Prevalence and quality of medical Spanish education in US osteopathic medical schools: a national survey.

CONTEXT: Spanish is the language in the United States with the greatest language-concordant physician deficit. Allopathic medical Spanish programs have proliferated, but the national prevalence of medical Spanish education at osteopathic medical schools has never been evaluated. OBJECTIVES: The objectives of this study are to describe the medical Spanish educational landscape at US osteopathic schools and evaluate program adherence to previously established basic standards. METHODS: Between March and October 2022, surveys were sent to all 44 member schools of the American Association of Colleges of Osteopathic Medicine (AACOM). For nonrespondents, data were obtained from publicly available websites. Primary surveys were sent to deans or diversity, equity, and inclusion officers at each osteopathic school to determine whether medical Spanish was offered and to identify a medical Spanish leader. Medical Spanish leaders received the secondary survey. The main measures of this study were the prevalence of medical Spanish programs at osteopathic schools and the extent to which existing programs met each of the four basic standards: having a faculty educator, providing a curricular structure, assessing learner skills, and awarding institutional course credit. RESULTS: We gathered medical Spanish information from 90.9 % (40/44) of osteopathic schools. Overall, 88.6 % (39/44) offered medical Spanish, of which 66.7 % (26/39) had formal curricula, 43.6 % (17/39) had faculty educators, 17.9 % (7/39) assessed learner skills, and 28.2 % (11/39) provided course credit. Only 12.8 % (5/39) of osteopathic schools with medical Spanish programs met all basic standards. Urban/suburban schools were likelier to offer medical Spanish than rural schools (p=0.020). Osteopathic schools in states with the highest Spanish-speaking populations were more likely to offer student-run initiatives (p=0.027). CONCLUSIONS: Most osteopathic schools provide medical Spanish education, but work is needed to improve consistency, quality, and sustainability. Future research should focus on osteopathic student language proficiency assessment, improve medical Spanish accessibility for students at rural programs, and explore the unique content areas of osteopathic medical Spanish education.

Validación del LupusQoL en Venezuela: una medida específica de la calidad de vida en pacientes con lupus eritematoso sistémico / Validation of the LupusQoL in Venezuela: A Specific Measurement of Quality of Life in Patients with Systemic Lupus Erythematosus

Antecedentes y objetivos: Tradicionalmente, la calidad de vida relacionada con la salud (CVRS) de los pacientes con lupus eritematoso sistémico (LES) ha sido evaluada utilizando instrumentos que desatienden las características específicas de la enfermedad. Este estudio determina la validez del cuestionario Lupus Quality of Life (LupusQoL) como instrumento psicométricamente estable para medir la CVRS de los pacientes con LES en Venezuela, y establece los puntos de corte del cuestionario para la población venezolana. Pacientes y métodos: Se realizó un estudio de corte transversal que incluyó pacientes con LES desde abril hasta julio de 2018. Los pacientes completaron el LupusQoL y la escala Generalitat de Catalunya (GENCAT); se obtuvieron los datos sociodemográficos, índices de actividad (SLEDAI) y daño acumulado (SLICC). Se evaluó la fiabilidad mediante consistencia interna y se determinó la validez convergente del LupusQoL con la escala GENCAT. Resultados: De los 100 pacientes, el 93% eran mujeres, la media de edad fue de 42años (DE: 13) y la media de duración de la enfermedad fue de 11años (DE: 9); la media de SLEDAI y SLICC fue de 3 y 1, respectivamente. El punto de corte que definió una «mejor» o «peor» CVRS para el LupusQoL fue 64,55 puntos. Se encontró una convergencia moderada posterior a la agrupación, según los puntos de corte, del LupusQoL con la escala GENCAT (coeficiente kappa de Cohen=0,556; p=0,000). Conclusiones: El LupusQoL es válido como instrumento psicométricamente estable para medir la CVRS de los pacientes con LES en Venezuela. Se establecieron los puntos de corte que permiten estratificar la CVRS de los pacientes venezolanos con LES, siendo de utilidad para complementar una evaluación integral.(AU)

