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.

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.

A public health framework for addressing black and white disparities in preterm delivery.

The Healthy People 2010 objectives call for the elimination of racial disparities in health, along with reductions in several multifactorial perinatal outcomes. Evidence-based interventions have been the focus of discussion to date. We propose a 6-component framework based on knowledge from the social, medical, psychological, and epidemiological literatures to guide development of interventions to reduce preterm delivery and eliminate disparities. Pilot testing and rigorous evaluation of the interventions developed from this framework are encouraged.

Prepregnancy body mass index and pregnancy weight gain: associations with preterm delivery. The NMIHS Collaborative Study Group.

OBJECTIVE: To examine associations between rate of pregnancy weight gain and preterm delivery among women of varying prepregnancy body mass indices (BMI). METHODS: Subjects were 3511 mother-infant pairs from the 1988 National Maternal and Infant Health Survey. Prenatal weight measured between 14 and 28 weeks' gestation was used to calculate rate of pregnancy weight gain for each woman. Weight gain (lb/week) was categorized as low (under 0.5), average (0.5-1.5), or high (above 1.5). Prepregnancy BMI was calculated as weight divided by height in (kg/m(2)) and categorized as low (under 19.8), average (19.8-26.0), and high (above 26). Delivery before 37 weeks' gestation was considered preterm. Associations between BMI, weight gain, and preterm delivery were examined before and after exclusion of medically indicated preterm deliveries and pregnancies complicated by maternal medical conditions potentially related to weight gain or fetal growth restriction. Associations were expressed as odds ratios (OR) adjusted for several potential confounding factors. RESULTS: Women with low pregnancy weight gain were at increased risk of preterm delivery. The magnitude of risk varied according to a woman's prepregnancy BMI. After all exclusions and adjustments for confounders, ORs, and 95% confidence intervals (CI) for low pregnancy weight gain were 6.7 (1.1, 40.6) for underweight women, 3.6 (1.6, 8.0) for average-weight women, and 1.6 (0.7, 3.5) for overweight women compared with average-weight women with average pregnancy weight gain. CONCLUSIONS: Low weight gain in pregnancy was associated with increased risk of preterm delivery, particularly if women were underweight or of average weight before pregnancy.

Multicentre evaluation of the Boehringer Mannheim/Hitachi 917 analysis system.

The new selective access analysis system BM/Hitachi 917 was evaluated in an international multicentre study, mainly according to the ECCLS protocol for the evaluation of analysers in clinical chemistry. Forty-three different analytes, covering 56 different methods--enzymes, substrates, electrolytes, specific proteins, drugs and urine applications--were tested in seven European clinical chemistry laboratories. Additionally, the practicability of the BM/ Hitachi 917 was tested according to a standardized questionnaire. Within-run CVs (median of 3 days) for enzymes, substrates and electrolytes were <2% except for creatine-kinase MB isoform and lipase at low concentration. For proteins, drugs and urine analytes the within-run CVs were < 4% except for digoxin and albumin in urine. Between-day median CVs were generally < 3% for enzymes, substrates and electrolytes, and < 6% for proteins, drugs and urine analytes, except for lipase, creatine kinase and MB isoform, D-dimer, glycosylated haemoglobin, rheumatoid factors, digoxin, digitoxin, theophylline and albumin in urine in some materials. Linearity was found according to the test specifications or better and there were no relevant effects seen in drift and carry-over testing. The interference results clearly show that also for the BM/Hitachi 917 interference exists sometimes, as could be expected because of the chemistries applied. It is a situation that can be found in equivalent analysers as well. The accuracy is acceptable regarding a 95-105% recovery in standard reference material, with the exception of the creatinine Jaffé method. Most of the 160 method comparisons showed acceptable agreement according to our criteria: enzymes, substrates, urine analytes deviation of slope +/- 5%, electrolytes +/- 3%, and proteins and drugs +/- 10%. The assessment of practicability for 14 groups of attributes resulted in a grading of one-three scores better for the BM/Hitachi 917 than the present laboratory situation. In conclusion, the results of the study showed good analytical performance and confirmed the usefulness of the system as a consolidated workstation in medium-sized to large clinical chemistry laboratories.

Validity of self-reported pregnancy delivery weight: an analysis of the 1988 National Maternal and Infant Health Survey. NMIHS Collaborative Working Group.

This study examined the validity of self-reported delivery weight among 3,518 respondents to the 1988 National Maternal and Infant Health Survey. Self-reported delivery weight was ascertained from a mail survey administered during the postpartum period. Measured delivery weight was obtained by abstraction of medical records from the hospital of delivery. On average, a woman's reported delivery weight was 2.82 pounds (1 pound = 0.45 kg) less than her measured delivery weight (p < 0.001). The level of underreporting increased significantly with increases in prepregnancy body mass index, current body mass index, pregnancy weight gain, and weight change from delivery to recall. Reporting error also increased among women who were non-White, less educated, and unmarried; whose pregnancy was unintended; and who initiated prenatal care late, responded late to the survey questionnaire, became pregnant again before responding, and reported a delivery weight ending in zero. When reported delivery weight was used to calculate weight gain and was categorized into typical weight gain categories, 30-40% of women were classified incorrectly. An empirical evaluation of how this misclassification might impact epidemiologic analyses indicated that associations between weight gain and birth weight were attenuated when weight gain was based on reported delivery weight rather than on measured delivery weight.