Characterization of the seminal bacterial microbiome of healthy, fertile stallions using next-generation sequencing

High-throughput sequencing studies have shown the important role microbial communities play in the male reproductive tract, indicating differences in the semen microbial composition between fertile and infertile males. Most of these studies were made on human beings but little is known regarding domestic animals. Seminal bacteria studies made in stallions mostly focus on pathogenic bacteria and on their impact on reproductive technology. However, little is known about stallion commensal seminal microflora. That ultimately hinders our capacity to associate specific bacteria to conditions or seminal quality. Therefore, the aim of this study was to characterize the seminal microbial composition of 12 healthy, fertile stallion using next-generation sequencing. Hypervariable region V3 was chosen for bacterial identification. A total of nine phyla was detected. The most abundant ones were Bacteroidetes (46.50%), Firmicutes (29.92%) and Actinobacteria (13.58%). At family level, we found 69 bacterial families, but only nine are common in all samples. Porphyromonadaceae (33.18%), Peptoniphilaceae (14.09%), Corynebacteriaceae (11.32%) and Prevotellaceae (9.05%) were the most representative ones, while the Firmicutes phylum displayed the highest number of families (23, a third of the total). Samples showed high inter-subject variability. Findings previously described in other species notably differ from our findings. Families found in human such as Lactobacillaceae, Staphylococcaceae and Streptococcaceae only represented a 0.00%, 0.17% and 0.22% abundance in our samples, respectively. In conclusion, Porphyromonadaceae, Prevotellaceae, Peptoniphilaceae and Corynebacteriaceae families are highly represented in the seminal microbiome of healthy, fertile stallions. A high variation among individuals is also observed

Nuevos antivirales de acción directa en el tratamiento del virus de la hepatitis C

La infección por el virus de la hepatitis C (VHC) constituye un problema importante de la salud pública a nivel mundial. Los primeros fármacos disponibles eran en la mayor parte de los casos poco eficaces, con una duración del tratamiento muy prolongada, y una gran cantidad de efectos adversos, que limitaba su uso. La aparición de los nuevos antivirales de acción directa frente al VHC ha supuesto un cambio radical en el tratamiento de esta infección, permitiendo alcanzar elevadas tasas de curación en todos los grupos de pacientes afectados, con menor duración y mucha mejor tolerancia. En este trabajo se revisan los nuevos fármacos frente al VHC con actividad antiviral directa, las principales pautas terapéuticas utilizadas en la actualidad, así como el cambio que ha supuesto la introducción de las mismas a nivel social, sanitario y económico

Street Art, de la calle al museo. Las exposiciones en museos españoles de Eltono y Susso33.

Este trabajo tiene como objetivo acercarnos al Street Art, como fenómeno de la subcultura que ha pasado al ámbito de los museos. Se ha realizado un estudio histórico artístico desde su inicio histórico, en los años setenta del siglo XX, hasta el momento actual, y cómo este movimiento ha pasado de un entorno urbano a un ámbito comercial e institucional como las ferias de arte, casas de subastas, galerías y museos. Se ha tratado el caso español de una forma más concreta. Se ha hecho una mención especial al festival Asalto de Zaragoza, por ser el primero en el ámbito nacional, así como a las primeras galerías especializadas en grafiti y las primeras ferias de arte urbano, para finalizar el presente trabajo con las primeras exposiciones de arte urbano en un ámbito museístico, como es el caso de los artistas Eltono y Susso33 en Artium y Centro de Arte Tomás y Valiente (CEART). <br /

Plan de mejora en la productividad de la pesquera VLACAR S.A.C, aplicando la metodología de Mantenimiento Productivo Total (TPM), Chimbote 2023

El objetivo principal de la presente investigación fue la implementación de un plan de mejora en la productividad en la planta de conserva VLACAR S.A.C, aplicando el mantenimiento productivo total. Se utilizó una metodología de tipo aplicada con un diseño de investigación de tipo preexperimental. La población estuvo conformada por todos los equipos del proceso productivo de conserva y harina de pescado, como muestra se consideró a los equipos del proceso productivo: caldero, selladora, autoclave, cocina estática, exhausting y faja transportadora. La investigación reveló que la empresa enfrentaba dificultades relacionadas con el mantenimiento, lo que provocaba fallas no planificadas en la producción y tiempo de inactividad, afectando así a la productividad. Esto se evidenció en los meses de enero a junio, con una eficiencia del 81%, una eficacia del 92% y una productividad inicial del 75%. Se implementó el mantenimiento productivo total, basado en 8 pilares: mejoras enfocadas, mantenimiento autónomo, mantenimiento planificado, mantenimiento de calidad, prevención del mantenimiento, áreas de soporte, capacitaciones y adiestramiento y seguridad y entorno. Como conclusión la implementación del TPM logró mejorar la productividad de los equipos de la empresa VLACAR S.A.C a 86%, la eficiencia y eficacia aumentaron a 90% y 96% respectivamente

Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19)

Altres ajuts: Funding was provided for the Gesta-COVID19 Study by Instituto de Salud Carlos III (ISCIII) (PR(AMI)181/2020) (ISCIII's reference: COV20/00188).Fetal skin edema in the second trimester might be associated with maternal coronavirus disease 2019 (COVID-19). The risk of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Positive reverse-transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 infection in neonates and placental tissue have been reported, and immunoglobulin M antibodies have been detected in neonates born to mothers with infection. The first case is a woman at 22 3/7 weeks of gestation with coronavirus disease 2019 (COVID-19) who was admitted to the intensive care unit. In the second case, the patient remained at home with mild symptoms, starting at 20 weeks of gestation. In both cases, fetal skin edema was observed on ultrasound examination while maternal SARS-COV-2 RT-PCR test results were positive and resolved when maternal SARS-COV-2 RT-PCR test results became negative. The RT-PCR test result for SARS-CoV-2 in amniotic fluid was negative in both cases. The two pregnancies are ongoing and uneventful. Transient fetal skin edema noted in these two patients with COVID-19 in the second trimester may represent results of fetal infection or altered fetal physiology due to maternal disease or may be unrelated to the maternal illness

Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to Candida albicans

Estradiol-based therapies predispose women to vaginal infections. Moreover, it has long been known that neutrophils are absent from the vaginal lumen during the ovulatory phase (high estradiol). However, the mechanisms that regulate neutrophil influx to the vagina remain unknown. We investigated the neutrophil transepithelial migration (TEM) into the vaginal lumen. We revealed that estradiol reduces the CD44 and CD47 epithelial expression in the vaginal ectocervix and fornix, which retain neutrophils at the apical epithelium through the estradiol receptor-alpha. In contrast, luteal progesterone increases epithelial expression of CD44 and CD47 to promote neutrophil migration into the vaginal lumen and Candida albicans destruction. Distinctive to vaginal mucosa, neutrophil infiltration is contingent to sex hormones to prevent sperm from neutrophil attack; although it may compromise immunity during ovulation. Thus, sex hormones orchestrate tolerance and immunity in the vaginal lumen by regulating neutrophil TEM.The authors thank the units of flow cytometry, cell culture and statistical analysis. We are grateful to J. Villarejo, M. Fernandez-Garcia, and F. Sanchez-Cobos, for expert help and support. This work was partially supported by Fundacion Mutua Madrilena and the Ministry of Economy and Competitiveness ISCIII-FIS grants PI13/00269, PI16/00050, and PI17/01324, co-financed by ERDF (FEDER) Funds from the European Commission, ``A way of making Europe.´´ MR holds a Miguel Servet II contract (CPII14/00009). LS-M holds a IiSGM intramural contract.S

Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study

Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD

The economic burden of disease of epithelial ovarian cancer in Spain: the OvarCost study

bjective: To assess the economic burden of epithelial ovarian cancer (EOC) in incident patients and the burden by disease stage in Spain. Methods: We developed a Markov model from a social perspective simulating the natural history of EOC and its four stages, with a 10-year time horizon, 3-week cycles, 3% discount rate, and 2016 euros. Healthcare resource utilization and costs were estimated by disease stage. Direct healthcare costs (DHC) included early screening, genetic counselling, medical visits, diagnostic tests, surgery, chemotherapy, hospitalizations, emergency services, and palliative care. Direct non-healthcare costs (DNHC) included formal and informal care. Indirect costs (IC) included labour productivity losses due to temporary and permanent leaves, and premature death. Epidemiology data and resource use were taken from the literature and validated for Spain by the OvarCost group using a Delphi method. Results: The total burden of EOC over 10 years was 3102 mill euros: 15.1% in stage I, 3.9% in stage II, 41.0% in stage III, and 40.2% in stage IV. Annual average cost/patient was 24,111 and it was 8,641; 14,184; 33,858, and 42,547 in stages I-IV, respectively. Of total costs, 71.2% were due to DHC, 24.7% to DNHC, and 4.1% to IC. Conclusions: EOC imposes a significant economic burden on the national healthcare system and society in Spain. Investment in better early diagnosis techniques might increase survival and patients' quality of life. This would likely reduce costs derived from late stages, consequently leading to a substantial reduction of the economic burden associated with EOC

Gestation and COVID-19 : clinical and microbiological observational study (Gesta-COVID19)

The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population

ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA

BACKGROUND: Liquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution. METHODS: To interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity. RESULTS: SCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour. CONCLUSIONS: This work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy