AAV-mediated expression of secreted and transmembrane αKlotho isoforms rescues relevant aging hallmarks in senescent SAMP8 mice.

Senescence represents a stage in life associated with elevated incidence of morbidity and increased risk of mortality due to the accumulation of molecular alterations and tissue dysfunction, promoting a decrease in the organism's protective systems. Thus, aging presents molecular and biological hallmarks, which include chronic inflammation, epigenetic alterations, neuronal dysfunction, and worsening of physical status. In this context, we explored the AAV9-mediated expression of the two main isoforms of the aging-protective factor Klotho (KL) as a strategy to prevent these general age-related features using the senescence-accelerated mouse prone 8 (SAMP8) model. Both secreted and transmembrane KL isoforms improved cognitive performance, physical state parameters, and different molecular variables associated with aging. Epigenetic landscape was recovered for the analyzed global markers DNA methylation (5-mC), hydroxymethylation (5-hmC), and restoration occurred in the acetylation levels of H3 and H4. Gene expression of pro- and anti-inflammatory mediators in central nervous system such as TNF-α and IL-10, respectively, had improved levels, which were comparable to the senescence-accelerated-mouse resistant 1 (SAMR1) healthy control. Additionally, this improvement in neuroinflammation was supported by changes in the histological markers Iba1, GFAP, and SA ß-gal. Furthermore, bone tissue structural variables, especially altered during senescence, recovered in SAMP8 mice to SAMR1 control values after treatment with both KL isoforms. This work presents evidence of the beneficial pleiotropic role of Klotho as an anti-aging therapy as well as new specific functions of the KL isoforms for the epigenetic regulation and aged bone structure alteration in an aging mouse model.

Acceptance of pregnant women's vaccination against pertussis among French women and health professionals: PREVACOQ-1 and -2 studies.

OBJECTIVES: Protection of French young infants against pertussis only relies on their relatives' vaccination. The alternative is vaccination of pregnant women against pertussis (cocooning strategy), but this strategy is not yet recommended in France. We assessed the acceptance of this strategy among French postpartum women and health professionals. PATIENTS AND METHODS: We performed a multicenter survey in 2016 among postpartum women and health professionals (family physicians, obstetricians-gynecologists, midwives, and medical students) to determine the acceptance of anti-pertussis vaccination. We evaluated knowledge, perception, and attitude towards vaccination to identify factors associated with acceptance. RESULTS: Questionnaires were completed by 52% (1208/2337) of women and 40% (694/1754) of health professionals. Seventy-seven per cent of women (95% CI: 74-79) and 93% of health professionals (95% CI: 91-95) were favorable to anti-pertussis vaccination of pregnant women. Thirty-three per cent (227/687) of health professionals believed that pertussis induced life-long immunity and 20% (136/687) of them were not aware of the cocooning strategy. In multivariate analysis, factors associated with acceptance among women were younger age, higher knowledge, having received advice during pregnancy, being vaccinated against influenza, and having never refused any vaccine; among health professionals, factors associated with acceptance were belief that inactivated vaccines are obstetrically safe, regular practice of influenza vaccination in pregnant women, pertussis cocooning strategy, and never prescribing preventive homeopathy for influenza. CONCLUSION: Vaccination of pregnant women against pertussis should be well-accepted by informed mothers and health professionals. If this strategy were to be implemented in France, efforts should be made towards adequate information.

Resveratrol modulates response against acute inflammatory stimuli in aged mouse brain.

With upcoming age, the capability to fight against harmful stimuli decreases and the organism becomes more susceptible to infections and diseases. Here, the objective was to demonstrate the effect of dietary resveratrol in aged mice in potentiating brain defenses against LipoPolySaccharide (LPS). Acute LPS injection induced a strong proinflammatory effect in 24-months-old C57/BL6 mice hippocampi, increasing InterLeukin (Il)-6, Tumor Necrosis Factor-alpha (Tnf-α), Il-1ß, and C-X-C motif chemokine (Cxcl10) gene expression levels. Resveratrol induced higher expression in those cytokines regarding to LPS. Oxidative Stress (OS) markers showed not significant changes after LPS or resveratrol, although for resveratrol treated groups a slight increment in most of the parameters studies was observed, reaching signification for NF-kB protein levels and iNOS expression. However, Endoplasmic Reticulum (ER) stress markers demonstrated significant changes in resveratrol-treated mice after LPS treatment, specifically in eIF2α, BIP, and ATF4. Moreover, as described, resveratrol is able to inhibit the mechanistic Target of Rapamycin (mTOR) pathway and this effect could be linked to (eIF2α) phosphorylation and the increase in the expression of the previously mentioned proinflammatory genes as a response to LPS treatment in aged animals. In conclusion, resveratrol treatment induced a different cellular response in aged animals when they encountered acute inflammatory stimuli.

Resveratrol Protects SAMP8 Brain Under Metabolic Stress: Focus on Mitochondrial Function and Wnt Pathway.

Metabolic stress induced by high-fat (HF) diet leads to cognitive dysfunction and aging, but the physiological mechanisms are not fully understood. Senescence-accelerated prone mouse (SAMP8) models were conducted under metabolic stress conditions by feeding HF for 15 weeks, and the preventive effect of resveratrol was studied. This dietary strategy demonstrates cognitive impairment in SAMP8-HF and significant preventive effect by resveratrol-treated animals. Hippocampal changes in the proteins involved in mitochondrial dynamics optic atrophy-1 protein (OPA1) and mitofusin 2 (MFN2) comprised a differential feature found in SAMP8-HF that was prevented by resveratrol. Electronic microscopy showed a larger mitochondria in SAMP8-HF + resveratrol (SAMP8-HF + RV) than in SAMP8-HF, indicating increases in fusion processes in resveratrol-treated mice. According to the mitochondrial morphology, significant increases in the I-NDUFB8, II-SDNB, III-UQCRC2, and V-ATPase complexes, in addition to that of voltage-dependent anion channel 1 (VDAC1)/porin, were found in resveratrol-treated animals with regard to SAMP8-HF, reaching control-animal levels. Moreover, tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) were increased after HF, and resveratrol prevents its increase. Moreover, we found that the HF diet affected the Wnt pathway, as demonstrated by ß-catenin inactivation and modification in the expression of several components of this pathway. Resveratrol induced strong activation of ß-catenin. The metabolic stress rendered in the cognitive and cellular pathways altered in SAMP8 focus on different targets in order to act on preventing cognitive impairment in neurodegeneration, and resveratrol can offer therapeutic possibilities for preventive strategies in aging or neurodegenerative conditions.

[Microbiología, sensibilidad antibiótica y factores asociados a bacteriemia en la prostatitis aguda]. / Microbiology, antibiotic susceptibility, and bacteraemia associated factors in acute prostatitis.

OBJECTIVE: The aim of the study was to analyze the characteristics of patients with acute prostatitis presenting to the Emergency Department, the microbiological findings, antibiotic susceptibility, and bacteraemia associated factors. METHODS: Observational and cohort study with prospective follow-up including patients with acute prostatitis presenting to the Emergency Department from January-December 2012. Data were collected for demographic variables, comorbidities, microbiological findings, antibiotic treatment and outcome. RESULTS: Two hundred and forty one episodes of acute prostatitis were included. Mean age was 62.9 ± 16 years, a history of prostate adenoma was reported in 54 cases (22.5%) and prior manipulation of the lower urinary tract in 40 (17%). Mean symptoms duration was 3.38 ± 4.04 days, voiding symptoms were present in 176 cases (73%) and fever in 154 (64%). Seventy patients (29%) were admitted to the hospital and 3 died. From 216 urine cultures, 128 were positive (59%) and 24 (17.6%) out of 136 blood cultures. Escherichia coli was the main pathogen (58.6% of urine cultures and 64% of blood cultures) with resistant strains to fluoroquinolones, cotrimoxazole and amoxicillin/clavulanic in 27.7%, 22.9% and 27.7% of cases respectively. In the univariate analysis, only chills were associated to bacteraemia (p=0.013). At 30-day follow-up, patients with bacteraemia returned more frequently to the Emergency Department (p=0.037) and were more often admitted to the hospital (p=0.003). CONCLUSIONS: Patients with acute prostatitis discharged from the Emergency Department need clinical follow-up and monitoring of microbiological findings in order to assure an adequate antibiotic treatment. Return to Emergency Department and admission to the hospital were significantly more frequent among patients with bacteraemia.

Amyloid and tau pathology of familial Alzheimer's disease APP/PS1 mouse model in a senescence phenotype background (SAMP8).

The amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of Alzheimer's disease (AD) has provided robust neuropathological hallmarks of familial AD-like pattern at early ages, whereas senescence-accelerated mouse prone 8 (SAMP8) has a remarkable early senescence phenotype with pathological similarities to AD. The aim of this study was the investigation and characterization of cognitive and neuropathological AD markers in a novel mouse model that combines the characteristics of the APP/PS1 transgenic mouse model with a senescence-accelerated background of SAMP8 mice. Initially, significant differences were found regarding amyloid plaque formation and cognitive abnormalities. Bearing these facts in mind, we determined a general characterization of the main AD brain molecular markers, such as alterations in amyloid pathway, neuroinflammation, and hyperphosphorylation of tau in these mice along their lifetimes. Results from this analysis revealed that APP/PS1 in SAMP8 background mice showed alterations in the pathways studied in comparison with SAMP8 and APP/PS1, demonstrating that a senescence-accelerated background exacerbated the amyloid pathology and maintained the cognitive dysfunction present in APP/PS1 mice. Changes in tau pathology, including the activity of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 ß (GSK3ß), differs, but not in a parallel manner, with amyloid disturbances.

Multiangle dynamic light scattering for the improvement of multimodal particle size distribution measurements.

Dynamic Light Scattering (DLS) is a widely used technique for measuring the size distributions of nano- and micro-particles dispersed in a liquid. The principle is based on the analysis of the temporal fluctuations of light scattered by the particles at a given scattering angle. However, single-angle DLS measurements may lack resolution and robustness, particularly for multimodal and/or polydisperse samples. Multi-angle Dynamic Light Scattering (MDLS) provides more robust, reproducible and accurate Particle Size Distributions (PSDs) than single-angle DLS. In this paper, a novel inversion method based on Bayesian inference is proposed for the estimation of the number PSD from MDLS measurements. The efficiency and robustness of this method is demonstrated through simulated and real data.

Depression in the elderly: study in a rural city in southern Catalonia.

Depression and anxiety are the most common psychiatric diseases among the elderly, and frequently go without diagnosis and treatment. However, evidence regarding the prevalence of depression related to the diagnostic systems utilized and the sociocultural variations in the different communities investigated (rural-urban) is contradictory. This study aims to evaluate the prevalence of depression in a rural area in the south of Catalonia, analysing the different age groups, identifying the causal factors of depression and determining whether there are gender differences. The descriptive and quantitative study includes 157 women and 160 men. The qualitative study evaluates 14 men and 52 women diagnosed with depression. Our results indicate a high risk of depression in elderly participants of our small rural community. Widowers suffer more depression than widows and the loneliness, illness, and task of caregiver were predictive variables for depression in these elderly men. The loss of the ability to perform activities of daily living associated with ageing has a greater effect on depression disorders in men than in women.

Análisis de la seguridad y la eficacia de una unidad de corta estancia en el tratamiento de la neumonía adquirida en la comunidad / Community-acquired pneumonia management in a short-stay unit: analysis of safety and efficacy

Introducción: La neumonía adquirida en la comunidad (NAC) es una patología de alta prevalencia que a menudo requiere ingreso hospitalario. El objetivo de nuestro estudio es evaluar la eficacia y seguridad en el tratamiento de la NAC de una unidad de corta estancia (UCE) como alternativa a las unidades de hospitalización convencional (UHC). Método: Estudio retrospectivo comparativo de pacientes ingresados en un hospital terciario con diagnóstico al alta de NAC entre noviembre del 2005 y abril del 2007. Se comparan dos grupos: pacientes ingresados en UCE frente a pacientes ingresados en UHC (se excluyen pacientes que requieren terapia intensiva). Variables analizadas: edady sexo, índice de Charlson, peso según el grupo relacionado de diagnóstico (GRD),CURB 65 y Pneumonia Severity Index (PSI), hallazgos microbiológicos, tasas de readmisión y de mortalidad. Resultados: Un total de 606 pacientes fueron reclutados, 187 ingresados en el UCE(grupo 1) y 419 en UHC (grupo 2 o grupo control). Las diferencias más significativas entre los dos grupos fueron el promedio de edad (77,3 vs 67,9 p < 0,001) y la estancia promedio (3,48 vs 7,89 p < 0,001). Estas diferencias se objetivan en el comparativo general y por subgrupos según la escala de riesgo (PSI). No se observaron diferencias significativas en la tasa de mortalidad ni en la de reingreso entre las dos formas de hospitalización. Conclusiones: La UCE es eficaz y segura en el manejo de los pacientes con NAC, con una estancia media significativamente inferior respecto a las UHC, y sin diferencias enl as tasas de mortalidad y reingreso (AU)

Background and objective: Community-acquired pneumonia (CAP) is a highly prevalent disease that often requires hospital admission. We aimed to assess the safety and efficacy of treating CAP in a short-stay unit as an alternative to conventional hospitalization. Methods: Retrospective comparison of patients admitted to a tertiary care hospital with a diagnosis of CAP between November 2005 and April 2007. We compared outcomes for cases managed in the 2 locations (short-stay unit vs conventional hospital ward), excluding patients who required intensive care. Variables and outcomes analyzed were age,sex, Charlson index, mean weight in the diagnosis-related group, scores on the CURB-65 criteria and the Pneumonia Severity Index (PSI), findings of microbiology, and readmission and mortality rates. Results: A total of 606 patients were studied; 187 were treated in the short-stay unit and 419 were admitted to the conventional ward. The main significant differences between the 2 groups were mean age (77.3 vs 67.9 years,respectively; P<.0001) and mean stay (3.48 vs 7.89 days; P<.0001). These differences were also reflected in thecomparison between severity subgroups (by PSI). Mortality rates did not differ. Conclusions: Our experience with the short-stay unit suggests it offers a safe and effective way to manage CAP andleads to a significantly shorter hospital stay in comparison with conventional hospitalization, without increasing readmission and mortality rates (AU)

Evaluación de la utilidad de la tinción de Gramdel esputo para el manejo de la neumonía en urgencias / Is sputum Gram staining useful in the emergency department’s management of pneumonia?

Objetivo: Evaluar la utilidad de la tinción de Gram del esputo (TGE) en el manejo de la neumonía adquirida en la comunidad (NAC) en el servicio de urgencias (SU).Método: Estudio descriptivo y retrospectivo entre octubre 2005 y noviembre 2007 de pacientes con NAC ingresados en el hospital tras su valoración en el SU. Se han analizado las variables demográficas, índice de Fine, TGE, antigenuria, cultivos y antibioterapia inicial. Se ha calculado la sensibilidad, la especificidad y los valores predictivos positivo y negativo de la TGE. Resultados: Se ha revisado 608 casos de neumonía (edad media 70,7, 64,3% hombres).Se obtuvo muestras de esputo en 168 pacientes (27,6%). La TGE mostró diplococos Gram positivos en 74 casos (DCGP), cocobacilos Gram negativos (CBGN) en 26, bacilos Gram negativos en 15, cocos Gram positivos en racimo o cadenas en 11 y presencia de polimorfonucleares sin predominio de microorganismos en 42. Se aisló Streptococcus pneumoniae en 57 casos y Haemophilus influenzae en 19. El hallazgo de DCGP o CBGN mostró una sensibilidad del 47,1% y 73% y una especificidad del 94,2%y 95% para la infección neumocócica y por Haemophilus respectivamente. Ceftriaxona fue el tratamiento más frecuente en pacientes con DGCP y levofloxacino en CBGN. Conclusiones: La TGE tiene un valor limitado en el manejo de la NAC del adulto en el SU con resultados variables según la infecciones por lo que resulta poco útil para orientarla antibioterapia inicial (AU)

Objective: To assess the utility of sputum Gram stains in the management of community-acquired pneumonia (CAP) in the emergency department. Methods: Descriptive, retrospective study of patients with CAP admitted to hospital after evaluation in the emergency department between October 2005 and November 2007. We analyzed patient variables; the Fine index; the results of Gram staining of sputum smears, urine antigen tests, and blood cultures; and the antibiotic therapy initially prescribed. The sensitivity, specificity, and positive and negative predictive values of the Gram stain results were calculated.Results: A total of 608 cases of CAP (mean age, 70.7 years; 64.3% men) were included. Sputum cultures were obtained for 168 patients (27.6%). Gram-negative diplococcal infection was demonstrated in 74 cases, gram-negative coccobacilliin 26, gram-negative stains in 15, gram-positive cocci in clusters or chains in 11, and polymorphonuclear cells with nopredominating microorganisms in 42. Streptococcus pneumoniae was isolated in 57 patients and Haemophilus influenza in 19. The sensitivity of a finding of gram-positive diplococci was 47.1% for pneumococcal infection, with a specificity of94.2%. The sensitivity of a finding of gram-negative coccobacilli was 73% for H. influenza e infection, with a specificity of95%. Ceftriaxone and levofloxacin were the most frequently assigned treatments in patients with diplococcal and H.influenzae infections, respectively. Conclusions: Gram staining of sputum is of limited value in the emergency department’s management of CAP in adult patients. As the results vary according to pathogen, they are of little use in choosing the antibiotic treatment (AU)

Eliminating disparities in perinatal outcomes--lessons learned.

The disparity between blacks and whites in perinatal health ranges from a 2.3-fold excess risk among black women for preterm delivery and infant mortality to a 4-fold excess risk among black women for maternal mortality. To stimulate concerted public health action to address such racial and ethnic disparities in health, the national Healthy People objectives call for elimination of all health disparities by the year 2010. Eliminating health disparities requires a greater understanding of the factors that contribute to their development. This commentary summarizes the state of the science of reducing such disparities and proposes a framework for using the results of qualitative studies on the social context of pregnancy to understand, study, and address disparities in infant mortality and preterm delivery. Understanding the social context of African American women's lives can lead to an improved understanding of the etiology of preterm birth, and can help identify promising new interventions to reduce racial and ethnic disparities in preterm delivery.