The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin.

BACKGROUND: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown. METHODS: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models. RESULTS: MiR-137/325 repressed human KISS1 3'-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3'-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats. CONCLUSIONS: Our data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity. SIGNIFICANCE STATEMENT: Up to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity.

Phylogeographic and Paleoclimatic Modelling Tools Improve Our Understanding of the Biogeographic History of Hierophis viridiflavus (Colubridae).

Phylogeographic and paleoclimatic modelling studies have been combined to infer the role of Pleistocene climatic oscillations as drivers of the genetic structure and distribution of Mediterranean taxa. For the European whip snake, Hierophis viridiflavus, previous studies based on paleoclimatic modelling have depicted a low reliability in the pattern of past climatic suitability across the central Mediterranean Basin, which barely fits the species' genetic structure. In this study, we combined phylogeographic and paleoclimatic modelling tools to improve our understanding of the biogeographic history of H. viridiflavus, particularly extending the sampling and phylogeographic inferences to previously under-sampled regions. Phylogeographic analyses recovered two major clades that diverged at the beginning of the Pleistocene and had diversified in different ways by the late Pleistocene: the east clade (composed of three subclades) and the west clade (with no further structure). Paleoclimatic models highlighted the temperate character of H. viridiflavus, indicating range contractions during both the last inter-glacial and last glacial maximum periods. Range expansions from southern-located climatic refugia likely occurred in the Bølling-Allerød and Middle Holocene periods, which are supported by signals of demographic growth in the west clade and South-East-North subclade. Overall, this work improves our understanding of the historical biogeography of H. viridiflavus, providing further insights into the evolutionary processes that occurred in the Mediterranean Basin hotspot.

Histological and biochemical evaluation of plasma rich in growth factors treatment for grade II muscle injuries in sheep.

The purpose of this study was to perform a histological and biochemical evaluation of the influence of plasma rich in growth factors (PRGF) on muscle regeneration process after a surgically induced grade II muscle laceration. A randomized, single blind, controlled experimental research was conducted including twenty-one adult healthy sheep, randomly divided in three groups (n = 7). A grade II surgical section was performed in the biceps femoris muscle of both hindlimbs. After two days (basal time), intralesional infiltration of autologous PRGF or Saline solution was randomly administered in both hindlimbs. Treatment was repeated once a week. Animal groups were euthanized at 1 (T1), 2 (T2) or 4 (T4) weeks. Histological assessment showed that PRGF intralesional injection induced a significant decrease of inflammatory cells density, significant higher centrally nucleated fibers percentage and significantly smaller fibrotic areas compared to Saline-treated muscles at T1, T2 and T4. Also, lower vascular density, with lower capillaries cross-sectional area, in PRGF group compared to Saline was observed. Biochemical analysis revealed a significant higher expression level of MYOD1, MYF5 and MYOG genes in PRGF groups at T1 compared to Saline treated muscles. At ultrastructural level, PRGF groups presented scarce edema and loss of connective tissue structure, as well as higher mitochondrial density adequately associated to the sarcomere unit in contrast to the Saline group. In conclusion, histological, biochemical, and ultrastructural results showed that PRGF treatment improved muscle regeneration process leading to more mature histological aspect in newly formed muscle tissue after a surgically induced grade II muscle injury.

The Brainstem-Vermis and Brainstem-Tentorium Angles in the Fetus: A Study of Their Reproducibility by Fetal Magnetic Resonance Imaging and Their Evolution Along the Gestation.

Aim: To assess the reproducibility of brainstem-vermis (BV) and brainstem-tentorium (BT) angles measured by fetal Magnetic Resonance Imaging (MRI) during second half of pregnancy in normal and abnormal fetuses. Secondly, to assess reproducibility of two alternative methodologies to measure the brainstem-tentorium angle (BT1 and BT2) proposed by our group that could be more reliable in fetuses with posterior fossa fluid collection (PFFC) anomalies. Finally, to describe the evolution of BV and BT angles along gestation in normal fetuses. Methods: We conducted a cross-sectional study of BV and BT angles obtained by MRI performed at our center, in 22 fetuses with PFFC and 8 fetuses without PFFC to calculate both angles' reproducibility and the correlation between them and the gestational age. Results: We found good interobserver reproducibility for the BV, BT1 and BT2 angles (Intraclass correlation coefficient: 0.98; 0.89 and 0.88 for each of these angles, with p < 0.001). In patients with PFFC the BT angle could not always be measured. BT angle presented a positive relationship with gestational age (p = 0.002) but BV angle stayed stable. The measurements of BV, BT1, and BT2 angles can be reliably performed by MRI with good interobserver reproducibility. Conclusion: BV angle stays stable during pregnancy, whereas BT angle tends to augment with gestational age.

Mitogenomics and hidden-trait models reveal the role of phoresy and host shifts in the diversification of parasitoid blister beetles (Coleoptera: Meloidae).

Changes in life history traits are often considered speciation triggers and can have dramatic effects on the evolutionary history of a lineage. Here, we examine the consequences of changes in two life history traits, host-type and phoresy, in the hypermetamorphic blister beetles, Meloidae. Subfamilies Nemognathinae and Meloinae exhibit a complex life cycle involving multiple metamorphoses and parasitoidism. Most genera and tribes are bee-parasitoids, and include phoretic or nonphoretic species, while two tribes feed on grasshopper eggs. These different life strategies are coupled with striking differences in species richness among clades. We generated a mitogenomic phylogeny for Nemognathinae and Meloinae, confirming the monophyly of these two clades, and used the dated phylogeny to explore the association between diversification rates and changes in host specificity and phoresy, using state-dependent speciation and extinction (SSE) models that include the effect of hidden traits. To account for the low taxon sampling, we implemented a phylogenetic-taxonomic approach based on birth-death simulations, and used a Bayesian framework to integrate parameter and phylogenetic uncertainty. Results show that the ancestral hypermetamorphic Meloidae was a nonphoretic bee-parasitoid, and that transitions towards a phoretic bee-parasitoid and grasshopper parasitoidism occurred multiple times. Nonphoretic bee-parasitoid lineages exhibit significantly higher relative extinction and lower diversification rates than phoretic bee-and grasshopper-parasitoids, but no significant differences were found between the latter two strategies. This suggests that Orthopteran host shifts and phoresy contributed jointly to the evolutionary success of the parasitoid meloidae. We also demonstrate that SSE models can be used to identify hidden traits coevolving with the focal trait in driving a lineage's diversification dynamics.

Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study.

OBJECTIVE: Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19. METHODS: Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1-C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed. RESULTS: We analysed 121 mild COVID-19 cases (mean age = 45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%; p = .008). PCS affected 35.8% of women and 20.8% of men (p = .07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP were in the range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87; p = .013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4-5-fold increased risk of prevalent PCS. A man with CRP in the range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10-17-fold increased risk of prevalent PCS. CONCLUSIONS: The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.

Catheter-Directed Therapies in Patients with Pulmonary Embolism: Predictive Factors of In-Hospital Mortality and Long-Term Follow-Up.

(1) Background: Catheter-directed therapies (CDT) may be considered for selected patients with pulmonary embolism (PE); (2) Methods: Retrospective observational study including all consecutive patients with acute PE undergoing CDT (mechanical or pharmacomechanical) from January 2010 through December 2020. The aim was to evaluate in-hospital and long-term mortality and its predictive factors; (3) Results: We included 63 patients, 43 (68.3%) with high-risk PE. All patients underwent mechanical CDT and, additionally, 27 (43%) underwent catheter-directed thrombolysis. Twelve (19%) patients received failed systemic thrombolysis (ST) prior to CDT, and an inferior vena cava (IVC) filter was inserted in 28 (44.5%) patients. In-hospital PE-related and all-cause mortality rates were 31.7%; 95% CI 20.6-44.7% and 42.9%; 95% CI 30.5-56%, respectively. In multivariate analysis, age > 70 years and previous ST were strongly associated with PE-related and all-cause mortality, while IVC filter insertion during the CDT was associated with lower mortality rates. After a median follow-up of 40 (12-60) months, 11 more patients died (mortality rate of 60.3%; 95% CI 47.2-72.4%). Long-term survival was significantly higher in patients who received an IVC filter; (4) Conclusions: Age > 70 years and failure of previous ST were associated with mortality in acute PE patients treated with CDT. In-hospital and long-term mortality were lower in patients who received IVC filter insertion.

Clinical Outcomes of Severe COVID-19 Patients Admitted to an Intermediate Respiratory Care Unit.

Introduction: Many severe COVID-19 patients require respiratory support and monitoring. An intermediate respiratory care unit (IMCU) may be a valuable element for optimizing patient care and limited health-care resources management. We aim to assess the clinical outcomes of severe COVID-19 patients admitted to an IMCU. Methods: Observational, retrospective study including patients admitted to the IMCU due to COVID-19 pneumonia during the months of March and April 2020. Patients were stratified based on their requirement of transfer to the intensive care unit (ICU) and on survival status at the end of follow-up. A multivariable Cox proportional hazards method was used to assess risk factors associated with mortality. Results: A total of 253 patients were included. Of them, 68% were male and median age was 65 years (IQR 18 years). Ninety-two patients (36.4%) required ICU transfer. Patients transferred to the ICU had a higher mortality rate (44.6 vs. 24.2%; p < 0.001). Multivariable proportional hazards model showed that age ≥65 years (HR 4.14; 95%CI 2.31-7.42; p < 0.001); chronic respiratory conditions (HR 2.34; 95%CI 1.38-3.99; p = 0.002) and chronic kidney disease (HR 2.96; 95%CI 1.61-5.43; p < 0.001) were independently associated with mortality. High-dose systemic corticosteroids followed by progressive dose tapering showed a lower risk of death (HR 0.15; 95%CI 0.06-0.40; p < 0.001). Conclusions: IMCU may be a useful tool for the multidisciplinary management of severe COVID-19 patients requiring respiratory support and non-invasive monitoring, therefore reducing ICU burden. Older age and chronic respiratory or renal conditions are associated with worse clinical outcomes, while treatment with systemic corticosteroids may have a protective effect on mortality.

Metagenomics Analysis Reveals an Extraordinary Inner Bacterial Diversity in Anisakids (Nematoda: Anisakidae) L3 Larvae.

L3 larvae of anisakid nematodes are an important problem for the fisheries industry and pose a potential risk for human health by acting as infectious agents causing allergies and as potential vectors of pathogens and microrganisms. In spite of the close bacteria-nematode relationship very little is known of the anisakids microbiota. Fresh fish could be contaminated by bacteria vectored in the cuticle or in the intestine of anisakids when the L3 larvae migrate through the muscles. As a consequence, the bacterial inoculum will be spread, with potential effects on the quality of the fish, and possible clinical effects cannot be discarded. A total of 2,689,113 16S rRNA gene sequences from a total of 113 L3 individuals obtained from fish captured along the FAO 27 fishing area were studied. Bacteria were taxonomically characterized through 1803 representative operational taxonomic units (OTUs) sequences. Fourteen phyla, 31 classes, 52 orders, 129 families and 187 genera were unambiguously identified. We have found as part of microbiome an average of 123 OTUs per L3 individual. Diversity indices (Shannon and Simpson) indicate an extraordinary diversity of bacteria at an OTU level. There are clusters of anisakids individuals (samples) defined by the associated bacteria which, however, are not significantly related to fish hosts or anisakid taxa. This suggests that association or relationship among bacteria in anisakids, exists without the influence of fishes or nematodes. The lack of relationships with hosts of anisakids taxa has to be expressed by the association among bacterial OTUs or other taxonomical levels which range from OTUs to the phylum level. There are significant biological structural associations of microbiota in anisakid nematodes which manifest in clusters of bacteria ranging from phylum to genus level, which could also be an indicator of fish contamination or the geographic zone of fish capture. Actinobacteria, Aquificae, Firmicutes, and Proteobacteria are the phyla whose abundance value discriminate for defining such structures.

Incidence and risk factors of central line catheter-related bloodstream infections. / Incidencia y factores de riesgo de infecciones del torrente sanguíneo asociadas a catéter central.

Central line catheter-related bloodstream infections (CLABSI) burdens great morbidity, mortality and unnecessary hospital expenses. Studies related to its incidence and epidemiological and clinical profile among neonates in Peru are scarce, not being clear it's actual impact. A prospective cohort study was conducted in a neonatal intensive care unit (ICU) of a public hospital in Lima, Peru between 2017-2018. 167 patients were included (52,7% male) with gestational age between 24-41 weeks, obtaining 1999 catheter-days and 16 cases of CLABSI. The incidence rate was 8/1000 catheter-days. Use of umbilical catheter (p=0,005) and multiple catheters (p<0,001) both showed a statistically significant correlation regarding the development of CLABSI. It's necessary to extend the study to other ICUs and stablish solid, efficient and long-lasting system of CLABSI surveillance that allows the evaluation of possible interventions to reduce the incidence of CLABSI.

Las infecciones del torrente sanguíneo asociadas a catéter central (ITSACC) generan gran morbimortalidad y elevados costos hospitalarios. Estudios sobre su incidencia y comportamiento clínico-epidemiológicos en la población neonatal en el Perú son escasos y no está del todo claro su impacto actual. Se realizó un estudio de cohorte prospectivo durante un año (2017-2018) en la unidad de cuidados intensivos (UCI) neonatales de un hospital público de Lima, Perú. Se incluyeron 167 pacientes (52,7% varones) con edades gestacionales entre las 24-41 semanas, se registraron 1999 días-catéter y 16 casos de ITSACC. La incidencia fue de 8/1000 días-catéter. El uso de catéter umbilical (p=0,005) y el uso de múltiples catéteres (p<0,001) mostraron relación estadísticamente significativa respecto al desarrollo de ITSACC. Es necesario ampliar el estudio a otras UCI y establecer sistemas eficientes y duraderos de monitoreo que permitan la evaluación de intervenciones para reducir las ITSACC.

Chemical and sensory evaluation of cold brew coffees using different roasting profiles and brewing methods.

This study evaluated the effects of different roasting profiles (time/temperature) and brewing methods on the physicochemical and sensory characteristics of coffee brews. Cold brewing (dripping and immersion) and hot brewing (French press) methods were studied to understand the effects of water temperature and technical brewing method conditions on the chemical compound extraction in coffees roasted at high-temperature short time (HTST) and low-temperature long time (LTLT). The results showed that coffee beverages were clearly differentiated concerning the roasting profile when hot water was used (90 ± 3 °C) in brewing. Separation of beverages according to the water temperature used in brewing was observed. Notably, hot brewing coffees were distinguished from cold brewing (19 ± 2 °C) based on a higher titratable acidity and abundance of some furan compounds. The non-volatile extraction rate increased at higher brewing temperatures. At the same brewing temperature, dripping exhibited a higher extraction rate than immersion brewing, which suggests that the coffee extraction process is affected by the design and operation of the cold brewing system. Coffee beverages brewed with HTST and cold dripping displayed the highest value in total dissolved solids (TDS), extraction yield, as well as the highest caffeine, trigonelline, 4- and 5-caffeoylquinic acids (CQAs) contents. Regardless of the roasting profile, coffees brewed by cold dripping were perceived with more bitter and roasted flavors. In contrast, cold immersion and hot coffee beverages showed remarkable sweetness, nutty, caramel, and malt attributes. In turn, these attributes showed an inverse correlation with caffeine concentration, trigonelline, CQAs, and TDS. The findings of this study demonstrate that volatile and non-volatile compounds present in roasted coffee depend on time-temperature roasting conditions; in turn, their presence in the resulting beverages are related to the extraction of the operational conditions of coffee brewing methods.

Non-retrieved inferior vena cava filters: causes and long-term follow-up.

BACKGROUND: Temporary inferior vena cava (IVC) filters are not always retrieved. Information about long-term outcomes of patients with indwelling filters is scarce. Aims of our study were to assess reasons that preclude retrieval of temporary IVC filters and long-term outcomes and causes of death in patients with indwelling filters. MATERIALS AND METHODS: Retrospective observational study including all consecutive patients undergoing IVC filter insertion from January 2009 through December 2018. Patients with permanent filters and those with temporary filters not retrieved were followed from insertion until June 2020. RESULTS: We included 271 patients with a mean age of 63.8 years. The main indication for filter insertion was acute venous thromboembolism and contraindication for anticoagulation (83%). The filter was deemed as permanent in 24.4% of patients and temporary in 75.6%. Sixty six percent of temporary filters were retrieved; the main cause of non-retrieval was lack of planning / follow-up (57.9%). One hundred twelve patients (41.3%) remained with indwelling filters. After follow-up, 54.5% were alive and 45.5% had died, with a median survival time of 6.19 (95% CI, 2.63-9.75) years. The most frequent cause of death during follow-up was cancer (49%). The frequency of anticoagulant therapy was similar in both groups (57.4%% versus 54.9%). CONCLUSIONS: The main preventable cause of non-retrieval of temporary IVC filters was lack of planning / follow-up. Structured follow-up programs should be implemented to increase retrieval rates. In patients with indwelling filters, the main cause of death was cancer and extended anticoagulation was not associated with survival.

