of rapamycin (mTOR) activity and also with decreased production of tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß). We also confirmed that the targeted deletion of the pe/ppe genes in M. tuberculosis resulted in enhanced autophagy and improved intracellular survival rates compared to those of wild-type bacteria in the infected macrophages. Differential expression of these PE/PPE proteins was observed in response to various stress conditions, suggesting that they may confer advantages to M. tuberculosis by modulating its interactions with host cells under various conditions. Our findings demonstrated that multiple M. tuberculosis PE/PPE proteins are involved in inhibiting autophagy during infection of host phagocytes and may provide strategic targets in developing therapeutics or vaccines against tuberculosis.


Assuntos
Autofagia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Macrófagos/metabolismo , Mycobacterium tuberculosis/genética , Tuberculose/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Biblioteca Gênica , Ensaios de Triagem em Larga Escala , Interações entre Hospedeiro e Microrganismos/genética , Imunidade Inata , Interleucina-1beta/metabolismo , Macrófagos/microbiologia , Camundongos , Mycobacterium smegmatis/fisiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , Células RAW 264.7 , Serina-Treonina Quinases TOR/metabolismo , Tuberculose/genética , Tuberculose/microbiologia , Fator de Necrose Tumoral alfa/metabolismo , Fatores de Virulência/genética
16.
Oncologist ; 24(12): e1450-e1459, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31147490

RESUMO

BACKGROUND: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. Currently, oncofertility competencies do not exist. The aim of this study was to develop an oncofertility competency framework that defines the key components of oncofertility care, develops a model for prioritizing service development, and defines the roles that health care professionals (HCPs) play. MATERIALS AND METHOD: A quantitative modified Delphi methodology was used to conduct two rounds of an electronic survey, querying and synthesizing opinions about statements regarding oncofertility care with HCPs and patient and family advocacy groups (PFAs) from 16 countries (12 high and 4 middle income). Statements included the roles of HCPs and priorities for service development care across ten domains (communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, oncofertility training, reproductive survivorship care and fertility-related psychosocial support, supportive care, and ethical frameworks) that represent 33 different elements of care. RESULTS: The first questionnaire was completed by 457 participants (332 HCPs and 125 PFAs). One hundred and thirty-eight participants completed the second questionnaire (122 HCPs and 16 PFAs). Consensus was agreed on 108 oncofertility competencies and the roles HCPs should play in oncofertility care. A three-tier service development model is proposed, with gradual implementation of different components of care. A total of 92.8% of the 108 agreed competencies also had agreement between high and middle income participants. CONCLUSION: FP guidelines establish best practice but do not consider the skills and requirements to implement these guidelines. The competency framework gives HCPs and services a structure for the training of HCPs and implementation of care, as well as defining a model for prioritizing oncofertility service development. IMPLICATIONS FOR PRACTICE: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. The competency framework gives 108 competencies that will allow health care professionals (HCPs) and services a structure for the development of oncofertility care, as well as define the role HCPs play to provide care and support. The framework also proposes a three-tier oncofertility service development model which prioritizes the development of components of oncofertility care into essential, enhanced, and expert services, giving clear recommendations for service development. The competency framework will enhance the implementation of FP guidelines, improving the equitable access to medical and psychological oncofertility care.


Assuntos
Preservação da Fertilidade/métodos , Feminino , Humanos , Inquéritos e Questionários
18.
JAAPA ; 32(1): 17-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30589729

RESUMO

Stenosing flexor tenosynovitis, more commonly known as trigger finger, is one of the most common causes of hand pain and dysfunction. Clinicians must be able to identify the disorder, know the broad range of treatment options, and counsel patients on the treatment best suited for their condition. Awareness of the economic burden each option entails is central to optimizing treatment outcomes and patient satisfaction.


Assuntos
Encarceramento do Tendão/terapia , Efeitos Psicossociais da Doença , Diagnóstico Diferencial , Tratamento por Ondas de Choque Extracorpóreas , Feminino , Glucocorticoides/administração & dosagem , Custos de Cuidados de Saúde , Humanos , Pessoa de Meia-Idade , Procedimentos Ortopédicos , Satisfação do Paciente , Modalidades de Fisioterapia , Índice de Gravidade de Doença , Encarceramento do Tendão/diagnóstico , Resultado do Tratamento
19.
J Clin Microbiol ; 56(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29212701

RESUMO

The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive "sample-to-answer" multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.


Assuntos
Bactérias/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Nasofaringe/microbiologia , Nasofaringe/virologia , Reação em Cadeia da Polimerase , Infecções Respiratórias/diagnóstico , Vírus/isolamento & purificação , Testes Diagnósticos de Rotina , Humanos , Reprodutibilidade dos Testes , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Estudos Retrospectivos
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