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Introduction: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with renal involvement primarily affects the renal cortex and presents with key histopathologic findings of a pauci-immune necrotizing and crescentic glomerulonephritis. Infrequently reported and poorly characterized is renal medullary angiitis (RMA), a pathologic variant of AAV primarily involving the renal medulla. This study seeks to describe the presentation and treatment outcomes of RMA. Methods: In this single-center cohort, renal pathology samples classified as AAV with renal involvement underwent secondary review to determine if they met histopathologic criteria for RMA. Demographic, clinical, and laboratory data were obtained via electronic medical record review. Descriptive statistical analysis was performed on key variables. Results: Of the 136 kidney biopsy samples classified as AAV with renal involvement, histopathologic features of RMA were present in 13 cases. The mean (SD) age at the time of RMA diagnosis was 65 (19) years, and 54% were female. Most cases presented with extrarenal manifestations of disease. Initial median (IQR) estimated glomerular filtration rate and proteinuria on presentation were 16 (10–19) mL/min/1.73 m2 and 1,100 (687–2,437) mg, respectively. The primary histologic features were high degrees of interstitial inflammation comprised leukocytes, neutrophils, plasma cells, and eosinophils along with either interstitial hemorrhage or necrosis. All patients were treated with glucocorticoids in combination with either cyclophosphamide, rituximab, or mycophenolate. All patients achieved disease remission. During a median (IQR) follow-up of 42 (14–68) months, 1 patient reached ESKD and 1 patient died. Conclusions: In this single-center case series, we identified the presence of RMA in 9.5% of AAV samples that underwent secondary review. RMA presented with severe impairment in renal function and multisystem disease. Standard of care immunosuppression for AAV was effective for remission induction in RMA. It remains unclear whether standard prognostication tools are useful in this population.

ABSTRACTNirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children’s wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants

Abstract Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n = 60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) as revealed by a multi-cohort study (n = 1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than in controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders.

Vaccine hesitancy is among the top 10 threats to global health, according to the World Health Organization (WHO). In this exploration, we delve into ChatGPT capacity to generate opinions on vaccine hesitancy by interrogating this AI chatbot for the 50 most prevalent counterfait messages, false and true contraindications, and myths circulating on the internet regarding vaccine safety. Our results indicate that, while the present version of ChatGPT’s default responses may be incomplete, they are generally satisfactory. Although ChatGPT cannot substitute an expert or the scientific evidence itself, this form of AI has the potential to guide users toward information that aligns well with scientific evidence.

Summary: Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.

Summary: Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

Abstract Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.

IntroductionThe relationship between music and Alzheimer’s disease (AD) has been approached by different disciplines, but most of our outstanding comes from neuroscience.MethodsFirst, we systematically reviewed the state-of-the-art of neuroscience and cognitive sciences research on music and AD (>100 studies), and the progress made on the therapeutic impact of music stimuli in memory. Next, we meta-analyzed transcriptomic and epigenomic data of AD patients to search for commonalities with genes and pathways previously connected to music in genome association, epigenetic, and gene expression studies.ResultsOur findings indicate that >93% of the neuroscience/ cognitive sciences studies indicate at least one beneficial effect of music on patients with neurodegenerative diseases, being improvements on memory and cognition the most frequent outcomes; other common benefits were on social behavior, mood and emotion, anxiety and agitation, quality of life, and depression. Out of the 334 music-related genes, 127 (38%) were found to be linked to epigenome/transcriptome analysis in AD (vs. healthy controls); some of them (SNCA, SLC6A4, ASCC2, FTH1, PLAUR and ARHGAP26) have been reported to be associated e.g. with musical aptitude and music effect on the transcriptome. Other music-related genes (GMPR, SELENBP1 and ADIPOR1) associated to neuropsychiatric, neurodegenerative diseases and music performance, emerged as hub genes in consensus co-expression modules detected between AD and music estimulated transcriptomes. In addition, we found connections between music, AD and dopamine related genes, with SCNA being the most remarkable – a gene previously associated with learning and memory, and neurodegenerative disorders (e.g., Parkinson’s disease and AD).DiscussionThe present study indicate that the vast majority of neuroscientific studies unambiguously show that music has a beneficial effect on health, being the most common benefits relevant to Alzheimer’s disease. These findings illuminate a new roadmap for genetic research in neurosciences, and musical interventions in AD and other neurodegenerative conditions.

TIPiCO is an annual expert meeting and workshop on infectious diseases and vaccination. The edition of 2020 changed its name and format to aTIPiCO, the first series and podcasts on infectious diseases and vaccines. A total of 13 prestigious experts from different countries participated in this edition launched on the 26 November 2020. The state of the art of coronavirus disease-2019 (COVID-19) and the responsible pathogen, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the options to tackle the pandemic situation were discussed in light of the knowledge in November 2020. Despite COVID-19, the status of other infectious diseases, including influenza infections, respiratory syncytial virus disease, human papillomavirus infection, measles, pertussis, tuberculosis, meningococcal disease, and pneumococcal disease, were also addressed. The essential lessons that can be learned from these diseases and their vaccines to use in the COVID-19 pandemic were also commented with the experts.

Abstract Historical records document medieval immigration from North Africa to Iberia to create Islamic al-Andalus. Here, we present a low-coverage genome of an eleventh century CE man buried in an Islamic necropolis in Segorbe, near Valencia, Spain. Uniparental lineages indicate North African ancestry, but at the autosomal level he displays a mosaic of North African and European-like ancestries, distinct from any present-day population. Altogether, the genome-wide evidence, stable isotope results and the age of the burial indicate that his ancestry was ultimately a result of admixture between recently arrived Amazigh people (Berbers) and the population inhabiting the Peninsula prior to the Islamic conquest. We detect differences between our sample and a previously published group of contemporary individuals from Valencia, exemplifying how detailed, small-scale aDNA studies can illuminate fine-grained regional and temporal differences. His genome demonstrates how ancient DNA studies can capture portraits of past genetic variation that have been erased by later demographic shifts—in this case, most likely the seventeenth century CE expulsion of formerly Islamic communities as tolerance dissipated following the Reconquista by the Catholic kingdoms of the north.

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

Abstract Background Previous studies suggested that Interleukin‐10 (IL‐10) depletion in Crohn's disease (CD) could predict outcome. Aim: To determine IL‐10 in blood and at different intestinal locations in patients with active CD and to assess its potential prognostic capacity to identify aggressive CD. Methods Twenty‐three patients with CD were included. Ulcerative colitis (UC), infectious colitis and healthy individuals acted as controls. Serum and mucosal samples were taken at baseline and 1 month after steroid initiation in CD patients. Patients were classified according to steroid response. Control samples were obtained from different intestinal locations. IL‐10 expression was measured with real‐time polymerase chain reaction, immunofluorescence (intestine) and ELISA (serum, biopsy cultures' supernatants and tissue homogenates). Results CD and UC showed an increase in IL‐10 messenger RNA (mRNA) versus controls (p

BackgroundRespiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV).MethodsProspective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV (n = 36), AS-RSV (n = 9), and CR-RSV (n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition.ResultsPatients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 (P-value = 2.77×10-10), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698, LOC102723354 and RPL15/NKIRAS1) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P-value = 4.71×10-2), DNA damage (FDP-value = 2.53×10-2), and DNA integrity checkpoint (FDR P-value = 2.56×10-2) in differentiating sequelae from CR-RSV patients.ConclusionsEpigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed.

IMPORTANCE:. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES:. To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN:. Data from two prospective cohort studies. SETTING AND PARTICIPANTS:. Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES:. Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS:. In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE:. In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.

The disease of COVID-19 is an infection of easy transmission like other respiratory viruses, reporting cases of Influenza coinfection in seasonal seasons. 5 cases of co-infection of COVID-19 and the Influenza virus are presented, the most frequent being the Influenza A virus, the symptoms of odynophagia and nasal congestion may suggest co-infection between these two viruses, in the patients evaluated, not Poor prognosis and mortality were observed.

Establishing the timeframe when a particular virus was circulating in a population could be useful in several areas of biomedical research, including microbiology and legal medicine. Using simulations, we demonstrate that the circulation timeframe of an unknown SARS-CoV-2 genome in a population (hereafter, estimated time of a queried genome [QG]; tE-QG) can be easily predicted using a phylogenetic model based on a robust reference genome database of the virus, and information on their sampling dates. We evaluate several phylogeny-based approaches, including modeling evolutionary (substitution) rates of the SARS-CoV-2 genome (~10−3 substitutions/nucleotide/year) and the mutational (substitutions) differences separating the QGs from the reference genomes (RGs) in the database. Owing to the mutational characteristics of the virus, the present Viral Molecular Clock Dating (VMCD) method covers timeframes going backwards from about a month in the past. The method has very low errors associated to the tE-QG estimates and narrow intervals of tE-QG, both ranging from a few days to a few weeks regardless of the mathematical model used. The SARS-CoV-2 model represents a proof of concept that can be extrapolated to any other microorganism, provided that a robust genome sequence database is available. Besides obvious applications in epidemiology and microbiology investigations, there are several contexts in forensic casework where estimating tE-QG could be useful, including estimation of the postmortem intervals (PMI) and the dating of samples stored in hospital settings.

Se reporta la frecuencia de mutaciones genéticas KatG e inhA que confieren resistencia a isoniacida en una muestra de 777 pacientes con resistencia a isoniacida. Se utilizó la prueba GenoType® MTBDRplus y la prueba de sensibilidad convencional por el método de agar en placa. Se encontró que 54 % presentó mutación en el gen KatG; este se asoció con resistencia a estreptomicina 76,6 % (p

Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro results.

The Ninth Interactive Infectious Disease workshop TIPICO was held on November 22–23, 2018, in Santiago de Compostela, Spain. This 2-day academic experience addressed current and topical issues in the field of infectious diseases and vaccination. Summary findings of the meeting include: cervical cancer elimination will be possible in the future, thanks to the implementation of global vaccination action plans in combination with appropriate screening interventions. The introduction of appropriate immunization programs is key to maintain the success of current effective vaccines such as those against meningococcal disease or rotavirus infection. Additionally, reduced dose schedules might improve the efficiency of some vaccines (i.e., PCV13). New vaccines to improve current preventive alternatives are under development (e.g., against tuberculosis or influenza virus), while others to protect against infectious diseases with no current available vaccines (e.g., enterovirus, parechovirus and flaviviruses) need to be developed. Vaccinomics will be fundamental in this process, while infectomics will allow the application of precision medicine. Further research is also required to understand the impact of heterologous vaccine effects. Finally, vaccination requires education at all levels (individuals, community, healthcare professionals) to ensure its success by helping to overcome major barriers such as vaccine hesitancy and false contraindications.

Despite the importance of ancient DNA for understanding human prehistoric dispersals, poor survival means that data remain sparse for many areas in the tropics, including in Africa. In such instances, analysis of contemporary genomes remains invaluable. One promising approach is founder analysis, which identifies and dates migration events in non-recombining systems. However, it has yet to be fully exploited as its application remains controversial. Here, we test the approach by evaluating the age of sub-Saharan mitogenome lineages sampled outside Africa. The analysis confirms that such lineages in the Americas date to recent centuries—the time of the Atlantic slave trade—thereby validating the approach. By contrast, in North Africa, Southwestern Asia and Europe, roughly half of the dispersal signal dates to the early Holocene, during the “greening” of the Sahara. We elaborate these results by showing that the main source regions for the two main dispersal episodes are distinct. For the recent dispersal, the major source was West Africa, but with two exceptions: South America, where the fraction from Southern Africa was greater, and Southwest Asia, where Eastern Africa was the primary source. These observations show the potential of founder analysis as both a supplement and complement to ancient DNA studies.

La tuberculosis en el lactante es un cuadro de difícil diagnóstico por las pruebas diagnósticas que muchas veces resultan negativas y por la dificultad de identificar la fuente de transmisión. Se presenta el caso de un lactante varón de un mes de vida que presenta irritabilidad, taquipnea, fiebre, pobre ganancia de peso desde el nacimiento y hepatomegalia, además, tiene el antecedente materno de tuberculosis pre-extensivamente resistente a drogas y reacción granulomatosa tuberculoide con tinción auramina positiva para bacilos ácido-alcohol resistentes en la histopatología de placenta. Ante la sospecha de tuberculosis congénita, es referido al Instituto Nacional de Salud del Niño para estudio diagnóstico y tratamiento; el paciente presenta una evolución clínica favorable y sin reacciones adversas al tratamiento. El diagnóstico de tuberculosis congénita debe considerarse en lactantes con signos clínicos sugestivos de la enfermedad y mantener la sospecha ante la presencia del antecedente materno de infección por Mycobacterium tuberculosis.

BackgroundRotavirus (RV) is an enteric pathogen that has devastating impact on childhood morbidity and mortality worldwide. The immunologic mechanism underlying the protection achieved after RV vaccination is not yet fully understood.MethodsWe compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq®).ResultsRV vaccination mimics the wild type infection causing similar changes in children’s transcriptome, including transcripts associated with cell cycle, diarrhea, nausea, vomiting, intussusception, and abnormal morphology of midgut. A machine learning approach allowed to detect a combination of nine-transcripts that differentiates vaccinated from convalescent-naturally infected children (AUC: 90%; 95%CI: 70–100) and distinguishes between acute-infected and healthy control children (in both cases, AUC: 100%; 95%CI: 100–100). We identified a miRNA hsa-mir-149 that seems to play a role in the host defense against viral pathogens and may have an antiviral role.DiscussionOur findings might shed further light in the understanding of RV infection, its functional link to intussusception causes, as well as guide development of antiviral treatments and safer and more effective vaccines. The nine-transcript signature may constitute a marker of vaccine protection and helps to differentiate vaccinated from naturally infected or susceptible children.

Spain is one of the countries most severely affected by the SARS-CoV-2 pandemic, with almost 190,000 cases as of April 18, 2020. As healthcare workers (HCW) are one of the groups hardest hit by the infection, it is important to know the seroprevalence of antibodies against SARS-CoV-2 in pediatric departments. We performed 175 immunoglobulin (Ig)M and IgG immunochromatographic rapid tests in the personnel working at the Pediatric Department of the Hospital Clínico Universitario of Santiago de Compostela (Spain), including pediatricians, residents, nurses, and other staff, on days 31–33 since the lockdown started. Seven out of the 175 tests were positive, including four for IgM and three for IgG, leading to a seroprevalence of 4.0% (95% CI: 1.1–6.9%). Only one of them had symptoms at the time of testing (sore throat). All seropositive cases yielded negative RT-PCR of the upper and lower respiratory tract. This is the first SARS-CoV-2 serological survey among HCWs reported in Spain. Notwithstanding the test limitations, our results reveal that personal protection policy and lockdown measures have been effective to limit population exposure. The low seroprevalence rate poses a significant challenge for the next strategic steps of pandemic control.

BackgroundEmerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind.MethodsFifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group.ResultssCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not.ConclusionsMonocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients.

There are significant tin reserves in the dumps and tailings from Llallagua. Currently, this waste is being processed using gravity concentration or a combination of gravity concentration with a final stage of froth flotation. A process mineralogy study of the tailings and their products after processing in Llallagua was carried out to determine the failings of the processing system in order to contribute to designing an improved new processing scheme. The mineralogy of the feed tailings, concentrate, and final tailings was determined by X-ray diffraction, scanning electron microscopy, and mineral liberation analysis. The tailings were composed of quartz, tourmaline, illite, K-feldspar, plagioclase, cassiterite, rutile, zircon, and monazite. The concentrate essentially contains cassiterite (57.4 wt.%), tourmaline, quartz, hematite, rutile and rare earth minerals, mainly monazite and minor amounts of xenotime and florencite. The concentrate contained 52–60 wt.% of SnO2 and 0.9–1.3 wt.% REE. The final tailings contained 0.23–0.37 wt.% SnO2 and 0.02 wt.% of Rare Earth Elements (REE). Only 57.6 wt.% of cassiterite from the concentrate was liberated. The non-liberated cassiterite was mainly associated with quartz, tourmaline, and rutile. The average grain size of monazite was 45 µm and 57.5 wt.% of this was liberated. In other cases, it occurs in mixed particles associated with tourmaline, quartz, cassiterite, and muscovite. To improve the sustainability of this mining activity, the concentrate grade and the metal recovery must be improved. Reducing the particle size reduction of the processed tailings would increase the beneficiation process rates. In addition, the recovery of the REE present in the concentrate as a by-product should be investigated.

La Investigación Operativa (IO) en Salud tiene como objetivo final proporcionar información útil para la toma de decisiones que sirven para mejorar las Políticas en Salud, a cualquier Nivel de gobierno. Las preguntas en las IO surgen de problemas detectados en el campo al implementar proyectos en Salud, y las respuestas a estas preguntas pretenden solucionar estas dificultades. Planteamos que una de las barreras para alcanzar los objetivos de desarrollo en Salud en nuestro medio es la debilidad de nuestro Sistema, por lo que la IO se presenta como una herramienta útil para intentar las soluciones que se planteen. Un proyecto de IO surge, de acuerdo al Documento Técnico del Instituto Nacional de Salud (INS)1, si existen tres elementos: una discrepancia entre lo que es y lo que debe ser; una pregunta sobre las causas de esta discrepancia; y por lo menos dos respuestas plausibles a esta discrepancia. Las enfermedades infectocontagiosas son un grupo prevalentes de patologías en nuestro medio, causantes de gran morbimortalidad. La Tuberculosis (TB) es un problema de Salud Pública en nuestro medio, siendo, el Perú, considerado como uno de los países con mayor carga de enfermedad en América Latina, solo superado por Haití; y representando, junto a Brasil, más de la mitad de casos de Sudamérica2. Las Facultades de Medicina, con apoyo de sus respectivos Institutos de Investigación, deben propiciar el desarrollo de Investigación Operacional desde pregrado hasta postgrado en nuestro medio o nuestras instituciones de salud independiente del nivel de complejidad, lo que nos permitirá conocer ciertas características propias de nuestra realidad y de nuestra población en particular.

ABSTRACT Cryptococcus neoformans is an important fungal pathogen, causing life-threatening pneumonia and meningoencephalitis. Brain dissemination of C. neoformans is thought to be a consequence of an active infection in the lung which then extravasates to other sites. Brain invasion results from dissemination via either transport by free yeast cells in the bloodstream or Trojan horse transport within mononuclear phagocytes. We assessed brain dissemination in three mouse models of infection: intravenous, intratracheal, and intranasal models. All three modes of infection resulted in dissemination of C. neoformans to the brain in less than 3 h. Further, C. neoformans was detected in the entirety of the upper respiratory tract and the ear canals of mice. In recent years, intranasal infection has become a popular mechanism to induce pulmonary infection because it avoids surgery, but our findings show that instillation of C. neoformans produces cryptococcal nasal infection. These findings imply that immunological studies using intranasal infection should assume that the initial sites of infection of infection are brain, lung, and upper respiratory tract, including the nasal airways. IMPORTANCE Cryptococcus neoformans causes an estimated 181, 000 deaths each year, mostly associated with untreated HIV/AIDS. C. neoformans has a ubiquitous worldwide distribution. Humans become infected from exposure to environmental sources, after which the fungus lays dormant within the human body. Upon AIDS-induced immunosuppression or therapy-induced immunosuppression (required for organ transplant recipients or those suffering from autoimmune disorders), cryptococcal disease reactivates and causes life-threatening meningitis and pneumonia. This study showed that upon contact with the host, C. neoformans can quickly (a few hours) reach the host brain and also colonizes the nose of infected animals. Therefore, this work paves the way to better knowledge of how C. neoformans travels through the host body. Understanding how C. neoformans infects, disseminates, and survives within the host is critically required so that we can prevent infections and the disease caused by this deadly fungus.

Objetivo: determinar las características de las pruebas de función pulmonar en pacientes con Bronquiectasias secundarias a Tuberculosis pulmonar en el Hospital Nacional Dos de Mayo (Lima, Perú) durante los años 2015 – 2016. Materiales y métodos: se realizó un estudio cuantitativo, observacional, descriptivo, retrospectivo. Se recolectó información de historias clínicas de pacientes con diagnóstico de bronquiectasias secundarias a tuberculosis pulmonar con pruebas de función pulmonar y otros variables asociadas. Resultados: se revisaron 76 historias clínicas de pacientes con pruebas de función pulmonar. En espirometría encontramos que el 40.8% tenía patrón obstructivo y el 22.3% patrón restrictivo. En pletismografía se determinó que 61.8% tenía criterios de atrapamiento aéreo por volumen residual > 120% y que 9.2% tenía criterios de hiperinflación pulmonar por capacidad pulmonar total > 120%. Asimismo, se pudo encontrar cambios estadísticamente significativos en los valores de pletismografía luego del uso del broncodilatador. Conclusiones: el patrón más frecuente fue el obstructivo con atrapamiento aéreo sin hiperinflación pulmonar.

The fight against the spread of antibiotic resistance is one of the most important challenges facing health systems worldwide. Given the limitations of current diagnostic methods, the development of fast and accurate tests for the diagnosis of viral and bacterial infections would improve patient management and treatment, as well as contribute to reducing antibiotic misuse in clinical settings. In this scenario, analysis of host transcriptomics constitutes a promising target to develop new diagnostic tests based on the host-specific response to infections. We carried out a multi-cohort meta-analysis of blood transcriptomic data available in public databases, including 11 different studies and 1209 samples from virus- (n = 695) and bacteria- (n = 514) infected patients. We applied a Parallel Regularized Regression Model Search (PReMS) on a set of previously reported genes that distinguished viral from bacterial infection to find a minimum gene expression bio-signature. This strategy allowed us to detect three genes, namely BAFT, ISG15 and DNMT1, that clearly differentiate groups of infection with high accuracy (training set: area under the curve (AUC) 0.86 (sensitivity: 0.81; specificity: 0.87); testing set: AUC 0.87 (sensitivity: 0.82; specificity: 0.86)). BAFT and ISG15 are involved in processes related to immune response, while DNMT1 is related to the preservation of methylation patterns, and its expression is modulated by pathogen infections. We successfully tested this three-transcript signature in the 11 independent studies, demonstrating its high performance under different scenarios. The main advantage of this three-gene signature is the low number of genes needed to differentiate both groups of patient categories.

There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.

Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection.

Salivary glands are known immune effector sites and considered to be part of the whole mucosal immune system. The aim of the present study was to assess the salivary immune response to rotavirus (RV) infection through the analysis of the cytokine immune profile in saliva.A prospective comparative study of serial saliva samples from 27 RV-infected patients (sampled upon admission to the hospital during acute phase and at convalescence-i.e. at least three months after recovery) and 36 healthy controls was performed. Concentrations of 11 salivary cytokines (IFN-γ, IFN-α2, IL-1β, IL-6, IL-8, IL-10, IL-15, IL12p70, TNF-α, IFN-λ1, IL-22) were determined. Cytokine levels were compared between healthy controls acute infection and convalescence. The correlation between clinical data and salivary cytokine profile in infected children was assessed.The salivary cytokine profile changes significantly in response to acute RV infection. In RV-infected patients, IL-22 levels were increased in the acute phase with respect to convalescence (P-value < 0.001). Comparisons between infected and control group showed significant differences in salivary IFN-α2, IL-1β, IL-6, IL-8, IL-10 and IL-22. Although acute-phase levels of IL-12, IL-10, IL-6 and IFN-γ showed nominal association with Vesikari's severity, this trend did not reach statistical significance after multiple test adjustment.RV infection induces a host salivary immune response, indicating that immune mucosal response to RV infection is not confined to the intestinal mucosa. Our data point to a whole mucosal implication in the RV infection as a result of the integrative mucosal immune response, and suggest the salivary gland as effector site for RV infection.

ABSTRACT Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS) screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development. IMPORTANCE Cryptococcosis is a neglected fungal meningitis that causes approximately half a million deaths annually. The most effective antifungal agent, amphotericin B, was developed in the 1950s, and no effective medicine has been developed for this disease since that time. A key aspect of amphotericin B’s effectiveness is thought to be because of its ability to kill the fungus (fungicidal activity), rather than just stop or slow its growth. The present study utilized a recently identified fungicidal agent, bithionol, to identify potential fungicidal drug targets that can be used in developing modern fungicidal agents. A combined protein and genetic analysis approach was used to identify a class of enzymes, dehydrogenases, that the fungus uses to maintain homeostasis with regard to sugar nutrients. Similarities in the drug target site were found that resulted in simultaneous inhibition and killing of the fungus by bithionol. These studies thus identify a common, multitarget site for antifungal development.

Introduction Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution.Methods This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders.Ethics and dissemination Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed.

The Iberian Peninsula has been the focus of attention of numerous studies dealing with mitochondrial DNA (mtDNA) variation, most of them targeting the control region segment. In the present study we sequenced the control region of 3,024 Spanish individuals from areas where available data were still limited. We also compiled mtDNA haplotypes from the literature involving 4,588 sequences and 28 population groups or small regions. We meta-analyzed all these data in order to shed further light on patterns of geographic variation, taking advantage of the large sample size and geographic coverage, in contrast with the atomized sampling strategy of previous work. The results indicate that the main mtDNA haplogroups show primarily clinal geographic patterns across the Iberian geography, roughly along a North-South axis. Haplogroup HV0 (where haplogroup U is nested) is more prevalent in the Franco Cantabrian region, in good agreement with previous findings that identified this area as a climate refuge during the Last Glacial Maximum (LGM), prior to a subsequent demographic re-expansion towards Central Europe and the Mediterranean. Typical sub-Saharan and North African lineages are slightly more prevalent in South Iberia, although at low frequencies; this pattern has been shaped mainly by the transatlantic slave trade and the Arab invasion of the Iberian Peninsula. The results also indicate that summary statistics that aim to measure molecular variation, or AMOVA, have limited sensitivity to detect population substructure, in contrast to patterns revealed by phylogeographic analysis. Overall, the results suggest that mtDNA variation in Iberia is substantially stratified. These patterns might be relevant in biomedical studies given that stratification is a common cause of false positives in case-control mtDNA association studies, and should be also considered when weighting the DNA evidence in forensic casework, which is strongly dependent on haplotype frequencies.

BACKGROUND:Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. OBJECTIVES:To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). METHODS:We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. RESULTS:204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. CONCLUSION:The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.

BACKGROUND AND AIMS:A properly validated scoring system allowing objective categorization of infants with acute respiratory infections (ARIs), avoiding the need for in-person assessment and that could also be used by non-health professionals is currently not available. We aimed to develop a new clinical assessment scale meeting these specifications. METHODS:We designed a clinical scale (ReSVinet scale) based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points.170 children under two years of age with ARI were assessed independently by three pediatricians using this scale. Parents also evaluated their offspring with an adapted version of the scale in a subset of 61 cases. The scale was tested for internal consistency (Cronbach's alpha), Pearson correlation coefficient for the items in the scale, inter-observer reliability (kappa index) and floor-ceiling effect. RESULTS:Internal consistency was good for all the observers, with the lowest Cronbach's alpha being 0.72. There was a strong correlation between the investigators (r-value ranged 0.76-0.83) and also between the results obtained by the parents and the investigators(r = 0.73). Light's kappa for the observations of the three investigators was 0.74. Weighted kappa in the group evaluated by the parents was 0.73. The final score was correlated with length of hospital stay, PICU admission and Wood-Downes Score. CONCLUSIONS:The ReSVinet scale may be useful and reliable in the evaluation of infants with ARI, particularly acute bronchiolitis, even with data obtained from medical records and when employed by parents. Although further studies are necessary, ReSVinet scale already complies with more score validation criteria than the vast majority of the alternatives currently available and used in the clinical practice.

The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques.A prospective multicenter study (GENDRES-network) was conducted between 2011-2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures.66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007).Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.

The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned.To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology.Double-blind randomized clinical trial of gluten vs placebo rechallenge.>18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated.91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p

Presentamos el caso de un paciente varón de 48 años de edad, con diagnóstico de diabetes mellitus tipo 2, no controlada, de diez años de evolución, a quien se le diagnosticó tuberculosis pulmonar mediante signos clínicos, radiográficos y cultivo en esputo positivo para Mycobacterium tuberculosis, sensible a drogas antituberculosas de primera línea. Recibió isoniacida, rifampicina, etambutol y pirazinamida. Dos meses después de iniciado el tratamiento presentó hipersensibilidad a medicamentos, con los siguientes signos y síntomas: rash dérmico generalizado, prurito generalizado, anemia Coombs positiva, eosinofilia y síntomas sistémicos, compatibles con el síndrome DRESS (drug rash with eosinophilia and systemic symptoms). Ante ello, se suspendió la medicación antituberculosa y se instaló tratamiento con antihistamínicos y corticoides sistémicos, con remisión y mejoría de síntomas. Posteriormente, recibió un esquema individualizado de tratamiento para tuberculosis consistente en medicamentos mínimamente hemato-hepatotóxicos, similar al indicado en pacientes inmunosuprimidos. Desde entonces presenta baciloscopias negativas.

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

Varón de 33 años, soltero, sin ocupación fija, promiscuo, con historia de relaciones homosexuales, ingesta crónica de alcohol, consumo de tabaco, marihuana, pasta básica y clorhidrato de cocaína, desde los 18 años. Infectado por el virus de la inmunodeficiencia humana, recibía tratamiento irregular con terapia antirretroviral de gran actividad (Targa) entre 2006 y 2008, regularizada en los últimos 12 meses. Por presentar bacilo ácido alcohol resistente (BAAR) pansensible en esputo, inició en junio 2008 tratamiento antituberculoso [2RHZE/4(HR)2)], retirándosele la medicación 6 meses después por presentar BAAR pulmonar negativo. En marzo de 2009, percibió dolor lumbar intenso, dificultad para caminar, hipertrofia de ganglios cervicales, tos, fiebre. Un cultivo de secreción ganglionar cervical descubrió M. tuberculosis resistente a rifampicina. La imagenología mostró lesiones osteolíticas múltiples en cráneo y vértebras dorsolumbares y tumefacciones renitentes en cuero cabelludo, antebrazo derecho y parrilla costal izquierda. Tras descartarse mieloma múltiple y metástasis cancerosas, se añadió tratamiento antituberculosis multidrogo resistente al Targa, notándose dos meses después involución de las tumefacciones renitentes, de la fiebre y mejoría del estado general. Tras 16 meses de tratamiento supervisado, el paciente aumentó 7 kg de peso, habiendo desaparecido la sintomatología que presentaba. Se discute la fisiopatología de las lesiones osteolíticas cráneo-vertebrales en un paciente con coinfección por el virus de la inmunodeficiencia humana y tuberculosis.

Genetic analyses have recently been carried out on present-day Tuscans (Central Italy) in order to investigate their presumable recent Near East ancestry in connection with the long-standing debate on the origins of the Etruscan civilization. We retrieved mitogenomes and genome-wide SNP data from 110 Tuscans analyzed within the context of The 1000 Genome Project. For phylogeographic and evolutionary analysis we made use of a large worldwide database of entire mitogenomes (>26,000) and partial control region sequences (>180,000).Different analyses reveal the presence of typical Near East haplotypes in Tuscans representing isolated members of various mtDNA phylogenetic branches. As a whole, the Near East component in Tuscan mitogenomes can be estimated at about 8%; a proportion that is comparable to previous estimates but significantly lower than admixture estimates obtained from autosomal SNP data (21%). Phylogeographic and evolutionary inter-population comparisons indicate that the main signal of Near Eastern Tuscan mitogenomes comes from Iran.Mitogenomes of recent Near East origin in present-day Tuscans do not show local or regional variation. This points to a demographic scenario that is compatible with a recent arrival of Near Easterners to this region in Italy with no founder events or bottlenecks.

During the period of the Transatlantic Slave Trade (TAST) some enslaved Africans were forced to move to Upper Peru (nowadays Bolivia). At first they were sent to Potosí, but later to the tropical Yungas valley where the Spanish colonizers established a so-called "hacienda system" that was based on slave labor, including African-descendants. Due to their isolation, very little attention has been paid so far to 'Afro-Bolivian' communities either within the research field of TAST or in genetic population studies. In this study, a total of 105 individuals from the Yungas were sequenced for their mitochondrial DNA (mtDNA) control region, and mitogenomes were obtained for a selected subset of these samples. We also genotyped 46 Ancestry Informative Markers (AIM) in order to investigate continental ancestry at the autosomal level. In addition, Y-chromosome STR and SNP data for a subset of the same individuals was also available from the literature. The data indicate that the partitioning of mtDNA ancestry in the Yungas differs significantly from that in the rest of the country: 81% Native American, 18% African, and 1% European. Interestingly, the great majority of 'Afro-descendant' mtDNA haplotypes in the Yungas (84%) concentrates in the locality of Tocaña. This high proportion of African ancestry in the Tocaña is also manifested in the Y-chromosome (44%) and in the autosomes (56%). In sharp contrast with previous studies on the TAST, the ancestry of about 1/3 of the 'Afro-Bolivian' mtDNA haplotypes can be traced back to East and South East Africa, which may be at least partially explained by the Arab slave trade connected to the TAST.

Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques.A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1-4), rhinovirus, adenovirus (A-F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011-2013. The results were corroborated in an independent cohort collected in the UK.A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12-24 months age group. The most frequently observed co-infection patterns were RSV-Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV-bocavirus / bocavirus-influenza (5 patients, 5.2%, UK cohort).The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12-24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.

We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in order to evaluate admixture using uniparental markers. Finally, we analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation. In the total sample, the average European, African and Native American contributions as estimated from autosomal AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed relatively higher African and Native American contributions than the Western provinces. In particular, the highest proportion of African ancestry was observed in the provinces of Guantánamo (40%) and Santiago de Cuba (39%), and the highest proportion of Native American ancestry in Granma (15%), Holguín (12%) and Las Tunas (12%). We found evidence of substantial population stratification in the current Cuban population, emphasizing the need to control for the effects of population stratification in association studies including individuals from Cuba. The results of the analyses of uniparental markers were concordant with those observed in the autosomes. These geographic patterns in admixture proportions are fully consistent with historical and archaeological information. Additionally, we identified a sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side, and higher Native American and African contributions from the maternal side. This sex-biased contribution was particularly evident for Native American ancestry. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with melanin levels in the sample.