Background and objectives: Traditionally, the health-related quality of life (HRQoL) of patients with systemic lupus erythematosus (SLE) has been assessed using instruments that neglect the specific characteristics of the disease. This study determines the validity of the Lupus Quality of Life (LupusQoL) questionnaire as a psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela and establishes the cutoff points of the questionnaire for the Venezuelan population. Patients and methods: A cross-sectional study was conducted that included patients with SLE from April to July 2018. Patients completed the LupusQoL and the Generalitat de Catalunya (GENCAT) scale; sociodemographic data, activity index (SLEDAI) and accumulated damage (SLICC), were obtained. Reliability was evaluated by internal consistency and the convergent validity of the LupusQoL was determined with the GENCAT scale. Results: Of the 100 patients, 93% were women, the mean age was 42years old (SD: 13) and the mean duration of the disease was 11years (SD: 9); the mean of SLEDAI and SLICC was 3 and 1, respectively. The cutoff point that defined a “better” or “worse” HRQoL for LupusQoL was 64.55 points. A moderate convergence was found after grouping, according to the cutoff points, of the LupusQoL with the GENCAT scale (Cohen's kappa coefficient=.556; p=.000). Conclusions: The LupusQoL is a valid psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela. Cutoff points were established to stratify the HRQoL in the Venezuelan population with LES, being useful to complement a comprehensive evaluation.(AU)

Impact of demographic, clinical, and treatment compliance characteristics on quality of life of Venezuelan patients with systemic lupus erythematosus.

BACKGROUND: We have here assessed the impact of demographic, clinical, and treatment compliance characteristics on health-related quality of life (HRQoL) of Venezuelan patients with systemic lupus erythematosus (SLE). We have used a disease-specific questionnaire, the Lupus Quality of Life (LupusQoL), validated in our patient population, to measure HRQoL. METHODS: A cross-sectional study was conducted among 100 patients with SLE from outpatient clinics. Patients completed a form with demographic, clinical, and treatment compliance data, and the LupusQoL questionnaire. HRQoL was classified as better or worse according to previously established cut-off points for this patient population. Spearman's r test was used to determine the correlations between age, years of education, disease duration, SLEDAI, and SLICC-DI with the eight domains of the LupusQoL. Mann-Whitney U test was used to compare the HRQoL between the two groups of patients according to treatment compliance. Binomial logistic regression using the backward stepwise selection method was performed to identify the risk factors associated with each of the eight domains of the LupusQoL among patients with inactive (SLEDAI < 4) and active (SLEDAI ≥ 4) SLE. RESULTS: HRQoL of our patients was classified as better in all domains of the LupusQoL. Age correlated negatively with all domains of the LupusQoL, except with "burden to others", and disease activity correlated negatively with all domains of the LupusQoL, except with "intimate relationships" and "burden to others" (p < 0.05). Patients who fully complied with indicated treatment had higher scores in "physical health" domain compared to patients who did not comply with at least one of the prescribed medications (p < 0.05). In patients with active SLE, a risk factor associated with worse "planning" and "intimate relationships" was advanced age, while having had SLE flare-ups in the previous six months was a risk factor associated with worse "physical health" (p < 0.05). CONCLUSION: Age and disease activity were negatively correlated with almost all domains of the LupusQoL, and treatment compliance was associated with higher score in the "physical health" domain. Disease control and treatment compliance should be the main goals for a better HRQoL in our patients with SLE.

Validation of the LupusQoL in Venezuela: A specific measurement of quality of life in patients with systemic lupus erythematosus.

BACKGROUND AND OBJECTIVES: Traditionally, the health-related quality of life (HRQoL) of patients with systemic lupus erythematosus (SLE) has been assessed using instruments that neglect the specific characteristics of the disease. This study determines the validity of the Lupus Quality of Life (LupusQoL) questionnaire as a psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela and establishes the cutoff points of the questionnaire for the Venezuelan population. PATIENTS AND METHODS: A cross-sectional study was conducted that included patients with SLE from April to July 2018. Patients completed the LupusQoL and the "Generalitat de Catalunya" (GENCAT) scale; sociodemographic data, activity index (SLEDAI) and accumulated damage (SLICC), were obtained. Reliability was evaluated by internal consistency and the convergent validity of the LupusQoL was determined with the GENCAT scale. RESULTS: Of the 100 patients, 93% were women, the mean age was 42 years old (SD: 13) and the mean duration of the disease was 11 years (SD: 9); the mean of SLEDAI and SLICC was 3 and 1, respectively. The cutoff point that defined a "better" or "worse" HRQoL for LupusQoL was 64.55 points. A moderate convergence was found after grouping, according to the cutoff points, of the LupusQoL with the GENCAT scale (Cohen's kappa coefficient = .556; p = .000). CONCLUSIONS: The LupusQoL is a valid psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela. Cutoff points were established to stratify the HRQoL in the Venezuelan population with LES, being useful to complement a comprehensive evaluation.

