Connectivity of the Cingulate Sulcus Visual Area (CSv) in Macaque Monkeys.

In humans, the posterior cingulate cortex contains an area sensitive to visual cues to self-motion. This cingulate sulcus visual area (CSv) is structurally and functionally connected with several (multi)sensory and (pre)motor areas recruited during locomotion. In nonhuman primates, electrophysiology has shown that the cingulate cortex is also related to spatial navigation. Recently, functional MRI in macaque monkeys identified a cingulate area with similar visual properties to human CSv. In order to bridge the gap between human and nonhuman primate research, we examined the structural and functional connectivity of putative CSv in three macaque monkeys adopting the same approach as in humans based on diffusion MRI and resting-state functional MRI. The results showed that putative monkey CSv connects with several visuo-vestibular areas (e.g., VIP/FEFsem/VPS/MSTd) as well as somatosensory cortex (e.g., dorsal aspects of areas 3/1/2), all known to process sensory signals that can be triggered by self-motion. Additionally, strong connections are observed with (pre)motor areas located in the dorsal prefrontal cortex (e.g., F3/F2/F1) and within the anterior cingulate cortex (e.g., area 24). This connectivity pattern is strikingly reminiscent of that described for human CSv, suggesting that the sensorimotor control of locomotion relies on similar organizational principles in human and nonhuman primates.

Family function and eating behaviours among Hispanic/Latino youth: results from the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth).

OBJECTIVE: To elucidate mechanisms across family function, home environment and eating behaviours within sociocultural context among Hispanic youth. DESIGN: Two models tested via path analysis (youth fruit and vegetable (FV) consumption; empty energy consumption) using data from the Study of Latino Youth (2011-2013). SETTING: Chicago, IL; Miami, FL; Bronx, NY; San Diego, CA. PARTICIPANTS: Youth (8-16-year-olds), n 1466. RESULTS: Youth ate 2·4 servings of FV per d and received 27 % of total energy from empty energies. Perceiving higher acculturative stress was indirectly associated with lower FV consumption via a pathway of low family function and family support for FV (ß = -0·013, P < 0·001) and via lower family closeness and family support (ß = -0·004, P = 0·004). Being >12-year-olds was indirectly associated with lower FV consumption via lower family closeness and family support (ß = -0·006, P < 0·001). Household food security was indirectly associated with greater FV consumption via family closeness and family support (ß = 0·005, P = 0·003). In contrast, perceiving higher acculturative stress was indirectly associated with higher empty energy consumption (via family closeness and family support: ß = 0·003, P = 0·028 and via low family function and low family support: ß = 0·008, P = 0·05). Being older was associated with higher consumption of empty energies via family closeness (related to family support: ß = 0·04, P = 0·016; parenting strategies for eating: ß = 0·002, P = 0·049). CONCLUSIONS: Findings suggest pathways of influence across demographic and sociocultural context, family dynamics and home environment. The directionality of these associations needs confirmation using longitudinal data.

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori.

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

Polymorphisms PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in a high risk population.

Genetic variants are considered risk factors for gastric cancer. To date, 61 polymorphisms have been identified as associated with this disease. The aim of the present study was to analyze the association of some of those polymorphisms with GC in Chile. We performed a case-control study including 310 gastric cancer cases and 311 controls to assess the association of 36 single-nucleotide polymorphisms genotyped by Global Screening Array (GSA). Three polymorphisms was significantly associated: PSCA rs2294008 (allele model, OR = 1.49, 95%CI 1.17-1.88, P = 1.08 × 10-3), IL-4 rs2243250 (allele model, OR = 1.28, 95%CI 1.01-1.62, P = 0.04), and MUC1 rs4072037 (allele model, OR = 0.78, 95%CI 0.61-0.99, P = 0.04).PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in Chile. It suggests that those polymorphisms could be used as biomarkers to assess the genetic risk for this cancer outside of the previously studied populations, not only for East Asians and Caucasians populations.

Modelling inactivation of wild-type and clinical Escherichia coli O26 strains using UV-C and thermal treatment and subsequent persistence in simulated gastric fluid.

