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

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

Gratitude mediates quality of life differences between fibromyalgia patients and healthy controls

Purpose: Despite a growing literature on the benefits of gratitude for adjustment to chronic illness, little is known about gratitude in medical populations compared to healthy populations, or the degree to which potential deficits in gratitude might impact quality of life. The purpose of the present study was to (1) examine levels of gratitude and quality of life in fibromyalgia patients and healthy controls and (2) consider the role of gratitude in explaining quality of life differences between fibromyalgia patients and healthy controls. Methods: Participants were 173 fibromyalgia patients and 81 healthy controls. All participants completed measures of gratitude, quality of life, and socio-demographics. Results: Although gratitude was positively associated with quality of life, levels of gratitude and quality of life were lower in the fibromyalgia sample relative to the healthy controls. This difference in gratitude partially mediated differences in quality of life between the two groups after controlling for socio-demographic variables. Conclusions: Our findings suggest that gratitude is a valuable positive psychological trait for quality of life in people with fibromyalgia. Interventions to improve gratitude in this patient population may also bring enhancement in quality of life

Efecto de la fuente de ácidos grasos sobre la respuesta productiva, características de la canal, concentración de urea en plasma y perfil de ácidos grasos en carne de cerdos alimentados con dietas estándar o con baja proteína

Thirty six Landrace × Yorkshire barrows with 18.6 kg of initial body weight were used to evaluate three sources of fatty acids: crude soybean oil, conjugated linoleic acid (CLA), and soybean soapstock in standard crude protein (CP) and low-protein diets for starter (21 d; 205, 160 g kg-1 CP), growing (28 d; 160, 145 g kg-1 CP), and finishing (29 d; 140, 125 g kg-1 CP) phases. Growth performance, carcass characteristics, plasma urea nitrogen concentration and fatty acid profile in meat were evaluated. The reduction of CP diminished average daily gain, feed:gain ratio, longissimus muscle area and plasma urea nitrogen concentration in nursery pigs; reduced longissimus muscle area and plasma urea nitrogen concentration in growing pigs; increased average daily feed intake, and reduced lean meat percentage and plasma urea nitrogen content in finishing pigs. It also increased c9, t11 and c11, t9 CLA isomers and total lipids and lowered eicosapentaenoic and docosahexaenoic acids concentrations in semimembranosus muscle; linolenic acid decreased with low-protein diets in longissimus and semimembranosus muscles; the oil type affected the concentration of c9, t11 and c11, t9 CLA isomers and total saturated fatty acids in semimembranosus muscle; CLA increased individually and total saturated fatty acids, reduced linoleic and docosapentaenoic acids, and increased total lipids in longissimus muscle. These results indicate that decreasing CP changes the profile of fatty acids. The soybean soapstock can replace crude soybean oil in pig diets; while conjugated linoleic acid does not improve response of pigs fed standard- or low-protein diets.Se utilizaron 36 cerdos machos castrados (18,6 ± 2,3 kg peso inicial) para evaluar tres fuentes de ácidos grasos: aceite crudo de soya, ácido linoleico conjugado (ALC) y aceite de soya acidulado en dietas estándar en proteína bruta (PB) y con baja proteína para iniciación (21 d; 205, 160 g kg-1 PC), crecimiento (28 d; 160, 145 g kg-1 PC), y finalización (29 d; 140, 125 g kg-1 PC). Se evaluó la respuesta productiva, características de la canal, urea en plasma y perfil de ácidos grasos en carne. La reducción de PB disminuyó la ganancia de peso, conversión alimenticia, área del músculo longissimus y urea en plasma en iniciación; redujo el área del músculo longissimus y urea en plasma durante el crecimiento; aumentó el consumo, disminuyó el porcentaje de carne magra y la urea en plasma en finalización. También aumentó los isómeros c9, t11 y c11, t9 del ALC y lípidos totales, redujo los ácidos eicosapentaenoico y docosahexaenoico en músculo semimembranosus y disminuyó el ácido linolénico en ambos músculos. El tipo de aceite afectó a la concentración de isómeros c9, t11 y c11, t9 del ALC y total de ácidos grasos saturados en músculo semimembranosus; el ALC aumentó los ácidos grasos individualmente y total de saturados, redujo el linoleico y docosapentaenoico; aumentó el total de lípidos en músculo longissimus. Esto indica que reducir PB cambia el perfil de ácidos grasos, que el aceite de soya acidulado puede reemplazar al aceite crudo de soya en dietas para cerdos y que el ALC no mejora la respuesta de cerdos alimentados con dietas estándar o con baja proteína

