La importància del gènere en la prevenció i l’atenció de les ITS/VIH en l’Atenció Primària

Género; Prevención; VIH; Atención primariaGènere; Prevenció; VIH; Atenció primàriaGender; Prevention; HIV; Primary careEn aquest article, es fa una introducció a la complexitat que hi ha al darrera del terme sexualitat i també es fa una sèrie de reflexions sobre com cal enfocar la relació entre els professionals de la salut i els pacients tenint en compte la diversitat sexual de les persones usuàries dels serveis sanitaris

Role of neurotrophins in depressive symptoms and executive function: Association analysis of NRN1 gene and its interaction with BDNF gene in a non-clinical sample

Background Neuritin-1 is a neurotrophic factor involved in synaptic plasticity that has been associated with depressive disorders, schizophrenia and cognitive performance. The study of genotype-phenotype relationships in healthy individuals is a useful framework to investigate the etiology of brain dysfunctions. We therefore aimed to investigate in a non-clinical sample whether NRN1 gene contributes to the psychopathological profile, with a particular focus on the clinical dimensions previously related to the NRN1 gene (i.e. depressive and psychotic). Furthermore, we aimed to analyze: i) the role of NRN1 on executive functions, ii) whether the association between either NRN1-psychopathological profile or NRN1-cognitive performance is moderated by the BDNF gene. Methods The sample is comprised of 410 non-clinical subjects who filled in the self-reported Brief Symptom Inventory (BSI) and were assessed for executive performance (Verbal Fluency, Wisconsin Card Sorting Test (WCST) and Letter-Number subscale (WAIS-III)). Genotyping included nine SNPs in NRN1 and one in BDNF. Results i) GG homozygotes (rs1475157-NRN1) showed higher scores on BSI depressive dimension and on total scores compared to A carriers (corrected p-values: 0.0004 and 0.0003, respectively). ii) A linear trend was detected between GG genotype of rs1475157 and a worse cognitive performance in WCST total correct responses (uncorrected p-value: 0.029). iii) Interaction between rs1475157-NRN1 and Val66Met-BDNF was found to modulate depressive symptoms (p=0.001, significant after correction). Limitations Moderate sample size; replication in a larger sample is needed. Conclusions NRN1 is associated with depressive symptoms and executive function in a non-clinical sample. Our results also suggest that the role of NRN1 seems to be modulated by BDNF.This study was supported by: i) Intramural Project CIBERSAM (P91E), ii) The Network of European Funding for Neuroscience Research, ERA-NET NEURON (PiM2010ERN-00642), iii) Instituto de Salud Carlos III through the project PI15/01420 (co-funded by European Regional Development Fund /European Social Fund, “Investing in your future”). Thanks to: i) the Comissionat per a Universitats i Recerca del DIUE (2014SGR1636), ii) Universitat de Barcelona and APIF-IBUB grant 2014. All funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

Drv Concentrations And Viral Load In Csf In Patients On Drv/r 600/100 Or 800/100mg Once Daily Plus Two Nrti

Introduction Darunavir/r (DRV/r) is currently used at a dose of 800/100 mg once daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV‐1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD. Methods DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs 600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011‐006272‐39). Here we present the results of a CSF sub‐study. A lumbar puncture (LP) was performed in participating patients after at least six months of inclusion in the study, 20–28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and in plasma using high‐performance liquid chromatography (HPLC). Results Sixteen patients were included (eight in each arm). All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range) age was 48 (17–71) years, CD4 cell count 532 cells/mL (190–1,394). Median total time on DRV/r was 30 (11–57) months, and since the beginning of the study 8 (6–12) months in DRV800 and 10 (7–12) months in DRV600 patients. LP was performed a median of 26 (24–28) hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326–3,742) ng/mL, CSF levels 17.08 (5.79–30.19) ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028–0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707 (958–3,910) ng/mL, CSF levels 13.23 (3.47–32.98) ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018–0.0262). All patients had VL<40 copies/mL in plasma and 14 patients VL<40 copies/mL in CSF. Two patients (1 in each arm, and taking TDF/FTC) had detectable VL in CSF (280 and 159 c/mL). These patients had the lowest CSF DRV concentrations (5.47 and 3.47 ng/mL), with plasma DRV concentrations of 802 and 958 ng/mL respectively. Conclusions CSF DRV concentrations and CSF VL were similar between patients receiving DRV/r 800/100 mg or 600/100 mg OD. Low CSF DRV concentrations might be associated with viral escape in CNS. This may be taken into account in patients receiving OD DRV/r. Larger studies should confirm these findings

Schistosomiasis Among Female Migrants in Non-endemic Countries : Neglected Among the Neglected? A Pilot Study

Schistosomiasis among migrant populations in Europe is an underdiagnosed infection, yet delayed treatment may have serious long-term consequences. In this study we aimed to characterize the clinical manifestations of Schistosoma infection among migrant women, and the degree of underdiagnosis. We carried out a prospective cross-sectional study among a migrant population living in the North Metropolitan Barcelona area and coming from schistosomiasis-endemic countries. We obtained clinical, laboratory and socio-demographic data from electronic clinical records, as well as information about years of residence and previous attendance at health services. Blood sample was obtained and schistosomiasis exposure was assessed using a specific ELISA serological test. Four hundred and five patients from schistosomiasis-endemic regions were screened, of whom 51 (12.6%) were female. Seropositivity prevalence was 54.8%, but considering women alone we found a prevalence of 58.8% (30 out of 51). The median age of the 51 women was 41.0 years [IQR (35-48)] and the median period of residence in the European Union was 13 years [IQR (10-16)]. Schistosoma -positive women (N = 30) showed a higher prevalence of gynecological signs and symptoms compared to the seronegative women (96.4 vs. 66.6%, p = 0.005). Among seropositive women, the median number of visits to Sexual and Reproductive Health unit prior to diagnosis of schistosomiasis was 41 [IQR (18-65)]. The high prevalence of signs and symptoms among seropositive women and number of previous visits suggest a high rate of underdiagnosis and/or delayed diagnosis of Schistosoma infection, particularly female genital schistosomiasis, among migrant females

Facial Biomarkers Detect Gender-Specific Traits for Bipolar Disorder

Bipolar disorder (BD) is a psychiatric disorder associated with brain and neurodevelopmental alterations. As in other disorders, patients with BD present minor Physical Anomalies (MPAs) in higher frequency than healthy subjects. MPAs are subtle signs of developmental deviation that appear in body regions that share the ectodermal origin of the brain and are likely triggered by the same insults altering early brain development in mental disorders. MPAs are thus considered potential biomarkers for neurodevelopmental disorders. In this study, we compared facial shape variation between patients with BD and healthy controls using 3D facial reconstructions from magnetic resonance images (MRI) to test the potential of MPAs as a biomarker of BD diagnosis. Moreover, we assessed sex-specific facial shape variation to test whether the disorder affects differently male and female patients. We collected the 3D coordinates of 20 anatomical facial landmarks in a sample of 174 subjects (87 patients with BD and 87 healthy controls) and analyzed global and local patterns of facial shape using Geometric Morphometrics and multivariate statistical techniques. Although Procrustes-ANOVA analysis revealed that diagnosis accounted for a low but significant effect (1.1% of total facial shape variance, P-value=0.016), global facial shape did not significantly discriminate between patients with BD and healthy controls (P-value=0.19). However, Euclidean Distance Matrix Analysis (EDMA) based on local distances of the face revealed that 16.8% of facial traits were significantly different between patients with BD and healthy controls. Remarkably, the patterns of facial differences were sex-specific, suggesting that BD has a different effect on male and female patients. These findings show that local facial differences could be used as biomarkers for an improved diagnosis of BD and raise awareness on the importance of studying sex differences on neurodevelopmental disorders to develop more specific and efficient treatments

Mycobacterium tuberculosis acquires limited genetic diversity in prolonged infections, reactivations and transmissions involving multiple hosts

Publisher Copyright: © 2018 Herranz, Pole, Ozere, Chiner-Oms, Martínez-Lirola, Pérez-García, Gijón, Serrano, Romero, Cuevas, Comas, Bouza, Pérez-Lago and García-de-Viedma.Background: Mycobacterium tuberculosis (MTB) has limited ability to acquire variability. Analysis of its microevolution might help us to evaluate the pathways followed to acquire greater infective success. Whole-genome sequencing (WGS) in the analysis of the transmission of MTB has elucidated the magnitude of variability in MTB. Analysis of transmission currently depends on the identification of clusters, according to the threshold of variability (<5 SNPs) between isolates. Objective: We evaluated whether the acquisition of variability in MTB, was more frequent in situations which could favor it, namely intrapatient, prolonged infections or reactivations and interpatient transmissions involving multiple sequential hosts. Methods: We used WGS to analyze the accumulation of variability in sequential isolates from prolonged infections or translations from latency to reactivation. We then measured microevolution in transmission clusters with prolonged transmission time, high number of involved cases, simultaneous involvement of latency and active transmission. Results: Intrapatient and interpatient acquisition of variability was limited, within the ranges expected according to the thresholds of variability proposed, even though bursts of variability were observed. Conclusions: The thresholds of variability proposed for MTB seem to be valid in most circumstances, including those theoretically favoring acquisition of variability. Our data point to multifactorial modulation of microevolution, although further studies are necessary to elucidate the factors underlying this modulation.publishersversionPeer reviewe

Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo

A complex link exists between HIV-1 and autophagy, and discordant results have been reported in different in vitro models regarding the way HIV and autophagy modulate each other. Despite this, there is very limited knowledge about the interplay between HIV and autophagy in vivo in lymphoid tissue, due in part by the lack of cell models that recapitulate the in vivo setting. Here, we evaluate the interrelationship between HIV and autophagy using human ex vivo lymphoid tissue cultures as an HIV infection model. Our results showed that human lymphoid aggregated cultures (HLACs) from tonsillar tissue displayed fully functional autophagic activity. In this system, HIV infection resulted in an increase in autophagy. Notably, we observed that both, autophagy-enhancing (rapamycin) or blocking drugs (3-methyladenine, chloroquine and bafilomycin), were able to decrease HIV-DNA levels and HIV replication. Therefore, efficient HIV-1 replication requires a fine-tuned level of autophagy, so modifications of this balance will have a negative impact on its replication. Therefore, targeting the autophagic pathway could be a new therapeutic approach to be explored to treat HIV-1 infection. Ex vivo cultures of human lymphoid tissue are a suitable model to obtain further insights into HIV and its intricate relationship with autophagy

High Potential of Facial Biomarkers to Diagnose Psychotic Disorders

Schizophrenia (SCZ) and Bipolar Disorder (BP) are severe psychiatric disorders (PD) that affect more than 3% of the world's population and are among the leading causes of disability worldwide. Current diagnostic systems represent these PD as independent categorical entities. However, recent studies propose that both disorders would be two different manifestations of the same psychotic spectrum continuum. Differential diagnosis is mainly based on their clinical presentation, and reliable biomarkers remain an unmet clinical need. Since the brain and the face are derived from the same ectodermal origins and their development is intimately integrated through common genetic signaling, facial biomarkers emerge as one of the most promising biological risk factors for PD. Here, we assessed the potential of facial anatomy in predicting the diagnosis of SCZ and BP. Analyses were performed in a sample of 180 adults distributed in three groups of BP patients (n=46), SCZ patients (n=67), and CNT (n=67) matched by age and premorbid IQ. Faces were manually annotated from reconstructions of magnetic resonance scans. Facial shape correctly discriminated patients with BP and SCZ, even when facial differences between patients and CNT were so subtle that are not recognizable to the untrained eye or by exploratory multivariate statistical techniques. After cross-validation, 62-65% of patients were correctly diagnosed based on face shape. This percentage is similar to the discriminatory power of other genetic and brain biomarkers. Using Artificial Neural Networks, we tested a machine learning algorithm based on facial morphology to diagnose SCZ. The overall accuracy in diagnostic classification was greater than 90%, whereas the precision ranged between 70-95% depending on the model. We also trained a Support Vector Machine classification algorithm to diagnose BP. Results showed that BP is harder to diagnose from facial biomarkers than SCZ, achieving a 72% accuracy. Euclidean Distance Matrix Analysis (EDMA) detected local facial differences involving the eyes, nose and mouth, and the relative separation/position between them. Facial anomalies were more abundant in SCZ patients, with 43-48% distances across the whole face significantly different from control subjects. In BP, the percentage of facial anomalies was lower, 24-32%, especially in women. Some facial differences were common to SCZ and BP, although the sense of change could be different among disorders. Remarkably, EDMA showed facial patterns that are disorder and gender-specific. These results demonstrate that an analysis of the spectrum of psychotic disorders under a gender perspective is crucial to further understand these disorders and to identify reliable biomarkers that can lead to early PD diagnosis

The atypical cyclin CNTD2 promotes colon cancer cell proliferation and migration

Colorectal cancer (CRC) is one of the most common cancers worldwide, with 8-10% of these tumours presenting a BRAF (V600E) mutation. Cyclins are known oncogenes deregulated in many cancers, but the role of the new subfamily of atypical cyclins remains elusive. Here we have performed a systematic analysis of the protein expression levels of eight atypical cyclins in human CRC tumours and several cell lines, and found that CNTD2 is significantly upregulated in CRC tissue compared to the adjacent normal one. CNTD2 overexpression in CRC cell lines increases their proliferation capacity and migration, as well as spheroid formation capacity and anchorage-independent growth. Moreover, CNTD2 increases tumour growth in vivo on xenograft models of CRC with wild-type BRAF. Accordingly, CNTD2 downregulation significantly diminished the proliferation of wild-type BRAF CRC cells, suggesting that CNTD2 may represent a new prognostic factor and a promising drug target in the management of CRC