Incidencia y factores de riesgo de infecciones del torrente sanguíneo asociadas a catéter central / Incidence and risk factors of central line catheter-related bloodstream infections

RESUMEN Las infecciones del torrente sanguíneo asociadas a catéter central (ITSACC) generan gran morbimortalidad y elevados costos hospitalarios. Estudios sobre su incidencia y comportamiento clínico-epidemiológicos en la población neonatal en el Perú son escasos y no está del todo claro su impacto actual. Se realizó un estudio de cohorte prospectivo durante un año (2017-2018) en la unidad de cuidados intensivos (UCI) neonatales de un hospital público de Lima, Perú. Se incluyeron 167 pacientes (52,7% varones) con edades gestacionales entre las 24-41 semanas, se registraron 1999 días-catéter y 16 casos de ITSACC. La incidencia fue de 8/1000 días-catéter. El uso de catéter umbilical (p=0,005) y el uso de múltiples catéteres (p<0,001) mostraron relación estadísticamente significativa respecto al desarrollo de ITSACC. Es necesario ampliar el estudio a otras UCI y establecer sistemas eficientes y duraderos de monitoreo que permitan la evaluación de intervenciones para reducir las ITSACC.

ABSTRACT Central line catheter-related bloodstream infections (CLABSI) burdens great morbidity, mortality and unnecessary hospital expenses. Studies related to its incidence and epidemiological and clinical profile among neonates in Peru are scarce, not being clear it's actual impact. A prospective cohort study was conducted in a neonatal intensive care unit (ICU) of a public hospital in Lima, Peru between 2017-2018. 167 patients were included (52,7% male) with gestational age between 24-41 weeks, obtaining 1999 catheter-days and 16 cases of CLABSI. The incidence rate was 8/1000 catheter-days. Use of umbilical catheter (p=0,005) and multiple catheters (p<0,001) both showed a statistically significant correlation regarding the development of CLABSI. It's necessary to extend the study to other ICUs and stablish solid, efficient and long-lasting system of CLABSI surveillance that allows the evaluation of possible interventions to reduce the incidence of CLABSI.

Incidencia y factores de riesgo de infecciones del torrente sanguíneo asociadas a catéter central / Incidence and risk factors of central line catheter-related bloodstream infections

RESUMEN Las infecciones del torrente sanguíneo asociadas a catéter central (ITSACC) generan gran morbimortalidad y elevados costos hospitalarios. Estudios sobre su incidencia y comportamiento clínico-epidemiológicos en la población neonatal en el Perú son escasos y no está del todo claro su impacto actual. Se realizó un estudio de cohorte prospectivo durante un año (2017-2018) en la unidad de cuidados intensivos (UCI) neonatales de un hospital público de Lima, Perú. Se incluyeron 167 pacientes (52,7% varones) con edades gestacionales entre las 24-41 semanas, se registraron 1999 días-catéter y 16 casos de ITSACC. La incidencia fue de 8/1000 días-catéter. El uso de catéter umbilical (p=0,005) y el uso de múltiples catéteres (p<0,001) mostraron relación estadísticamente significativa respecto al desarrollo de ITSACC. Es necesario ampliar el estudio a otras UCI y establecer sistemas eficientes y duraderos de monitoreo que permitan la evaluación de intervenciones para reducir las ITSACC.

ABSTRACT Central line catheter-related bloodstream infections (CLABSI) burdens great morbidity, mortality and unnecessary hospital expenses. Studies related to its incidence and epidemiological and clinical profile among neonates in Peru are scarce, not being clear it's actual impact. A prospective cohort study was conducted in a neonatal intensive care unit (ICU) of a public hospital in Lima, Peru between 2017-2018. 167 patients were included (52,7% male) with gestational age between 24-41 weeks, obtaining 1999 catheter-days and 16 cases of CLABSI. The incidence rate was 8/1000 catheter-days. Use of umbilical catheter (p=0,005) and multiple catheters (p<0,001) both showed a statistically significant correlation regarding the development of CLABSI. It's necessary to extend the study to other ICUs and stablish solid, efficient and long-lasting system of CLABSI surveillance that allows the evaluation of possible interventions to reduce the incidence of CLABSI.

PRO-Mueve Relaciones Sanas - A Gender-Based Violence Prevention Program for Adolescents: Assessment of Its Efficacy in the First Year of Intervention.

PRO-Mueve Relaciones Sanas (PRO-Mote Healthy Relationships) is a gender-based violence and dating violence prevention program targeted at adolescents. The program has been designed to be implemented during three consecutive courses [from the first to third year of Spanish mandatory secondary education (ESO)] in 8 annual sessions, imparted by university students who have been previously trained and supervised by university professors. The present study evaluates the effects of the program after the first year of implementation through a quasi-experimental design (Intervention Group N = 181; Quasi-control group N = 62; M age = 12.11; SDage = 0.57; 54.7% girls) and assesses whether there are gender differences in the outcomes. The results obtained evidenced a significant reduction in benevolent sexism in the intervention group compared to the quasi-control group. Regarding hostile sexism, it was found to increase significantly in the quasi-control group, while it remained stable in the intervention group. Thus, there were significant differences between both groups after the intervention. Likewise, romantic love myths were found to decrease significantly, and knowledge about gender-based violence increased significantly in the intervention group between the two time points assessed, although there were no significant differences with the quasi-control group. No gender differences in the outcomes of the program were observed. The obtained results supported the efficacy of the program during the first year of intervention in the first course of the ESO and laid the foundation for the following phases of intervention.

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain.

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.

Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis.

BACKGROUND: A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE. METHODS: This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients. RESULTS: Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively. CONCLUSIONS: Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.

Effect of albumin administration on outcomes in hypoalbuminemic patients hospitalized with community-acquired pneumonia (ALBUCAP): a prospective, randomized, phase III clinical controlled trial-a trial protocol.

BACKGROUND: Community-acquired pneumonia (CAP) remains a leading cause of death worldwide, and hypoalbuminemia is associated with worse outcomes. However, it remains uncertain whether albumin administration could have any beneficial effects. We aim to assess whether the administration of albumin in hypoalbuminemic patients with CAP increases the proportion of clinically stable patients at day 5 compared with the standard of care alone. METHODS: This is a trial protocol for a superiority, non-blinded, multicenter, randomized, phase 3, interventional controlled clinical trial. The primary endpoint will be the proportion of clinical stable patients at day 5 (intention to treat), defined as those with stable vital signs for at least 24 h. The secondary endpoints will be time to clinical stability, duration of intravenous and total antibiotic treatment, length of hospital stay, intensive care unit admission, duration of mechanical ventilation and vasopressor treatment, adverse events, readmission within 30 days, and all-cause mortality. The trial has been approved by the Spanish Medicines and Healthcare Products Regulatory Agency. The investigators commit to publish the data in peer-reviewed journals within a year of the study completion date. Subjects will be recruited from three Spanish hospitals over a planned enrolment period of 2 years. A follow-up visit will be performed 1 month after discharge. We have estimated the need for a sample size of 360 patients at a two-sided 5% alpha-level with a power of 80% based on intention to treat. Eligible participants must be hospitalized, hypoalbuminemic (≤ 30 g/L), non-immunosuppressed, adults, and diagnosed with CAP. They will be randomly assigned (1:1) to receive standard care plus albumin (20 g in 100 mL) every 12 h for 4 days or standard care alone. DISCUSSION: If this randomized trial confirms the hypothesis, it should lead to a change in current clinical practice for the management of hypoalbuminemic patients with CAP. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT) 2018-003117-18 . Registered on 12 April 2019. ClinicalTrials.gov NCT04071041 . Registered on 27 August 2019.

Embolismo aéreo cerebral en neonatos / Cerebral air embolism in neonates

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Limited long-distance dispersal success in a Western European fairy shrimp evidenced by nuclear and mitochondrial lineage structuring.

Anostraca are known by their ability for long-distance dispersal, but the existence in several species of deep, geographically structured mtDNA lineages suggests their populations are subjected to allopatric differentiation, isolation, and prevalence of local scale dispersion. Tanymastix stagnalis is one of the most widespread species of Anostraca and previous studies revealed an unclear geographical pattern of mtDNA genetic diversity. Here, we analyze populations from the Iberian and Italian Peninsulas, Central Europe, and Scandinavia, with the aim to characterize the patterns of genetic diversity in a spatio-temporal framework using mtDNA and nuclear markers to test gene flow among close populations. For these aims we built a time-calibrated phylogeny and carried out Bayesian phylogeographic analyses using a continuous diffusion model. Our results indicated that T. stagnalis presents a deeply structured genetic diversity, including 7 ancient lineages, some of them even predating the Pleistocene. The Iberian Peninsula harbors high diversity of lineages, with strong isolation and recent absence of gene flow between populations. Dispersal at local scale seems to be the prevailing dispersal mode of T. stagnalis, which exhibits a pattern of isolation-by-distance in the Iberian Peninsula. We remark the vulnerability of most of these lineages, given the limited known geographic distribution of some of them, and the high risk of losing important evolutionary potential for the species.