AIMS: First, two inactivation models were compared for different phenotypic profiles of Escherichia coli O26 using ultraviolet-C light (UV-C) and thermal treatment (T), by means of Central Composite Rotatable Design of Experiment (CCRD). Second, we aimed to evaluate the subsequent survival and persistence of cells in simulated gastric fluid (SGF). METHODS AND RESULTS: Two strains of E. coli O26, a wild-type strain and a clinical ATCC strain were used in both steps. A CCRD was used in a 22 arrangement in random order. The goodness-of-fit of the models was determined. The lack of fit, and the normality of residual data were checked with the Shapiro-Wilk test, and the model accuracy factor, bias factor and the model mean square error (MSE) were measured. Subsequently, the resistance capacity of the strains was evaluated after exposure to simulated gastric acid. The CCRD results obtained indicate that the mild heat (<70°C) has a recovery effect. In addition, for the clinical strain, the UV-C and heat (above 70°C) has an additive inactivation effect. Moreover, temperature (65°C) induced SGF resistance by the wild-type and clinical strain. For the clinical strain, cells exposed to UV-C were more sensitive to SGF. In contrast to clinical strain, exposing cells of the wild-type strain to UV-C increased the survival capacity in the SGF. CONCLUSION: Response surface analyses showed that the wild-type O26 strain has higher persistence under unfavourable conditions than the clinical strain, and the stresses caused by applied microbial control technologies can increase the survival capacity in the SGF. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study shed light on different phenotypic responses in the same bacterium serogroup. Moreover, the impact of the study was that strain selection criteria must be adequate to develop effective models of inactivation.

Cytochrome P450 interactions are common and consequential in Massachusetts hospital discharges.

Despite the recognition that drug-drug interactions contribute substantially to preventable health-care costs, the prevalence of such interactions related to the cytochrome P450 system in clinical practice remains poorly characterized. This study drew retrospective hospital discharge cohorts from a large health claims data set and a large health system data set. For every hospital discharge, frequency of co-occurrence of substrates and inducers or inhibitors at cytochrome P450 2D6, 2C19, 3A4 and 1A2 were determined. A total of 124 520 individuals in the state of Massachusetts (health claims cohort) and 77 026 individuals in two large academic medical centers (electronic health record (EHR) cohort) were examined. In the claims cohort, 35 157 (28.2%) exhibited at least one CYP450 drug-drug interaction at hospital discharge, whereas in the EHR cohort, 36 750 (47.7%) had at least one interaction. The most commonly affected CYP450 systems were 2C19 and 2D6, with putative interactions observed in at least 10% of individuals at discharge in each cohort. Odds of hospital readmission within 90 days among those discharged with at least one interaction were 10-16% greater, with mean health-care cost $574/month greater over the subsequent year, after adjusting for age, sex, insurance type, total number of medications prescribed, Charlson comorbidity score and presence or absence of a psychiatric diagnosis. These two distinct clinical data types show that CYP450 drug-drug interactions are prevalent and associated with greater probability of early hospital readmission and greater health-care cost, despite the widespread availability and application of drug-drug interaction checking software.

Prevalence of clarithromycin resistance in Helicobacter pylori in Santiago, Chile, estimated by real-time PCR directly from gastric mucosa.

BACKGROUND: Current available treatments for Helicobacter pylori eradication are chosen according to local clarithromycin and metronidazole resistance prevalence. The aim of this study was to estimate, by means of molecular methods, both clarithromycin and metronidazole resistance in gastric mucosa from patients infected with H.pylori. METHODS: A total of 191 DNA samples were analyzed. DNA was purified from gastric mucosa obtained from patients who underwent an upper gastrointestinal endoscopy at an university hospital from Santiago, Chile, between 2011 and 2014. H.pylori was detected by real-time PCR. A 5'exonuclease assay was developed to detect A2142G and A2143G mutations among H.pylori-positive samples. rdxA gene was sequenced in samples harboring A2142G and A2143G mutations in order to detect mutations that potentially confer dual clarithromycin and metronidazole resistance. RESULTS: Ninety-three (93) out of 191 DNA samples obtained from gastric mucosa were H.pylori-positive (48.7%). Clarithromycin-resistance was detected in 29 samples (31.2% [95%CI 22.0-41.6%]). The sequencing of rdxA gene revealed that two samples harbored truncating mutations in rdxA, one sample had an in-frame deletion, and 11 had amino acid changes that likely cause metronidazole resistance. CONCLUSIONS: We estimated a prevalence of clarithomycin-resistance of 31.8% in Santiago, Chile. Three of them harbor inactivating mutations in rdxA and 11 had missense mutations likely conferring metronidazole resistance. Our results require further confirmation. Nevertheless, they are significant as an initial approximation in re-evaluating the guidelines for H.pylori eradication currently used in Chile.

Prevalence and implications of cytochrome P450 substrates in Massachusetts hospital discharges.

The cytochrome P450 (CYP450) system of drug-metabolizing enzymes may contribute to individual variation in drug response. We examined prevalence of CYP450 substrates at hospital discharge for patients in two cohorts: insurance claims of Massachusetts residents and the medical records of two academic medical centers. The claims cohort included 47 473 individuals (38.2%) treated with at least one CYP450 2D6, 2C19, 3A4 or 1A2 substrate. The electronic medical records cohort included 45 905 individuals (57.4%) treated with at least one substrate. In adjusted models, substrates of CYP450 2D6 and 2C19 were associated with greater risk for 90-day readmission in both cohorts (odds ratios of 1.104 and 1.128 (P<0.001), respectively). Presence of any CYP450 substrate was associated with increased monthly medical costs (+$397, P<0.003). These analyses of more than 300 000 admissions using two different cohorts and data types indicate that CYP450 substrates are associated with greater readmission rates and greater health-care cost.

Multicenter prospective crossover study on new prosthetic opportunities in post-laryngectomy voice rehabilitation.

The aim of this study was to assess the clinical experience of three Italian centers using the third generation Provox Vega prosthesis, in terms of device life and voice outcome, comparing the results with the second generation Provox 2 prosthesis in the same sample. A prospective multicenter crossover study was performed in three phases. In the first phase we performed a reassessment, for enrollment purposes, of patients who were categorized into four different groups [normal ­ group A; radio-treated ­ group B; gastroesophageal reflux disease (GERD) ­ group C; and elderly subjects ­ group D]. In the second and third phases, all patients were monitored for prosthetic device life and assessed for objective and subjective voice characteristics after introducing Provox 2 and Provox Vega prostheses. In patients with Provox 2 prosthesis, the mean life was 165 days in group A, 148 days in group B, 91 days in group C and 188 days in group D. In Provox Vega patients, mean in situ prosthesis life was 213 days in group A, 182 days in group B, 118 days in group C and 227 days in group D. The perceptual voice data showed a better rating across all parameters for the Provox Vega samples compared to those of Provox 2. In this paper, we report the first multicenter crossover study comparing different prosthetic models in the same patients, categorized in relation to different typologies of tracheoesophageal rehabilitative status. Result analyses confirmed an optimal stability of the Provox Vega compared to the Provox 2, in terms of device life and perceptual voice parameters.

An assessesment of telephone assistance systems for caregivers of patients with Alzheimer's disease. / Evaluación de la asistencia telefónica a demanda en cuidadores de pacientes con enfermedad de Alzheimer.

INTRODUCTION: Telephone assistance is a common practice in neurology, although there are only a few studies about this type of healthcare. We have evaluated a Telephone Assistance System (TAS) for caregivers of patients with Alzheimer's disease (AD) from 2 points of view: financially and according to the level of satisfaction of the caregiver. PATIENTS AND METHODS: 97 patients with a diagnosis of AD according to NINCDS-ADRDA criteria and their 97 informal caregivers were selected. We studied cost differences between on-site assistance and telephone assistance (TAS) for 12 months. We used a self-administered questionnaire to assess the level of satisfaction of caregivers at the end of the study period. RESULTS: TAS savings amounted to 80.05 ± 27.07 euros per user. 73.6% of the caregivers consider TAS a better or much better system than on-site assistance, while only 2.6% of the caregivers considered TAS a worse or much worse system than on-site assistance. CONCLUSIONS: Telephone assistance systems are an efficient healthcare resource for monitoring patients with AD in neurology departments. Furthermore, the level of user satisfaction was high. We therefore consider that telephone assistance service should be offered by healthcare services.

Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system.

Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hyperactivity disorder (ADHD) delivered in a large New England health-care system were identified from electronic health records (EHR), and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and EHRs to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1377 children diagnosed with ASD and 2243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression (odds ratio (OR) 1.10 (0.70-1.70)). Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression (OR 1.81 (1.22-2.70)). These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression.

