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SHARPIN forms a linear-ubiquitin-chain-assembly complex that promotes signaling via the transcription factor NF-κB. SHARPIN deficiency leads to progressive multi-organ inflammation and immune system malfunction, but how SHARPIN regulates T cell responses is unclear. Here we found that SHARPIN deficiency resulted in a substantial reduction in the number of and defective function of regulatory T cells (Treg cells). Transfer of SHARPIN-sufficient Treg cells into SHARPIN-deficient mice considerably alleviated their systemic inflammation. SHARPIN-deficient T cells displayed enhanced proximal signaling via the T cell antigen receptor (TCR) without an effect on the activation of NF-κB. SHARPIN conjugated with Lys63 (K63)-linked ubiquitin chains, which led to inhibition of the association of TCRζ with the signaling kinase Zap70; this affected the generation of Treg cells. Our study therefore identifies a role for SHARPIN in TCR signaling whereby it maintains immunological homeostasis and tolerance by regulating Treg cells.
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Proteínas de Transporte/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Animais , Proteínas de Transporte/genética , Colite/imunologia , Citocinas/imunologia , Feminino , Citometria de Fluxo , Humanos , Tolerância Imunológica/imunologia , Immunoblotting , Imunoprecipitação , Técnicas In Vitro , Inflamação , Peptídeos e Proteínas de Sinalização Intracelular , Células Jurkat , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , NF-kappa B/imunologia , Transdução de Sinais , Ubiquitinação , Proteína-Tirosina Quinase ZAP-70/imunologiaRESUMO
Double-strand breaks (DSBs) are critical DNA lesions that robustly activate the elaborate DNA damage response (DDR) network. We identified a critical player in DDR fine-tuning: the E3/E4 ubiquitin ligase UBE4A. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites. This pathway is essential for optimal end resection at DSBs, and its abrogation leads to upregulation of the highly mutagenic alternative end-joining repair at the expense of error-free homologous recombination repair. Our data uncover a critical regulatory level in the DSB response and underscore the importance of fine-tuning the complex DDR network for accurate and balanced execution of DSB repair.
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Proteína BRCA1/metabolismo , Proteínas de Transporte/metabolismo , Quebras de DNA de Cadeia Dupla , Proteínas Nucleares/metabolismo , Reparo de DNA por Recombinação/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/fisiologia , Proteína BRCA1/genética , Proteínas de Transporte/genética , Proteínas de Ligação a DNA , Células HeLa , Chaperonas de Histonas , Humanos , Proteínas Nucleares/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinas/genética , Ubiquitinas/metabolismoRESUMO
The gut microbiome influences cancer development and the efficacy and safety of chemotherapy but little is known about its effects on lymphoma. We obtained stool samples from treatment-naive, newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) (n = 189). We first performed 16S ribosomal RNA gene sequencing (n = 158) and then conducted whole-genome shotgun sequencing on additional samples (n = 106). We compared the microbiome data from these patients with data from healthy controls and assessed whether microbiome characteristics were associated with treatment outcomes. The alpha diversity was significantly lower in patients with DLBCL than in healthy controls (P < .001), and the microbial composition differed significantly between the groups (P < .001). The abundance of the Enterobacteriaceae family belonging to the Proteobacteria phylum was markedly higher in patients than in healthy controls. Functional analysis of the microbiome revealed an association with opportunistic pathogenesis through type 1 pili, biofilm formation, and antibiotics resistance. Enterobacteriaceae members were significantly enriched in patients who experienced febrile neutropenia and in those who experienced relapse or progression (P < .001). Interestingly, greater abundance of Enterobacteriaceae correlated with shorter progression-free survival (P = .007). The cytokine profiles of patients whose microbiome was enriched with Enterobacteriaceae were significantly associated with interleukin 6 (P = .035) and interferon gamma (P = .045) levels. In summary, patients with DLBCL exhibited gut microbial dysbiosis. The abundance of Enterobacteriaceae correlated with treatment outcomes and febrile neutropenia. Further study is required to elucidate the origin and role of gut dysbiosis in DLBCL.
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Neutropenia Febril , Microbioma Gastrointestinal , Linfoma Difuso de Grandes Células B , Humanos , Disbiose/complicações , Recidiva Local de Neoplasia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/complicações , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Fezes/microbiologiaRESUMO
BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.
