Association Between Changes in Sleep, Nap Duration and Bone Mineral Density in Mexican Adults.

Studies have found associations between sleep, nap duration, and bone mineral density (BMD). However, the longitudinal relationship between sleep, nap duration, and BMD has not been explored. We evaluated the association between the change in sleep and nap duration and BMD in Mexican adults. Data come from 1,337 adult participants of the Health Workers Cohort Study (341 were men and 996 were women, including 450 women < 45 years old and 546 ≥ 45 years old), with two study waves. At each wave, sleep and nap duration was assessed using self-administered questionnaires and BMD in g/cm2 was determined by dual X-ray absorptiometry. We used fixed-effect regression models stratified by sex and adjusted for BMI, diet, physical activity, vitamin supplements, and hormone replacement therapy. Women who changed from < 7 to ≥ 7 h/day of sleep from baseline to follow-up were associated with increases in the total hip (ß = 0.012 g/cm2; 95% CI: 0.002, 0.022) and lumbar spine BMD (ß = 0.024 g/cm2; 95% CI: 0.009, 0.039). Furthermore, most of these associations were observed in women ≥ 45 years. For women, a changing from 0 to > 60 min/day of napping was associated with a significant increase in total hip BMD of 0.012 g/cm2 (95% CI: 0.004, 0.024) and lumbar spine BMD of 0.027 g/cm2 (95% CI: 0.009, 0.045). No significant associations were observed for men. Our results suggest that increased sleep and nap duration are associated with gains in BMD in Mexican women, emphasizing sleep's role in promoting bone health and supporting established recommendations.

Adsorption of naphthalene and its derivatives onto high-density polyethylene microplastic: Computational, isotherm, thermodynamic, and kinetic study.

Microplastics (MP) have received great attention due to the mass-produced residues discharged into the environment. MP are ideal for adhering to organic pollutants that can be easily dispersed, thus posing risks to human health. Furthermore, little has been reported on how different functional groups in polycyclic aromatic hydrocarbons (PAH) derivatives influence the adsorption behavior on MP. To better understand this process, groups methyl (-CH3) and hydroxyl (-OH) were selected and commercial and waste high-density polyethylene (HDPE, ≤ 1 mm) were used as adsorbents, and Naphthalene (Nap), 1-Methyl-Naphthalene (Me-Nap) and α-Naphthol as adsorbates. The results showed different behaviors for nonpolar and polar adsorbates. Dispersion forces were the main type of interaction between HDPE and Nap/Me-Nap, while dipole-induced dipole forces and H-bonding were the chief interactions involving MP and polar compounds. Regardless the HDPE source, Nap and Me-Nap have a Type III isotherm, and α-Naphthol presents a Type II isotherm. Nap and Me-Nap fitted to Freundlich isotherm of an unfavorable process (n = 2.12 and 1.11; 1.87 and 1.31, respectively), with positive values of ΔH° (50 and 77.17; 66 and 64.63 kJ mol-1) and ΔS° (0.070 and 0.0145; 0.122 and 0.103 kJ mol-1) for commercial and waste MP, respectively. Besides, the adsorption isotherm of α-Naphthol on commercial and waste HDPE fitted to the Langmuir model (Qmax = 42.5 and 27.2 µmol g-1, respectively), presenting negative values of ΔH° (-43.71 and -44.10 kJ mol-1) and ΔS° (-0.037 and -0.025 kJ mol-1). The adsorption kinetic study presents a nonlinear pseudo-second-order model for all cases. The K2 values follow the order Me-Nap > Nap > α-Naphthol in both MP. Therefore, this experimental study provides new insights into the affinity of PAH derivatives for a specific class of MP, helping to understand the environmental fate of residual MP and organic pollutants.

Identification of a novel mechanism for LFA-1 organization during NK cytolytic response.

The elimination of transformed and viral infected cells by natural killer (NK) cells requires a specialized junction between NK and target cells, denominated immunological synapse (IS). After initial recognition, the IS enables the directed secretion of lytic granules content into the susceptible target cell. The lymphocyte function-associated antigen (LFA)-1 regulates NK effector function by enabling NK-IS assembly and maturation. The pathways underlying LFA-1 accumulation at the IS in NK cells remained uncharacterized. A kinase anchoring protein 350 (AKAP350) is a centrosome/Golgi-associated protein, which, in T cells, participates in LFA-1 activation by mechanisms that have not been elucidated. We first evaluated AKAP350 participation in NK cytolytic activity. Our results showed that the decrease in AKAP350 levels by RNA interference (AKAP350KD) inhibited NK-YTS cytolytic activity, without affecting conjugate formation. The impairment of NK effector function in AKAP350KD cells correlated with decreased LFA-1 clustering and defective IS maturation. AKAP350KD cells that were exclusively activated via LFA-1 showed impaired LFA-1 organization and deficient lytic granule translocation as well. In NK AKAP350KD cells, activation signaling through Vav1 was preserved up to 10 min of interaction with target cells, but significantly decreased afterwards. Experiments in YTS and in ex vivo NK cells identified an intracellular pool of LFA-1, which partially associated with the Golgi apparatus and, upon NK activation, redistributed to the IS in an AKAP350-dependent manner. The analysis of Golgi organization indicated that the decrease in AKAP350 expression led to the disruption of the Golgi integrity in NK cells. Alteration of Golgi function by BFA treatment or AKAP350 delocalization from this organelle also led to impaired LFA-1 localization at the IS. Therefore, this study characterizes AKAP350 participation in the modulation of NK effector function, revealing the existence of a Golgi-dependent trafficking pathway for LFA-1, which is relevant for LFA-1 organization at NK-lytic IS.

Comparative biofilm-forming ability between Clostridioides difficile strains isolated in Latin America and the epidemic NAP1/027 strain.

Introduction: One of the challenges in treating Clostridioides difficile infection (CDI) is that the bacterium forms biofilms, a critical virulence mechanism known to promote antibiotic resistance and, as a result, consequently, a higher recurrence of the disease. The goal of this study was to compare the ability of three MLST Clade 2 strains to form a biofilm in vitro: ICC-45 (ribotype SLO231/UK[CE]821), a ST41 toxinotype IXb isolated in Brazil; and two epidemic NAP1/027/ST01 strains: NAP1/027/ST01 (LIBA5756), isolated during a 2010 outbreak in Costa Rica and the reference epidemic strain NAP1/027/ST01 (R20291); and ATCC700057, a non-toxigenic strain. Methods: The ability of strains to form biofilm was evaluated using crystal violet staining. In addition, samples were stained with the Film Tracer biofilm matrix (Invitrogen®) and the biofilm matrix thickness was measured using confocal microscopy. The matrix architecture was determined using Scanning electron microscop. Confocal microscopy was used to detect the presence of toxin A (tcdA) using an anti-Clostridioides difficile TcdA antibody. The expression of virulence genes (tcdA, tcdB, tcdC, cdtB, spo0A, slpA, cwp66 and cwp84) was examined, as well as the effect of antibiotics metronidazole (MTZ) and vancomycin (VAN) on biofilm growth. Results: All of the strains tested formed a moderate biofilm with 1.1 3.5. After 72h, biofilm biomass of the NAP1/027/ST01 epidemic strains (LIBA5756 and R20291) was significantly higher than ICC-45 and ATCC 700057 biofilms, as confirmed by electron and confocal microscopy. At 120h, the LIBA5756 biofilm biomass decreased compared to other strains. The toxigenic strains R20291 or LIBA 5756 had higher expression of genes tcdA, tcdB, tcdC, cdtA, slpA and spo0A than ICC-45, but there were no significant differences in the expression levels of cdtB, cwp66 and cwp84. In epidemic strains, VAN and MTZ inhibited biofilm formation; however, in the ICC-45 strain, MIC concentrations of VAN and MIC and 4MIC of MTZ did not inhibit biofilm formation. Conclusion: The three MLST Clade 2 isolated from different rybotipes, two of which were isolated from Latin America, are competent biofilm-forming bacteria, indicating their ability to induce C. difficile infection recurrence, making treatment difficult.

Chronic sleep restriction triggers inadequate napping habits in adolescents: a population-based study.

BACKGROUND: The prevalence of chronic sleep restriction during adolescence is a major public health issue. Napping has been adopted to alleviate sleep pressure complaints. However, it also has the potential to amplify sleep restriction due to a vicious cycle triggered by delayed sleep times. The aim of this study was to investigate sleep and napping habits in a sample of Brazilian adolescents. METHODS: This study enrolled 1554 high school students and included the evaluation of sleep times, daytime sleepiness, sleep quality, and circadian preference. The students were asked about their napping routine, ie its frequency and duration per week. RESULTS: The adolescent sleep recommendation was achieved by only 27.6% of the sample. Napping habit was reported by 58.1%, with 36.2% of nappers informing naps in 1-2 times per week. Prolonged naps were reported by 44.9% of nappers. Nappers had later median bedtime (23:30) and reduced time in bed (TIB) (median = 07:00 h) compared to non-nappers. The frequency of nappers who did not achieve satisfactory TIB was higher than non-nappers. In addition, nappers reported increased daytime sleepiness and poor sleep quality. Later bedtimes and reduced TIB were associated with longer nap duration. Increased sleepiness and poor sleep quality were linked to a higher nap frequency. CONCLUSIONS: This exploratory survey demonstrated a severe sleep restriction faced by Brazilian adolescents. Napping can be an efficient strategy to counteract sleep restriction, but it needs to be adopted with caution due to the detrimental effects of frequent and prolonged naps on nocturnal sleep.

On-shift naps are associated with systolic and diastolic blood pressure level among night working nursing professionals.

Few studies have analyzed on-shift naps with regard to shift workers' health. The aim of this study was to examine the association between exposure to night work (intensity and length of exposure to night work) and blood pressure (BP), considering the impact of on-shift naps. A cross-sectional study was carried out at a hospital based on a questionnaire and measurement of BP. The outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and casual hypertension (HTN), i.e., SBP > 140 mmHg, or DBP > 90 mmHg, or reporting a prescription of antihypertensive medication. The sample comprised 449 fixed 12 h night workers who were (unofficially) allowed to nap during the night shift for up to 3 h. Approximately 42% of the sample reported napping. Among non-nappers (but not among nappers), those exposed to more work nights (≥5/fortnight) showed a DBP that was 3.66 mmHg higher than that of the reference group. The likelihood of casual HTN was more than three-fold greater among non-nappers working more nights/fortnight than among those working fewer nights/fortnight. A similar tendency was observed in a subsample of workers who did not take antihypertensive medication. The results were less consistent regarding length of exposure to night work (in years). A possible explanation is that workers who usually take on-shift naps could experience suppression of the BP increase derived from the many nights worked, while the non-nappers did not experience this suppression. The results may be explained by the relationship between napping, melatonin secretion, and attenuation of circadian misalignment. Napping likely contributes to creating a "physiologically nocturnal environment" that tends to favor the circadian system and, therefore, health. Possible negative effects related to sleep inertia deserve attention. The findings encourage new studies on this topic to improve the management of night work at hospitals in regard to workers' health.

In vivo animal models confirm an increased virulence potential and pathogenicity of the NAP1/RT027/ST01 genotype within the Clostridium difficile MLST Clade 2.

BACKGROUND: Based on MLST analyses the global population of C. difficile is distributed in eight clades, of which Clade 2 includes the "hypervirulent" NAP1/RT027/ST01 strain along with various unexplored sequence types (STs). METHODS: To clarify whether this clinically relevant phenotype is a widespread feature of C. difficile Clade 2, we used the murine ileal loop model to compare the in vivo pro-inflammatory (TNF-α, IL-1ß, IL-6) and oxidative stress activities (MPO) of five Clade 2 clinical C. difficile isolates from sequence types (STs) 01, 41, 67, and 252. Besides, we infected Golden Syrian hamsters with spores from these strains to determine their lethality, and obtain a histological evaluation of tissue damage, WBC counts, and serum injury biomarkers (LDH, ALT, AST, albumin, BUN, creatinine, Na+, and Cl-). Genomic distances were calculated using Mash and FastANI to explore whether the responses were dictated by phylogeny. RESULTS: The ST01 isolate tested ranked first in all assays, as it induced the highest overall levels of pro-inflammatory cytokines, MPO activity, epithelial damage, biochemical markers, and mortality measured in both animal models. Statistically indistinguishable or rather similar outputs were obtained for a ST67 isolate in tests such as tissue damage, neutrophils count, and lethal activity. The results recorded for the two ST41 isolates tested were of intermediate magnitude and the ST252 isolate displayed the lowest pathogenic potential in all animal experiments. This ordering matched the genomic distance of the ST01 isolate to the non-ST01 isolates. CONCLUSIONS: Despite their close phylogenic relatedness, our results demonstrate differences in pathogenicity and virulence levels in Clade 2 C. difficile strains, confirm the high severity of infections caused by the NAP1/RT027/ST01 strain, and highlight the importance of C. difficile typing.

Origin, genomic diversity and microevolution of the Clostridium difficile B1/NAP1/RT027/ST01 strain in Costa Rica, Chile, Honduras and Mexico.

Clostridium difficile B1/NAP1/RT027/ST01 has been responsible for outbreaks of antibiotic-associated diarrhoea in clinical settings worldwide and is associated with severe disease presentations and increased mortality rates. Two fluoroquinolone-resistant (FQR) lineages of the epidemic B1/NAP1/RT027/ST01 strain emerged in the USA in the early 1990s and disseminated trans continentally (FQR1 and FQR2). However, it is unclear when and from where they entered Latin America (LA) and whether isolates from LA exhibit unique genomic features when compared to B1/NAP1/RT027/ST01 isolates from other regions of the world. To answer the first issue we compared whole-genome sequences (WGS) of 25 clinical isolates typed as NAP1, RT027 or ST01 in Costa Rica (n=16), Chile (n=5), Honduras (n=3) and Mexico (n=1) to WGS of 129 global isolates from the same genotype using Bayesian phylogenomics. The second question was addressed through a detailed analysis of the number and type of mutations of the LA isolates and their mobile resistome. All but two B1/NAP1/RT027/ST01 isolates from LA belong to the FQR2 lineage (n=23, 92 %), confirming its widespread distribution. As indicated by analysis of a dataset composed of 154 WGS, the B1/NAP1/RT027/ST01 strain was introduced into the four LA countries analysed between 1998 and 2005 from North America (twice) and Europe (at least four times). These events occurred soon after the emergence of the FQR lineages and more than one decade before the first report of the detection of the B1/NAP1/RT027/ST01 in LA. A total of 552 SNPs were identified across all genomes examined (3.8-4.3 Mb) in pairwise comparisons to the R20291 reference genome. Moreover, pairwise SNP distances were among the smallest distances determined in this species so far (0 to 55). Despite this high level of genomic conservation, 39 unique SNPs (7 %) in genes that play roles in the infection process (i.e. slpA) or antibiotic resistance (i.e. rpoB, fusA) distinguished the LA isolates. In addition, isolates from Chile, Honduras and Mexico had twice as many antibiotic resistance genes (ARGs, n=4) than related isolates from other regions. Their unique set of ARGs includes a cfr-like gene and tetM, which were found as part of putative mobile genetic elements whose sequences resemble undescribed integrative and conjugative elements. These results show multiple, independent introductions of B1/NAP1/RT027/ST01 isolates from the FQR1 and FQR2 lineages from different geographical sources into LA and a rather rapid accumulation of distinct mutations and acquired ARG by the LA isolates.

Endogenous and Foreign Nucleoid-Associated Proteins of Bacteria: Occurrence, Interactions and Effects on Mobile Genetic Elements and Host's Biology.

Mobile Genetic Elements (MGEs) are mosaics of functional gene modules of diverse evolutionary origin and are generally divergent from the hosts´ genetic background. Existing biases in base composition and codon usage of these elements` genes impose transcription and translation limitations that may affect the physical and regulatory integration of MGEs in new hosts. Stable appropriation of the foreign DNA depends on a number of host factors among which are the Nucleoid-Associated Proteins (NAPs). These small, basic, highly abundant proteins bind and bend DNA, altering its topology and folding, thereby affecting all known essential DNA metabolism related processes. Both chromosomally- (endogenous) and MGE- (foreign) encoded NAPs have been shown to exist in bacteria. While the role of host-encoded NAPs in xenogeneic silencing of both episomal (plasmids) and integrative MGEs (pathogenicity islands and prophages) is well acknowledged, less is known about the role of MGE-encoded NAPs in the foreign elements biology or their influence on the host's chromosome expression dynamics. Here we review existing literature on the topic, present examples on the positive and negative effects that endogenous and foreign NAPs exert on global transcriptional gene expression, MGE integrative and excisive recombination dynamics, persistence and transfer to suitable hosts and discuss the nature and relevance of synergistic and antagonizing higher order interactions between diverse types of NAPs.

Toxin B Variants from Clostridium difficile Strains VPI 10463 and NAP1/027 Share Similar Substrate Profile and Cellular Intoxication Kinetics but Use Different Host Cell Entry Factors.

Clostridium difficile induces antibiotic-associated diarrhea due to the release of toxin A (TcdA) and toxin B (TcdB), the latter being its main virulence factor. The epidemic strain NAP1/027 has an increased virulence attributed to different factors. We compared cellular intoxication by TcdBNAP1 with that by the reference strain VPI 10463 (TcdBVPI). In a mouse ligated intestinal loop model, TcdBNAP1 induced higher neutrophil recruitment, cytokine release, and epithelial damage than TcdBVPI. Both toxins modified the same panel of small GTPases and exhibited similar in vitro autoprocessing kinetics. On the basis of sequence variations in the frizzled-binding domain (FBD), we reasoned that TcdBVPI and TcdBNAP1 might have different receptor specificities. To test this possibility, we used a TcdB from a NAP1 variant strain (TcdBNAP1v) unable to glucosylate RhoA but with the same receptor-binding domains as TcdBNAP1. Cells were preincubated with TcdBNAP1v to block cellular receptors, prior to intoxication with either TcdBVPI or TcdBNAP1. Preincubation with TcdBNAP1v blocked RhoA glucosylation by TcdBNAP1 but not by TcdBVPI, indicating that the toxins use different host factors for cell entry. This crucial difference might explain the increased biological activity of TcdBNAP1 in the intestine, representing a contributing factor for the increased virulence of the NAP1/027 strain.

Midday napping in children: associations between nap frequency and duration across cognitive, positive psychological well-being, behavioral, and metabolic health outcomes.

STUDY OBJECTIVES: Poor sleep and daytime sleepiness in children and adolescents have short- and long-term consequences on various aspects of health. Midday napping may be a useful strategy to reduce such negative impacts. The effect of habitual napping on a wide spectrum of cognitive, behavioral, psychological, and metabolic outcomes has not been systematically investigated. METHODS: This study characterized midday napping habits in 3819 elementary school children from the China Jintan Cohort Study. In 2011, weekly nap frequency and average duration were collected once from students at grades 4-6. Prior to their completion of elementary school at grade 6 (in 2011-2013 respective to each grade), the following outcomes were collected once: behavioral and academic achievement evaluated by teachers, and self-reported positive psychology measures including grit, self-control, and happiness. IQ tests were conducted on a subgroup. Metabolic indices, including body mass index and fasting glucose concentration, were measured through physical exams. For the whole sample, we assessed associations between napping and each outcome, adjusted for sex, grade, school location, parental education, and time in bed at night. We also conducted stratified analyses on grade 6 (cross-sectional), grade 4 (2-year gap), and grade 5 (1-year gap) data. RESULTS: Overall, napping was significantly associated with higher happiness, grit, and self-control, reduced internalizing behavior problem, higher verbal IQs, and better academic achievement, although specific patterns varied across frequency and duration for different outcomes. More limited significant associations were found for decreased externalizing behavior problems, compared to non-nappers, while no significant associations were found for performance IQ and metabolic outcomes. CONCLUSIONS: Results indicate benefits of regular napping across a wide range of adolescent outcomes, including better cognition, better psychological wellness, and reduced emotional/behavioral problems. The current study underscores the need for further large-scale intervention studies to establish causal effects.

Clinical and endoscopic features in patients with hospital-acquired diarrhea associated with Clostridium difficile infection. / Características clínicas y endoscópicas en diarrea hospitalaria asociada a infección por Clostridium difficile.

INTRODUCTION AND AIMS: Clostridium difficile infection is the main cause of hospital-acquired diarrhea, and the clinical and endoscopic findings in those patients have been studied very little in Mexico. The aim of the present study was to describe those findings. MATERIALS AND METHODS: A prospective cohort study was conducted that included patients with hospital-acquired diarrhea associated with Clostridium difficile diagnosed through polymerase chain reaction. The hypervirulent NAP027 strain was also determined. The clinical and endoscopic findings in the study patients, as well as the variables associated with severity, were analyzed. RESULTS: Of the 127 patients with hospital-acquired diarrhea, 97 were excluded from the study due to lack of colonoscopy. The remaining 39 study patients had a mean age of 48 years, and their most common signs/symptoms were abdominal pain (49%), mucus in stools (41%), and blood in stools (10%). The most common alterations in the laboratory results were leukocytosis in 49%, fecal leukocytes (61%), and hypoalbuminemia (67%). The main risk factor was antibiotic use in 62%, and ceftriaxone was the most widely used. The hypervirulent strain was present in 54% of the cases. Endoscopic abnormalities were found in 87% of the patients. Thirty-eight percent presented with pseudomembranous colitis, with lesions in the left colon in 53%, and in the right colon in 13%. No association was found between proton-pump inhibitor use and Clostridium difficile-associated diarrhea. There was a significant association between hypoalbuminemia (< 3.3g/dL) and a greater risk for severe colitis, with a RR of 8.2 (p=0.008). CONCLUSIONS: Pseudomembranous colitis lesions associated with the hypervirulent Clostridium difficile strain were predominant in the left colon. Hypoalbuminemia was a significant severity predictor.

Work-Family Conflict and Employee Sleep: Evidence from IT Workers in the Work, Family and Health Study.

STUDY OBJECTIVES: Work-family conflict is a threat to healthy sleep behaviors among employees. This study aimed to examine how Work-to-Family Conflict (demands from work that interfere with one's family/personal life; WTFC) and Family-to-Work Conflict (demands from family/personal life that interfere with work; FTWC) are associated with several dimensions of sleep among information technology workers. METHODS: Employees at a U.S. IT firm (n = 799) provided self-reports of sleep sufficiency (feeling rested upon waking), sleep quality, and sleep maintenance insomnia symptoms (waking up in the middle of the night or early morning) in the last month. They also provided a week of actigraphy for nighttime sleep duration, napping, sleep timing, and a novel sleep inconsistency measure. Analyses adjusted for work conditions (job demands, decision authority, schedule control, and family-supportive supervisor behavior), and household and sociodemographic characteristics. RESULTS: Employees who experienced higher WTFC reported less sleep sufficiency, poorer sleep quality, and more insomnia symptoms. Higher WTFC also predicted shorter nighttime sleep duration, greater likelihood of napping, and longer nap duration. Furthermore, higher WTFC was linked to greater inconsistency of nighttime sleep duration and sleep clock times, whereas higher FTWC was associated with more rigidity of sleep timing mostly driven by wake time. CONCLUSIONS: Results highlight the unique associations of WTFC/FTWC with employee sleep independent of other work conditions and household and sociodemographic characteristics. Our novel methodological approach demonstrates differential associations of WTFC and FTWC with inconsistency of sleep timing. Given the strong associations between WTFC and poor sleep, future research should focus on reducing WTFC.

The experience of a Power Nap Center in the largest city of Brazil.

We evaluated the frequency of naps and features of nappers who took a nap in a Power Nap Center located in downtown area of São Paulo. Company database was retrospectively analyzed and 4.625 naps were evaluated (January-December 2014). Most naps (57%) lasted 30 min. 33% of subjects took a nap more than once a week (73% male). Progressive growth in the number of naps across the months was observed (January=110 to December=505). Results suggest that the society is sleep deprived and taking a nap during the day could be an important strategy to improve quality of life and increase productivity.

Re-examining sleep׳s effect on motor skills: How to access performance on the finger tapping task?

Here our goal was to determine the magnitude of sleep-related motor skill enhancement. Performance on the finger tapping task (FTT) was evaluated after a 90 min daytime nap (n=15) or after quiet wakefulness (n=15). By introducing a slight modification in the formula used to calculate the offline gains we were able to refine the estimated magnitude of sleep׳s effect on motor skills. The raw value of improvement after a nap decreased after this correction (from ~15% to ~5%), but remained significantly higher than the control. These results suggest that sleep does indeed play a role in motor skill consolidation.

Descripción clínica y epidemiológica de la infección por Clostridium difficile en población pediátrica / Clinic and epidemiologic description of Clostridium difficile infection in a pediatric population

Background: Clostridium difficile (CUj-associated disease (CDAD) and the role of the hypervirulent strain NAP1 have not been well characterized in Pediatrics. Aims: To describe clinical features of CDAD, and to estimate NAP1 frequency and association with disease severity in Pediatrics. Methods: Descriptive, transversal surveillance of diarrheal episodes in Chilean children, hospitalized between February 2012 and December 2013, positive for CD by molecular diagnosis. Results: A total of 66 episodes of diarrhea with identification of CD occurred thougout the study period in children between 1 month and 19 years of age of which 39% were younger than one year old. CD acquisition was predominantly nosocomial and the most common risk factors were: presence of comorbidities (98.6%), use of antibiotics (93.9%), proton pump inhibitors (84.8%), invasive mechanic ventilation (54.5%), feeding tube (48.5%) and immunosuppression (40.9%). Clinical course was mostly mild, but 12 cases presented an unfavorable course, of which 3/26 occurred in children less than one year. Only one case was positive for NAP1 and had a mild course. Conclusion: Diarrhea with identification of CD was present throughout all pediatric ages, including children less than one year old. Analytical and longitudinal studies are required to better characterize the pathogenic role of CD in this age group. CDAD occurred mostly in patients with risk factors, and the clinical course was predominantly mild.

Introducción: Aún no ha sido bien caracterizada la infección por Clostridium difficile ni el rol de la cepa hipervirulenta NAP1 en pediatría. Objetivos: Describir las características clínicas de la infección por C. difficile, la frecuencia de NAP1 y su asociación con gravedad en población pediátrica. Material y Método: Estudio transversal, descriptivo, de episodios de diarrea con identificación molecular de C. difficile en niños chilenos hospitalizados entre febrero de 2012 y diciembre de 2013. Resultados: Se estudiaron 66 episodios de diarrea por C. difficile, en niños entre 1 mes y 19 años, teniendo 39% menos de un año de edad. La adquisición fue predominantemente nosocomial. Los factores de riesgo más frecuentes fueron: co-morbilidades, uso de antimicrobianos, inhibidores de bomba de protones, ventilación mecánica invasora, sonda de alimentación e inmunosupresión. El curso clínico fue mayoritariamente benigno, con 12 casos de evolución desfavorable incluyendo lactantes bajo un año de edad. Un niño presentó la cepa NAP1, con un curso clínico leve. Discusión: En esta serie, la diarrea con identificación de C. difficile se presentó en niños de todas las edades, incluyendo aquellos bajo un año. Se necesitan estudios analíticos y longitudinales para determinar el rol patógeno en este último grupo etario. La infección afecta a niños con factores de riesgo y es de evolución predominantemente satisfactoria.

Efeitos da sobrecarga de fósforo dietético na expressão dos cotransportadores NaP-IIb e PiT-1 em ratos controles e urêmicos / Phosphorus overload effects on NaP-IIb and PiT-1 cotransporters in control and uremic rats

O fósforo é um dos minerais mais abundantes no corpo além de ser essencial para muitos processos biológicos. A homeostase do fósforo depende da absorção no intestino, da excreção renal, da remodelação óssea e de hormônios como o paratormônio, calcitriol e FGF-23. Nos pacientes com doença renal crônica, a excreção urinária de fósforo está comprometida levando à hiperfosfatemia, que contribui para o aumento da morbidade e mortalidade desses pacientes. A absorção intestinal de fósforo no intestino delgado, particularmente via cotransportadores NaP-IIb e PiT-1, é pouco estudada. O objetivo desse estudo foi avaliar os efeitos de dietas com diferentes concentrações de fósforo na expressão proteica e gênica dos cotransportadores NaP-IIb e PiT-1, bem como na apoptose dos enterócitos dos diferentes segmentos do intestino delgado de animais controles e urêmicos. Estudamos setenta e seis ratos Wistar machos, inicialmente divididos em dois grupos: controles (C) e urêmicos (Nx). Cada grupo foi subdividido em outros três, de acordo com a concentração de fósforo (P) na dieta: dieta Baixa (0,2%), dieta Padrão (0,54%) e dieta Alta (0,9%). Analisamos parâmetros bioquímicos (creatinina, P, Cai, PTH e FGF-23), a expressão proteica dos cotransportadores, através de Western Blotting, ELISA e imunofluorescência, a expressão gênica por PCR em tempo real e a apoptose dos enterócitos pela técnica TUNEL. Os resultados mostraram que os níveis séricos de creatinina, P, PTH e FGF-23 foram significativamente mais elevados nos animais Nx. Nos animais C com dieta baixa em P observamos aumento da expressão proteica do cotransportador NaP-IIb em todos os segmentos do intestino enquanto, no Nx Baixo, a expressão desse cotransportador foi menor somente no jejuno. Quanto ao PiT-1, sua expressão foi menor no íleo do grupo Nx Alto comparado ao seu respectivo controle. A expressão gênica do cotransportador NaP-IIb foi menor no jejuno do Nx Alto e maior no íleo desse mesmo grupo em relação aos seus...

Phosphorus is one of the most abundant minerals in the body besides being essential for many biological processes. Phosphorus homeostasis depends on absorption in the small intestine, renal excretion, bone remodeling and hormones such as parathyroid hormone, calcitriol and FGF-23. In patients with chronic kidney disease phosphorus urinary excretion is compromised leading to hyperphosphatemia, which contributes to increased morbidity and mortality of these patients. Intestinal absorption of phosphorus in the small intestine, particularly of NaP-IIb and PiT-1 cotransporters is poorly studied. The aim of this study was to evaluate the effects of diets with different concentrations of phosphorus in protein expression and gene of NaP-IIb and PiT-1 cotransporters as well as in apoptosis of enterocytes of different segments of intestine in control and uremic animals. We studied seventy-six male Wistar rats initially divided into two groups: controls (C) and uremic (Nx). Each group was subdivided into three others, according to the phosphorus concentration in the diet: Low diet (0.2% P), Standard diet (0.54% P) and High diet (0.9% P). We analyzed biochemical parameters (creatinine, P, iCa, PTH and FGF-23), protein expression of cotransporters, using Western Blot, ELISA, immunofluorescence, real-time PCR and apoptosis of enterocytes using the TUNEL technique. Results showed that serum creatinine, P, PTH and FGF-23 were significantly higher in Nx animals. In C animals with a diet low in P we observed increase in protein expression of NaP-IIb cotransporter in all segments of the intestine while in low Nx expression of this cotransporter was lower only in jejunum. As for PiT-1 expression was lower in the ileum of the high Nx group compared to their respective control. Gene expression of NaP-IIb cotransporter was lower in the jejunum of high Nx and higher in the ileum of the same group as compared to their respective controls. PiT-1 gene expression was higher in all...

Trends in hospitalizations and mortality from asthma in Costa Rica over a 12- to 15-year period.

BACKGROUND: Little is known about trends in morbidity and/or mortality due to asthma in Latin America. OBJECTIVE: To examine trends in hospitalizations and mortality due to asthma from 1997-2000 to 2011 in Costa Rica. METHODS: The rates of hospitalization due to asthma were calculated for each sex in 3 age groups from 1997 to 2011. The number of deaths due to asthma was first calculated for all groups and then for each sex in 3 age groups from 2000 to 2011. All analyses were conducted over the entire period and separately for the periods before and after a National Asthma Program (NAP) in 2003. Data also were available for prescriptions for beclomethasone since 2004. All analyses were conducted by using Epi Info. RESULTS: Substantial reductions were found in hospitalizations and deaths due to asthma in Costa Ricans (eg, from 25 deaths in 2000 to 5 deaths in 2011). Although, the percentage decrement in the rates of hospitalization for asthma in subjects <20 years old was similar before and after the NAP, the reduction in both deaths due to asthma and rates of asthma hospitalizations in older subjects were more pronounced after the NAP, when prescriptions for beclomethasone were also increased by approximately 129%. CONCLUSION: In Costa Rica, there was a marked decrement in hospitalizations and mortality due to asthma from 1997-2000 to 2011. In younger subjects, this is likely due to guidelines that, since 1988, recommend inhaled corticosteroids for persistent asthma. In older adults, the NAP probably enhanced reductions in hospitalizations and deaths due to asthma through inhaled corticosteroid use.

Objectively measured sleep duration and hyperglycemia in pregnancy.

OBJECTIVE: Our primary purpose was to assess the impact of objectively measured nighttime sleep duration on gestational glucose tolerance. We additionally examined associations of objectively measured daytime sleep duration and nap frequency on maternal glycemic control. METHODS: Sixty-three urban, low-income, pregnant women wore wrist actigraphs for an average of 6 full days in mid-pregnancy prior to screening for hyperglycemia using the 1-h oral glucose tolerance test (OGTT). Correlations of nighttime and daytime sleep durations with 1-h OGTT values were analyzed. Multivariable logistic regression was used to evaluate independent associations between sleep parameters and hyperglycemia, defined as 1-h OGTT values ≥130 mg/dL. RESULTS: Mean nighttime sleep duration was 6.9±0.9 h which was inversely correlated with 1-h OGTT values (r=-0.28, P=.03). Shorter nighttime sleep was associated with hyperglycemia, even after controlling for age and body mass index (adjusted odds ratio [OR], 0.2 [95% confidence interval {CI}, 0.1-0.8]). There were no associations of daytime sleep duration and nap frequency with 1-h OGTT values or hyperglycemia. CONCLUSIONS: Using objective measures of maternal sleep time, we found that women with shorter nighttime sleep durations had an increased risk for gestational hyperglycemia. Larger prospective studies are needed to confirm our negative daytime sleep findings.

Centrosomal AKAP350 modulates the G1/S transition.

AKAP350 (AKAP450/AKAP9/CG-NAP) is an A-kinase anchoring protein, which recruits multiple signaling proteins to the Golgi apparatus and the centrosomes. Several proteins recruited to the centrosomes by this scaffold participate in the regulation of the cell cycle. Previous studies indicated that AKAP350 participates in centrosome duplication. In the present study we specifically assessed the role of AKAP350 in the progression of the cell cycle. Our results showed that interference with AKAP350 expression inhibits G1/S transition, decreasing the initiation of both DNA synthesis and centrosome duplication. We identified an AKAP350 carboxyl-terminal domain (AKAP350CTD), which contained the centrosomal targeting domain of AKAP350 and induced the initiation of DNA synthesis. Nevertheless, AKAP350CTD expression did not induce centrosomal duplication. AKAP350CTD partially delocalized endogenous AKAP350 from the centrosomes, but increased the centrosomal levels of the cyclin-dependent kinase 2 (Cdk2). Accordingly, the expression of this AKAP350 domain increased the endogenous phosphorylation of nucleophosmin by Cdk2, which occurs at the G1/S transition and is a marker of the centrosomal activity of the cyclin E-Cdk2 complex. Cdk2 recruitment to the centrosomes is a necessary event for the development of the G1/S transition. Altogether, our results indicate that AKAP350 facilitates the initiation of DNA synthesis by scaffolding Cdk2 to the centrosomes, and enabling its specific activity at this organelle. Although this mechanism could also be involved in AKAP350-dependent modulation of centrosomal duplication, it is not sufficient to account for this process.