Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism.

Mutations in GBA1, the gene encoding the lysosomal enzyme ß-glucocerebrosidase (GCase), which cause Gaucher's disease, are the most frequent genetic risk factor for Parkinson's disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration.

Two independent respiratory chains adapt OXPHOS performance to glycolytic switch.

The structural and functional organization of the mitochondrial respiratory chain (MRC) remains intensely debated. Here, we show the co-existence of two separate MRC organizations in human cells and postmitotic tissues, C-MRC and S-MRC, defined by the preferential expression of three COX7A subunit isoforms, COX7A1/2 and SCAFI (COX7A2L). COX7A isoforms promote the functional reorganization of distinct co-existing MRC structures to prevent metabolic exhaustion and MRC deficiency. Notably, prevalence of each MRC organization is reversibly regulated by the activation state of the pyruvate dehydrogenase complex (PDC). Under oxidative conditions, the C-MRC is bioenergetically more efficient, whereas the S-MRC preferentially maintains oxidative phosphorylation (OXPHOS) upon metabolic rewiring toward glycolysis. We show a link between the metabolic signatures converging at the PDC and the structural and functional organization of the MRC, challenging the widespread notion of the MRC as a single functional unit and concluding that its structural heterogeneity warrants optimal adaptation to metabolic function.

Effect of Trichoderma asperellum on Wheat Plants' Biochemical and Molecular Responses, and Yield under Different Water Stress Conditions.

Eight Trichoderma strains were evaluated for their potential to protect wheat seedlings against severe (no irrigation within two weeks) water stress (WS). Considering the plant fresh weight and phenotype, T. asperellum T140, which displays 1-aminocyclopropane-1-carboxylic acid deaminase activity and which is able to produce several phytohormones, was selected. The molecular and biochemical results obtained from 4-week-old wheat seedlings linked T140 application with a downregulation in the WS-response genes, a decrease in antioxidant activities, and a drop in the proline content, as well as low levels of hydrogen peroxide and malondialdehyde in response to severe WS. All of these responses are indicative of T140-primed seedlings having a higher tolerance to drought than those that are left untreated. A greenhouse assay performed under high nitrogen fertilization served to explore the long-term effects of T140 on wheat plants subjected to moderate (halved irrigation) WS. Even though all of the plants showed acclimation to moderate WS regardless of T140 application, there was a positive effect exerted by T. asperellum on the level of tolerance of the wheat plants to this stress. Strain T140 modulated the expression of a plant ABA-dependent WS marker and produced increased plant superoxide dismutase activity, which would explain the positive effect of Trichoderma on increasing crop yields under moderate WS conditions. The results demonstrate the effectiveness of T. asperellum T140 as a biostimulant for wheat plants under WS conditions, making them more tolerant to drought.

Síndrome inflamatorio multisistémico en niños y adolescentes como complicación de COVID-19 / Multisystemic inflammatory syndrome in children and adolescents as a complication of COVID-19

Objetivo: Analizar el síndrome inflamatorio multisistémico en niños y adolescentes como complicación de COVID-19. Método: Se trabajó con una revisión sistemática de 15 artículos relacionados al tema de investigación, ubicados en base de datos PubMed. Conclusión: Los datos actuales sobre el Síndrome Inflamatorio Multisistémico (SIM), que, pese a tener una baja frecuencia y ser relativamente nuevo tiene un alto índice de gravedad por su efecto sobre el sistema cardiovascular, neurológico, la presencia de shock y el ingreso a la Unidad de Cuidados Intensivos. Es por esto que se debe tener un conocimiento clave sobre el diagnóstico y tratamiento de SIM para evitar llegar a un evento fatal.

Objective: To analyze multisystemic inflammatory syndrome in children and adolescents as a complication of COVID-19. Method: We worked with a systematic review of 15 articles related to the research topic, located in PubMed database. Conclusion: Current data on Multisystemic Inflammatory Syndrome (SIM), which, despite having a low frequency and being relatively new, has a high severity index due to its effect on the cardiovascular and neurological systems, the presence of shock and admission to the Intensive Care Unit. This is why it is necessary to have a key knowledge about the diagnosis and treatment of SIM to avoid reaching a fatal event.

Why Is the Correct Selection of Trichoderma Strains Important? The Case of Wheat Endophytic Strains of T. harzianum and T. simmonsii.

The search for endophytic fungi in the roots of healthy wheat plants from a non-irrigation field trial allowed us to select 4 out of a total of 54 cultivable isolates belonging to the genus Trichoderma, identified as T. harzianum T136 and T139, T. simmonsii T137, and T. afroharzianum T138. In vitro assays against the phytopathogenic fungus Fusarium graminearum showed that the T. harzianum strains had the highest biocontrol potential and that T136 exhibited the highest cellulase and chitinase activities. Production patterns of eight phytohormones varied among the Trichoderma strains. All four, when applied alone or in combination, colonized roots of other wheat cultivars and promoted seed germination, tillering, and plant growth under optimal irrigation conditions in the greenhouse. Apart from T136, the endophytic Trichoderma strains showed plant protection capacity against drought as they activated the antioxidant enzyme machinery of the wheat plants. However, T. simmonsii T137 gave the best plant size and spike weight performance in water-stressed plants at the end of the crop. This trait correlated with significantly increased production of indole acetic acid and abscisic acid and increased 1-aminocyclopropane-1-carboxylic acid deaminase activity by T137. This study shows the potential of Trichoderma endophytes and that their success in agricultural systems requires careful selection of suitable strains.

Phytohormone Production Profiles in Trichoderma Species and Their Relationship to Wheat Plant Responses to Water Stress.

The production of eight phytohormones by Trichoderma species is described, as well as the 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase (ACCD) activity, which diverts the ethylene biosynthetic pathway in plants. The use of the Trichoderma strains T. virens T49, T. longibrachiatum T68, T. spirale T75 and T. harzianum T115 served to demonstrate the diverse production of the phytohormones gibberellins (GA) GA1 and GA4, abscisic acid (ABA), salicylic acid (SA), auxin (indole-3-acetic acid: IAA) and the cytokinins (CK) dihydrozeatin (DHZ), isopenteniladenine (iP) and trans-zeatin (tZ) in this genus. Such production is dependent on strain and/or culture medium. These four strains showed different degrees of wheat root colonization. Fresh and dry weights, conductance, H2O2 content and antioxidant activities such as superoxide dismutase, peroxidase and catalase were analyzed, under optimal irrigation and water stress conditions, on 30-days-old wheat plants treated with four-day-old Trichoderma cultures, obtained from potato dextrose broth (PDB) and PDB-tryptophan (Trp). The application of Trichoderma PDB cultures to wheat plants could be linked to the plants' ability to adapt the antioxidant machinery and to tolerate water stress. Plants treated with PDB cultures of T49 and T115 had the significantly highest weights under water stress. Compared to controls, treatments with strains T68 and T75, with constrained GA1 and GA4 production, resulted in smaller plants regardless of fungal growth medium and irrigation regime.

Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders.

Mitochondrial disorders (MD) comprise a group of heterogeneous clinical disorders for which non-invasive diagnosis remains a challenge. Two protein biomarkers have so far emerged for MD detection, FGF-21 and GDF-15, but the identification of additional biomarkers capable of improving their diagnostic accuracy is highly relevant. Previous studies identified Gelsolin as a regulator of cell survival adaptations triggered by mitochondrial defects. Gelsolin presents a circulating plasma isoform (pGSN), whose altered levels could be a hallmark of mitochondrial dysfunction. Therefore, we investigated the diagnostic performance of pGSN for MD relative to FGF-21 and GDF-15. Using ELISA assays, we quantified plasma levels of pGSN, FGF-21, and GDF-15 in three age- and gender-matched adult cohorts: 60 genetically diagnosed MD patients, 56 healthy donors, and 41 patients with unrelated neuromuscular pathologies (non-MD). Clinical variables and biomarkers' plasma levels were compared between groups. Discrimination ability was calculated using the area under the ROC curve (AUC). Optimal cut-offs and the following diagnostic parameters were determined: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and efficiency. Comprehensive statistical analyses revealed significant discrimination ability for the three biomarkers to classify between MD and healthy individuals, with the best diagnostic performance for the GDF-15/pGSN combination. pGSN and GDF-15 preferentially discriminated between MD and non-MD patients under 50 years, whereas FGF-21 best classified older subjects. Conclusion: pGSN improves the diagnosis accuracy for MD provided by FGF-21 and GDF-15.

Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

Regulation of Mitochondrial Function by the Actin Cytoskeleton.

The regulatory role of actin cytoskeleton on mitochondrial function is a growing research field, but the underlying molecular mechanisms remain poorly understood. Specific actin-binding proteins (ABPs), such as Gelsolin, have also been shown to participate in the pathophysiology of mitochondrial OXPHOS disorders through yet to be defined mechanisms. In this mini-review, we will summarize the experimental evidence supporting the fundamental roles of actin cytoskeleton and ABPs on mitochondrial trafficking, dynamics, biogenesis, metabolism and apoptosis, with a particular focus on Gelsolin involvement in mitochondrial disorders. The functional interplay between the actin cytoskeleton, ABPs and mitochondrial membranes for the regulation of cellular homeostasis thus emerges as a new exciting field for future research and therapeutic approaches.

Effect of Inorganic N Top Dressing and Trichoderma harzianum Seed-Inoculation on Crop Yield and the Shaping of Root Microbial Communities of Wheat Plants Cultivated Under High Basal N Fertilization.

Wheat crop production needs nitrogen (N) for ensuring yield and quality. High doses of inorganic N fertilizer are applied to soil before sowing (basal dressing), with additional doses supplied along the cultivation (top dressing). Here, a long-term wheat field trial (12 plots), including four conditions (control, N top dressing, Trichoderma harzianum T34 seed-inoculation, and top dressing plus T34) in triplicate, was performed to assess, under high basal N fertilization, the influence of these treatments on crop yield and root microbial community shaping. Crop yield was not affected by top dressing and T. harzianum T34, but top dressing significantly increased grain protein and gluten contents. Twenty-seven-week old wheat plants were collected at 12 days after top dressing application and sampled as bulk soil, rhizosphere and root endosphere compartments in order to analyze their bacterial and fungal assemblies by 16S rDNA and ITS2 high-throughput sequencing, respectively. Significant differences for bacterial and fungal richness and diversity were detected among the three compartments with a microbial decline from bulk soil to root endosphere. The most abundant wheat root phyla were Proteobacteria and Actinobacteria for bacteria, and Ascomycota and Basidiomycota for fungi. An enrichment of genera commonly associated with soils subjected to chemical N fertilization was observed: Kaistobacter, Mortierella, and Solicoccozyma in bulk soil, Olpidium in rhizosphere, and Janthinobacterium and Pedobacter in root endosphere. Taxa whose abundance significantly differed among conditions within each compartment were identified. Results show that: (i) single or strain T34-combined application of N top dressing affected to a greater extent the bulk soil bacterial levels than the use of T34 alone; (ii) when N top dressing and T34 were applied in combination, the N fertilizer played a more decisive role in the bacterial microbiome than T34; (iii) many genera of plant beneficial bacteria, negatively affected by N top dressing, were increased by the application of T34 alone; (iv) bulk soil and rhizosphere fungal microbiomes were affected by any of the three treatments assayed; and (v) all treatments reduced Claroideoglomus in bulk soil but the single application of T34 raised the rhizosphere levels of this mycorrhizal fungus.

Altered Expression Ratio of Actin-Binding Gelsolin Isoforms Is a Novel Hallmark of Mitochondrial OXPHOS Dysfunction.

Mitochondrial oxidative phosphorylation (OXPHOS) defects are the primary cause of inborn errors of energy metabolism. Despite considerable progress on their genetic basis, their global pathophysiological consequences remain undefined. Previous studies reported that OXPHOS dysfunction associated with complex III deficiency exacerbated the expression and mitochondrial location of cytoskeletal gelsolin (GSN) to promote cell survival responses. In humans, besides the cytosolic isoform, GSN presents a plasma isoform secreted to extracellular environments. We analyzed the interplay between both GSN isoforms in human cellular and clinical models of OXPHOS dysfunction. Regardless of its pathogenic origin, OXPHOS dysfunction induced the physiological upregulation of cytosolic GSN in the mitochondria (mGSN), in parallel with a significant downregulation of plasma GSN (pGSN) levels. Consequently, significantly high mGSN-to-pGSN ratios were associated with OXPHOS deficiency both in human cells and blood. In contrast, control cells subjected to hydrogen peroxide or staurosporine treatments showed no correlation between oxidative stress or cell death induction and the altered levels and subcellular location of GSN isoforms, suggesting their specificity for OXPHOS dysfunction. In conclusion, a high mitochondrial-to-plasma GSN ratio represents a useful cellular indicator of OXPHOS defects, with potential use for future research of a wide range of clinical conditions with mitochondrial involvement.

Baseline urinalysis values in common bottlenose dolphins under human care in the Caribbean.

Urinalysis is a rapid, simple, inexpensive, and reliable test that documents urine abnormalities reflecting various types of renal, hormonal, or metabolic diseases. Urinalysis could assist proper monitoring of the health of dolphins under human care; however, normal baseline values for dolphin urinalysis have not been reported, to our knowledge. We sampled urine from 193 common bottlenose dolphins ( Tursiops truncatus), living under human care in 24 Caribbean dolphinariums, by voluntary free-catch and analyzed the urine for chemical and microscopic variables using multi-agent dry reagent chemistry dipstick test strips, dedicated pH reagent strips, and unstained sediment slides. Most urine was clear, pale yellow to dark yellow, and had a fishy odor. Dipstick glucose, bilirubin, ketones, and nitrites were negative in all dolphins. The urine pH was acidic ( x¯ ± SD; 5.88 ± 0.58) and specific gravity (SG) was 1.035 ± 0.008. Most animals had 0-2 red blood cells and white blood cells per 40× field, and were negative for proteins. On microscopic sediment, 42.7% of samples had few-to-many squamous epithelial cells; hyaline and epithelial casts were observed only rarely. Crystals were observed in 36.6% of the samples; most were calcium oxalate dihydrate (48.2%) and amorphous urates (42.4%). The values obtained in our study can be used as a reference for health monitoring of dolphins in dolphinariums, and to monitor renal conditions and function in dolphins being rehabilitated or under human care.

Proyecto URISCAM: Evaluación multicéntrica del citómetro UF-Series en el despistaje de infecciones urinarias / URISCAM project: multicenter evaluation of the UF-Series cytometer in the urinary tract infections screening

Introducción. El urocultivo, prueba de referencia para confirmar la existencia de Infección del tracto urinario (ITU), es la solicitud más demandada a Microbiología. Nuestro objetivo fue determinar la rentabilidad diagnóstica del citómetro UF-Series como método de cribado en la detección de ITU. Material y métodos. Se analizaron las orinas remitidas a los seis laboratorios de Microbiología participantes en un periodo de 5 días laborables. Se recogieron variables demográficas y de origen de la muestra, tipo de muestra (orina de media micción, sondaje, nefrostomía), recogida con/sin ácido bórico, lectura del citómetro (leucocituria, bacteriuria, morfología bacteriana y células epiteliales) y resultado del urocultivo. Para determinar la capacidad predictiva del citómetro se representaron las curvas ROC. Resultados. Se procesaron 2.468 muestras de pacientes con edad media de 53 años (ratio mujeres:hombres 2:1). El urocultivo detectó un 23% de orinas positivas. Las variables predictoras de ITU fueron: lectura morfológica de bacilos, bacteriuria ≥ 21 bacterias/μL, edad ≥ 65 años, procedencia de las muestras recogidas en urgencias y hospitalización, y presencia de conservante. Con el punto de corte de 21 bacterias, obtuvimos una sensibilidad del 93,3% y un VPN del 94,5%, lo que permitiría dejar de sembrar el 28,9% de las orinas recibidas con 1,6% de falsos negativos. Conclusiones. Consideramos que el UF-Series es una herramienta válida y precisa para la detección de ITU, por lo que podría utilizarse como cribado previo al urocultivo en la práctica clínica, reduciendo el número de orinas a sembrar en aproximadamente un 30% con una tasa baja de falsos negativos (AU)

Introduction. Urine culture, the gold standard to confirm the presence of urinary tract infection (UTI), is the most requested assay in the microbiology department. Our objective was to determine the diagnostic yield of the UF-Series cytometer as a screening method for UTI. Material and methods. All the urine samples sent to the six Microbiology Laboratories participating in a period of 5 working days were analyzed. We collected demographic variables, apart from those variables related to urine samples: source and sample type (midstream, catheterized or nephrostomy urines), collection with/without boric acid, cytometer parameters (leukocyturia, bacteriuria, bacteria morphology and epithelial cells) and urine culture results. ROC curves were plotted to determine predictive capacity of the cytometer. Results. A sample of 2,468 patients with average age of 53 years were processed (ratio women:men 2:1). Urine culture detected 23% of positive urine samples. The predictor variables of UTI were: morphology of bacilli, bacteriuria ≥21 bacteria/μL, age ≥65 years, samples collected in the emergency service and hospitalization and preserving conditions. With 21 bacteria/ μL as a cut-off point, we obtained a sensitivity of 93.3% and 94.5% negative predictive value, then reducing the samples to be cultured by 28.9% with 1.6% false negatives. Conclusions. We consider that the UF-Series is a valid and accurate tool for the detection of UTI. Therefore, it could be used as screening method in the clinical practice prior to the urine culture, reducing culture requirement by approximately 30%, with a low false negative rate (AU)

Cefalea post punción dural en embarazadas sometidas a cesárea con anestesia raquidea ¿problema actual o pasado? / Cefalea post dural puncture in pregnant submissions to caesárea with raquidea anesthesia problem current or past?

Objetivos: Conocer la incidencia de cefaleas postpunción dural (CPPD) en raquianestesia para cesárea y factores de riesgo reconocidos. Efectividad del tratamiento médico y necesidad de parche hemático peridural. Metodología: Estudio prospectivo, descriptivo, con seguimiento postoperatorio por 72 horas de 914 embarazadas que recibieron raquianestesia para cesárea en el Hospital de la Mujer durante 1 año. Datos registrados por anestesiólogo actuante, seguimiento por un residente. Al diagnosticar una CPPD, se instaló tratamiento según protocolo. Resultados: la incidencia de CPPD fue 2,6 casos/ 100 pacientes, 24 en la población estudiada. 66.7%, aparecieron a las 24 horas; 16,7% a las 48 horas. 54,2% mejoraron a las 24 horas, ninguna requirió parche hemático. 86,3% de las punciones fueron con agujan 25 punta de lápiz, 11,2% con 27 punta de lápiz 23 casos de CPPD para la primera y 1 caso para la segunda, no encontrando asociación estadística (p= 0,759). 76,6% fueron punción única, 15,2% 2 punciones, 7% más de 2. 80,7 % cesáreas urgencia, 65,2% en horario diurno. 42% realizadas por anestesiólogos, 54% por residentes. 8,6% tenían antecedente de cefalea y 2,7% antecedente de CPPD; encontrándose asociación estadística entre la primera y CPPD actual (p=0,001) y entre la segunda y la presencia de CPPD (p=0,004). Conclusiones: obtuvimos una incidencia de CPPD de 2,6%, concordante con datos de la literatura; la mayoría apareció a las 24 horas y todas mejoraron con tratamiento médico. Las pacientes con cefalea y CPPD previa presentaron un RR 5,8 y 5,4 respectivamente (IC 95%), no encontrando asociación con otros factores de riesgo.

Objectives: To know the incidence of post-dural puncture headaches (CPPD) in spinal anesthesia for caesarean section and recognized risk factors. Effectiveness of medical treatment and need for an epidural blood patch Methodology: Prospective, descriptive, postoperative follow-up for 72 hours of 914 pregnant women who received spinal anesthesia for cesarean section, Women 's Hospital during one year study. Data recorded by acting anesthesiologist monitoring by a resident. CPPD to diagnose, treatment was installed according to protocol. Results: CPPD incidence was 2.6 cases / 100 patients, 24 in the study population. 66.7% appeared at 24 hours; 16.7% at 48 hours. 54.2% improved within 24 hours, none required blood patch. 86.3% of punctures were 25G tip pen, 11.2% with 27G tip pen, 23 cases of CPPD for the first and 1 case for the second, finding no statistical association (p = 0.759). 76.6% were single puncture, 15.2% two punctures, 7% more than two. 80.7% cesarean urgency, 65.2% in daytime. 42% made by anesthesiologists, 54% by residents. 8.6% had a history of headache and 2.7% history of CPPD; statistical association was found between the first and current CPPD (p = 0.001) and between the second and the presence of CPPD (p = 0.004). Conclusions: We obtained a CPPD incidence of 2.6%, consistent with data from the literature; Most appeared within 24 hours and all improved with medical treatment. Patients with headache and previous PDCH presented RR 5.8 and 5.4 respectively (95% CI), and found no association with other risk factors.

Analysis of the R1b-DF27 haplogroup shows that a large fraction of Iberian Y-chromosome lineages originated recently in situ.

Haplogroup R1b-M269 comprises most Western European Y chromosomes; of its main branches, R1b-DF27 is by far the least known, and it appears to be highly prevalent only in Iberia. We have genotyped 1072 R1b-DF27 chromosomes for six additional SNPs and 17 Y-STRs in population samples from Spain, Portugal and France in order to further characterize this lineage and, in particular, to ascertain the time and place where it originated, as well as its subsequent dynamics. We found that R1b-DF27 is present in frequencies ~40% in Iberian populations and up to 70% in Basques, but it drops quickly to 6-20% in France. Overall, the age of R1b-DF27 is estimated at ~4,200 years ago, at the transition between the Neolithic and the Bronze Age, when the Y chromosome landscape of W Europe was thoroughly remodeled. In spite of its high frequency in Basques, Y-STR internal diversity of R1b-DF27 is lower there, and results in more recent age estimates; NE Iberia is the most likely place of origin of DF27. Subhaplogroup frequencies within R1b-DF27 are geographically structured, and show domains that are reminiscent of the pre-Roman Celtic/Iberian division, or of the medieval Christian kingdoms.

Characterization of the Iberian Y chromosome haplogroup R-DF27 in Northern Spain.

The European paternal lineage R-DF27 has been proposed as a haplogroup of Iberian origin due to its maximum frequencies in the Iberian Peninsula. In this study, the distribution and structure of DF27 were characterized in 591 unrelated male individuals from four key populations of the north area of the Iberian Peninsula through the analysis of 12 Y-SNPs that define DF27 main sublineages. Additionally, Y-SNP allele frequencies were also gathered from the reference populations in the 1000 Genomes Project to compare and obtain a better landscape of the distribution of DF27. Our results reveal frequencies over 35% of DF27 haplogroup in the four North Iberian populations analyzed and high frequencies for its subhaplogroups. Considering the low frequency of DF27 and its sublineages in most populations outside of the Iberian Peninsula, this haplogroup seems to have geographical significance; thus, indicating a possible Iberian patrilineal origin of vestiges bearing this haplogroup. The dataset presented here contributes with new data to better understand the complex genetic variability of the Y chromosome in the Iberian Peninsula, that can be applied in Forensic Genetics.

Gemcitabine-induced hemolytic-uremic syndrome treated with eculizumab or plasmapheresis: two case reports
.

BACKGROUND: Drug-induced hemolytic-uremic syndrome (HUS) has shown good response to eculizumab (ECU). We present 2 cases of patients with gemcitabine-induced HUS (GEM-HUS), one of whom was treated with ECU and the other with conventional treatment. Patient 1: A 74-year-old male with resected adenocarcinoma of the pancreas started adjuvant treatment with GEM, but after 5 months GEM was discontinued due to acute kidney injury and severe hypertension. Laboratory analyses identified microangiopathic hemolytic anemia (MHA) and thrombocytopenia. Plasmapheresis (Pph) was initiated but was stopped due to a severe adverse reaction. Treatment with ECU was initiated at the time of clinical progression requiring hemodialysis. After 7 doses of ECU, hemolysis and kidney function improved and the patient was able to stop hemodialysis. 1 month after the last dose of ECU serum creatinine (sCr) was 1.8 mg/dL. Patient 2: A 68-year-old male with resected urothelial carcinoma stopped GEM after 2 months due to hematologic toxicity. 1 month later the patient visited the emergency room due to minimal effort dyspnea, hypertension, and peripheral edema. Laboratory analyses showed decreased kidney function, MHA, and thrombocytopenia. Symptomatic treatment was started. After an initial recovery, kidney dysfunction, hemolysis, and thrombocytopenia progressed. Corticoid boluses were ineffective and hemodialysis was initiated. Eleven Pph treatments were necessary to recover hematologic data. The patient remained on hemodialysis for 2 months and evolved to stage IV chronic kidney disease. 8 months after hospital release, sCr was 3.5 mg/dL. CONCLUSION: ECU successfully improved kidney function in a patient with GEM-HUS, while conventional treatment did not.
.

Prevalencia de obesidad en la embarazada coordinada para cesárea / Prevalence of obesity in pregnant women coordinated for cesarean section

Introducción: El estado nutricional materno tiene un efecto determinante sobre la morbimortalidad obstétrica y perinatal. Las embarazadas obesas representan un reto para el anestesiólogo ya que habitualmente presentan otras patologías asociadas, mayor riesgo de nacimiento por cesárea y dificultades técnicas asociadas tanto con la anestesia regional como general. La Organización de las Naciones Unidas para la Agricultura y la Alimentación (FAO), la Organización Mundial de la Salud (OMS) y American College of Obstetricians and Gynecologists (ACOG) recomienda usar el índice de masa corporal (IMC) para evaluar el estado nutricional de la mujer embarazada. Material y métodos: Realizamos un estudio prospectivo, descriptivo que incluyó 893 pacientes sometidas a cesárea con anestesia raquídea en el Centro Hospitalario Pereira Rossell desde octubre de 2014 a octubre del 2015. Resultados: Se obtuvo un promedio de IMC 29.8 ± 0.2 Kg. /m2, con un mínimo y un máximo en 16.01 y 51.56 respectivamente. Con una incidencia de obesidad del 43,2%. Conclusiones: Los resultados de nuestro estudio muestran una alta prevalencia de obesidad, consideramos que estos datos pueden ser representativos de la realidad obstétrica de nuestro país ya que hasta el momento no hemos encontrado un estudio nacional en el que se determine la incidencia de obesidad en la población obstétrica.

Introduction: Maternal nutritional status has a decisive effect on obstetric and perinatal morbidity and mortality. Obese pregnant pose a challenge to the anesthesiologist because usually have other associated diseases, increased risk of caesarean delivery and technical difficulties associated with both regional and general anesthesia. The United Nations Food and Agriculture Organization (FAO), the World Health Organization (WHO) and American College of Obstetricians and Gynecologists (ACOG) recommends using body mass index (BMI) to assess the nutritional status in pregnant woman. Methods: We conducted a prospective study that included 893 patients undergoing cesarean section with spinal anesthesia in the CHPR from October 2014 to October 2015. Results: An average BMI 29.8 ± 0.2 kg / m2 was obtained, with a minimum and a maximum at 16.01 and 51.56 respectively. With an incidence of obesity of 43.2%. Conclusions: The results of our study show a high prevalence of obesity, we believe that these data may be representative of obstetric reality of our country and so far have not found a national study in which the incidence of obesity is determined in the obstetric population.

New clues to the evolutionary history of the main European paternal lineage M269: dissection of the Y-SNP S116 in Atlantic Europe and Iberia.

The dissection of S116 in more than 1500 individuals from Atlantic Europe and the Iberian Peninsula has provided important clues about the controversial evolutionary history of M269. First, the results do not point to an origin of M269 in the Franco-Cantabrian refuge, owing to the lack of sublineage diversity within M269, which supports the new theories proposing its origin in Eastern Europe. Second, S116 shows frequency peaks and spatial distribution that differ from those previously proposed, indicating an origin farther west, and it also shows a high frequency in the Atlantic coastline. Third, an outstanding frequency of the DF27 sublineage has been found in Iberia, with a restricted distribution pattern inside this peninsula and a frequency maximum in the area of the Franco-Cantabrian refuge. This entire panorama indicates an old arrival of M269 into Western Europe, because it has generated at least two episodes of expansion in the Franco-Cantabrian area. This study demonstrates the importance of continuing the dissection of the M269 lineage in different European populations because the discovery and study of new sublineages can adjust or even completely revise the theories about European peopling, as has been the case for the place of origin of M269.

Analysis of 16 autosomal STRs and 17 Y-STRs in an indigenous Maya population from Guatemala.

The aim of this study was to contribute new data on autosomal STR and Y-STR markers of the Mayas from Guatemala in order to improve available databases of forensic interest. We analyzed 16 autosomal STR markers in a population sample of 155 indigenous Maya and 17 Y-chromosomal STR markers in the 100 males of the sample. Deviations from Hardy-Weinberg equilibrium and linkage disequilibrium between autosomal STR markers were not observed at any loci. The combined power of exclusion was estimated as 99.9991% and the combined power of discrimination was >99.999999999999%. Haplotype diversity of Y-STRs was calculated as 0.9984 ± 0.0018 and analysis of pairwise genetic distances (Rst) supported the Native American background of the population.