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Fenótipo , Rinite Alérgica , Transcriptoma , Humanos , Pré-Escolar , Feminino , Masculino , Criança , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Lactente , Recém-Nascido , Coorte de Nascimento , Idade de Início , Perfilação da Expressão Gênica , Estudos de Coortes , Asma/genética , Asma/imunologiaRESUMO
Considering patient room shortages and prevalence of other communicable diseases, reassessing the isolation of patients with Clostridioides difficile infection (CDI) is imperative. We conducted a retrospective study to investigate the secondary CDI transmission rate in a hospital in South Korea, where patients with CDI were not isolated. Using data from a real-time locating system and electronic medical records, we investigated patients who had both direct and indirect contact with CDI index patients. The primary outcome was secondary CDI transmission, identified by whole-genome sequencing. Among 909 direct and 2,711 indirect contact cases, 2 instances of secondary transmission were observed (2 [0.05%] of 3,620 cases), 1 transmission via direct contact and 1 via environmental sources. A low level of direct contact (113 minutes) was required for secondary CDI transmission. Our findings support the adoption of exhaustive standard preventive measures, including environmental decontamination, rather than contact isolation of CDI patients in nonoutbreak settings.
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Clostridioides difficile , Infecções por Clostridium , Humanos , Infecções por Clostridium/transmissão , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , República da Coreia/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Infecção Hospitalar/microbiologia , Fatores de Tempo , Idoso , Pessoa de Meia-Idade , Adulto , Busca de ComunicanteRESUMO
OBJECTIVE: To determine the relationship between, and predictive utility of, milestone ratings and subsequent American Board of Surgery (ABS) vascular surgery in-training examination (VSITE), vascular qualifying examination (VQE), and vascular certifying examination (VCE) performance in a national cohort of vascular surgery trainees. BACKGROUND: Specialty board certification is an important indicator of physician competence. However, predicting future board certification examination performance during training continues to be challenging. METHODS: This is a national longitudinal cohort study examining relational and predictive associations between Accreditation Council for Graduate Medical Education (ACGME) Milestone ratings and performance on VSITE, VQE, and VCE for all vascular surgery trainees from 2015 to 2021. Predictive associations between milestone ratings and VSITE were conducted using cross-classified random-effects regression. Cross-classified random-effects logistic regression was used to identify predictive associations between milestone ratings and VQE and VCE. RESULTS: Milestone ratings were obtained for all residents and fellows(n=1,118) from 164 programs during the study period (from July 2015 to June 2021), including 145,959 total trainee assessments. Medical knowledge (MK) and patient care (PC) milestone ratings were strongly predictive of VSITE performance across all postgraduate years (PGYs) of training, with MK ratings demonstrating a slightly stronger predictive association overall (MK coefficient 17.26 to 35.76, ß = 0.15 to 0.23). All core competency ratings were predictive of VSITE performance in PGYs 4 and 5. PGY 5 MK was highly predictive of VQE performance [OR 4.73, (95% CI, 3.87-5.78), P <0.001]. PC subcompetencies were also highly predictive of VQE performance in the final year of training [OR 4.14, (95% CI, 3.17-5.41), P <0.001]. All other competencies were also significantly predictive of first-attempt VQE pass with ORs of 1.53 and higher. PGY 4 ICS ratings [OR 4.0, (95% CI, 3.06-5.21), P <0.001] emerged as the strongest predictor of VCE first-attempt pass. Again, all subcompetency ratings remained significant predictors of first-attempt pass on CE with ORs of 1.48 and higher. CONCLUSIONS: ACGME Milestone ratings are highly predictive of future VSITE performance, and first-attempt pass achievement on VQE and VCE in a national cohort of surgical trainees.
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Internato e Residência , Humanos , Estados Unidos , Estudos Longitudinais , Avaliação Educacional , Competência Clínica , Educação de Pós-Graduação em Medicina , AcreditaçãoRESUMO
OBJECTIVES: A recent study of 21 institutions noted significant differences between number of cases reported during general surgery residency by trainees who are Underrepresented in Medicine (URiM) versus trainees who are not Underrepresented in Medicine (non-URiM). This study also identified differences between female residents and male residents. We partnered with the Accreditation Council for Graduate Medical Education to examine case logs reported from all accredited general surgery programs in the United States. This is the first time this data has been examined nationally. METHODS: We examined total case logs submitted by graduating residents between 2017 and 2022. Group differences in mean reported case logs were examined using paired t- tests for female versus male and URiM versus non- URiM overall case numbers. RESULTS: A total of 6,458 residents submitted case logs from 319 accredited programs. Eight-hundred and fifty-four (13%) were URiM and 5,604 (87%) were non-URiM. Over the 5-year study period, URM residents submitted 1096.95 (SD +/- 160.57) major cases versus 1115.96 (+/- 160.53) for non-URiM residents (difference =19 cases, P=0.001). Case logs were submitted by 3,833 (60.1%) male residents and 2,625 (39.9%) female residents over the five-year study period. Male residents reported 1128.56 (SD +/- 168.32) cases versus 1091.38 (+/- 145.98) cases reported by females (difference=37.18, P<0.001). When looking at Surgeon Chief and Teaching Assistant cases, there was no significant difference noted between cases submitted by URiM versus non- URiM residents. However, male residents reported significantly more in both categories than their female peers (P<0.001). CONCLUSIONS: Overall, URiM residents submitted fewer cases in the five- year study period than their non-URiM peers. The gap in submitted cases between male and female residents was more pronounced, with male residents submitting significantly more cases than their female counterparts. This finding was consistent and statistically significant throughout the entire study period, in most case categories, and without narrowing of difference over time. A difference of 30-40 cases can amount to 1-3 months of surgical training and is a concerning national trend deserving the attention of every training program and our governing institutions.
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Stress granule (SG) is a temporary cellular structure that plays a crucial role in the regulation of mRNA and protein sequestration during various cellular stress conditions. SG enables cells to cope with stress more effectively, conserving vital energy and resources. Focusing on the NTF2-like domain of G3BP1, a key protein in SG dynamics, we explore to identify and characterize novel small molecules involved in SG modulation without external stressors. Through in silico molecular docking approach to simulate the interaction between various compounds and the NTF2-like domain of G3BP1, we identified three compounds as potential candidates that could bind to the NTF2-like domain of G3BP1. Subsequent immunofluorescence experiments demonstrated that these compounds induce the formation of SG-like, G3BP1-positive granules. Importantly, the granule formation by these compounds occurs independent from the phosphorylation of eIF2α, a common mechanism in SG formation, suggesting that it might offer a new strategy for influencing SG dynamics implicated in various diseases.
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DNA Helicases , RNA Helicases , DNA Helicases/metabolismo , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Simulação de Acoplamento Molecular , Grânulos Citoplasmáticos/metabolismoRESUMO
BACKGROUND: The objective of this study was to compare long-term oncologic outcomes of robot and laparoscopic surgeries for patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by radical resection. METHODS: This study analyzed 3240 rectal cancer patients who underwent radical surgery from 2008 to 2019. Among them, 1204 patients who received nCRT (robotic, n = 316; laparoscopic, n = 888) were analyzed. The oncological outcome according to the number of unfavorable factors (male, body mass index ≥ 25, receiving CCRT) present in patients also was analyzed. We used 1:1 propensity score matching (PSM) to adjust for potential baseline confounders between groups. RESULTS: After PSM, two groups showed similar demographics and pathological results. After PSM analysis, the robotic group showed higher 5-year disease-free survival (DFS) and local recurrence-free survival rates than the laparoscopic group, whereas 5-year overall survival and distant recurrence-free survival rates were similar between the two groups. In addition, by comparing survival rates for each yp stage, it was found 5-year DFS and local recurrence-free survival of the robotic group in yp stage III were significantly higher than those of the laparoscopic group. Five-year DFS was conducted according to the number of unfavorable factors (male, body mass index ≥ 25 kg/m2, and undergoing nCRT) as a subgroup analysis. In patients with all three unfavorable factors, the robotic group showed significantly higher DFS than the laparoscopic group. CONCLUSIONS: Robotic approach for rectal cancer after nCRT, especially for patients with yp stage III and unfavorable factors, have the advantage of improving oncologic outcomes even for surgeons specializing in colorectal cancer.
