Traumatic experiences and place of occurrence: An analysis of sex differences among a sample of recently arrived immigrant adults from Latin America.

With increasing violence, political, and economic instability in Latin America, there is a record number of migrants crossing the U.S. southern border. Latin American migrants are often exposed to traumatic events before leaving their home country and during migration. While prior studies document that sex may play a role in types of traumatic exposure, few studies compare differences in traumatic exposure by sex and place of occurrence of recently arrived immigrants. Addressing this gap, we recruited 120 adults who had recently crossed the U.S.-Mexico border. Participants completed questionnaires to characterize trauma exposures in their home country and during their migration journey. Results found that men reported higher levels of exposure to combat situations, while women were more likely to experience sexual assault. Both combat exposure and sexual traumas occurred more often in home countries than during migration. More than half of the full sample reported being threatened with a firearm. These data confirm gender differences in type of trauma and that exposures in the country of origin may provide the impetus to migrate.

Genetic ancestry is related to potential sources of breast cancer health disparities among Colombian women.

Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These factors collectively interact in complex ways, influencing disease behavior, especially among highly admixed populations like Colombians. In this study, we assessed contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. We collected non-tumoral paraffin embedded (FFPE) blocks from 361 women diagnosed with breast cancer at the National Cancer Institute (NCI) to estimate genetic ancestry using a 106-ancestry informative marker (AIM) panel. Differences in European, Indigenous American (IA) and African ancestry fractions were analyzed according to potential sources of breast cancer health disparities, like etiology, tumor-biology, treatment administration, and socioeconomic-related factors using a Kruskal-Wallis test. Our analysis revealed a significantly higher IA ancestry among overweight patients with larger tumors and those covered by a subsidized health insurance. Conversely, we found a significantly higher European ancestry among patients with smaller tumors, residing in middle-income households, and affiliated to the contributory health regime, whereas a higher median of African ancestry was observed among patients with either a clinical, pathological, or stable response to neoadjuvant treatment. Altogether, our results suggest that the genetic legacy among Colombian patients, measured as genetic ancestry fractions, may be reflected in many of the clinical-pathological variables and socioeconomic factors that end up contributing to health disparities for this disease.

Feasibility and reliability of a quality indicator system for an ambulatory dispensing service.

Background: For a medication dispensing service to function with quality, continuous evaluation is required, which is why it is necessary to have reliable measurement tools that make it possible. Quality indicators can serve as tools for managing quality, as they are variables that directly or indirectly measure changes in a situation and help evaluate the progress made in addressing it. This article aims to determine the feasibility and reliability of a quality indicator system for a drug dispensing service for paediatric outpatients in two Mexican hospitals. Methods: A study of the development type of health systems and services at a microlevel was conducted from October 2020 to October 2021 in the pharmaceutical service of two Mexican hospitals. To determine the feasibility of the quality indicators, a retrospective evaluation was performed, which considered the indicators that could be calculated with the available information to be feasible. To determine reliability, an inter-observer agreement study (Kappa (κ)) was performed. Results: The feasibility analysis revealed that all five reference indicators related to the structure were feasible in both hospitals. In the Infantil of the Californias hospital, all six process indicators evaluated were feasible, whilst only one was found feasible in H+ Querétaro. As for outcome indicators, only one was feasible in the Infantil of the Californias hospital. The causes of non-feasibility in both hospitals were the non-documentation of the primary data related to the stages of the process and the lack of instruments to measure patient satisfaction. The reliability of the indicators showed little variability. Conclusion: Although not all indicators were feasible, solutions were proposed so that the 15 reference indicators could be used if an organization decided to do so. The reliability of the indicators was demonstrated, evidencing the importance of the data sheet as a tool to generate valid reliable measures.This article is part of the Hospital pharmacy, rational use of medicines and patient safety in Latin America Special Issue: https://www.drugsincontext.com/special_issues/hospital-pharmacy-rational-use-of-medicines-and-patient-safety-in-latin-america/.

Treatment patterns and persistence on disease modifying therapies for multiple sclerosis and its associated factors.

BACKGROUND: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. OBJECTIVES: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. METHODS: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. RESULTS: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. CONCLUSIONS: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.

Seasonality and clinical characteristics of MS in an equatorial country.

BACKGROUND: Month and season of birth have been associated with risk of multiple sclerosis (MS), but there is relatively little evidence regarding their influence on the timing and severity of disease at onset. OBJECTIVE: To assess whether month and season of birth influence the age and phenotype at onset of MS as well as its severity in a cohort of Colombian patients. METHODS: This study is an analysis on MS cases only, drawn from a previously published case-control study. MS cases confirmed with current diagnostic criteria cared for at least once in our center were included. We assessed the influence of the month and season of birth in the age at MS onset, MS severity score, and age-related MS severity score using multiple and pairwise comparisons. Age at onset was also studied using Kaplan-Meier survival estimates compared with the log-rank test. The likelihood of progressive MS onset was evaluated with OR estimated from logistic regression models adjusted for age at onset and sex. RESULTS: 668 MS cases were included. No significant differences were found in the age at MS onset according to month of birth or season of birth. Neither month of birth nor season of birth conferred significant differences in MS severity score or age-related MS severity score. No significant association was found between month (ORs ranging from 0.62 to 3.11, none significant) or season of birth (OR 0.91; 95 %CI: 0.46-1.84) with primary progressive MS. CONCLUSION: The month or season of birth do not appear to influence the age onset and phenotype of MS in our country.

Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico.

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.

Tumor infiltrating lymphocytes (TILs) are a prognosis biomarker in Colombian patients with triple negative breast cancer.

Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with favorable clinical-pathological features. Survival analysis showed that longer overall survival times were observed in patients with a higher infiltration of sTILs (p = 0.00043), CD4 + (p = 0.0074) and CD8 + (p = 0.008). In the multivariate analysis, low levels of sTILs were found to be associated with a higher mortality hazard (HR: 1.59, 95% CI 1.01-2.48). CD4 and CD8 immune infiltration were associated with higher odds for pathological complete response (OR: 1.20, 95% CI 1.00-1.46, OR: 1.28, 1.02-1.65, respectively). Our results suggest that immune infiltration could be used as a prognostic marker for overall survival in TNBC patients.

Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study / Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto.

Introduction: Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective: To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods: We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results: Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions: We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

Introducción: El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo: Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos: Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados: Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones: Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

A comparison of PTSD and traumatic event rates in a clinical sample of non-refugee immigrants and native-born individuals with a psychotic disorder: a case-control study.

Background: Migration is a multi-stage social process linked to traumatic event exposure and a notably increased risk of psychosis. Although these conditions affect refugee and non-refugee immigrants, prior trauma research has focused mainly on the refugee population.Objective: To compare and describe the rate and the clinical characterization of PTSD and traumatic events between non-refugee immigrants and native-born individuals with psychotic disorder.Methods: 99 immigrants and 99 native-born individuals (n = 198) with at least one psychotic episode according to DSM-5 criteria were compared on the rate of PTSD diagnosis and traumatic events, using standardized and validated trauma scales.Results: In the non-refugee immigrant group, 31% met diagnostic criteria for PTSD compared to only 7.1% in the native-born group. Total scores in childhood trauma and last year stressful events were 1.5 and 2 times higher in non-refugee immigrants, respectively. Likewise, cumulative lifetime trauma was three times higher in non-refugee immigrants. Finally, non-refugee immigrants reported more violent and life-threatening traumatic events than native-born individuals.Conclusions: These results are relevant since they highlight that non-refugee immigrants with psychotic disorders are highly trauma-exposed, meaning a routine trauma assessment and a trauma-focused intervention for this population should be included in individualized treatment plans.

Traumatic events and PTSD rates in the non-refugee immigrant population with psychotic disorder have previously received scant attention.This study found that in a psychotic population, 31% of the non-refugee immigrants presented a PTSD diagnosis compared to only 7.1% of the native-born individuals.Compared to native-born individuals with psychosis, non-refugee immigrants with psychosis have 1.5 times more childhood trauma exposure, 2 times more stressful events in the past year and 3 times more cumulative trauma over their lifetime.

Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto / Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study

Introducción. El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo. Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos. Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados. Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones. Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

Introduction. Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective. To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods. We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results. Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions. We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

In Vitro and In Silico Study on the Impact of Chlorogenic Acid in Colorectal Cancer Cells: Proliferation, Apoptosis, and Interaction with ß-Catenin and LRP6.

Colorectal cancer mortality rate and highly altered proteins from the Wnt/ß-catenin pathway increase the scientific community's interest in finding alternatives for prevention and treatment. This study aims to determine the biological effect of chlorogenic acid (CGA) on two colorectal cancer cell lines, HT-29 and SW480, and its interactions with ß-catenin and LRP6 to elucidate a possible modulatory mechanism on the Wnt/ß-catenin pathway. These effects were determined by propidium iodide and DiOC6 for mitochondrial membrane permeability, MitoTracker Red for mitochondrial ROS production, DNA content for cell distribution on cell cycle phases, and molecular docking for protein-ligand interactions and binding affinity. Here, it was found that CGA at 2000 µM significantly affects cell viability and causes DNA fragmentation in SW480 cells rather than in HT-29 cells, but in both cell lines, it induces ROS production. Additionally, CGA has similar affinity and interactions for LRP6 as niclosamide but has a higher affinity for both ß-catenin sites than C2 and iCRT14. These results suggest a possible modulatory role of CGA over the Wnt/ß-catenin pathway in colorectal cancer.

Análisis de la coexpresión de HER2/GRB7 y su asociación con variables clinicopatológicas en un grupo de mujeres colombianas con diagnóstico de cáncer de mama invasivo / Analysis of HER2/GRB7 co-expression and its association with clinicopathological variables in a group of Colombian women diagnosed with invasive breast cancer

Objetivo. Analizar las diferencias en la presentación de variables clínico-patológicas, de acuerdo con la expresión proteica de GRB7, en tumores HER2 positivos en mujeres colombianas con cáncer de mama invasivo, diagnosticado entre los años 2013 y 2015 en el Instituto Nacional de Cancerología E.S.E (INC). Métodos. Se incluyeron 158 pacientes con diagnóstico confirmado de cáncer de mama ductal invasivo. Se evaluó la expresión de los receptores hormonales (receptor de estrógeno (RE) y de progesterona (RP)), HER2, Ki67 y GRB7, mediante inmunohistoquímica (IHQ), y a partir de estos, se clasificaron los tumores en subtipos intrínsecos. Los análisis estadísticos incluyeron las pruebas de Chi-cuadrado/test exacto de Fisher para las variables categóricas, y la prueba U Mann Whitney/ Kruskal Wallis para las variables cuantitativas. Se evaluó la supervivencia global (SG) y libre de enfermedad (SLR) según la coexpresión de HER2/GRB7 usando el método de Kaplan-Meier y el test de log-rank. Resultados. La expresión de GRB7 se observó exclusivamente en tumores HER2-positivos (luminal B/HER2+ y HER2-enriquecidos: p<0,001). Los casos HER2+/GRB7+ mostraron una mayor expresión de Ki67 (40% vs. 27,5%, p=0,029), pero una tendencia a presentar un menor tamaño tumoral (30 mm vs. 51 mm, p=0,097), comparado con los tumores HER2+/GRB7-. No obstante, no se observaron diferencias en la supervivencia según la coexpresión de HER2/GRB7 (SG: p=0,6; SLR: p=0,07). Conclusiones. En nuestra muestra de estudio, la expresión de GRB7 en tumores HER2+ no se asoció con características clínico-patológicas de pronóstico desfavorable.

Objective: To analyze differences in the presentation of clinicopathological variables according to GRB7 protein expression in HER2-positive tumors in Colombian patients with invasive ductal breast carcinomas diagnosed between 2013 and 2015 at the Instituto Nacional de Cancerología (Bogotá, Colombia).Methods: A total of 158 breast cancer patients were included with a confirmed diagnosis of invasive ductal carcinoma. A single pathologist evaluated the protein expression of hormone receptors (estrogen (ER) and progesterone receptor (PR)), HER2, Ki67, and GRB7 by immunohistochemistry (IHC). The chi-square and Fisher's exact tests were used to assess differences between categorical variables, as well as the Mann-Whitney/Kruskal-Wallis U test for numerical variables. Overall (OS) and disease-free (DFS) survival were evaluated according to HER2/GRB7 co-expression using the Kaplan-Meier method and log-rank test.Results:GRB7 expression was observed exclusively in HER2-positive tumors (luminal B/HER2+ and HER2-enriched: p<0.001). HER2+/GRB7+ cases showed higher Ki67 expression (40% vs. 27.5%, p=0.029) and a tendency to present a smaller tumor (30 mm vs. 51 mm, p=0.097) compared to HER2+/GRB7- tumors. However, no differences in OS or DFS were observed by HER2/GRB7 co-expression (OS: p=0.6; DFS: p=0.07).Conclusions:Our results in Colombian patients indicate that GRB7 expression in HER2-positive breast tumors is not associated with unfavorable clinicopathological features.

The role of in-person focus groups in the management of urinary incontinence in women from a mixed-methods, randomized pilot study.

PURPOSE: To assess the quantitative and qualitative components of in-person focus groups as a potential intervention for female patients with urinary incontinence. METHODS: Women over the age of 18 seeking treatment for UI were randomized to standard care with focus group participation or to standard care alone. All participants completed validated questionnaires: MESA, UDI-6, OAB-SAT-q, PGI-S, PGI-I, SQoL-F, PHQ-9, IPAQ at the beginning and conclusion of the study. Questionnaires were analyzed with repeated measures of ANOVA models in an intention-to-treat manner. Three moderated focus group sessions were held and audio recorded. Recordings were transcribed and categorized by frequency into themes using grounded theory methodology. RESULTS: A total of ten control and eight intervention participants agreed to participate. Seven women attended all three focus group sessions and were included in the final analysis. Transcripts from focus group sessions observed women identified most with (1) urinary incontinence (UI) as a chronic disease, (2) shame managing UI, and (3) social constraints of toileting. Participants self-reported appreciation of focus group participation and desire for on-going sessions. Analysis of the questionnaires did not demonstrate statistically significant differences. CONCLUSION: Data ascertained from questionnaires were unable to demonstrate a meaningful effect in improved treatment outcomes for control and intervention participants. Grounded theory analysis of transcripts identified four primary themes: (1) appreciation of the focus group, (2) UI as a gendered issue, (3) lack of public awareness, and (4) history of negative provider interactions. All focus group participants self-reported interest in attending future focus group sessions.

Meningoencefalitis por virus Varicella-Zóster posterior a infección por SARS-CoV2: Reporte de dos casos / Meningoencephalitis caused by Varicella-Zoster virus after SARS-CoV2 infection: Two cases report

RESUMEN La meningoencefalitis por el VZV es una patología poco frecuente que se presenta con la reactivación del virus dentro del organismo. OBJETIVO: Describir la presentación clínica de dos pacientes con neuroinfección por VZV posteriormente a infección por SARS-CoV-2. REPORTE DEL CASO: El primer caso corresponde a un hombre de 59 años con antecedente de neumonía moderada por SARS-CoV-2 que después cursó con meningoencefalitis por VZV y, además, desarrolló un síndrome de Ramsay Hunt. El segundo caso es el de una mujer de 37 años con antecedente de infección leve por SARS CoV-2 con un cuadro de cefalea con signos de alarma, en quien se documentó neuroinfección por VZV

ABSTRACT Meningoencephalitis caused by varicella zoster virus is a rare pathology that presents due to the reactivation of the virus in the organism OBJECTIVE: To describe the clinical presentation of two patients with VZV neuroinfection presented after a SARS CoV-2 infection. CASE REPORT: The first case is a 59 year old male with previous moderate SARS CoV-2 infection who presented meningoencephalitis and was diagnosed with Ramsay Hunt's Syndrome. The second case is a 37 year old female with previous SARS CoV-2 infection who presented with an acute onset headache and was documented with VZV neuroinfection.

