Complicated grief and its relationship with anxiety, depression, and suicidal ideation in older adults in the context of the COVID-19 pandemic in Peru: a cross-sectional analysis.

BACKGROUND: Complicated grief (CG) resulting from poor adaptation to the death of a close person may have been related with the presence of other mental health problems in older adults in Peru during the COVID-19 pandemic. Our study aimed to assess the association between CG and anxiety, depression, and suicidal ideation in older adults in Peru in the context of the COVID-19 pandemic. METHODS: We conducted a cross-sectional analysis using data from the "Socioemotional evaluation form" applied in 2020 to mental health problems in older adults attending the Peruvian Social Security (EsSalud). For our study, we included older adults who reported the death of a close person during the last six months when this assessment was performed. CG, depression, anxiety, and suicidal ideation were initially evaluated using validated questionnaires. The association between CG and the presence of mental health problems was calculated through multivariate analysis, where prevalence ratios (PR) were estimated with 95% confidence intervals (CI). RESULTS: Of the 249 older adults included, 175 (70.3%) were female with a median age of 71 years (interquartile range: 9), and 35 (14.1%) reported the presence of CG. It was found that CG in this population was associated with the presence of anxiety (PR: 1.35, 95% CI: 0.98 to 1.85), depression (PR: 1.44, 95% CI: 1.06 to 1.95), and suicidal ideation (PR: 2.84, 95% CI: 1.06 to 7.59). CONCLUSIONS: CG is related to the presence of mental health problems in older adults in Peru. It is essential to implement measures that facilitate the prevention and proper management of this condition in this population, especially in the context of high population mortality such as the COVID-19 pandemic.

Factors Associated with Anxiety, Depression, and Stress in Peruvian University Students during the COVID-19 Pandemic.

During the COVID-19 pandemic, university students have adopted measures that completely transformed their educational environment, and this has generated an increase in psychological stress. The present study aimed to identify the factors associated with anxiety, depression, and stress in students at a university in Peru during the COVID-19 pandemic in 2020. We conducted a cross-sectional analytical study in students in Lima, Peru. The DASS-21 scale was used to measure levels of depression, anxiety, and stress and associate it with socio-educational and COVID-19-related variables using generalized linear models with Poisson distribution, log link, and robust variance. Of 400 students surveyed, 19.2%, 23.2% and 17.2% of students presented depression, anxiety, and stress, respectively. The frequency of depression (PR = 0.91, 95%CI: 0.84-0.99), anxiety (PR = 0.90, 95%CI: 0.83-0.99) and stress (PR = 0.92, 95%CI: 0.86-0.99) was lower in women. The students of the engineering and business faculty presented a higher frequency of anxiety (PR = 1.11, 95%CI: 1.00-1.22). There was a greater frequency of presenting anxiety, depression and stress in students who worked in a different area of health or did not work. Our results suggest the importance of promoting mental health awareness campaigns in university students due to the constant academic load they have.

Programa de Teleconsulta Docente: percepciones de profesores y alumnos de una facultad de medicina peruana / Teaching Teleconsultation Program: perceptions of professors and students of a peruvian medical school

RESUMEN Introducción: La llegada de la pandemia de COVID-19 al Perú requirió una respuesta inmediata y múltiples cambios tanto en la atención sanitaria como en el entrenamiento de los profesionales de la salud. La Facultad de Medicina de la Universidad Peruana Cayetano Heredia implementó el Programa de Teleconsulta Docente (PTD), para continuar con la formación de estudiantes de medicina en un entorno virtual, sin embargo, se desconoce la aceptación de los involucrados respecto a una educación virtual, condición que puede reflejar lo ocurrido en otras escuelas de medicina del país. Objetivo: nuestro estudio buscó evaluar la percepción de alumnos y docentes respecto al PTD. Métodos: estudio observacional, descriptivo y transversal. Se elaboró un cuestionario para explorar las percepciones de la telemedicina en el escenario de la enseñanza. Resultados: más del 80 % de los profesores y el 60 % de los alumnos consideraron que la PTD podía utilizarse como herramienta de enseñanza. Más del 90 % de los profesores y los estudiantes consideran que realizar la telemedicina no fue más difícil que hacer una consulta presencial. El 60 % de los estudiantes y el 80 % de los profesores perciben que los estudiantes deben desarrollar habilidades en telemedicina; el 80 % de los profesores y estudiantes consideran que la PTD constituye un servicio de responsabilidad social. Profesores y alumnos consideran que el éxito en la implantación de un PTD está influenciado por el nivel de aceptación de la población (20,2 %), el uso de la historia clínica electrónica (19,4 %) y la formación en competencias digitales (18,6 %). Conclusión: los profesores y los estudiantes del PTD perciben la telemedicina como una herramienta útil para evaluar los problemas de salud de la población. Ambos perciben que a través de las sesiones de telemedicina se podrían adquirir las habilidades necesarias para completar el perfil de egresado de la carrera de medicina.

ABSTRACT Introduction : The occurrence of the COVID-19 pandemic in Peru required an immediate response and multiple changes in both healthcare and health professional training. The School of Medicine in Universidad Peruana Cayetano Heredia implemented the Teleconsultation Faculty Program (FTP), aiming to continue with training medicine students in a virtual environment. However, the acceptance of those involved in virtual education is unknown, a condition that may reflect what has happened in other medical schools in our country. Main : our study sought to assess the perception of students and teachers regarding FTP. Methods : observational, descriptive, cross-sectional study. A questionnaire was developed to explore perceptions of telemedicine in a teaching scenario. Results : More than 80% of teachers and 60% of students considered that the FTP could be used as a teaching tool. More than 90% of teachers and students consider that performing telemedicine was not more difficult than doing a face-to-face consultation. Sixty percent of students and 80% of teachers perceive that students must develop skills in telemedicine; 80% of teachers and students consider that FTP constitutes a service with social responsibility. Teachers and students consider that the success in the implementation of an FTP is influenced by the level of acceptance of the population (20.2%), the use of electronic medical records (19.4%), and training in digital skills (18.6%). Conclusion : Teachers and students using FTP perceive telemedicine as a useful tool for assessing health problems. Both perceive that through telemedicine sessions, skills required to complete the medical school graduate profile could be acquired.

Factores asociados al rendimiento académico en estudiantes de medicina

RESUMEN Introducción: El rendimiento académico universitario puede verse afectado por diversos factores personales y ambientales. Objetivo: Determinar los factores asociados al rendimiento académico en estudiantes de medicina de una universidad peruana. Métodos: Estudio transversal realizado en 247 estudiantes del primer al noveno ciclo. Se recopiló las calificaciones de la asignatura con el mayor número de créditos y se aplicó una encuesta para recolectar datos sobre sexo, estado civil, carrera previa, estado laboral y nivel de ansiedad. Se realizó un análisis de regresión simple y múltiple para estimar la asociación entre el rendimiento académico y las variables sociodemográficas de los encuestados. Resultados: El 70 % fueron mujeres, la mediana de edad fue 21 años. El 79,4 % reportó haber culminado una carrera. Casi la cuarta parte reportó tener una actividad laboral (24,3 %). El 46,2 % de universitarios presentó ansiedad. La mediana de nota obtenida fue 16 puntos. En el análisis de regresión simple se encontró que haber realizado una carrera previa (p= 0,044) y tener actividad laboral (p= 0,038) estuvieron asociados positivamente al puntaje de rendimiento académico. Sin embargo, en el análisis de regresión múltiple, no se mantuvo las diferencias observadas en ambas variables (p> 0,05). Conclusión: La mediana de nota en el período de estudio es 16 puntos. La mayoría tiene carrera previa y casi un tercio se encuentra laborando. La prevalencia de ansiedad es importante. Sin embargo, no se observa una asociación estadísticamente significativa entre los factores estudiados y el rendimiento académico.

ABSTRACT Introduction: University academic performance can be affected by various personal and environmental factors. Objective: To determine the factors associated with academic performance in medical students at a Peruvian university. Methods: Cross-sectional study conducted in 247 students from the first to the ninth cycle. The grades of the subject with the highest number of credits were collected and a survey was applied to collect data on sex, marital status, previous career, work status, and anxiety level. A simple and multiple regression analysis was performed to estimate the association between academic performance and sociodemographic variables of the respondents. Results: 70 % were female, median age was 21 years. Seventy-nine-point four percent reported having completed a career. Almost a quarter reported having a job (24,3 %). Anxiety was reported by 46,2 % of university students. The median grade obtained was 16 points. In the simple regression analysis, it was found that having a previous career (p= 0,044) and having a job (p= 0,038) were positively associated with the academic performance score. However, in the multiple regression analysis, the differences observed in both variables were not maintained (p> 0,05). Conclusion: The median grade in the study period is 16 points. Most of them have a previous career and almost a third are working. The prevalence of anxiety is significant. However, there is no statistically significant association between the factors studied and academic performance.

Description of frequent and persistent symptoms of COVID-19 among older adults who attend senior centers. / Descripción de síntomas frecuentes y persistentes de COVID-19 en asistentes a centros del adulto mayor.

INTRODUCTION: COVID-19 not only acutely compromises peoples health but can also generate symptoms that remain weeks after the infection. Moreover, older adults may have different symptomatologic patterns than other age groups. OBJECTIVE: To describe the acute and persistent symptoms of COVID-19 in older adult users of Social Security senior centers. METHODS: A retrospective descriptive study was carried out by telephone call to older adults from five Peruvian senior centers, from July to September 2020, who reported being positive for COVID-19 in the last three months. Older adults were asked about associated symptoms, with a follow-up of up to four months. RESULTS: The most frequent acute symptoms were cough, fever, headache, and myalgia. The mean num- ber of symptoms per person was one to three. We also found that 4.4% of COVID-19 cases had symptoms that persisted over three weeks. CONCLUSIONS: Older persons in senior centers have a low frequency of persistent COVID-19 symptoms.

INTRODUCCIÓN: COVID-19 no sólo compromete agudamente la salud de las personas, sino que puede generar síntomas que permanecen luego de la infección aguda, incluso por más de tres semanas. Más aún, las personas adultas mayores podrían tener patrones sintomatológicos diferentes a otros grupos etarios. OBJETIVO: Describir los síntomas agudos y persistentes de COVID-19 en personas adultas mayores usuarias de centros del adulto mayor de la Seguridad Social. MÉTODO: Se realizó un estudio descriptivo retrospectivo por llamada telefónica a adultos mayores de cinco centros del adulto mayor peruanos, de julio a septiembre de 2020, quienes habían reportado ser positivos a COVID-19 en el monitoreo telefónico de los últimos tres meses. En las llamadas se les pregunto por los síntomas asociados, con un seguimiento de hasta cuatro meses. RESULTADOS: Los síntomas agudos más frecuentes fueron tos, fiebre, cefalea y mialgia. La media de síntomas por persona fue de uno a tres. Un 4,4% de los casos tuvo COVID-19 prolongado. CONCLUSIONES: Las personas mayores de los centros del adulto mayor presentan una baja frecuencia de síntomas post COVID-19 agudo.

Social vulnerability during the COVID-19 pandemic in Peru.

The COVID-19 pandemic has demanded governments and diverse organizations to work on strategies to prepare and help communities. Increasing recognition of the importance of identifying vulnerable populations has raised a demand for better tools. One of these tools is the Social Vulnerability Index (SVI). The SVI was created in 2011 to identify and plan assistance for socially vulnerable populations during hazardous events, by providing disaster management personnel information to target specific areas. We aimed to evaluate and determine the social vulnerability in different provinces and districts of Peru in the context of the COVID-19 pandemic using an adapted version of the SVI index. Ecological, observational, and cross-sectional study was conducted. We adapted the SVI and collected indicators related to COVID-19. We organized and analyzed the population data of the 196 provinces of Peru, using data from government institutions. We found a distribution of high and very high SVI in the mountainous areas of Peru. High and very high social vulnerability indexes, due to the presence of some or all the variables were predominantly distributed in the provinces located in the southern and highlands of the country. The association between mortality rate and social SVI-COVID19 was inverse, the higher the vulnerability, the lower the mortality. Our results identify that the provinces with high and very high vulnerability indexes are mostly located in rural areas nearby the Andes Mountains, not having a direct correlation with COVID-19 mortality.

Clinical characteristics and sociodemographic factors associated with COVID-19 infection in pregnant women in a maternal and children's public hospital. / Características clínicas y factores sociodemográficos asociados a infección por COVID-19 en gestantes de un hospital público materno infantil.

