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Based on the data from PISA 2018, the study investigates the relationship between gender and immigration status on exposure and attitudes towards bullying and students' perception of teachers' intercultural attitudes in Spanish high schools. While boys and first‐generation immigrants experience significantly more bullying, girls and students without immigration background showed overall stronger negative attitudes towards bullying. Finally, boys and children with an immigration background perceived higher degrees of teachers' cultural biases. These findings provide new insights into the importance of addressing gender and ethnic biases in anti‐bullying programmes. [ABSTRACT FROM AUTHOR]

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome‐wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta‐analyzed with additional genome‐wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta‐analysis strategy revealed the ANKRD31‐rs4704171 and NDUFAF6‐rs10098778 and confirmed SCIMP‐rs7225151 and CD33‐rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta‐analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series. Highlights: We detected three gene categories operating differently in AD subgroups of patients.Vasculature regulation may be an essential part of the causative mechanism in pure AD.Two novel signals reached genome‐wide significance in ANKRD31 and NDUFAF6loci.We confirmed SCIMP‐rs7225151 and CD33‐rs3865444 to be genome‐wide significant.Genetic discoveries are strongly impacted by the presence of subgroups of AD. [ABSTRACT FROM AUTHOR]

Introduction: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. Methods: We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta‐analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Results: Analysis of the FACEHBI cohort and the meta‐analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion: The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype. Highlights: The FACEHBI sample presents APOE ε4 enrichment, suggesting it contains a pool of AD patients.APOE ε4 is a risk factor of being diagnosed with SCD.APOE ε4 only explains ≈10% of brain amyloid burden variability in SCD.The relationship between APOE and brain amyloid burden across clinical diagnoses highlights the importance of adjusting for clinical status when conducting GWAS of cerebral Aβ levels. [ABSTRACT FROM AUTHOR]

ABSTRACT [ABSTRACT FROM AUTHOR]

Introduction We evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI). Methods We selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E ( APOE ) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (aβ, tau, ptau). Results PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (β ± SE:−0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10 −4 ; ptau: 1.40 ± 0.36, P = 1.02 × 10 −4 ). Discussion In MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition. [ABSTRACT FROM AUTHOR]

ABSTRACT Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Alzheimer's disease (AD) affects people worldwide, and the prevalence is increasing as the population ages. There is an international effort to understand the biology of AD to develop primary and secondary prevention strategies, and to develop effective therapeutic interventions for individuals who are already symptomatic. One of the critically important pieces of all national plans to address AD is the call for the development of service models to deliver quality, effective care based on the best evidence available. Methods: We describe one type of care model developed by the Fundacio ACE, Institut Catala de Neurociencies Aplicades (Fundacio ACE, Barcelona, Spain) that integrates diagnosis, therapy, follow-up care, daycare, and a day hospital, and does so in the context of an active clinical research and educational program. Results: There were 13,048 individuals newly evaluated and diagnosed in Fundacio ACE between 1996 and 2011. Of these, 6132 had AD (47.0%), 3871 had mild cognitive impairment (MCI) (29.7%), and 1958 had no cognitive impairment (15.0%). Follow-up information is available on 4735 (47.3%) AD and MCI patients, and these data indicate that MCI develops into dementia at a rate of 222.6/1000 person-years. Apolipoprotein E (APOE) genotyping was available in 22.4% of the patients. The ε4 allele occurred in 45.7% of the AD patients, in 37.8% of the MCI subjects, and in 31.6% of those without cognitive impairment. Conclusions: Fundació ACE can serve as a model system that can be adapted to other settings within their specific cultural, governmental, and legal constraints. [Copyright &y& Elsevier]