Validation of the LupusQoL in Venezuela: A Specific Measurement of Quality of Life in Patients with Systemic Lupus Erythematosus. / Validación del LupusQoL en Venezuela: una medida específica de la calidad de vida en pacientes con lupus eritematoso sistémico.

BACKGROUND AND OBJECTIVES: Traditionally, the health-related quality of life (HRQoL) of patients with systemic lupus erythematosus (SLE) has been assessed using instruments that neglect the specific characteristics of the disease. This study determines the validity of the Lupus Quality of Life (LupusQoL) questionnaire as a psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela and establishes the cutoff points of the questionnaire for the Venezuelan population. PATIENTS AND METHODS: A cross-sectional study was conducted that included patients with SLE from April to July 2018. Patients completed the LupusQoL and the Generalitat de Catalunya (GENCAT) scale; sociodemographic data, activity index (SLEDAI) and accumulated damage (SLICC), were obtained. Reliability was evaluated by internal consistency and the convergent validity of the LupusQoL was determined with the GENCAT scale. RESULTS: Of the 100 patients, 93% were women, the mean age was 42years old (SD: 13) and the mean duration of the disease was 11years (SD: 9); the mean of SLEDAI and SLICC was 3 and 1, respectively. The cutoff point that defined a "better" or "worse" HRQoL for LupusQoL was 64.55 points. A moderate convergence was found after grouping, according to the cutoff points, of the LupusQoL with the GENCAT scale (Cohen's kappa coefficient=.556; p=.000). CONCLUSIONS: The LupusQoL is a valid psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela. Cutoff points were established to stratify the HRQoL in the Venezuelan population with LES, being useful to complement a comprehensive evaluation.

The Interaction between NKAP and HDAC3 Is Critical for T Cell Maturation.

NKAP and HDAC3 are critical for T cell maturation. NKAP and HDAC3 physically associate, and a point mutation in NKAP, NKAP(Y352A), abrogates this interaction. To evaluate the significance of NKAP and HDAC3 association in T cell maturation, transgenic mice were engineered for cre-mediated endogenous NKAP gene deletion coupled to induction of NKAP(Y352A) or a wild type (WT) control transgene, NKAP(WT), in double positive thymocytes or regulatory T cells (Tregs). T cell maturation was normal in mice with endogenous NKAP deletion coupled to NKAP(WT) induction. However, severe defects occurred in T cell and Treg maturation and in iNKT cell development when NKAP(Y352A) was induced, recapitulating NKAP deficiency. Conventional T cells expressing NKAP(Y352A) failed to enter the long-term T cell pool, did not produce cytokines, and remained complement susceptible, whereas Tregs expressing NKAP(Y352A) were eliminated as recent thymic emigrants leading to lethal autoimmunity. Overall, these results demonstrate the significance of NKAP-HDAC3 association in T cells.

NKAP Must Associate with HDAC3 to Regulate Hematopoietic Stem Cell Maintenance and Survival.

NKAP is a multifunctional nuclear protein that associates with the histone deacetylase HDAC3. Although both NKAP and HDAC3 are critical for hematopoietic stem cell (HSC) maintenance and survival, it was not known whether these two proteins work together. To assess the importance of their association in vivo, serial truncation and alanine scanning was performed on NKAP to identify the minimal binding site for HDAC3. Mutation of either Y352 or F347 to alanine abrogated the association of NKAP with HDAC3, but did not alter NKAP localization or expression. Using a linked conditional deletion/re-expression system in vivo, we demonstrated that re-expression of the Y352A NKAP mutant failed to restore HSC maintenance and survival in mice when endogenous NKAP expression was eliminated using Mx1-cre and poly-IC, whereas re-expression of wild type NKAP maintained the HSC pool. However, Y352A NKAP did restore proliferation in murine embryonic fibroblasts when endogenous NKAP expression was eliminated using ER-cre and tamoxifen. Therefore, Y352 in NKAP is critical for association with HDAC3 and for HSC maintenance and survival but is not important for proliferation of murine embryonic fibroblasts, demonstrating that NKAP functions in different complexes in different cell types.

HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment.

CD4 and CD8 T cells are vital components of the immune system. We found that histone deacetylase 3 (HDAC3) is critical for the development of CD4 T cells, as HDAC3-deficient DP thymocytes generate only CD8SP thymocytes in mice. In the absence of HDAC3, MHC Class II-restricted OT-II thymocytes are redirected to the CD8 cytotoxic lineage, which occurs with accelerated kinetics. Analysis of histone acetylation and RNA-seq reveals that HDAC3-deficient DP thymocytes are biased towards the CD8 lineage prior to positive selection. Commitment to the CD4 or CD8 lineage is determined by whether persistent TCR signaling or cytokine signaling predominates, respectively. Despite elevated IL-21R/γc/STAT5 signaling in HDAC3-deficient DP thymocytes, blocking IL-21R does not restore CD4 lineage commitment. Instead, HDAC3 binds directly to CD8-lineage promoting genes. Thus, HDAC3 is required to restrain CD8-lineage genes in DP thymocytes for the generation of CD4 T cells.

Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs.

Regulatory T cells are critical for the generation and maintenance of peripheral tolerance. Conditional deletion of the transcriptional repressor NKAP in Tregs using Foxp3-YFP-cre NKAP conditional knockout mice causes aggressive autoimmunity characterized by thymic atrophy, lymphadenopathy, peripheral T cell activation, generation of autoantibodies, immune infiltration into several organs, and crusty skin at 3 weeks of age, similar to that of "scurfy" Foxp3-mutant mice. While Treg development in the thymus proceeds normally in the absence of NKAP, there is a severe loss of thymically-derived Tregs in the periphery. NKAP-deficient Tregs have a recent thymic emigrant phenotype, and are attacked by complement in a cell-intrinsic manner in the periphery. Previously, we demonstrated that NKAP is required for conventional T cell maturation as it prevents complement-mediated attack in the periphery. We now show that Tregs undergo a similar maturation process as conventional T cells, requiring NKAP to acquire complement resistance after thymic egress.

Histone deacetylase 3 is required for iNKT cell development.

NKT cells are a distinct subset that have developmental requirements that often differ from conventional T cells. Here, we show that NKT-specific deletion of Hdac3 results in a severe reduction in the number of iNKT cells, particularly of NKT1 cells. In addition, there is decreased cytokine production by Hdac3-deficient NKT2 and NKT17 cells. Hdac3-deficient iNKT cells have increased cell death that is not rescued by transgenic expression of Bcl-2 or Bcl-xL. Hdac3-deficient iNKT cells have less Cyto-ID staining and lower LC3A/B expression, indicative of reduced autophagy. Interestingly, Hdac3-deficient iNKT cells also have lower expression of the nutrient receptors GLUT1, CD71 and CD98, which would increase the need for autophagy when nutrients are limiting. Therefore, Hdac3 is required for iNKT cell development and differentiation.

An Essential Role for the Transcription Factor Runx1 in T Cell Maturation.

The transcription factor Runx1 has essential roles throughout hematopoiesis. Here, we demonstrate that Runx1 is critical for T cell maturation. Peripheral naïve CD4(+) T cells from CD4-cre Runx1 cKO mice are phenotypically and functionally immature as shown by decreased production of TNF-α upon TCR stimulation. The loss of peripheral CD4(+) T cells in CD4-cre Runx1 cKO mice is not due to defects in homeostasis or decreased expression of IL-7Rα, as transgenic expression of IL-7Rα does not rescue the loss of CD4(+) T cells. Rather, immature Runx1-deficient CD4(+) T cells are eliminated in the periphery by the activation and fixation of the classical complement pathway. In the thymus, there is a severe block in all aspects of intrathymic T cell maturation, although both positive and negative selection are unaltered. Thus, loss of Runx1 leads to the earliest characterized block in post-positive selection intrathymic maturation of CD4 T cells.