OBJECTIVE: To describe the clinical characteristics and sociodemographic factors associated with COVID-19 among pregnant women in a maternal and children's hospital in Lima, Peru. METHODS: Quantitative observational study. The population under study consisted of pregnant women who attended an emergency room and had a COVID-19 test. These women were assessed for age, gestational age, place of origin, occupation, education, marital status, number of children, previous body mass index, gestational body mass index, tetanus vaccination, prenatal controls, and hemoglobin. After bivariate analysis, a generalized linear regression model was applied. RESULTS: We included 200 women aged between 18 and 34 years (84.5%) with a median gestational age of 36 weeks. More than half were from Lima (52.5%), most were housewives (79%), had high school education (71.9%), and had a cohabiting marital status (60%). The COVID-19 test positivity was 31.5% by rapid tests. Pregestational body mass index assessment showed that 36.7% of normal weight, 38,1% of overweight, and 30.3% of obese pregnant women had COVID-19 infection. 39.7% of patients with hemoglobin levels greater than or equal to 11 g/dL, 21.2% of patients with values between 10 and 10.9 g/dL, and 20% of patients with values between 7 and 9.9 g/dL had COVID-19 infection. The prevalence ratio (with a 95% confidence interval) found that cohabitation was associated with a lower risk of having COVID-19 infection in pregnant women (prevalence ratio: 0.41, p < 0.001). CONCLUSION: Cohabiting pregnant women had a lower risk of COVID-19 infection compared with other marital statuses. Further research is needed to evaluate COVID-19 associated factors in pregnant women and possible sociodemographic or economic factors behind cohabiting marital status association among this population.

OBJETIVO: Describir las características clínicas y factores sociodemográficos asociados a COVID-19 en gestantes de un hospital materno infantil de Lima, Perú. MÉTODO: Estudio cuantitativo observacional. La población estuvo compuesta por gestantes atendidas en la unidad de emergencia, con la prueba para el diagnóstico de COVID-19. A las madres se les valoró edad, edad gestacional, lugar de procedencia, ocupación, nivel de estudios, estado civil, número de hijos, índice de masa corporal previa, índice de masa corporal de la gestación, vacuna antitetánica, controles prenatales, y hemoglobina. Después de un análisis bivariado se aplicó un modelo de regresión lineal generalizado. RESULTADOS: Incluimos a 200 mujeres, con edades de 18 a 34 años (84,5%). Más de la mitad procedía de Lima (52,5%), 79% tenía como ocupación el ser ama de casa, 71,9% alcanzó estudios secundarios y 60% registró estado civil de conviviente. La incidencia de COVID-19 fue de 31,5% mediante pruebas rápidas. La mediana de edad gestacional al momento de la evaluación para COVID-19 fue de 36 semanas. El índice de masa corporal pregestacional, comparado entre las gestantes con COVID-19 y las que no lo tuvieron, fue normal en 36,7 y 63,3%. Se detectó sobrepeso en 38,1 y 61,9% de las pacientes, obesidad en 30,3 y 69,7%, respectivamente. Los niveles de hemoglobina superiores o iguales a 11 gramos por decilitro se reportaron en 39,7 y 60,3% en cada grupo; hemoglobina entre 10 y 10,9 gramos por decilitro, en 21,2 y 78,8%; y hemoglobina entre 7 y 9,9 gramos por decilitro, en 20 y 80%, respectivamente. La razón de prevalencia con un intervalo de confianza al 95%, identificó al estado civil conviviente asociado a menor riesgo de tener COVID-19 en gestantes (razón de prevalencia: 0,41, valor p < 0,001). CONCLUSIÓN: Las gestantes cuyo estado civil fue de conviviente presentaron menor riesgo de experimentar COVID-19. Es necesario seguir estudiando los factores que se asocian a la presencia de COVID-19 en gestantes, así como posibles factores sociodemográficos o económicos detrás del estado civil conviviente.

CCR5Delta32 deletion as a protective factor in Czech first-wave COVID-19 subjects.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Delta32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5?32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Delta32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5?32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.

COVID-19: Epidemia de información no científica en grupos peruanos de Facebook / COVID-19: Epidemic of non-scientific information on Peruvian Facebook groups

El fenómeno denominado infodemia consiste en un flujo masivo de información que se produce durante las crisis sociales. La difusión y el consumo de información por diversos medios oficiales y no oficiales sobre la enfermedad del coronavirus (COVID-19) y los aspectos relacionados con los métodos de prevención, los síntomas de la enfermedad, las opciones terapéuticas, entre otros, han crecido de forma continua desde su reporte oficial a finales del año 2019.1) La información sin sustento científico o la información científica indebidamente utilizada y disponible en las redes sociales podría favorecer la promoción de medidas de seguridad ineficientes, opciones terapéuticas de eficacia desconocida, o ambos,2,3 por lo que resulta importante cuantificar ese tipo de información como una de las estrategias de afrontamiento4 y de aproximación a la almetría de las publicaciones científicas sobre COVID-19 en las redes sociales.5 En ese sentido, nuestro objetivo fue estimar la proporción de publicaciones con contenido verificado en artículos científicos que son compartidos en grupos de Facebook dedicados a la COVID-19 y que fueron creados entre los meses de enero y marzo del año 2020(AU)

Do patients with familial nonmedullary thyroid cancer present with more aggressive disease? Implications for initial surgical treatment.

BACKGROUND: There are conflicting reports on whether familial nonmedullary thyroid cancer is more aggressive than sporadic nonmedullary thyroid cancer. Our aim was to determine if the clinical and pathologic characteristics of familial nonmedullary thyroid cancer are different than nonmedullary thyroid cancer. METHODS: We compared patients with familial nonmedullary thyroid cancer to a cohort of 53,571 nonmedullary thyroid cancer patients from the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 78 patients with familial nonmedullary thyroid cancer from 31 kindreds presented at a younger age (P = .04) and had a greater rate of T1 disease (P = .019), lymph node metastasis (P = .002), and the classic variant of papillary thyroid cancer on histology (P < .001) compared with the Surveillance, Epidemiology, and End Results cohort. Patients with ≥3 affected family members presented at a younger age (P = .04), had a lesser female-to-male ratio (P = .04), and had a greater rate of lymph node metastasis (P = .009). Compared with the Surveillance, Epidemiology, and End Results cohort, we found a higher prevalence of lymph node metastasis in familial nonmedullary thyroid cancer index cases (P = .003) but not in those diagnosed by screening ultrasonography (P = .58). CONCLUSION: Patients with familial nonmedullary thyroid cancer present at a younger age and have a greater rate of lymph node metastasis. The treatment for familial nonmedullary thyroid cancer should be more aggressive in patients who present clinically and in those who have ≥3 first-degree relatives affected.

Long-term donors versus non-donor men: Iron metabolism and the atherosclerotic process.

BACKGROUND AND AIMS: The increased iron level and the labile iron pool (LIP) in circulating monocytes are connected to a higher frequency of cardiovascular events. METHODS: The study investigates the relationship between LIP in circulating monocytes and markers of iron metabolism and atherosclerosis (inflammation, oxidative stress, endothelial dysfunction and arterial elasticity) in long-term blood donors and non-donor volunteers. RESULTS: We found that donors had significantly higher LIP values than the control group (1.89 ±â€¯0.47 µM vs. 1.50 ±â€¯0.41 µM, p = 0.007). Despite the observed tendency for the donor group to have higher blood pressure, cholesterol, glucose and HOMAR-IR (homeostasis model assessment of insulin resistance), the groups did not differ in inflammatory markers, markers of endothelial dysfunction and markers of impaired arterial elasticity. The donor group had significant changes in iron metabolism (higher serum Fe, ceruloplasmin, and TfR/Ft ratio (transferrin receptor/ferritin ratio) and lower hepcidin, ferritin, and CD163), indicating depletion of body iron stores and activation of iron turnover. CONCLUSIONS: LIP seems to be a good marker of iron turnover activity in these individuals despite the lack of a decrease in the hemoglobin concentration. We did not find a significant correlation between LIP levels and atherosclerosis progression in the two groups. However, further studies are needed to assess long-term donorship as a protective factor against atherosclerosis.

Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity.

The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease.

Chronic Mild Hyperglycemia in GCK-MODY Patients Does Not Increase Carotid Intima-Media Thickness.