The use of a potential novel tool in virtual crossmatching for platelet transfusion in platelet refractoriness.

BACKGROUND AND OBJECTIVES: Transfusion support for immune-mediated platelet refractoriness (PR) is clinically challenging, technically laborious and costly. The development of 'EpHLA/EpVix software' has been used successfully to select kidney donors. Here, we sought to evaluate this new software as a tool for platelet virtual crossmatch (VxM). MATERIALS AND METHODS: This is a prospective study from 2007 to 2014 of PR patients in a tertiary hospital. Platelet components selected by HLAMatchmaker program were crossmatched by EpHLA/EpVix, anti-human globulin complement-dependent lymphocytotoxicity test (AHG-CDC), flow cytometry platelet crossmatch (FCxM) and then compared. Effectiveness of platelet components transfused was evaluated by CCI. RESULTS: Ninety-seven crossmatched platelet transfusions for 27 patients were enrolled. Partial matches were analysed for 75 transfusions by the 3 methods, and 22% showed discrepant results among the assays. After further analysis, data showed that all divergent cases could be explained by HPA alloimmunization, prozone effect (FCxM), low sensitivity of AHG-CDC and possible interference in FCxM/AHG-CDC assays. Notably, sensitivity and specificity of VxM analysis was excellent (100%). Satisfactory CCI counts were obtained for the majority (22/30) of the transfusions. CONCLUSION: The new EpHLA/EpVix method showed to be effective, feasible and fast for VxM at no cost and able to minimize labour on donor identification. However, platelet crossmatching may be a necessary step because EpHLA/EpVix does not formally exclude HPA alloimmunization.

Tackling pollution by organic farming is capable of increasing fortified foods.

The global pollution stage is poisoning the biosphere and causing global temperatures to rise, necessitating a drastic change in the way man is dealing with nature. One change that may produce many beneficial effects on the biosphere and human health is the use of specific organic farming to produce food in a more integrated way in nature and to increase the capacity of man's own response. Despite many experts' opinion another way to deal with environmental contamination is possible: organic farming, which can increase man's ability to fortify foods. After more than 20 years working under this discipline, Bodegas Dagon is able to achieve the highest stilbenes concentrations (as resveratrol). Versus 14.3 mg/l, "Bodegas Dagón" wines contain resveratrol (HPLC and UV-spectroscopy) up to 1611.73 ± 72.66 mg/l, standing as world's potentially healthiest wine reported to date.

Epidemiology of asthma exacerbations and their relation with environmental factors in the Basque Country.

BACKGROUND: Asthma is a highly prevalent chronic inflammatory disease characterised by reversible airflow obstruction and hyperreactivity and inflammation of the airways. Factors that cause and/or trigger asthma attacks include host-related factors (genetic predisposition, obesity and sex) and environmental factors (allergens, infections, occupational sensitisation, smoking status, pollution and diet). OBJECTIVE: To describe the epidemiology of asthma exacerbations (AEs) in the Basque Country and to explore its relationship with potentially associated environmental variables. We studied a total of 31,579 emergency department (ED) visits and 28,189 hospitalisations due to asthma. We describe the trends, incidence, seasonality and the influence of age and sex, as well as of exposure to NO2 , CO, PM, O3 , and pollen, temperature, relative humidity and flu status. We calculated the Pearson's R correlation coefficient for the study variables. RESULTS: The incidence was 486 and 88.9 cases per 100,000 people for ED visits and hospitalisations, respectively. Slightly over half (53.5%) of the ED cases were male, while females represented 62.6% of the hospital admissions. Hospitalisations are tending to decrease in children and increase in over 64-year-olds. Peaks in cases occur at the beginning of autumn in children and in winter in adults. AEs were correlated positively with exposure to NO2 , CO and to the influenza virus and negatively with temperature and exposure to O3 . These relationships vary, however, with age and season. CONCLUSIONS AND CLINICAL RELEVANCE: Rates of hospitalisation for AEs and trends in these rates over time are different in adults and children with the patterns varying by sex, season and environmental conditions.

Biomarker Evaluation in Fish After Prolonged Exposure to Nano-TiO2: Influence of Illumination Conditions and Crystal Phase.

In this study, we evaluated the effects of prolonged exposure to two different nano-TiO2 crystal phases under different illumination conditions. Fish (Piaractus mesopotamicus) were exposed for 21 days to 100 mg/L of nano-TiO2 anatase and a mixture of anatase:rutile (80%:20%) under visible light and UV light (UVA and B, 22.47 J/cm2/h). The following oxidative stress biomarkers were mon- itored: concentrations of lipid hydroperoxide (LPO), carbonylated proteins (PCO), and specific activ- ities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). Other biomarkers as well as specific activities of acid phosphatase (AP), Na+, K(+)-ATPase and metalloth- ionein levels (MT) were also evaluated. Moreover, micronucleus and comet assays were performed to assess genotoxicity. Our results showed low toxicity of nano-TiO2 to fish and lack of titanium accumulation in muscle tissue. However, it was observed the occurrence of sublethal effects that were influenced by nano-TiO2 crystal phase and illumination condition. Pure anatase caused more oxidative damage without co-exposure to UV, while the mixture anatase:rutile caused more sub- lethal effects when exposure occurred under UV. These findings show that the specific activity of CAT, GST, PCO levels and comet assay are useful as biomarkers of prolonged exposure to nano- TiO2. Overall, our study substantiates the development and implementation of nanoecotoxicological protocols.

Forced expression of OCT4 influences the expression of pluripotent genes in human mesenchymal stem cells and fibroblasts.

Genetic reprogramming of adult cells to generate induced pluripotent stem (iPS) cells is a new and important step in sidestepping some of the ethical issues and risks involved in the use of embryonic stem cells. iPS cells can be generated by introduction of transcription factors, such as OCT4, SOX2, KLF4, and CMYC. iPS cells resemble embryonic stem cells in their properties and differentiation potential. The mechanisms that lead to induced pluripotency and the effect of each transcription factor are not completely understood. We performed a critical evaluation of the effect of overexpressing OCT4 in mesenchymal stem cells and fibroblasts and found that OCT4 can activate the expression of other stemness genes, such as SOX2, NANOG, CMYC, FOXD3, KLF4, and ßCATENIN, which are not normally or are very weakly expressed in mesenchymal stem cells. Transient expression of OCT4 was also performed to evaluate whether these genes are affected by its overexpression in the first 48 h. Transfected fibroblast cells expressed around 275-fold more OCT4 than non-transfected cells. In transient expression, in which cells were analyzed after 48 h, we detected only the up-regulation of FOXD3, SOX2, and KLF4 genes, suggesting that these genes are the earlier targets of OCT4 in this cellular type. We conclude that forced expression of OCT4 can alter cell status and activate the pluripotent network. Knowledge gained through study of these systems may help us to understand the kinetics and mechanism of cell reprogramming.

Using electronic medical records to enable large-scale studies in psychiatry: treatment resistant depression as a model.

BACKGROUND: Electronic medical records (EMR) provide a unique opportunity for efficient, large-scale clinical investigation in psychiatry. However, such studies will require development of tools to define treatment outcome. METHOD: Natural language processing (NLP) was applied to classify notes from 127 504 patients with a billing diagnosis of major depressive disorder, drawn from out-patient psychiatry practices affiliated with multiple, large New England hospitals. Classifications were compared with results using billing data (ICD-9 codes) alone and to a clinical gold standard based on chart review by a panel of senior clinicians. These cross-sectional classifications were then used to define longitudinal treatment outcomes, which were compared with a clinician-rated gold standard. RESULTS: Models incorporating NLP were superior to those relying on billing data alone for classifying current mood state (area under receiver operating characteristic curve of 0.85-0.88 v. 0.54-0.55). When these cross-sectional visits were integrated to define longitudinal outcomes and incorporate treatment data, 15% of the cohort remitted with a single antidepressant treatment, while 13% were identified as failing to remit despite at least two antidepressant trials. Non-remitting patients were more likely to be non-Caucasian (p<0.001). CONCLUSIONS: The application of bioinformatics tools such as NLP should enable accurate and efficient determination of longitudinal outcomes, enabling existing EMR data to be applied to clinical research, including biomarker investigations. Continued development will be required to better address moderators of outcome such as adherence and co-morbidity.