Concentración de urea en plasma y respuesta productiva de cerdos en iniciación alimentados con dietas sorgo-pasta de soya bajas en proteína

Existe poca información acerca del uso de dietas con baja proteína cruda (PC) para cerdos en iniciación. Por tanto, se realizaron dos experimentos para determinar el porcentaje mínimo de PC en dietas sorgo-pasta de soya que no afecte el comportamiento productivo, utilizando urea en plasma como indicador. En el experimento 1, los tratamientos (% PC) fueron: T1) testigo 20.5; T2) 19.0; T3) 17.5; T4) 16.0; T5) 14.5, y se aplicaron a 10 cerditas en iniciación usando un diseño cruzado con periodos de 7 d. El último día de cada periodo se obtuvo una muestra de sangre de la vena cava para determinar urea. La menor concentración de este metabolito indicó que la PC en la dieta puede reducirse hasta 16%. Mediante regresión no lineal exponencial se determinó que la PC en la dieta se puede reducir hasta 14.86% y aumentar hasta 20.12% para obtener la mínima y máxima concentración de urea en plasma. En el experimento 2, los tratamientos (%PC y Mcal EM kg-1) fueron: T1) dieta estándar, 20.5 y 3.265; T2) 20.5 y 3.165; T3) 16 y 3.265; T4) 16 y 3.165; T5) 14.5 y 3.265; T6) 14.5 y 3.165, para 24 machos castrados usando un diseño en bloques completos al azar. El menor nivel de proteína redujo la urea en plasma, mientras que al reducir la energía disminuyó la grasa dorsal y aumentó la conversión alimenticia. Lo anterior indica que la urea se reduce al disminuir la PC en la dieta; que la grasa dorsal es menor al bajar la energía; y que otros factores como el peso inicial también influyen en la respuesta de los cerdos en iniciación

Effect of fatty acids source on growth performance, carcass characteristics, plasma urea nitrogen concentration, and fatty acid profile in meat of pigs fed standard- or low-protein diets

Thirty six Landrace × Yorkshire barrows with 18.6 kg of initial body weight were used to evaluate three sources of fatty acids: crude soybean oil, conjugated linoleic acid (CLA), and soybean soapstock in standard crude protein (CP) and low-protein diets for starter (21 d; 205, 160 g kg-1 CP), growing (28 d; 160, 145 g kg-1 CP), and finishing (29 d; 140, 125 g kg-1 CP) phases. Growth performance, carcass characteristics, plasma urea nitrogen concentration and fatty acid profile in meat were evaluated. The reduction of CP diminished average daily gain, feed:gain ratio, longissimus muscle area and plasma urea nitrogen concentration in nursery pigs; reduced longissimus muscle area and plasma urea nitrogen concentration in growing pigs; increased average daily feed intake, and reduced lean meat percentage and plasma urea nitrogen content in finishing pigs. It also increased c9, t11 and c11, t9 CLA isomers and total lipids and lowered eicosapentaenoic and docosahexaenoic acids concentrations in semimembranosus muscle; linolenic acid decreased with low-protein diets in longissimus and semimembranosus muscles; the oil type affected the concentration of c9, t11 and c11, t9 CLA isomers and total saturated fatty acids in semimembranosus muscle; CLA increased individually and total saturated fatty acids, reduced linoleic and docosapentaenoic acids, and increased total lipids in longissimus muscle. These results indicate that decreasing CP changes the profile of fatty acids. The soybean soapstock can replace crude soybean oil in pig diets; while conjugated linoleic acid does not improve response of pigs fed standard- or low-protein diets

Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia

Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice : A multicentre cohort study

Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads