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Additional file 2. Virtopsy Study Group.

Additional file 1. Overcalled and undetected abnormalities identified at virtopsy.

BACKGROUND Since it is currently not possible to eradicate hepatitis B virus (HBV) infection with existing treatments, research continues to uncover new therapeutic strategies. HBV core protein, encoded by the HBV core gene (HBC), intervenes in both structural and functional processes, and is a key protein in the HBV life cycle. For this reason, both the protein and the gene could be valuable targets for new therapeutic and diagnostic strategies. Moreover, alterations in the protein sequence could serve as potential markers of disease progression. AIM To detect, by next-generation sequencing, HBC hyper-conserved regions that could potentially be prognostic factors and targets for new therapies. METHODS Thirty-eight of 45 patients with chronic HBV initially selected were included and grouped according to liver disease stage [chronic hepatitis B infection without liver damage (CHB, n = 16), liver cirrhosis (LC, n = 5), and hepatocellular carcinoma (HCC, n = 17)]. HBV DNA was extracted from patients' plasma. A region between nucleotide (nt) 1863 and 2483, which includes HBC, was amplified and analyzed by next-generation sequencing (Illumina MiSeq platform). Sequences were genotyped by distance-based discriminant analysis. General and intergroup nt and amino acid (aa) conservation was determined by sliding window analysis. The presence of nt insertion and deletions and/or aa substitutions in the different groups was determined by aligning the sequences with genotype-specific consensus sequences. RESULTS Three nt (nt 1900-1929, 2249-2284, 2364-2398) and 2 aa (aa 117-120, 159-167) hyper-conserved regions were shared by all the clinical groups. All groups showed a similar pattern of conservation, except for five nt regions (nt 1946-1992, 2060-2095, 2145-2175, 2230-2250, 2270-2293) and one aa region (aa 140-160), where CHB and LC, respectively, were less conserved (P < 0.05). Some group-specific conserved regions were also observed at both nt (2306-2334 in CHB and 1935-1976 and 2402-2435 in LC) and aa (between aa 98-103 in CHB and 28-30 and 51-54 in LC) levels. No differences in insertion and deletions frequencies were observed. An aa substitution (P79Q) was observed in the HCC group with a median (interquartile range) frequency of 15.82 (0-78.88) vs 0 (0-0) in the other groups (P < 0.05 vs CHB group). CONCLUSION The differentially conserved HBC and HBV core protein regions and the P79Q substitution could be involved in disease progression. The hyper-conserved regions detected could be targets for future therapeutic and diagnostic strategies.

Table S1: Classification of the coral species according to their form and contribution to the reef-structure.; Table S2: Mann-Whitney U-test values; Figure S1: Average coral cover for the studied sites for the back- and fore-reef zones. The error bars are the confidence intervals from the mean; Table S3: Coral cover on the surveyed sites (n = 16) with their respective reef-zone for each year.; Table S4: Mann-Whitney U-test values of the reef function parameters

Objective Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease. We also evaluated the extra value of ZnT8A in addition to the classical IAA, GADA and IA2A autoantibodies to improve the accuracy of type 1 diabetes diagnosis. Methods Four hundred Spanish pediatric patients with recent-onset diabetes (mean age 8.9 +/- 3.9 years) were analyzed for IAA, GADA, IA2A and ZnT8A pancreatic-autoantibodies and HLA-DRB1 alleles. Patients without autoimmunity and those with only ZnT8A positive were screened for 12 monogenic diabetes genes by next generation sequencing. Results ZnT8A testing increased the number of autoantibody-positive patients from 373 (93.3%) to 377 (94.3%). An isolated positivity for ZnT8A allowed diagnosing autoimmune diabetes in 14.8% (4/27) of pediatric patients negative for the rest of the antibodies tested. At least 2 of the 23 patients with no detectable autoimmunity (8%) carried heterozygous pathogenic variants: one previously reported missense variant in the INS gene (p.Gly32Ser) and one novel frameshift variant (p.Val264fs) in the HNF1A gene. One variant of uncertain significance was also found. Carriers of pathogenic variants had HLA-DRB1 risk alleles for autoimmune diabetes and clinical characteristics compatible with type 1 diabetes except for the absence of autoimmunity. Conclusion ZnT8A determination improves the diagnosis of autoimmune diabetes in pediatrics. At least 8% of pediatric patients suspected of type 1 diabetes and with undetectable autoimmunity have monogenic diabetes and can benefit from the correct diagnosis of the disease by genetic study., This work was partially supported by grants from Menarini Group Spain (BCA/16/030), University of the Basque Country, UPV/EHU (IT795-13), Department of Health of the Basque Government (GV2016111035) and ISCIII (PI14/01104) integrated into the National R&D&I Plan 2013-2016 and co-financed by FEDER (European Funds for Regional Development). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Programa de Doctorat : Traducció, Gènere i Estudis Culturals Las Mbie Binga o parteras tradicionales de la etnia fang de Guinea Ecuatorial, han transmitido oralmente sus conocimientos y costumbres en relación a la atención a la mujer durante el embarazo y el parto. Objetivos. Definir las costumbres ancestrales y funciones de las Mbie Binga en relación a la salud sexual y reproductiva de las mujeres de la etnia fang. Metodología. Estudio descriptivo cualitativo etnográfico que se nutre de diversas fuentes: la observación directa durante dos años de residencia en el lugar (2011-2013), que queda reflejada en un diario de campo y soporte audiovisual; entrevistas a parteras tradicionales durante el periodo 2013-2014 (complementadas con el contenido de las entrevistas previas a otras parteras tradicionales fang, cedidas y realizadas por un Pediatra perteneciente a la Cooperación Sanitaria española en el país entre 1988-1989), y en 2014 a comadronas educadas de acuerdo con el sistema biomédico de salud; y búsqueda bibliográfica de diferentes disciplinas, complementada con el acceso a archivos y documentos privados relativos a la etapa colonial y la cooperación sanitaria española. Resultados. Se ha elaborado un listado de las costumbres de las Mbie Binga relacionadas con la salud sexual y reproductiva de las mujeres fang, así como una descripción de los rituales femeninos relacionados con el embarazo, parto y postparto. Discusión. Del análisis de los datos recogidos se consigue realizar un detallado listado de costumbres y remedios naturales de las Mbie Binga que permite obtener un documento de incalculable valor para futuras generaciones y diferentes disciplinas de estudio. Mbie Binga or Traditional Birth Attendant (TBA) from Equatorial Guinea fang’s ethnic group, since many years ago they transmitted orally customs related to the cure of women during the pregnancy and delivery. Objective. Define the ancestral functions and customs of Mbie Binga in relation to sexual health and reproduction of women from ethnic group fang. Methodology. Qualitative ethnographic descriptive study with main sources: Direct observation reflected in a field Diary during two years residency in the country (2011-2013) and some recordings and related photographic material. Interviews traditional midwives during the period 2013- 2014 (supplemented with the content of previous interviews with other traditional fang midwives, donated and performed by a Paediatrician belonging to the Spanish Health Cooperation in the country between 1988-1989), and midwives educate following the health biomedical model during 2014. Bibliographic search of different disciplines together with access to private sources and documents on Colonialism and Spanish sanitary cooperation. Results. It has been possible to elaborate lists about the Mbie Binga customs related to sexual and reproductive capacity of women in the ethnic group fang, as well as description of feminine rituals around the pregnancy period, delivery and post-delivery period. Discussion. From the analysis of data collected it is possible to elaborate in detail the ancestral customs and natural remedies from the Mbie Binga, allowing to obtain a source for enquiry of invaluable importance for future generations and different disciplines of study.

