31 research outputs found

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

    Full text link
    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

    Get PDF
    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

    Phylogenetic Analysis of Trypanosoma cruzi from Pregnant Women and Newborns from Argentina, Honduras, and Mexico Suggests an Association of Parasite Haplotypes with Congenital Transmission of the Parasite

    No full text
    Trypanosoma cruzi, the causative agent of Chagas disease, exhibits a high genetic variability and has been classified into six discrete typing units (DTUs) named TcI through TcVI. This genetic diversity is believed to be associated with clinical characteristics and outcomes, but evidence supporting such associations has been limited. Herein, we performed a phylogenetic analysis of T. cruzi sequences of the mini-exon intergenic region obtained from a large cohort of pregnant women and newborns from Argentina, Honduras, and Mexico, to assess parasite genetic diversity and possible associations with congenital transmission. Analysis of 105 samples (including five paired samples) from maternal and umbilical cord blood indicated that T. cruzi DTU distribution was similar among pregnant women and newborns from these three countries, with a high frequency of TcII-TcV-TcVI DTUs, including mixed infections with TcI. However, phylogenetic analysis revealed that although the same parasite haplotypes circulated in these three countries, they were present at different frequencies, leading to significant geographic differences. Of importance, a strong association was observed between parasite haplotypes and congenital infection of newborns. Thus, the identification of parasite haplotypes in pregnant women, but not of parasite DTUs, may help predict congenital transmission of T. cruzi.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Evaluación de la capacidad antioxidante y metabolitos secundarios de extractos de dieciséis plantas medicinales / Evaluation of antioxidant capacity and secondary metabolites of sixteen medicinal plants extracts

    Get PDF
    El presente estudio evaluó la capacidad antioxidante de los extractos de dieciséis plantas medicinales: escoba amarga (Parthenium hysterophons), ajenjo (Artemisia absinthium), guarumo (t), chaya (Cnidoscolus chayamansa), borraja (Borago officinalis), balsa (Ochroma sp.), linaza (Linum usitatissimum), hierba Luisa (Cymbopogon citratus), toronjil (Melissa officinalis), buganvilla (Bougainvillea spectabilis), alcachofa (Cynara scolymus), guaviduca (Piper carpunya), altamisa (Ambrosia cumanensis), diente de león (Taxacum officinales), buscapina (Parietaria officinalis) y moringa (Moringa oleifera). Para ello, se usó el método DPPH (radical 1,1-difenil-2-picrilhidrazil); además, se realizaron ensayos de reconocimiento de metabolitos secundarios a fin de obtener los primeros indicios de compuestos de interés fitoquímico. La actividad captadora de radicales libres de los extractos se expresó como valor de IC50 (μg/mL) (cantidad necesaria para inhibir la formación de radicales DPPH en un 50%). El valor bajo de IC50 refleja mejor acción eliminadora de radicales libres. Aunque la mayoría de las muestras evaluadas mostraron buena capacidad antioxidante con este método (DPPH), los ensayos de los extractos hidro-alcohólicos demuestran que la alcachofa (IC50 9,89 μg/mL), moringa (IC50 11,4 μg/mL) y borraja (IC50 14,0 μg/mL) presentaron mayor capacidad antioxidante. Mediante las pruebas químicas de caracterización, se detectó la presencia de flavonoides, taninos, triterpenos, alcaloides y saponinas en la mayoría de las especies analizadas (aproximadamente 56-69%); tan sólo un 20% de las mismas mostró la presencia de polifenoles, glucósidos cianogénicos, lactonas, cumarinas, esteroles y antraquinonas. Según los resultados, se podría considerar a estas plantas como fuentes prometedoras de metabolitos secundarios con actividad antioxidante. ABSTRACTThis study evaluated the antioxidant capacity of sixteen medicinal plants: Escoba amarga (Parthenium hysterophons), ajenjo (Artemisia absinthium), guarumo (Cecropia obtusifolia), chaya (Cnidoscolus chayamansa), borraja (Borago officinalis), balsa (Ochroma sp.), linaza (Linum usitatissimum), hierba Luisa (Cymbopogon citratus), toronjil (Melissa officinalis), buganvilla (Bougainvillea spectabilis), alcachofa (Cynara scolymus), guaviduca (Piper carpunya), altamisa (Ambrosia cumanensis), diente de León (Taxacum officinales), buscapina (Parietaria officinalis)and moringa (Moringa oleifera). For this, the DPPH (radical 1, 1-difenil-2-picrilhidrazil) method was used; furthermore, recognition assays of secondary metabolites were performed, in order to obtain the first signs of phytochemical compounds of interest. The free radical scavenging activity of the extracts was expressed as IC50 value (g/mL) (necessary amount to inhibit the formation of 50% of DPPH radical). The low value of IC50 reflects better free radical scavenging action. Although most of the samples tested showed good antioxidant capacity with this method (DPPH), tests of hydroalcoholic extracts show that alcachofa (IC50 9.89 mg/mL), moringa (IC50 11.4 mg/mL) and borraja (IC50 14.0 mg/mL) were those with higher antioxidant capacity. Through chemical characterization tests, the presence of flavonoids, tannins, triterpenes, alkaloids and saponins were detected in most of the analyzed species (approximately 56-69%); only 20% of them showed the presence of polyphenols, cyanogenic glycosides, lactones, coumarins, anthraquinones and sterols. According to the results obtained, these plantsmight be considered as promising sources of secondary metabolites with antioxidant activity

    Congenital Transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: An Observational Prospective Study.

    No full text
    Compared with South America, there is a lack of epidemiologic studies about the risk of congenital transmission of Trypanosoma cruzi in Central America and Mexico. It has been suggested that T. cruzi genotypes might differ by region and that congenital transmission might vary according to the parasite's genotype. Our objective was to compare T. cruzi congenital transmission rates in three countries. We performed an observational prospective study in 2011-2014 enrolling women at delivery in one hospital in Argentina, two hospitals in Honduras, and two hospitals in Mexico. Congenital T. cruzi infection was defined as the presence of one or more of the following criteria: presence of parasites in cord blood (direct parasitological microscopic examination) with positive polymerase chain reaction (PCR) in cord blood, presence of parasites in infant's blood at 4-8 weeks (direct parasitological microscopic examination), and persistence of T. cruzi-specific antibodies at 10 months, as measured by at least two tests. Among 28,145 enrolled women, 347 had at least one antibody rapid test positive in cord blood and a positive enzyme-linked immunosorbent assay in maternal blood. PCR in maternal blood was positive in 73.2% of the cases, and genotyping identified a majority of non-TcI in the three countries. We found no (0.0%; 95% confidence interval [CI]: 0.0, 2.0) confirmed congenital case in Honduras. Congenital transmission was 6.6% (95% CI: 3.1, 12.2) in Argentina and 6.3% (95% CI: 0.8, 20.8) in Mexico. Trypanosoma cruzi non-TcI predominated and risks of congenital transmission were similar in Argentina and Mexico.info:eu-repo/semantics/publishe

    Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: study protocol.

    Get PDF
    Trypanosoma cruzi has been divided into Discrete Typing Units I and non-I (II-VI). T. cruzi I is predominant in Mexico and Central America, while non-I is predominant in most of South America, including Argentina. Little is known about congenital transmission of T. cruzi I. The specific aim of this study is to determine the rate of congenital transmission of T. cruzi I compared to non-I.Journal ArticleResearch Support, N.I.H. ExtramuralSCOPUS: ar.jinfo:eu-repo/semantics/publishe
    corecore