Comparison of two screeners predicting the future development of depression and posttraumatic stress disorder in Black men after serious injury.

Background To assess the predictive performance of two established, short clinical screeners in predicting the future development of post-injury depression and PTSD. Methods This was a prospective, cohort design with a 3-month follow-up. Black adult male trauma patients were enrolled at an urban, Level 1 trauma center. The Penn Richmond Screener and the Posttraumatic Adjustment Scale (PAS) were collected in-hospital. Participants were categorized as depressed using the Quick Inventory of Depressive Symptoms-Self Report and as positive for PTSD using the PTSD Check List - 5 (PCL-5) at 3-months post-discharge. Sensitivity, specificity, PPV and NPV of each screener were calculated. We used receiver operating curve (ROC) analyses to calculate the area under the curve (AUC) with 95% CI to assess predictive performance of each screener. Results A cohort of 623 hospitalized, injured Black men were enrolled during acute hospitalization. 503 participants (80.6%) were retained at 3-months and formed the analytic sample. Mean age was 36.8 years (SD 15.4), 53.1% of injuries were intentional; median injury severity score was 9. At 3 months, 35.3% had moderate to severe depression, 32.7% had significant PTSD symptoms, and 22.4% met criteria for both depression and PTSD. Penn Richmond Screener: sensitivity 0.68, specificity 0.56, and AUC 0.62 for PTSD, and sensitivity 0.64, specificity 0.63, and AUC 0.64 for depression. PAS: sensitivity 0.59, specificity 0.73, and AUC 0.66 for PTSD, and sensitivity 0.75, specificity 0.49, and AUC 0.62 for depression. Conclusions This study validated the performance of both screeners within the same population, allowing a direct comparison. Two predictive screeners, developed through different methods and in different countries, showed comparable predictive ability. These findings indicate that risk markers for adverse psychological consequences of traumatic injury share some core similarities across populations and countries.

The Permeating Effects of Violence on Health Services and Health in Mexico.

Mexico's violence related to organized crime activity has grown to epidemic levels in the last 12 years. We interviewed 22 Mexican health care providers from five states to examine how violence impacts health care services and health. We transcribed and analyzed semi-structured interviews using framework analysis. Our findings describe the ways in which community violence in Mexico permeates health care services, impacting health care providers, and the health of patients. We developed a model to reflect our main themes that illustrate how violence permeates health care services over geographic space and time. We identified three thematic categories: (a) the impact of violence on health care facilities and service provision, (b) the impact of violence on providers, and (c) the impact of violence on the health of the community. Our model articulates a dynamic process of the spread and permeation of violence. Prior literature focuses on the impact of violence as an occupational hazard and the effect of war or civil conflict on health care services. We extend this literature by documenting the impacts of widespread violence on Mexican health care services and providers. We discuss how violence impacts services, providers, and health in a country that is not officially at war. We compare our findings to previous literature on occupational violence in health professions and the impacts on health services in official war zones. Finally, we highlight the implications for health care practice and policy. We suggest that violence should be considered throughout the care continuum in Mexico and make the case for violence as a structural contributor to health and health disparities in Mexico. We suggest additional research on this under-investigated topic.

Perinatal inflammation and gestational intermittent hypoxia disturbs respiratory rhythm generation and long-term facilitation in vitro: Partial protection by acute minocycline.

Perinatal inflammation triggers breathing disturbances early in life and affects the respiratory adaptations to challenging conditions, including the generation of amplitude long-term facilitation (LTF) by acute intermittent hypoxia (AIH). Some of these effects can be avoided by anti-inflammatory treatments like minocycline. Since little is known about the effects of perinatal inflammation on the inspiratory rhythm generator, located in the preBötzinger complex (preBötC), we tested the impact of acute lipopolysaccharide (LPS) systemic administration (sLPS), as well as gestational LPS (gLPS) and gestational chronic IH (gCIH), on respiratory rhythm generation and its long-term response to AIH in a brainstem slice preparation from neonatal mice. We also evaluated whether acute minocycline administration could influence these effects. We found that perinatal inflammation induced by sLPS or gLPS, as well as gCIH, modulate the frequency, signal-to-noise ratio and/or amplitude (and their regularity) of the respiratory rhythm recorded from the preBötC in the brainstem slice. Moreover, all these perinatal conditions inhibited frequency LTF and amplitude long-term depression (LTD); gCIH even induced frequency LTD of the respiratory rhythm after AIH. Some of these alterations were not observed in slices pre-treated in vitro with minocycline, when compared with slices obtained from naïve pups, suggesting that ongoing inflammatory conditions affect respiratory rhythm generation and its plasticity. Thus, it is likely that alterations in the inspiratory rhythm generator and its adaptive responses could contribute to the respiratory disturbances observed in neonates that suffered from perinatal inflammatory challenges.

Association of genetic ancestry with HER2, GRB7 AND estrogen receptor expression among Colombian women with breast cancer.

Background: Our previous study reported higher mRNA levels of the human epidermal growth factor receptor 2 (HER2)-amplicon genes ERBB2 and GRB7 in estrogen receptor (ER)-positive breast cancer patients with relatively high Indigenous American (IA) ancestry from Colombia. Even though the protein expression of HER2 and GRB7 is highly correlated, they may also express independently, an event that could change the patients' prognosis. In this study, we aimed to explore the differences in ER, HER2 and GRB7 protein expression according to genetic ancestry, to further assess the clinical implications of this association. Methods: We estimated genetic ancestry from non-tumoral breast tissue DNA and assessed tumoral protein expression of ER, HER2, and GRB7 by immunohistochemistry in a cohort of Colombian patients from different health institutions. We used binomial and multinomial logistic regression models to test the association between genetic ancestry and protein expression. Kaplan-Meier and log-rank tests were used to evaluate the effect of HER2/GRB7 co-expression on patients' survival. Results: Our results show that patients with higher IA ancestry have higher odds of having HER2+/GRB7- breast tumors, compared to the HER2-/GRB7- subtype, and this association seems to be stronger among ER-positive tumors (ER+/HER2+/GRB7-: OR=3.04, 95% CI, 1.47-6.37, p<0.05). However, in the multivariate model this association was attenuated (OR=1.80, 95% CI, 0.72-4.44, p=0.19). On the other hand, it was observed that having a higher European ancestry patients presented lower odds of ER+/HER2+/GRB7- breast tumors, this association remained significant in the multivariate model (OR=0.36, 95% CI, 0.13 - 0.93, p= 0.0395). The survival analysis according to HER2/GRB7 co-expression did not show statistically significant differences in the overall survival and recurrence-free survival. Conclusions: Our results suggest that Colombian patients with higher IA ancestry and a lower European fraction have higher odds of ER+/HER2+/GRB7- tumors compared to ER+/HER2-/GRB7- disease. However, this association does not seem to be associated with patients' overall or recurrence-free survival.

Evaluation of Inhibitory Activity In Silico of In-House Thiomorpholine Compounds between the ACE2 Receptor and S1 Subunit of SARS-CoV-2 Spike.

At the end of 2019, the world was struck by the COVID-19 pandemic, which resulted in dire repercussions of unimaginable proportions. From the beginning, the international scientific community employed several strategies to tackle the spread of this disease. Most notably, these consisted of the development of a COVID-19 vaccine and the discovery of antiviral agents through the repositioning of already known drugs with methods such as de novo design. Previously, methylthiomorphic compounds, designed by our group as antihypertensive agents, have been shown to display an affinity with the ACE2 (angiotensin converting enzyme) receptor, a key mechanism required for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) entry into target cells. Therefore, the objective of this work consists of evaluating, in silico, the inhibitory activity of these compounds between the ACE2 receptor and the S1 subunit of the SARS-CoV-2 spike protein. Supported by the advances of different research groups on the structure of the coronavirus spike and the interaction of the latter with its receptor, ACE2, we carried out a computational study that examined the effect of in-house designed compounds on the inhibition of said interaction. Our results indicate that the polyphenol LQM322 is one of the candidates that should be considered as a possible anti-COVID-19 agent.