A Combined Biomarker That Includes Plasma Fibroblast Growth Factor 23, Erythropoietin, and Klotho Predicts Short- and Long-Term Morbimortality and Development of Chronic Kidney Disease in Critical Care Patients with Sepsis: A Prospective Cohort.

Acute Kidney Injury (AKI) is a frequent complication in intensive care unit (ICU) patients that increases mortality and chronic kidney disease (CKD) development. AKI is associated with elevated plasma fibroblast growth factor 23 (FGF23), which can be modulated by erythropoietin (EPO) and Klotho. We aimed to evaluate whether a combined biomarker that includes these molecules predicted short-/long-term outcomes. We performed a prospective cohort of ICU patients with sepsis and previously normal renal function. They were followed during their inpatient stay and for one year after admission. We measured plasma FGF23, EPO, and Klotho levels at admission and calculated a combined biomarker (FEK). A total of 164 patients were recruited. Of these, 50 (30.5%) had AKI at admission, and 55 (33.5%) developed AKI within 48 h. Patients with AKI at admission and those who developed AKI within 48 h had 12- and 5-fold higher FEK values than non-AKI patients, respectively. Additionally, patients with higher FEK values had increased 1-year mortality (41.9% vs. 18.6%, p = 0.003) and CKD progression (26.2% vs. 8.3%, p = 0.023). Our data suggest that the FEK indicator predicts the risk of AKI, short-/long-term mortality, and CKD progression in ICU patients with sepsis. This new indicator can improve clinical outcome prediction and guide early therapeutic strategies.

Epidemiology, patterns of care and prognosis of acute kidney injury in critically ill patients: A multicenter study in Argentina (The EPIRA study).

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality rates in the intensive care unit (ICU). In low- and middle-income countries (LMICs), epidemiological information about this condition is still scarce. Our main objective was to characterize its epidemiology, prognosis, and its treatment. METHODS: This multicenter prospective cohort study included 1466 patients from 35 ICUs during 6 months in Argentina in 2018. Risk factors and outcomes in patients with and without AKI, and between AKI on admission (AKIadm) and that developed during hospitalization (AKIhosp) were analyzed. RESULTS: AKI occurred in 61.3% of patients (900/1466); 72.6% were AKIadm and 27.3% AKIhosp. Risk factors were age, BMI, arterial hypertension, cardiovascular diseases, diabetes, SOFA, APACHE II, dehydration, sepsis, vasopressor use, radiocontrast, diuresis/h and mechanical ventilation. Independent predictors for AKI were sepsis, diabetes, dehydration, vasopressors on admission, APACHE II and radiocontrast use. Renal replacement therapies (RRT) requirement in AKI patients was 14.8%. Hospital mortality in AKI vs. non-AKI was 38.7% and 23.3% (p < 0.001); and in AKIadm vs. AKIhosp, 41.2% and 37.8% (p = 0.53). CONCLUSIONS: ICU-acquired AKI has high incidence, complications and mortality. Risk factors for AKI and RRT utilization were similar to those described in other epidemiological studies. AKIadm was more frequent than AKIhosp, but had equal prognosis.

Mate Selection on Anastrepha curvicauda: Effect of Weight, Age, and Virginity.

Sexual selection determines the evolution of the species by favoring some attributes that confer a reproductive advantage to those individuals with those attributes. Tephritidae flies do not always select the same traits when looking for a mating partner. Some aspects of the mating system of Anastrepha curvicauda are known; nevertheless, there is no information on the effect of age, size, and virginity when selecting a mating partner. We set up a series of experiments where a selector (male or female) may select between (a) an old or young partner, (b) a small or large partner, and (c) a virgin or mated partner. Males of A. curvicauda significantly preferred large, young, and virgin females, while females showed no preference for high- or low-quality males. The females' non-preference for a particular male is discussed in the light of their mating system.

Frecuencia y asociación entre funcionalidad familiar y adherencia al tratamiento en pacientes diabéticos

Introducción: La familia representa el entorno más cercano al paciente y por ello, la funcionalidad familiar es el soporte más importante, pues con ello el paciente logra una óptima adherencia al tratamiento de enfermedades crónicas, entre ellas, la diabetes. Objetivo: Determinar la frecuencia y asociación entre la funcionalidad familiar y la adherencia al tratamiento de la diabetes en pacientes atendidos en el programa de pacientes crónicos en un establecimiento de salud de atención primaria de Lima. Métodos: Estudio transversal realizado en 2020. Se recopiló información sobre la adherencia al tratamiento y la funcionalidad familiar de los pacientes. Se midieron variables sociodemográficas y variables relacionadas a la diabetes. Se realizó un análisis de regresión simple y múltiple para estimar la asociación entre la adherencia al tratamiento y la funcionalidad familiar y variables sociodemográficas. Resultados: El 71,6 % de encuestados fueron mujeres. El 78,4 % de los pacientes presentaron alguna comorbilidad, el promedio de hemoglobina glicosilada de los encuestados fue de 8,9 %. Se encontró que el 59,7 % de pacientes perteneció a una familia disfuncional y el 87,3 % no cumplió de forma óptima con el tratamiento para su enfermedad. En el análisis bivariado se encontró asociación significativa entre la funcionalidad familiar y la adherencia al tratamiento (p= 0,028). En el análisis de regresión múltiple, se mantuvo la asociación (RP= 2,78, IC95 %: 1,13-6,83). Conclusiones: La frecuencia de una mala adherencia al tratamiento en pacientes diabéticos es alta. La funcionalidad familiar está asociada a la adherencia al tratamiento farmacológico.

Introduction: The family represents the closest environment to the patient and for this reason, family functionality is the most important support because with it the patient achieves optimal adherence to the treatment of chronic diseases, including diabetes. Objective: To determine the relationship between family functionality and adherence to diabetes treatment in patients treated in the chronic patients' program in a primary care health facility in Lima. Methods: Cross-sectional study carried out in 2020. Information was collected on adherence to treatment and family functionality of the patients. Likewise, sociodemographic variables and variables related to diabetes were measured. A simple and multiple regression analysis were performed to estimate the association between adherence to treatment and the sociodemographic variables. Results: 71.6% of respondents were women. 78.4% of the patients reported having some comorbidity. In addition, the average glycated hemoglobin of the respondents was 8.9%. It was found that 59.7% of patients belonged to a dysfunctional family and 87.3% did not optimally comply with the treatment for their disease. In the bivariate analysis, a significant association was found between family functionality and adherence to treatment (p= 0.028). In the multiple regression analysis, the association was maintained (PR= 2.73, 95% CI: 1.08-6.87). Conclusions: The frequency of poor adherence to treatment in diabetic patients is high. Family functionality is associated with adherence to drug treatment.

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort.

End-stage renal disease (ESRD) patients are a population with high rates of COVID-19 and mortality. These patients present a low response to anti-SARS-CoV-2 immunization, which is associated with immune dysfunction. ESRD patients also present high plasma titers of Fibroblast Growth Factor 23 (FGF23), a protein hormone that reduces immune response in vivo and in vitro. Increased FGF23 levels associate with higher infection-related hospitalizations and adverse infectious outcomes. Thus, we evaluated whether ESRD patients with high FGF23 titers have an increased rate of SARS-CoV-2 infection. METHODS: We performed a prospective cohort of ESRD patients in hemodialysis who had measurements of plasma intact FGF23 in 2019. We determined COVID-19 infections, hospitalizations, and mortality between January 2020 and December 2021. RESULTS: We evaluated 243 patients. Age: 60.4 ± 10.8 years. Female: 120 (49.3%), diabetes: 110 (45.2%). During follow-up, 45 patients developed COVID-19 (18.5%), 35 patients were hospitalized, and 12 patients died (mortality rate: 26.6%). We found that patients with higher FGF23 levels (defined as equal or above median) had a higher rate of SARS-CoV-2 infection versus those with lower levels (18.8% versus 9.9%; Hazard ratio: 1.92 [1.03-3.56], p = 0.039). Multivariate analysis showed that increased plasma FGF23 was independently associated with SARS-CoV-2 infection and severe COVID-19. DISCUSSION: Our results suggest that high plasma FGF23 levels are a risk factor for developing COVID-19 in ESRD patients. These data support the potential immunosuppressive effects of high circulating FGF23 as a factor implicated in the association with worse clinical outcomes. Further data are needed to confirm this hypothesis.

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.

Interacciones farmacocinéticas de la azitromicina e implicación clínica / Pharmacokinetic interactions of azithromycin and clinical implication

Introducción: El síndrome respiratorio agudo grave (por la COVID-19) es en la actualidad la primera causa de muerte en el Perú, por lo que se requiere de fármacos eficaces y seguros para mitigar la enfermedad. Se realizó una búsqueda bibliográfica en SciELO y PubMed/ Medline; se seleccionaron 37 de 58 artículos sobre el tema. Objetivos: Revisar e integrar la información sobre las interacciones farmacocinéticas de la azitromicina que se prescriben en el tratamiento ambulatorio de la COVID-19 en el Perú, y evaluar su implicación clínica. Desarrollo: La azitromicina es usada en la COVID-19, por su actividad antiinflamatoria, al inhibir a las interleucinas (IL1, 6, 8 y TNF-α), y a las moléculas de adhesión intracelular 1 (ICAM1); y por inducir la producción de interferón tipo I (IFN-α, IFN-β) y III (IFN-λ) en células de pacientes con enfermedad pulmonar obstructiva crónica. Los estudios de tres brazos, aleatorizado y abierto, indican que la azitromicina no genera cambios en los parámetros farmacocinéticos de la ivermectina, sildenafilo, rupatadina y desloratadina; los estudios de un solo centro, abierto, sin ayuno y de dos períodos, evidencian que la azitromicina influye en los parámetros farmacocinéticos de venetoclax y de los psicotrópicos. Conclusiones: Basado en la evidencia de los estudios clínicos revisados e integrados, se concluye que estas son limitadas y de poca relevancia clínica, sin embargo, se propone usar el antibiótico bajo el criterio científico del médico, para evitar las interacciones farmacocinéticas y las reacciones adversas de los fármacos(AU)

Introduction: The severe acute respiratory syndrome (due to COVID-19) is currently the leading cause of death in Peru, so effective and safe drugs are required to mitigate the disease. A bibliographic search was carried out in SciELO and PubMed/Medline; 37 of 58 articles on the topic were selected. Objectives: Review and integrate the information on the pharmacokinetic interactions of azithromycin that are prescribed in the outpatient treatment of COVID-19 in Peru, and evaluate their clinical implication. Development: Azithromycin is used in COVID-19, due to its anti-inflammatory activity, by inhibiting interleukins (IL1, 6, 8 and TNF-α), and intracellular adhesion molecules 1 (ICAM1); and by inducing the production of type I interferon (IFN-α, IFN-β) and III (IFN-λ) in cells of patients with chronic obstructive pulmonary disease. The three-arm, randomized and open-label studies indicate that azithromycin does not cause changes in the pharmacokinetic parameters of ivermectin, sildenafil, rupatadine, and desloratadine; single-center, open-label, non-fasting, and two-period studies show that azithromycin influences the pharmacokinetic parameters of venetoclax and psychotropics. Conclusions: Based on the evidence from the reviewed and integrated clinical studies, it is concluded that these are limited and of little clinical relevance, however, it is proposed to use the antibiotic under the scientific criteria of the doctor, to avoid pharmacokinetic interactions and adverse reactions of drugs(AU)

Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus.

Klotho is an aging-related protein associated with hippocampal cognitive performance in mammals. Klotho regulates progenitor cell proliferation in non-neuronal tissues, but its role in adult hippocampal neurogenesis (AHN) has not been explored. Klotho expression in the adult mouse hippocampus was examined by immunofluorescence and polymerase chain reaction. AHN was evaluated in the hippocampus of klotho knock-out mice (KO), klotho KO/vitamin D-receptor mutant mice, and in a model of local klotho hippocampal knockdown. The recombinant Klotho effect on proliferation was measured in mouse-derived hippocampal neural progenitor cells. Hippocampal-dependent memory was assessed by a dry-land version of the Morris water maze. Klotho was expressed in the granular cell layer of the adult Dentate Gyrus. AHN was increased in klotho KO mice, but not in klotho KO/vitamin D-receptor mutant mice. Inversely, local downregulation of hippocampal Klotho diminished AHN. Recombinant Klotho increased the proliferation rate of neural progenitors. Downregulation of hippocampal Klotho correlated with a decreased performance in hippocampal-dependent memory. These results suggest that Klotho directly participates in regulating AHN. Our observations indicate that Klotho promotes proliferation, AHN and hippocampal-dependent cognition. Increased neurogenesis in klotho KO mice may be secondary to the activation of other pathways altered in the model, such as vitamin D.

Biochemical analyses reveal amino acid residues critical for cell cycle-dependent phosphorylation of human Cdc14A phosphatase by cyclin-dependent kinase 1.

Cdc14 enzymes compose a family of highly conserved phosphatases that are present in a wide range of organisms, including yeast and humans, and that preferentially reverse the phosphorylation of Cyclin-Dependent Kinase (Cdk) substrates. The budding yeast Cdc14 orthologue has essential functions in the control of late mitosis and cytokinesis. In mammals, however, the two Cdc14 homologues, Cdc14A and Cdc14B, do not play a prominent role in controlling late mitotic events, suggesting that some Cdc14 functions are not conserved across species. Moreover, in yeast, Cdc14 is regulated by changes in its subcellular location and by phosphorylation events. In contrast, little is known about the regulation of human Cdc14 phosphatases. Here, we have studied how the human Cdc14A orthologue is regulated during the cell cycle. We found that Cdc14A is phosphorylated on Ser411, Ser453 and Ser549 by Cdk1 early in mitosis and becomes dephosphorylated during late mitotic stages. Interestingly, in vivo and in vitro experiments revealed that, unlike in yeast, Cdk1-mediated phosphorylation of human Cdc14A did not control its catalytic activity but likely modulated its interaction with other proteins in early mitosis. These findings point to differences in Cdk1-mediated mechanisms of regulation between human and yeast Cdc14 orthologues.

Trends in cancer incidence and mortality over three decades in Quito - Ecuador.

INTRODUCTION: The National Registry of Tumors has collected, processed, analyzed and regularly disseminated information on new cases of cancer diagnosed in the city of Quito, Ecuador over the last three decades. AIM: This article analyzed the trend of cancer incidence and mortality rates for the period 1985-2013. METHODS: Incidence and mortality rates standardized by age were estimated by the direct method, using the world standard population. Analysis of the time trends, from selected locations, the joinpoint regression was used. RESULTS: A decrease in the incidence and mortality rates of cervical and stomach cancers were documented. There was an increase in breast and colorectal cancer rates. The increase of the incidence rate of thyroid cancer in women was notorious. Lung cancer also increased in women while in men their values remained stable. CONCLUSION: There are important variations in the evolution of cancer in Quito; the information presented is an instrument for monitoring and evaluating the interventions that are developed in the Country.

INTRODUCCIÓN: El Registro Nacional de Tumores ha recolectado, procesado, analizado y divulgado regularmente la información de los casos nuevos de cáncer diagnosticados en la ciudad de Quito, Ecuador durante las últimas tres décadas. OBJETIVO: Analizar la tendencia de las tasas de incidencia y mortalidad por cáncer durante el periodo 1985-2013. MÉTODOS: Se estimaron las tasas de incidencia y mortalidad estandarizadas por edad a través del método directo, utilizando la población estándar mundial. Para el análisis de la tendencia de las tasas, de localizaciones seleccionadas, se utilizó la regresión joinpoint. RESULTADOS: Se documentó un descenso de las tasas de incidencia y mortalidad de los tipos de cáncer de cuello uterino y estómago. Existe incremento de las tasas de cánceres de mama y colon-recto. Es notorio el crecimiento de la tasa de incidencia de cáncer de tiroides en mujeres. El cáncer de pulmón se incrementó en las mujeres en tanto que en los varones sus valores se mantuvieron estables. CONCLUSIÓN: Se evidencian importantes variaciones en la evolución del cáncer en Quito, la información presentada constituye un instrumento para el seguimiento y evaluación de las intervenciones que se desarrollen.

Trends in cancer incidence and mortality over three decades in Quito - Ecuador / Tendencias en incidencia y mortalidad por cáncer durante tres decadas en Quito - Ecuador

Abstract Introduction: The National Registry of Tumors has collected, processed, analyzed and regularly disseminated information on new cases of cancer diagnosed in the city of Quito, Ecuador over the last three decades. Aim: This article analyzed the trend of cancer incidence and mortality rates for the period 1985-2013. Methods: Incidence and mortality rates standardized by age were estimated by the direct method, using the world standard population. Analysis of the time trends, from selected locations, the joinpoint regression was used. Results: A decrease in the incidence and mortality rates of cervical and stomach cancers were documented. There was an increase in breast and colorectal cancer rates. The increase of the incidence rate of thyroid cancer in women was notorious. Lung cancer also increased in women while in men their values remained stable. Conclusion: There are important variations in the evolution of cancer in Quito; the information presented is an instrument for monitoring and evaluating the interventions that are developed in the Country.

Resumen Introducción: El Registro Nacional de Tumores ha recolectado, procesado, analizado y divulgado regularmente la información de los casos nuevos de cáncer diagnosticados en la ciudad de Quito, Ecuador durante las últimas tres décadas. Objetivo: Analizar la tendencia de las tasas de incidencia y mortalidad por cáncer durante el periodo 1985-2013. Métodos: Se estimaron las tasas de incidencia y mortalidad estandarizadas por edad a través del método directo, utilizando la población estándar mundial. Para el análisis de la tendencia de las tasas, de localizaciones seleccionadas, se utilizó la regresión joinpoint. Resultados: Se documentó un descenso de las tasas de incidencia y mortalidad de los tipos de cáncer de cuello uterino y estómago. Existe incremento de las tasas de cánceres de mama y colon-recto. Es notorio el crecimiento de la tasa de incidencia de cáncer de tiroides en mujeres. El cáncer de pulmón se incrementó en las mujeres en tanto que en los varones sus valores se mantuvieron estables. Conclusión: Se evidencian importantes variaciones en la evolución del cáncer en Quito, la información presentada constituye un instrumento para el seguimiento y evaluación de las intervenciones que se desarrollen.

Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation.

The activity of Cdk1-cyclin B1 mitotic complexes is regulated by the balance between the counteracting activities of Wee1/Myt1 kinases and Cdc25 phosphatases. These kinases and phosphatases must be strictly regulated to ensure proper mitotic timing. One masterpiece of this regulatory network is Cdk1, which promotes Cdc25 activity and suppresses inhibitory Wee1/Myt1 kinases through direct phosphorylation. The Cdk1-dependent phosphorylation of Wee1 primes phosphorylation by additional kinases such as Plk1, triggering Wee1 degradation at the onset of mitosis. Here we report that Cdc14A plays an important role in the regulation of Wee1 stability. Depletion of Cdc14A results in a significant reduction in Wee1 protein levels. Cdc14A binds to Wee1 at its amino-terminal domain and reverses CDK-mediated Wee1 phosphorylation. In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues. Thus the lack of phosphorylation of these two residues prevents the interaction with Plk1 and the consequent efficient Wee1 degradation at the onset of mitosis. These data support the hypothesis that Cdc14A counteracts Cdk1-cyclin B1 activity through Wee1 dephosphorylation.

Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice.

Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed as a partial TCR agonist for myelin oligodendrocyte glycoprotein (MOG)-reactive T cells and has demonstrated the capacity to limit infarct volume and inflammation in brain when administered to mice undergoing middle cerebral artery occlusion (MCAO). The goal of this study was to determine if RTL551 could retain protection when given within the therapeutically relevant 4 h time window currently in clinical practice for stroke patients. RTL551 was administered subcutaneously 4 h after MCAO, with repeated doses every 24 h until the time of euthanasia. Cell numbers were assessed in the brain, blood, spleen and lymph nodes and infarct size was measured after 24 and 96 h reperfusion. RTL551 reduced infarct size in both cortex and striatum at 24 h and in cortex at 96 h after MCAO and inhibited the accumulation of inflammatory cells in brain at both time points. At 24 h post-MCAO, RTL551 reduced the frequency of the activation marker, CD44, on T-cells in blood and in the ischemic hemisphere. Moreover, RTL551 reduced expression of the chemokine receptors, CCR5 in lymph nodes and spleen, and CCR7 in the blood and lymph nodes. These data demonstrate effective treatment of experimental stroke with RTL551 within a therapeutically relevant 4 h time window through immune regulation of myelin-reactive inflammatory T-cells.

Androgen receptor overexpression is neuroprotective in experimental stroke.

Male sex is a known risk factor in human stroke. However, the role of the cognate receptor for androgens-the androgen receptor (AR)-in stroke outcome remains unclear. Here, we found that AR mRNA is downregulated in the peri-infarct tissue of gonadally intact male mice subjected to middle cerebral artery occlusion (MCAO) and 6 h reperfusion. We then used genetically engineered mice overexpressing AR in brain (AR-Tg) to compare outcomes from MCAO in intact or castrated males and to evaluate the neuroprotective role of dihydrotestosterone (DHT) replacement in AR-Tg castrates. A further evaluation of AR overexpression in ischemic paradigms was performed using rat PC12 cells transfected with human AR and treated with oxidative and apoptotic stressors. We then studied the role of DHT in cultures overexpressing AR. Our results show (1) ischemia alters the expression of AR by decreasing AR mRNA levels, (2) AR overexpression is protective in vivo against MCAO in intact and castrated AR-Tg mice and in vitro against oxidative and apoptotic stressors in AR-PC12 cells, and (3) DHT does not enhance the protection triggered by AR overexpression in AR-Tg castrated mice nor in AR-PC12 cells.

CCR6: a biomarker for Alzheimer's-like disease in a triple transgenic mouse model.

The inflammatory status of the brain in patients as well as animal models of Alzheimer's disease (AD) has been extensively studied. Accumulation of activated microglia producing tumor necrosis factor-α and monocyte chemotactic protein-1 contribute to the pathology of the disease. However, little is known about the changes in the spleen and associated peripheral immunity that might contribute to AD pathology. The goal of this study was to characterize phenotypic and functional changes in spleen, blood and brain cell populations that contribute to development of an AD-like disease in a triple transgenic (3xTg-AD) mouse model. The 3xTg-AD mice had increased percentages of brain Gr-1+ granulocytes, dendritic cells and macrophages, spleen and blood derived CD8+Ly6C+ memory T cells and CCR6+ B cells, as well as increased levels of secreted interleukin-6. Brain tissue from older 12 month old symptomatic 3xTg-AD female mice exhibited highly elevated mRNA expression of CCR6 compared to wild-type mice. Importantly, this pronounced increase in expression of CCR6 was also detected in brain and spleen tissue from pre-symptomatic 5--6 month old 3xTg-AD females and males. Our data demonstrate increased expression of CCR6 in the brain and peripheral immune organs of both pre-symptomatic and symptomatic 3xTg-AD mice, strongly suggesting an ongoing inflammatory process that precedes onset of clinical AD-like disease.

First record of Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae) attacking Toxotrypana curvicauda Gerstaecker (Diptera: Tephritidae).

A new host record is reported for the braconid wasp Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae), parasitizing papaya fruit fly larvae Toxotrypana curvicauda Gerstaecker (Diptera: Tephritidae) in México.

First record of Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae) attacking Toxotrypana curvicauda Gerstaecker (Diptera: Tephritidae)

A new host record is reported for the braconid wasp Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae), parasitizing papaya fruit fly larvae Toxotrypana curvicauda Gerstaecker (Diptera: Tephritidae) in México.

Se registra por primera vez a Diachasmimorpha longicaudata (Ashmead) parasitando a larvas de la mosca de la papaya, Toxotrypana curvicauda Gerstaecker en México.

The pilus and porin of Neisseria gonorrhoeae cooperatively induce Ca(2+) transients in infected epithelial cells.

Purified pili and porin from Neisseria quickly mobilize calcium (Ca(2+)) stores in monocytes and epithelial cells, ultimately influencing host cell viability as well as bacterial intracellular survival. Here, we examined the Ca(2+) transients induced in human epithelial cells during infection by live, piliated N. gonorrhoeae. Porin induced an influx of Ca(2+) from the extracellular medium less than 60 s post infection. The porin-induced transient is followed by a pilus-induced release of Ca(2+) from intracellular stores. The timing of these events is similar to that observed using purified proteins. Interestingly, the porin-induced Ca(2+) flux is required for the pilus-induced transient, indicating that the pilus-induced Ca(2+) release is, itself, Ca(2+) dependent. Several lines of evidence indicate that porin is present on pili. Moreover, pilus retraction strongly influences the porin- and pilus-induced Ca(2+) fluxes. These and other results strongly suggest that the pilus and porin cooperate to modulate calcium signalling in epithelial cells, and propose a model to explain how N. gonorrhoeae triggers Ca(2+) transients in the initial stages of pilus-mediated attachment.

Clean indoor air in El Paso, Texas: a case study.

BACKGROUND: Exposure to secondhand smoke is an important preventable cause of illness and death. A Smoke-Free Paso del Norte Coalition in El Paso, Texas, led a drive to introduce an ordinance to protect nonsmoking persons from the health effects of secondhand smoke in public places. The ordinance was introduced in April 2001 and was passed on June 26, 2001. CONTEXT: El Paso is the fifth largest city in Texas and the largest border city in the United States. It is the 10th poorest city in the United States; 37% of its residents do not have health insurance. Seventy-eight percent of El Paso's residents are Hispanic/Latino. A large percentage of El Paso's restaurant and bar workers are recent immigrants from Mexico. METHODS: Campaign activities included a letter-writing campaign to the El Paso Times, petition gathering, community outreach education, meetings with city council members, print and television advertising, a proactive media advocacy campaign, and a youth rally. CONSEQUENCES: One month after the ordinance went into effect, an opinion poll found solid support for the new ordinance. Another survey conducted in December 2002 also found a 22% decline in adult smoking, from 22.1% in 1996 to 17.3% at the time of the survey. INTERPRETATION: The El Paso campaign is an example of a successful grassroots campaign. El Paso's campaign relied on direct organizing to identify, recruit, and mobilize supporters, and involved relatively little paid media or paid advocacy efforts. These lessons are transferable to other communities, and the El Paso coalition serves as a model for developing a diverse, representative coalition in a predominantly Mexican American community.

Neisseria gonorrhoeae porin P1.B induces endosome exocytosis and a redistribution of Lamp1 to the plasma membrane.

The immunoglobulin A (IgA) protease secreted by pathogenic Neisseria spp. cleaves Lamp1, thereby altering lysosomes in a cell and promoting bacterial intracellular survival. We sought to determine how the IgA protease gains access to cellular Lamp1 in order to better understand the role of this cleavage event in bacterial infection. In a previous report, we demonstrated that the pilus-induced Ca(2+) transient triggers lysosome exocytosis in human epithelial cells. This, in turn, increases the level of Lamp1 at the plasma membrane, where it can be cleaved by IgA protease. Here, we show that porin also induces a Ca(2+) flux in epithelial cells. This transient is similar in nature to that observed in phagocytes exposed to porin. In contrast to the pilus-induced Ca(2+) transient, the porin-induced event does not trigger lysosome exocytosis. Instead, it stimulates exocytosis of early and late endosomes and increases Lamp1 on the cell surface. These results indicate that Neisseria pili and porin perturb Lamp1 trafficking in epithelial cells by triggering separate and distinct Ca(2+)-dependent exocytic events, bringing Lamp1 to the cell surface, where it can be cleaved by IgA protease.