Aim. GCK-MODY is an autosomal dominant form of diabetes caused by heterozygous mutations in the glucokinase gene leading to a lifelong mild hyperglycemia. The risk of macrovascular complications is considered low, but studies are limited. We, therefore, investigated the carotid intima-media thickness (CIMT) as an indicator of macrovascular complications in a group of patients with GCK-MODY. Methods. Twenty-seven GCK mutation carriers and 24 controls recruited among their first-degree relatives were compared, all aging over 35 years. The CIMT was tested using a high-resolution B-mode carotid ultrasonography. Medical history, anthropometry, and biochemical blood workup were obtained. Results. The mean CIMT was 0.707 ± 0.215 mm (mean ± SD) in GCK mutation carriers and 0.690 ± 0.180 mm in control individuals. When adjusted for age, gender, and family status, the estimated mean difference in CIMT between the two groups increased to 0.049 mm (P = 0.19). No difference was detected for other characteristics, with the exception of fasting blood glucose (GCK-MODY 7.6 mmol/L ± 1.2 (136.4 mg/dL); controls 5.3 mmol/L ± 0.3 (95.4 mg/dL); P < 0.0001) and glycated hemoglobin HbA1c (GCK-MODY 6.9% ± 1.0%, 52 mmol/mol ± 10; controls 5.7% ± 0.4%, 39 mmol/mol ± 3; P < 0.0001). The frequency of myocardial infarction and ischemic stroke did not differ between groups. Conclusion. Our data indicate that the persistent hyperglycemia in GCK-MODY is associated with a low risk of developing diabetic macrovascular complications.

Mortality in patients with premature lower extremity atherosclerosis.

OBJECTIVE: Lower extremity peripheral artery disease occurs mostly in the elderly and is associated with high mortality. Limited data are available regarding long-term mortality in patients with premature lower extremity atherosclerosis (PLEA). Our objective was to determine the all-cause mortality and its predictors in younger PLEA patients. METHODS: We studied patients with severe PLEA who were <55 years of age at diagnosis and treated at a single academic vascular center between 1998 and 2010. Data were collected prospectively at the initial evaluation for vascular care. National Death Index and hospital records were used to determine all-cause mortality. Demographic and clinical characteristics were summarized using count (%), mean (standard deviation), or median (interquartile range), and associations with aspirin use were tested using χ2 test, t-test, or Wilcoxon test. Survival times were estimated using Kaplan-Meier estimates, and associations with covariates were tested using simple and multivariable Cox proportional hazards models. RESULTS: A total of 564 patients were analyzed (46% female; 20% nonwhite; mean age 49.4 [6.4] years). Ninety-five percent of patients had ≥2 cardiovascular risk factors, 31% had coronary artery disease (CAD), and 10% had a history of cancer. During median follow-up of 5.6 years (interquartile range, 2.3-8.3 years), 108 deaths (19%) were recorded. Two-year estimated mortality (standard error) was 6% (0.01), and 5-year estimated mortality was 16% (0.02). In univariate regression analysis, patient age (P=.04), prior amputation (P<.01), history of cancer (P=.03), and established CAD (P=.04) were associated with increased risk of mortality. Aspirin use and lipid-lowering therapy at the time of first evaluation were associated with improved survival (P<.01 and P=.02, respectively). A multivariable Cox proportional hazards model identified age (hazard ratio [HR] for 5-year increase, 1.17; 95% CI, 1.01-1.36; P=.04), prior amputation (HR, 1.99; 95% CI, 1.18-3.34; P=.01), history of cancer (HR, 2.35; 95% CI, 1.36-4.07; P<.01), and CAD (HR, 1.76; 95% CI, 1.16-2.67; P<.01) as independent predictors of mortality in patients with PLEA. Importantly, history of aspirin use had a significant protective effect (HR, 0.45; 95% CI, 0.30-0.69; P<.01). The impact of lipid-lowering therapy was no longer significant in multivariable modeling. CONCLUSIONS: Patients with PLEA demonstrate high all-cause mortality. No traditional cardiovascular risk factors predicted mortality. Aspirin therapy at the time of first evaluation was a significant and independent predictor of improved survival in patients with PLEA.

The oxidized low-density lipoprotein/ß2-glycoprotein I complex is associated with abdominal obesity in healthy middle-aged men.