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Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Terapia Neoadjuvante , Resultado do Tratamento , Quimiorradioterapia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Retais/patologiaRESUMO
BACKGROUND: While some prior studies of work-based assessment (WBA) numeric ratings have not shown gender differences, they have been unable to account for the true performance of the resident or explore narrative differences by gender. OBJECTIVE: To explore gender differences in WBA ratings as well as narrative comments (when scripted performance was known). DESIGN: Secondary analysis of WBAs obtained from a randomized controlled trial of a longitudinal rater training intervention in 2018-2019. Participating faculty (n = 77) observed standardized resident-patient encounters and subsequently completed rater assessment forms (RAFs). SUBJECTS: Participating faculty in longitudinal rater training. MAIN MEASURES: Gender differences in mean entrustment ratings (4-point scale) were assessed with multivariable regression (adjusted for scripted performance, rater and resident demographics, and the interaction between study arm and time period [pre- versus post-intervention]). Using pre-specified natural language processing categories (masculine, feminine, agentic, and communal words), multivariable linear regression was used to determine associations of word use in the narrative comments with resident gender, race, and skill level, faculty demographics, and interaction between the study arm and the time period (pre- versus post-intervention). KEY RESULTS: Across 1527 RAFs, there were significant differences in entrustment ratings between women and men standardized residents (2.29 versus 2.54, respectively, p < 0.001) after correction for resident skill level. As compared to men, feminine terms were more common for comments of what the resident did poorly among women residents (ß 0.45, CI 0.12-0.78, p 0.01). This persisted despite adjusting for the faculty's entrustment ratings. There were no other significant linguistic differences by gender. CONCLUSIONS: Contrasting prior studies, we found entrustment rating differences in a simulated WBA which persisted after adjusting for the resident's scripted performance. There were also linguistic differences by gender after adjusting for entrustment ratings, with feminine terms being used more frequently in comments about women in some, but not all narrative comments.
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Competência Clínica , Internato e Residência , Humanos , Feminino , Masculino , Competência Clínica/normas , Fatores Sexuais , Narração , Adulto , Avaliação Educacional/métodosRESUMO
Foxp3(+) regulatory T (Treg) cells play a critical role in immune homeostasis; however, the mechanisms to maintain their function remain unclear. Here, we report that the E3 ubiquitin ligase VHL is essential for Treg cell function. Mice with Foxp3-restricted VHL deletion displayed massive inflammation associated with excessive Treg cell interferon-γ (IFN-γ) production. VHL-deficient Treg cells failed to prevent colitis induction, but converted into Th1-like effector T cells. VHL intrinsically orchestrated such conversion under both steady and inflammatory conditions followed by Foxp3 downregulation, which was reversed by IFN-γ deficiency. Augmented hypoxia-inducible factor 1α (HIF-1α)-induced glycolytic reprogramming was required for IFN-γ production. Furthermore, HIF-1α bound directly to the Ifng promoter. HIF-1α knockdown or knockout could reverse the increased IFN-γ by VHL-deficient Treg cells and restore their suppressive function in vivo. These findings indicate that regulation of HIF-1α pathway by VHL is crucial to maintain the stability and suppressive function of Foxp3(+) T cells.
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Colite/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Animais , Células Cultivadas , Reprogramação Celular/genética , Regulação para Baixo/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Tolerância Imunológica , Inflamação/genética , Interferon gama/genética , Interferon gama/metabolismo , Ativação Linfocitária/genética , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Camundongos Transgênicos , RNA Interferente Pequeno/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genéticaRESUMO
Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA.
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Hipersensibilidade Alimentar , Metabolômica , Humanos , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/diagnóstico , Metabolômica/métodos , Criança , Biomarcadores/metabolismo , Metaboloma , Alérgenos/imunologiaRESUMO
PURPOSE: Hepatotoxicity has emerged as a major cause of statin treatment interruption. Although organic anion-transporting polypeptide 1B1 (SLCO1B1), multidrug resistance protein 1 (ABCB1), and breast cancer resistance protein (ABCG2) have been identified as transporters of statins, knowledge of their role in statin-associated hepatotoxicity remains limited. Therefore, we aimed to conduct a comprehensive analysis to elucidate the association between hepatotoxicity and SLCO1B1, ABCB1, and ABCG2 polymorphisms. METHODS: This study retrospectively analyzed prospectively collected samples. We selected 10 single nucleotide polymorphisms (SNPs) of SLCO1B1, 9 SNPs of ABCB1, and 12 SNPs of ABCG2. We developed two models for multivariable analyses (Model I: clinical factors only; Model II: both clinical and genetic factors), and the attributable risk (%) of variables in Model II was determined. RESULTS: Among 851 patients, 66 (7.8%) developed hepatotoxicity. In Model I, lipophilic statins, atrial fibrillation (Afib), and diabetes mellitus showed a significant association with hepatotoxicity. In Model II, lipophilic statins and Afib, SLCO1B1 rs11045818 A allele, SLCO1B1 rs4149035 T allele, and ABCG2 rs2622629 TT genotype were associated with higher hepatotoxicity risk. Among them, the SLCO1B1 rs11045818 A allele exhibited the highest attributable risk (93.2%). The area under the receiver operating characteristic curve in Model I was 0.62 (95% CI: 0.55-0.69), and it was increased to 0.71 in Model II (95% CI: 0.64-0.77). CONCLUSION: This study investigated the correlation between hepatotoxicity and polymorphisms of transporter genes in patients taking statins. The findings could help improve personalized treatments for patients receiving statin therapy.
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BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.
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BACKGROUND: After the revision of the Korean Pharmaceutical Affairs Act, the certification of specialized pharmacists is scheduled to be legally recognized in 2023. Considering that the specialized pharmacist certification was developed based on the working model of hospital clinical pharmacists, it is necessary to establish standards for clinical pharmacists in hospitals and to calculate appropriate manpower. Through this study, we aim to establish practical standards for clinical pharmacists and propose a method for calculating staffing levels based on an investigation of actual workloads. METHODS: This survey-based study consisted of two phases. In the first phase, a literature review was conducted to establish standards for clinical pharmacy services, and tasks in relevant literature were classified to identify clinical pharmacy service tasks that are applicable to the practice of Korean hospitals. Additionally, a preliminary survey was conducted to investigate the essential tasks. In the second phase of the investigation, a multicenter survey was conducted targeting pharmacists in facilities with more than 1,000 beds to explore their perceptions and actual workloads related to tasks. RESULTS: According to the standards for clinical pharmacists in Korea, clinical pharmacy services consist of a total of 23 tasks, of which 16 have been identified as essential tasks. Essential tasks accounted for 93% of the total tasks in clinical pharmacy services. The average full-time equivalent (FTE) through workload calculation was 2.5 ± 1.9 for each field, while the FTE allocated to actual practice was 2.1 ± 1.6. The distribution of each type of clinical pharmacy service was as follows: 77% for medication therapy management, 13% for medication education, 8% for multidisciplinary team activities, and 3% for medication use evaluation. CONCLUSION: This study identified essential tasks common to clinical pharmacy services across different healthcare institutions. However, the FTE of clinical pharmacists in actual practice was insufficient compared to the required amount. In order to establish and expand clinical pharmacy services in a hospital, it is necessary to ensure an adequate workforce for essential tasks.
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Farmácias , Farmácia , Humanos , República da Coreia , Recursos Humanos , Hospitais , Estudos Multicêntricos como AssuntoRESUMO
White adipose tissue (WAT) is a key regulator of systemic energy metabolism, and impaired WAT plasticity characterized by enlargement of preexisting adipocytes associates with WAT dysfunction, obesity, and metabolic complications. However, the mechanisms that retain proper adipose tissue plasticity required for metabolic fitness are unclear. Here, we comprehensively showed that adipocyte-specific DNA methylation, manifested in enhancers and CTCF sites, directs distal enhancer-mediated transcriptomic features required to conserve metabolic functions of white adipocytes. Particularly, genetic ablation of adipocyte Dnmt1, the major methylation writer, led to increased adiposity characterized by increased adipocyte hypertrophy along with reduced expansion of adipocyte precursors (APs). These effects of Dnmt1 deficiency provoked systemic hyperlipidemia and impaired energy metabolism both in lean and obese mice. Mechanistically, Dnmt1 deficiency abrogated mitochondrial bioenergetics by inhibiting mitochondrial fission and promoted aberrant lipid metabolism in adipocytes, rendering adipocyte hypertrophy and WAT dysfunction. Dnmt1-dependent DNA methylation prevented aberrant CTCF binding and, in turn, sustained the proper chromosome architecture to permit interactions between enhancer and dynamin-1-like protein gene Dnm1l (Drp1) in adipocytes. Also, adipose DNMT1 expression inversely correlated with adiposity and markers of metabolic health but positively correlated with AP-specific markers in obese human subjects. Thus, these findings support strategies utilizing Dnmt1 action on mitochondrial bioenergetics in adipocytes to combat obesity and related metabolic pathology.
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Adipócitos/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Epigênese Genética , Dinâmica Mitocondrial , Adipócitos/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adiposidade , Animais , Fator de Ligação a CCCTC/metabolismo , Estruturas Cromossômicas , DNA (Citosina-5-)-Metiltransferase 1/deficiência , DNA (Citosina-5-)-Metiltransferase 1/genética , Metilação de DNA , Dinaminas/genética , Dinaminas/metabolismo , Metabolismo Energético , Elementos Facilitadores Genéticos , Perfilação da Expressão Gênica , Metabolismo dos Lipídeos , Camundongos , Mitocôndrias/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Regiões Promotoras Genéticas , Ligação ProteicaRESUMO
PURPOSE: This study explores international trends and standards of Master's degree programs through a comprehensive environmental scan and focus group interviews to understand curricular structure, content, program director expectations, educational context, and future directions. METHOD: Authors conducted a two-phase mixed-methods sequential explanatory design to conduct the environmental scan (phase 1), and subsequently conducting focus groups (phase 2) with program directors. A population list of Master's programs was used to generate a sampling frame, considering the geographic region (continent) and institution type (university, organization, public institution). Qualitative data were coded to analyze the breadth and depth of courses. Three one-hour virtual focus group interviews were conducted with ten program directors. RESULTS: The population list of 159 Masters programs worldwide was used to create a sample for analysis in the environmental scan (n = 46 Masters programs), representing programs from North America, Europe, Australia, and South Africa. Most programs (39%) delivered their courses online, with 20% exclusively offering an in-person program. Focus group participants indicated expectations of graduates, context in which they learn, as well as future directions for improving health professions education graduate programs. CONCLUSION: Program directors should consider programmatic aims, localized needs, and quality/standard of the program in designing Masters programs, with individualized growth opportunities for learners.
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Currículo , Ocupações em Saúde , Humanos , 3-Metoxi-4-Hidroxifeniletanol , América do Norte , Europa (Continente) , Ocupações em Saúde/educaçãoRESUMO
Phenomenon: Central to competency-based medical education is the need for a seamless developmental continuum of training and practice. Trainees currently experience significant discontinuity in the transition from undergraduate (UME) to graduate medical education (GME). The learner handover is intended to smooth this transition, but little is known about how well this is working from the GME perspective. In an attempt to gather preliminary evidence, this study explores U.S. program directors (PDs) perspective of the learner handover from UME to GME. Approach: Using exploratory qualitative methodology, we conducted semi-structured interviews with 12 Emergency Medicine PDs within the U.S. from October to November, 2020. We asked participants to describe their current perception of the learner handover from UME to GME. Then we performed thematic analysis using an inductive approach. Findings: We identified two main themes: The inconspicuous learner handover and barrier to creating a successful UME to GME learner handover. PDs described the current state of the learner handover as "nonexistent," yet acknowledged that information is transmitted from UME to GME. Participants also highlighted key challenges preventing a successful learner handover from UME to GME. These included: conflicting expectations, issues of trust and transparency, and a dearth of assessment data to actually hand over. Insights: PDs highlight the inconspicuous nature of learner handovers, suggesting that assessment information is not shared in the way it should be in the transition from UME to GME. Challenges with the learner handover demonstrate a lack of trust, transparency, and explicit communication between UME and GME. Our findings can inform how national organizations establish a unified approach to transmitting growth-oriented assessment data and formalize transparent learner handovers from UME to GME.
Assuntos
Educação de Graduação em Medicina , Medicina de Emergência , Internato e Residência , Humanos , Faculdades de Medicina , Educação de Graduação em Medicina/métodos , Educação de Pós-Graduação em Medicina/métodosRESUMO
BACKGROUND: Despite the prevalence of non-English languages in the US population, existing medical training to teach communication with linguistically diverse communities is limited to electives or solely focuses on medical interpreting. Language-appropriate communication skills are seldom comprehensively integrated in medical education. This study describes the development and evaluation of an intervention to teach foundational language equity concepts. METHODS: The authors implemented a pre-clinical language equity course at three medical school campuses between August 2020 and March 2022. Sessions focused on the impact of language in health, physician language proficiency standards, and working with medical interpreters. The study sought to (1) understand students' language skills and prior clinical experiences with patients with non-English language preference and (2) evaluate the curriculum's impact. Students self-reported their language skills and experiences as part of a voluntary pre-questionnaire. Pre and post-questionnaires evaluated knowledge, attitudes, and intent to apply language equity concepts. Descriptive statistics and chi-squared tests were used to examine trends; themes were identified from free-text responses. RESULTS: Overall, 301 students completed the course, 252 (83%) completed at least one questionnaire; for each session, between 35% and 46% of learners completed both pre and post-questionnaires. Three quarters (189/252) reported non-English languages. Over half (138/252) reported previous non-English language patient care, and 28% (62/224) had served as ad hoc (untrained) interpreters. Only two students (< 1%) had ever been assessed for medical language abilities. Students demonstrated improved post-course language equity knowledge, strategies for interpreter-mediated encounters, and likelihood to report a plan for language skills assessment (all p < .001). Most plans were multifaceted (61%, 38/62), involving goals like completing a language course, taking a proficiency exam, openly discussing skills and uncertainties with team members, and increasing professional interpreter utilization. CONCLUSIONS: A longitudinal language equity curriculum can be feasibly integrated in pre-clinical education, highlight the linguistic diversity of the student body, and serve as a first step in ensuring that all students have a strong language equity foundation prior to clinical rotations. Future steps include evaluating the intervention's potential long-term effects on professional interpreter utilization, student clinical performance, and institutional culture that promotes multilingualism.
Assuntos
Barreiras de Comunicação , Currículo , Humanos , Educação de Graduação em Medicina , Idioma , Masculino , Feminino , Estudantes de Medicina/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Equitable assessment is critical in competency-based medical education. This study explores differences in key characteristics of qualitative assessments (i.e., narrative comments or assessment feedback) of internal medicine postgraduate resident performance associated with gender and race and ethnicity. METHODS: Analysis of narrative comments included in faculty assessments of resident performance from six internal medicine residency programs was conducted. Content analysis was used to assess two key characteristics of comments- valence (overall positive or negative orientation) and specificity (detailed nature and actionability of comment) - via a blinded, multi-analyst approach. Differences in comment valence and specificity with gender and race and ethnicity were assessed using multilevel regression, controlling for multiple covariates including quantitative competency ratings. RESULTS: Data included 3,383 evaluations with narrative comments by 597 faculty of 698 residents, including 45% of comments about women residents and 13.2% about residents who identified with race and ethnicities underrepresented in medicine. Most comments were moderately specific and positive. Comments about women residents were more positive (estimate 0.06, p 0.045) but less specific (estimate - 0.07, p 0.002) compared to men. Women residents were more likely to receive non-specific, weakly specific or no comments (adjusted OR 1.29, p 0.012) and less likely to receive highly specific comments (adjusted OR 0.71, p 0.003) or comments with specific examples of things done well or areas for growth (adjusted OR 0.74, p 0.003) than men. Gendered differences in comment specificity and valence were most notable early in training. Comment specificity and valence did not differ with resident race and ethnicity (specificity: estimate 0.03, p 0.32; valence: estimate - 0.05, p 0.26) or faculty gender (specificity: estimate 0.06, p 0.15; valence: estimate 0.02 p 0.54). CONCLUSION: There were significant differences in the specificity and valence of qualitative assessments associated with resident gender with women receiving more praising but less specific and actionable comments. This suggests a lost opportunity for well-rounded assessment feedback to the disadvantage of women.