Elevated anti-Müllerian hormone (AMH) and adrenal androgen levels have been observed during childhood in girls at risk of developing polycystic ovarian syndrome (PCOS). The aim of this study was to evaluate ovarian function and adrenal steroid levels in prepubertal girls with type 1 diabetes mellitus (T1D). Cross-sectional study. We evaluated hormonal and ultrasonographic characteristics in girls with T1D ( N = 73) and compared them to characteristics found in a control group of healthy girls ( N = 86). Data are reported as geometric means (95% CI). Prepubertal girls with T1D had higher levels of AMH (29·1 pmol/l (23·2-36·3) vs 20·9 pmol/l (16·6-26·1), P = 0·038), inhibin B (arithmetic mean: 16·7 pg/ml (11·6-21·7) vs 11·7 pg/ml (10·0-13·5), P = 0·044) and dehydroepiandrosterone sulphate (DHEAS) (0·3 nmol/l (0·2-0·6) vs 0·2 nmol/l (0·1-0·3)) than controls ( P = 0·045). During puberty, decreasing AMH levels were observed in girls with T1D only ( P < 0·0001). Girls with T1D in Tanner stages 4-5 had lower AMH levels than their paired healthy controls (10·1 pmol/l (7·4-13·9) vs 15·7 pmol/l (11·6-21·3), respectively, P = 0·047). Our observations indicate that prepubertal girls with T1D may exhibit similar endocrine findings to those of other girls at risk of developing PCOS. The elevated levels of AMH and inhibin B suggest that higher numbers of follicles are present in the ovary during childhood in these patients and that insulin treatment may act as a local growth factor. In addition, AMH levels differed in prepubertal and pubertal girls, suggesting that the effect of T1D on ovarian folliculogenesis changes once gonadotrophin levels rise during puberty [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate whether the acute haemodynamic effects of angiotensin-converting enzyme inhibition with captopril could be enhanced by oestrogen administration, and then to evaluate the mechanisms involved in this enhancement. All experiments were performed in 18-week-old female spontaneously hypertensive rats arranged in three experimental groups: intact; ovariectomized (OVX); and ovariectomized plus treatment with 17β-oestradiol (OVX + E2). These groups were used to evaluate the effects of captopril administration alone, or following bradykinin B2 receptor blockade or nitric oxide synthase inhibition, on a number of haemodynamic parameters (mean arterial pressure, cardiac index, vascular resistance and heart rate). The drop in mean arterial pressure and vascular resistance index in response to captopril was more pronounced in intact and ovariectomized rats treated with 17β-oestradiol than in ovariectomized animals. Blockade of bradykinin B2 receptors or inhibition of nitric oxide synthesis attenuated the synergy between 17β-oestradiol and captopril. It is concluded that ovariectomy blunted the blood pressure and vascular resistance index drop observed in intact rats in response to captopril. Treatment with 17β-oestradiol prevented the blunted response to captopril in ovariectomized rats. Kinins and nitric oxide may be involved in the mechanisms of 17β-oestradiol potentiation of the haemodynamic effects of captopril. [ABSTRACT FROM AUTHOR]

We investigated the role of oestrogen in the function and structure of the microcirculation of female spontaneously hypertensive rats (SHRs), and evaluated the effect of 17β-oestradiol on their cardiovascular response to pharmacological agents that block the formation of angiotensin II. Ten-week-old SHRs were randomly assigned to the following groups: intact, ovariectomized, and ovariectomized treated with 17β-oestradiol (1.5 mg delivered over 60 days) and/or captopril (5 mg kg−1 day−1 for 8 weeks). Systolic blood pressure was determined from the time of ovariectomy up to 18 weeks of age, at which time endothelial function and microvascular density in skeletal muscle were evaluated. Both 17β-oestradiol and captopril prevented development of hypertension in ovariectomized rats. Furthermore, coadministration of both drugs had a greater antihypertensive effect than either one alone. Acetylcholine-induced vasodilatation was impaired in ovariectomized SHRs, and the response was improved by treatment with 17β-oestradiol and/or captopril. In addition, 17β-oestradiol replacement in ovariectomized rats enhanced the effect of captopril on acetylcholine-induced vasodilatation. Ovariectomized rats also showed lower microvascular density than intact rats, an effect that was prevented by 17β-oestradiol replacement or captopril treatment and, to a significantly larger extent, by coadministration of both. We concluded that both 17β-oestradiol and captopril attenuated the development of hypertension and improved the impairment in microvascular density of ovariectomized SHRs. Moreover, when simultaneously administered, oestradiol and captopril had an additive effect on blood pressure and the microvasculature. [ABSTRACT FROM AUTHOR]