Este trabajo se enmarca en un proyecto de investigación-dependiente de la Universidad Nacional del Comahue, Argentina- que pretende construir conjuntamente, investigadores y profesores, un modo posible donde la didáctica de la matemática se convierta en un marco posible para que los docentes puedan pensar sus clases de matemática. A partir de encuentros periódicos pretendemos crear un ambiente de estudio y producción de conocimiento matemático-didáctico para hacer más visible el complejo marco de decisiones del docente en su tarea diaria. Estamos convencidos que los investigadores necesitamos conocer más sobre las necesidades y desafíos que enfrentan los docentes en su trabajo, intentando encontrar posibles nexos entre la didáctica de la matemática y el quehacer docente. Autores como Bednarz (1999), Desgagné (2001) y Anadón (2001, 2008), destacan la importancia de incorporar a los docentes de las escuelas medias a los grupos de estudio para realizar investigaciones “con” ellos más que “sobre” ellos.

Background: Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications. Methods: A thorough search of bibliographic databases for peer-reviewed research was performed including only classic experiments or high quality reviews for the antibiotic mechanisms of beta-lactam molecules and only experimental research papers where included when the non-antibiotic properties of these molecules were searched. Only published articles from indexed journals were included. Quality of retrieved papers was assessed using standard tools. The characteristics of screened papers were described and findings of included studies were contextualized to either a mechanistic or a clinical framework. Results: Seventy-eight papers were included in the review; the majority (56) were relative to the non-antibiotic properties of beta-lactam molecules. The non-antibiotic effects reviewed were divided accordingly to the amount of information available for each one. Twelve papers outlined the epileptogenic effects induced by beta-lactam molecules administration; these included both clinical and basic research as well as probable mechanistic explanations. Eighteen papers described a potential neuroprotective effect, mostly in basic in vitro and in vivo experiments. Analgesic properties where identified in twelve papers and basic research was described alongside with both experimental and serendipic clinical findings. Seven papers described a down-regulation effect exerted by beta-lactam molecules administration in different addiction animal models. Finally other effects such as penile erection, dopamine release facilitation and anti-neoplasic effects where described from seven papers. Conclusion: The findings of this review show that beta-lactam molecules may induce several effects, which may be clinically relevant in a lot of different diseases. This paper is, to our knowledge, the first comprehensive review of the non-antibiotic effects shown by beta-lactam molecules and may help increase the interest in this field, which may result in a direct translation of this effects to a clinical context.

A case of an anomalous origin of the left coronary artery from the right coronary cusp with interarterial course between the aorta and pulmonary artery, detected by autopsy and retrospectively on postmortem computed tomography (PMCT) and magnetic resonance (PMMR) imaging is presented. According to the literature, this type of coronary artery anomaly is highly related with sudden death in young people. Encountering this anomaly in a 75 years old individual as in the case presented here is considered rare, since the anomaly remains mainly undiagnosed if no symptoms are present. The deceased underwent both, PMCT and PMMR examination, prior to autopsy. The autopsy finding could be confirmed on PMCT and PMMR and a three-dimensional segmentation-based reconstruction was performed. With this case report we present a rare coronary artery anomaly which was survived 75 years long and found by coincidence in autopsy, and discuss the distinct advantage of re-evaluation of postmortem images by experts.