BACKGROUND/AIMS: Oxidized low-density lipoprotein (oxLDL) in complex with ß2-glycoprotein I (ß2GPI) has been associated with autoimmune diseases, diabetes mellitus, chronic renal disease and coronary atherosclerosis. The aim of our study was to determine whether plasma levels of oxLDL/ß2GPI complexes are associated with insulin resistance, inflammation and markers of endothelial damage in obese middle-aged men and, if so, whether oxLDL/ß2GPI correlates better with insulin resistance parameters than oxLDL, advanced oxidation protein products (AOPP) or thioredoxin. METHODS: A total of 72 healthy men were recruited (41 obese and 31 nonobese individuals). Waist circumference >94 cm was used as the criterion for abdominal obesity. RESULTS: The obese men demonstrated higher oxLDL/ß2GPI levels (p < 0.001), homeostasis model assessment of insulin resistance (p < 0.01) and intima-media thickness of the common carotid artery (p < 0.01). oxLDL/ß2GPI correlated with more insulin resistance parameters compared to AOPP, thioredoxin or oxLDL. Furthermore, oxLDL/ß2GPI was associated with plasminogen activator inhibitor-I (PAI-I; r = 0.365, p < 0.001) and negatively with interleukin-8 (r = -0.297, p < 0.05). CONCLUSIONS: In summary, oxLDL/ß2GPI reflects the criterion for abdominal obesity and markers of insulin resistance in our study. The independent positive correlation with PAI-I indicates that oxLDL/ß2GPI may serve as an early marker of low-grade inflammation and atherosclerosis initiation.

4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures.

Coenzyme Q (Q) is an electron transporter in the respiratory chain and a lipid-soluble antioxidant that decreases in humans with age. Here we show that 4-nitrobenzoate inhibited 4-hydroxybenzoate:polyprenyl transferase (Coq2) in a competitive manner and dose-dependently decreased Q in mammalian cells without accumulation of Q intermediates. As 4-nitrobenzoate neither interfered with mitochondrial respiration nor induced oxidative stress, it should prove a valuable tool for studies on both Q deficiency and Q supplementation.

Region-specific sensitivity of the spinal cord to ischemia/reperfusion: the dynamic of changes in catalytic NOS activity.

This study was designed in order to consider whether the release of neuronally derived nitric oxide (NO) in the lumbosacral spinal cord during ischemia/reperfusion is region-specific and whether changes in Ca(2+)-dependent NO synthase (cNOS) activity paralell with functional outcome. The cNOS activity was measured in the spinal cord regions after 13-, 15- and 17-min ischemia alone and that followed by 24 h of reperfusion. In addition, the Tarlov's criteria were applied to define the neurological consequences of ischemia/reperfusion in experimental animals. Based on the results, it is evident that only the 17-min ischemia alone was quite sufficient to cause changes in cNOS activity, however, without alterations in functional outcomes. On the other hand, the ischemic episodes followed by reperfusion caused dynamic, region-specific alterations in cNOS activity and consequently led to deterioration of motor function of hindlimbs in affected animals. Our results indicate that the motoneurons in the ventral horns respond more sensitively to ischemia/reperfusion than do neurons localized in the other spinal cord regions and that changes in cNOS activity may also influence the axonal conductance in the white matter and account for the impairment of motoneuronal activity in affected animals.

Angiotensin II AT(1) receptor blockade selectively enhances brain AT(2) receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats.

Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT(1) receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT(1) receptor binding in the median eminence and basolateral amygdala, increased AT(2) receptor binding in the medial subnucleus of the inferior olive, decreased AT(2) binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT(1) receptor blockade reduced AT(1) receptor binding in all areas studied and enhanced AT(2) receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT(1) binding after stress, and prevented the stress-induced AT(2) receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT(1) blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT(1) receptors, selectively increased central AT(2) receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT(1) and AT(2) receptors in the regulation of the stress response, and the hypothesis that AT(1) receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties.

New techniques for assessment of vascular function.

The noninvasive measurement of hemodynamic variables associated with hypertension and cardiovascular disease processes needs to be recognized as a viable adjunct to clinical practice. This review traces the history of the inception and development of noninvasive measurement of hemodynamic variable. It then identifies well established, useful, and available devices, and then notes clinical studies verifying the clinical relevance of these measurements. Given the need to intervene earlier in the course of cardiovascular disease processes, tools are needed to assist the medical team to evaluate, prognosticate, and guide their patient's therapy correctly. It is the goal of this review to heighten the awareness and enhance and encourage the implementation of these devices in our armamentarium for the betterment of our patient's health.