To determine the prevalence of histoplasmosis and paracoccidiomycosis in Upata, a city in Bolívar state, Venezuela.Cutaneous tests on 397 volunteers, 204 with histoplasmine and 193 with paracoccidioidine. Epidemiological data were collected in a protocol sheet. Readings were performed at 24 and 48 h post-injection, by the same observer, and a positive reaction was defined as hardened papule of 5 mm or more.Histoplasmine tests were positive in 19.6% and 34.0% at 24 and 48 h after antigens injection with a significant increase of reactivity (P = 0.0019). Paracoccidiodine tests were positive in 11.3% and 19.7% at 24 and 48 h respectively and this difference was also significant (P = 0.004). Risk factors which could explain these levels of reactivity could not be clearly identified. Cultures and animal inoculation from soil samples for fungus isolation were negative.Paracoccidioidomycoses and histoplasmosis are endemic in Upata. [ABSTRACT FROM AUTHOR]

Background The advent of combined antiretroviral therapy (ART) in the past decade has led to HIV suppression in most cases. Virological failure was the main reason for ART switch a few years ago; however, toxicity and treatment simplification have now gained importance due to the availability of more effective and convenient drugs. This study assessed the reasons for ART switch in daily practice. Material and Methods Observational retrospective study that included patients whose ART was switched between January 2011 and July 2012. Patients with any other switch during the follow-up period (until September 2013) were excluded. Results A total of 246 patients were included. Main reasons for ART switch were simplification (33%) and toxicity (31%), followed by clinical trial inclusion (13%), virological failure (6%), drug interaction (4%), patient decision (3%), lack of adherence (2%), pregnancy (1%) and other (8%). Eighty patients switched to a simpler regimen (median age 48 [40-53], mean CD4 count 608±265 cells/cl, 89% <50 copies/ml, mean number of previous regimens 6±5, mean time on previous ART 3±2 years). In this case, previous ART mostly included 2NRTI+1PI/r (54%) (Figure 1). The simplification strategy mainly contained nuke-sparing regimens (60%) based on PI (DRV/r 48%): monotherapy 46%, dual therapy 13% (PI/r+maraviroc 9%, PI/r+NNRTI 4%) and triple therapy 1% (PI/r+maraviroc+raltegravir). The second preferred simplification option was 2NRTI+1NNRTI (24%). Seventy-seven patients switched due to toxicities (median age 47 [43-53], mean CD4 count 606±350 cells/μl, <50 copies/ml 82%, mean number of previous regimens 4±3, mean time on previous ART 3±3 years). Renal (25%) and CNS (18%) toxicities were the main reasons for ART switch, followed by diarrhoea (16%), liver enzyme elevation (ALT 10%; AST 9%; bilirubin 7%), lipid elevation (cholesterol 5%; triglycerides 8%), nausea (7%) and other (=5%) (Figure 2). All patients with renal toxicity were under TDF and in most cases this drug was removed from the new regimen (with 3TC/ABC or nuke-sparing). Among patients with CNS toxicity, 79% were taking EFV; the main new treatment was a second-generation NNRTI (ETR)+2NRTI. Toxicities were completely resolved in 66% of patients, partially resolved in 22% and not resolved in only 12%; the median time from ART switch to toxicity resolution was 4 (2-8) months. Conclusions The main reasons for ART switch in daily practice are simplification and toxicities, renal and CNS toxicities being the most prevalent. The preferred simplification strategies are nuke-sparing regimens, mainly DRV/r-based monotherapy and dual therapy. ART switch leads to a complete resolution of toxicities in most cases in the short term. [ABSTRACT FROM AUTHOR]

Introduction Sexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition []. It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) []. The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV-MSM and the related factors. Materials and Methods Prospective study of a cohort of asymptomatic HIV-MSM with follow-up in Malaga (southern Spain) during October 2012-May 2014. Patients with an opportunistic event or who received active antibiotic therapy for CT and/or NG in the previous month were excluded. All of them completed a questionnaire about sexual behaviour, barrier methods and recreational drugs use. Demographical, epidemiological, clinical, analytical and therapeutic data were also collected. Pharyngeal and rectal swabs, and urine samples were collected to be tested for CT and NG by nucleic acid amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) []. Statistics analysis: SPSS 17.0. Results 255 patients were asked to participate and 248 of them accepted. Median age was 37.7 (30.6-46.3) years, median time since HIV diagnosis was 47.7 (10.5-104.1) months, and median CD4 cells count was 607 (440-824) cell/µL. There were 195 (78.6%) patients on antiretroviral therapy; 81.5% of them had undetectable viral load. 80.5% of the patients had a past history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients. Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients were co-infected by CT and NG: one with CT in urine and both in rectum, another with CT in urine and rectum and NG in pharynx. One patient presented CT in pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2-7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or recreational drugs use. Conclusions STI screening had a great acceptance in this population. There was a high prevalence of asymptomatic CT and/or NG infections. Rectum sample was the most effective one. Viral suppression could protect from these STI. Screening should be recommended in HIV-MSM. [ABSTRACT FROM AUTHOR]

Introduction Rilpivirine (RPV) has a better lipid profile than efavirenz (EFV) in naïve patients []. Switching to RPV may be convenient for many patients, while maintaining a good immunovirological control []. The aim of this study was to analyze lipid changes in HIV-patients at 24 weeks after switching to Eviplera® (emtricitabine/RPV/tenofovir disoproxil fumarate [FTC/RPV/TDF]). Materials and Methods Retrospective, multicentre study of a cohort of asymptomatic HIV-patients who switched from a regimen based on 2 nucleoside reverse transcriptase inhibitors (NRTI)+protease inhibitor (PI)/non nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir boosted PI monotherapy to Eviplera® during February-December, 2013; all had undetectable HIV viral load for ≥3 months prior to switching. Patients with previous failures on antiretroviral therapy (ART) including TDF and/or FTC/3TC, with genotype tests showing resistance to components of Eviplera®, or who had changed the third drug of the ART during the study period were excluded. Changes in lipid profile and cardiovascular risk (CVR), and efficacy and safety at 24 weeks were analyzed. Results Among 305 patients included in the study, 298 were analyzed (7 cases were excluded due to lack of data). Men 81.2%, mean age 44.5 years, 75.8% of HIV sexually transmitted. 233 (78.2%) patients switched from a regimen based on 2 NRTI+NNRTI (90.5% EFV/FTC/TDF). The most frequent reasons for switching were central nervous system (CNS) adverse events (31.0%), convenience (27.6%) and metabolic disorders (23.2%). At this time, 293 patients have reached 24 weeks: 281 (95.9%) have continued Eviplera®, 6 stopped it (3 adverse events, 2 virologic failures, 1 discontinuation) and 6 have been lost to follow up. Lipid profiles of 283 cases were available at 24 weeks and mean (mg/dL) baseline vs 24 weeks are: total cholesterol (193 vs 169; p=0.0001), HDL-c (49 vs 45; p=0.0001), LDL-c (114 vs 103; p=0.001), tryglycerides (158 vs 115; p=0.0001), total cholesterol to HDL-c ratio (4.2 vs 4.1; p=0.3). CVR decreased (8.7 vs 7.5%; p= 0.0001). CD4 counts were similar to baseline (653 vs 674 cells/µL; p=0.08), and 274 (96.8%) patients maintained viral suppression. Conclusions At 24 weeks after switching to Eviplera®, lipid profile and CVR improved while maintaining a good immunovirological control. Most subjects switched to Eviplera® from a regimen based on NNRTI, mainly EFV/FTC/TDF. CNS adverse events, convenience and metabolic disorders were the most frequent reasons for switching. [ABSTRACT FROM AUTHOR]

Abstract: Complement receptor 1 gene polymorphism rs3818361 was recently shown to increase the risk of Alzheimer’s disease (AD). We performed an independent replication study of this genetic variant in 2470 individuals from Spain. By applying an allelic model, we observed a trend toward an association between this marker and late-onset AD susceptibility in our case–control study (odds ratio = 1.114, 95% confidence interval: 0.958–1.296, P = .16). Meta-analysis of available studies (n = 31,771 individuals), including previous studies and public genome-wide association study resources (Alzheimer’s Disease Neuroimaging Initiative, Translational Genomics Research Institute, and Multi-site Collaborative Study for Genotype-Phenotype Associations in Alzheimer''s Disease), strongly supports the effect of rs3818361 (odds ratio = 1.180, 95% confidence interval: 1.113–1.252, P < 2.99E-8) and suggests the existence of between-study heterogeneity (P < .05). We concluded that the complement receptor 1 gene may contribute to AD risk, although its effect size could be smaller than previously estimated. [Copyright &y& Elsevier]