RESUMO
Background and Aim: The most intensive nutritional requirements occur during milk production's peak. Ewe milk contains more protein and fat than cow milk. The nutritional factors significantly determine the composition. The liver undergoes high stress during lactation but is relieved by essential nutrients. Choline acts metabolically as a lipotrope. This compound functions in cell structure construction, maintenance, and acetylcholine synthesis. The animal nutrition industry provides choline from various sources, such as synthetic and natural kinds. This study evaluated the influence of two distinct choline sources on dairy ewes' peripartum and postpartum milk production, composition, and offspring growth. Materials and Methods: Twenty-four Rambouillet ewes, each weighing around 63.7 ± 1.7 kg, aged three with two previous births, spent 30-day pre-partum and post-partum in individual pens (2 × 2 m). They were given different experimental treatments 30 days before and after birth according to a randomized design; no choline (a), 4 g/day rumen-protected choline (RPC) (b), or 4 g/day thiocholine (c). Milk samples for milk composition and long-chain fatty acid (FA) analysis were taken every 30 days during milk collection. Results: Significant differences (p < 0.05) in ewe body weight, lamb birth weight, and 30-day-old lamb body weight were observed at lambing and on day 30 of lactation due to choline treatment. Milk yield was significantly higher (1.57 kg/day) compared to the control (1.02 kg/day) and RPC (1.39 kg/day), due to the herbal choline source. There was no significant difference in the milk's protein, lactose, fat, non-fat solids, and total milk solids content between the treatments. Herbal choline lowers (p < 0.05) the concentrations of caproic, caprylic, capric, lauric, and myristic acids while boosting (p < 0.05) those of oleic and cis-11-eicosenoic acid, the changes influencing long-chain FA levels (p < 0.05). Conclusion: Providing choline from both sources to ewes enhanced milk production and body weight at lambing and on 30-day post-lambing. The herbal choline supplement altered short-chain milk FAs, while representative concentration pathways affected medium-chain ones.
RESUMO
Our study objectives were to evaluate the effects of divergent rates of body weight (BW) gain during early gestation in beef heifers on F0 performance, metabolic and endocrine status, colostrum immunoglobulins, and subsequent F1 calf characteristics, growth performance, concentrations of hormones and metabolites, and response to vaccination. Angus-based heifers (n = 100; BW = 369 ± 2.5 kg) were adapted to individual feeding for 14 d and bred using artificial insemination with female-sexed semen. Heifers were ranked by BW assigned to either a basal diet targeting 0.28 kg/d gain (LG, n = 50) or the basal diet plus an energy/protein supplement targeting 0.79 kg/d gain (MG, n = 50) until d 84 of gestation. Dam BW and blood samples were collected at 6 time points during gestation; body composition was evaluated at d -10 and 84; and fetal measurements were taken on d 42, 63, and 84. At calving (LG, n = 23; MG, n = 23), dam and calf BW were recorded; and colostrum, calf body measurements, and blood samples were collected. Cow-calf pairs were managed on a common diet from calving to weaning, followed by a common postnatal development period for all F1 female offspring. Growth performance, hormone and metabolite profiles, feeding behavior, and reproductive performance were assessed from birth to pre-breeding in F1 heifers. Offspring were vaccinated against respiratory disease and bovine viral diarrhea pathogens on d 62.3 ± 4.13 and 220.3 ± 4.13 post-calving. By design, MG dams were heavier (P < 0.0001) than LG at d 84, and the BW advantage persisted until subsequent weaning of F1 calves. Concentrations of serum IGF-1 and glucose were increased throughout gestation (P < 0.001) for MG dams, whereas concentrations of NEFA were decreased (P < 0.001) in LG dams. Calves from MG dams were 2.14 kg heavier (P = 0.03) and had larger chest circumference (P = 0.04) at birth compared with LG cohorts. Heifers from MG dams continued to have greater (P ≤ 0.03) BW gain and feed efficiency during the development period, but no differences were observed (P ≥ 0.13) in body composition, concentrations of hormones and metabolites, feeding behavior, puberty attainment, and response to vaccination in F1 offspring. Hence, early gestation rate of gain impacted BW and concentrations of glucose and IGF-1 throughout gestation in the F0 dam, resulting in altered F1 calf BW and measurements at birth and increased gain and efficiency during the development period.
RESUMO
Using first-principles calculations, we investigate the origin of magnetocrystalline anisotropy in a series of 4f-electron-free intermetallics with CaCu5-based structures: YCo5, YCo4B, and Y3Co13B2. The electronic structure of these compounds is characterized by a set of narrow 3dbands near the Fermi level. In YCo5the easy-axis anisotropy originates primarily in the spin-orbit coupling-induced mixing of the electronic states with Codx2-y2anddxycharacter. The analysis ofk-resolved anisotropy shows that positive contributions accumulate from the entire Brillouin zone but are particularly large near thekz=0plane. The analysis of the single-site and two-site terms reveals a large positive single-site contribution to the magnetocrystalline anisotropy from the Co atoms on the honeycomb sublattice, along with two-site contributions from both honeycomb and kagome sublattices.
RESUMO
Molten salts play an important role in various energy-related applications such as high-temperature heat transfer fluids and reaction media. However, the extreme molten salt environment causes the degradation of materials, raising safety and sustainability challenges. A fundamental understanding of material-molten salt interfacial evolution is needed. This work studies the transformation of metallic Cr in molten 50/50 mol% KCl-MgCl2via multi-modal in situ synchrotron X-ray nano-tomography, diffraction and spectroscopy combined with density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Notably, in addition to the dissolution of Cr in the molten salt to form porous structures, a δ-A15 Cr phase was found to gradually form as a result of the metal-salt interaction. This phase change of Cr is associated with a change in the coordination environment of Cr at the interface. DFT and AIMD simulations provide a basis for understanding the enhanced stability of δ-A15 Cr vs. bcc Cr, by revealing their competitive phase thermodynamics at elevated temperatures and probing the interfacial behavior of the molten salt at relevant facets. This study provides critical insights into the morphological and chemical evolution of metal-molten salt interfaces. The combination of multimodal synchrotron analysis and atomic simulation also offers an opportunity to explore a broader range of systems critical to energy applications.
RESUMO
This study aimed to assess the impact of protein supplementation and its interaction with calf sex (CS) on the performance, metabolism and physiology of pregnant beef cows. Fifty-two multiparous Zebu beef cows carrying female (n = 22) and male (n = 30) fetuses were used. Cows were individually housed from day 100 to 200 of gestation and randomly assigned to restricted (RES, n = 26) or supplemented (SUP, n = 26) groups. The RES cows were ad libitum fed a basal diet (corn silage + sugarcane bagasse + mineral mixture), achieving 5.5% crude protein (CP), while SUP cows received the same basal diet plus a protein supplement (40% CP, at 3.5 g/kg of body weight). All cows were fed the same diet during late gestation. Differences were declared at p < 0.05. No significant interaction between maternal nutrition and calf sex was found for maternal outcomes (p ≥ 0.34). The SUP treatment increased the total dry matter (DM) intake (p ≤ 0.01) by 32% and 19% at mid- and late-gestation respectively. The total tract digestibility of all diet components was improved by SUP treatment at day 200 of gestation (p ≤ 0.02), as well as the ruminal microbial CP production (p ≤ 0.01). The SUP treatment increased (p ≤ 0.03) the cows' body score condition, ribeye area, the average daily gain (ADG) of pregnant components (PREG; i.e., weight accretion of cows caused by pregnancy) and the ADG of maternal tissues (i.e., weight accretion discounting the gain related to gestation) in the mid-gestation. The SUP cows exhibited a lower maternal ADG (p < 0.01) compared to RES cows in late pregnancy. There was a 24% additional gain (p < 0.01) in the PREG components for SUP cows during late gestation, which in turn improved the calf birthweight (p = 0.05). The uterine arterial resistance and pulsatility indexes (p ≤ 0.01) at mid-gestation were greater for RES cows. In conclusion, protein supplementation during mid-gestation is an effective practice for improving maternal performance, growth of the gravid uterus and the offspring's birth weight.
RESUMO
BACKGROUND AND AIMS: Smokers tend to have a lower body weight than non-smokers, but also more abdominal fat. It remains unclear whether or not the relationship between smoking and abdominal obesity is causal. Previous Mendelian randomization (MR) studies have investigated this relationship by relying upon a single genetic variant for smoking heaviness. This approach is sensitive to pleiotropic effects and may produce imprecise causal estimates. We aimed to estimate causality between smoking and abdominal obesity using multiple genetic instruments. DESIGN: MR study using causal analysis using summary effect estimates (CAUSE) and latent heritable confounder MR (LHC-MR) methods that instrument smoking using genome-wide data, and also two-sample MR (2SMR) methods. SETTING: Genome-wide association studies (GWAS) summary statistics from participants of European ancestry, obtained from the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), Genetic Investigation of Anthropometric Traits (GIANT) Consortium and the UK Biobank. PARTICIPANTS: We used GWAS results for smoking initiation (n = 1 232 091), life-time smoking (n = 462 690) and smoking heaviness (n = 337 334) as exposure traits, and waist-hip ratio (WHR) and waist and hip circumferences (WC and HC) (n up to 697 734), with and without adjustment for body mass index (adjBMI), as outcome traits. MEASUREMENTS: Smoking initiation, life-time smoking, smoking heaviness, WHR, WC, HC, WHRadjBMI, WCadjBMI and HCadjBMI. FINDINGS: Both CAUSE and LHC-MR indicated a positive causal effect of smoking initiation on WHR (0.13 [95% confidence interval (CI) = 0.10, 0.16 and 0.49 (0.41, 0.57), respectively] and WHRadjBMI (0.07 (0.03, 0.10) and 0.31 (0.26, 0.37). Similarly, they indicated a positive causal effect of life-time smoking on WHR [0.35 (0.29, 0.41) and 0.44 (0.38, 0.51)] and WHRadjBMI [0.18 (0.13, 0.24) and 0.26 (0.20, 0.31)]. In follow-up analyses, smoking particularly increased visceral fat. There was no evidence of a mediating role by cortisol or sex hormones. CONCLUSIONS: Smoking initiation and higher life-time smoking may lead to increased abdominal fat distribution. The increase in abdominal fat due to smoking is characterized by an increase in visceral fat. Thus, efforts to prevent and cease smoking can have the added benefit of reducing abdominal fat.
Assuntos
Causalidade , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Obesidade Abdominal , Fumar , Relação Cintura-Quadril , Humanos , Obesidade Abdominal/genética , Obesidade Abdominal/epidemiologia , Fumar/genética , Fumar/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , AdultoRESUMO
This study examined the impact of maternal protein supplementation during mid-gestation on offspring, considering potential sex-related effects. Forty-three pregnant purebred Tabapuã beef cows (20 female and 23 male fetuses) were collectively managed in a pasture until 100 d of gestation. From 100 to 200 d of gestation, they were randomly assigned to the restricted group [(RES) - basal diet (75% corn silageâ +â 25% sugar cane bagasseâ +â mineral mixture); nâ =â 24] or control group [(CON) - same basal dietâ +â based-plant supplement [40% of crude protein, 3.5 g/kg of body weight (BW); nâ =â 19]. From 200 d of gestation until parturition, all cows were equally fed corn silage and mineral mixture. During the cow-calf phase, cows and their calves were maintained in a pasture area. After weaning, calves were individually housed and evaluated during the backgrounding (255 to 320 d), growing 1 (321 to 381 d), and growing 2 (382 to 445 d) phases. Offspring's blood samples were collected at 210 and 445 d of age. Samples of skeletal muscle tissue were collected through biopsies at 7, 30, and 445 d of age. Muscle tissue samples were subjected to reverse-transcription quantitative polymerase chain reaction analysis. Prenatal treatment and offspring's sex (when pertinent) were considered fixed effects. The significance level was set at 5%. At mid-gestation, cows supplemented with protein reached 98% and 92% of their protein and energy requirements, while nonsupplemented cows attained only 30% and 50% of these requirements, respectively. The RES offspring were lighter at birth (27 vs. 31 kg), weaning (197 vs. 214 kg), and 445 d of age (398 vs. 429 kg) (Pâ ≤â 0.05). The CON calves had greater (Pâ <â 0.05) morphometric measurements overall. The CON offspring had ~26% greater muscle fiber area (Pâ ≤â 0.01). There was a trend (Pâ =â 0.06) for a greater Mechanistic target of rapamycin kinase mRNA expression in the Longissimus thoracis in the CON group at 7 d of age. The Myogenic differentiation 1 expression was greater (Pâ =â 0.02) in RES-females. Upregulation of Carnitine palmitoyltransferase 2 was observed in RES offspring at 445 d (Pâ =â 0.04). Expression of Fatty acid binding protein 4 (Pâ <â 0.001), Peroxisome proliferator-activated receptor gamma (Pâ <â 0.001), and Stearoyl-Coenzyme A desaturase (Pâ <â 0.001) was upregulated in CON-females. Therefore, protein supplementation during gestation enhances offspring growth and promotes favorable responses to lipogenesis, particularly in females.
In tropical conditions, beef cows on pasture often experience protein restriction during mid-to-late gestation, potentially impacting offspring development negatively. To address this, we investigated the effects of strategic protein supplementation for pregnant beef cows fed low-quality forage during mid-gestation on the postnatal growth trajectory of their offspring. The supplementation program, implemented during mid-gestation, increased dry matter intake by addressing nitrogen deficiency in the rumen, resulting in meeting 98% and 92% of protein and energy requirements in supplemented cows. In contrast, nonsupplemented cows met only 30% and 50% of these requirements, respectively. Consequently, protein supplementation positively influenced the postnatal growth trajectory of the offspring, attributed to beneficial changes in secondary myogenesis and hypertrophy processes. Supplementing cows with crude protein also stimulated lipogenesis, potentially contributing to intramuscular fat deposition, particularly in females. Therefore, this study emphasizes the importance of nutritional interventions for pregnant beef cows fed low-quality forage.
Assuntos
Ração Animal , Suplementos Nutricionais , Animais , Bovinos , Feminino , Gravidez , Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais/análise , Minerais , Músculo Esquelético , MasculinoRESUMO
ABSTRACT: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.
Assuntos
Moléculas de Adesão Celular , Fator VIII , Cininogênios , Lectinas Tipo C , Receptores de Superfície Celular , Fator de von Willebrand , Humanos , Fator de von Willebrand/genética , Fator de von Willebrand/metabolismo , Fator VIII/genética , Fator VIII/metabolismo , Polimorfismo de Nucleotídeo Único , Células Endoteliais da Veia Umbilical Humana/metabolismo , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Trombose/genética , Trombose/sangue , Estudos de Associação Genética , Masculino , Células Endoteliais/metabolismo , FemininoRESUMO
BACKGROUND: Diagnostic testing is essential for disease surveillance and test-trace-isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates. METHODS: We included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8-1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood. RESULTS: We observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5-69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5-14 years) ranging from 0.56 (95% CI 0.47-0.67) to 0.87 (95% CI 0.80-0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10-18% decrease in inhabitants 15-29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70-105, supporting an intervention effect. CONCLUSIONS: Ensuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.
Assuntos
COVID-19 , Criança , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Teste para COVID-19 , Suécia/epidemiologia , PandemiasRESUMO
AIMS/HYPOTHESIS: Childhood overweight increases the risk of type 2 diabetes and cardiovascular disease in adulthood. However, the impact of childhood leanness on adult obesity and disease risk has been overlooked. We examined the independent and combined influences of child and adult body size on the risk of type 2 diabetes and cardiovascular disease. METHODS: Data from the UK Biobank on 364,695 individuals of European ancestry and free of type 2 diabetes and cardiovascular disease were divided into nine categories based on their self-reported body size at age 10 and measured BMI in adulthood. After a median follow-up of 12.8 years, 33,460 individuals had developed type 2 diabetes and/or cardiovascular disease. We used Cox regression models to assess the associations of body size categories with disease incidence. RESULTS: Individuals with low body size in childhood and high body size in adulthood had the highest risk of type 2 diabetes (HR 4.73; 95% CI 4.50, 4.99), compared to those with average body size in both childhood and adulthood. This was significantly higher than the risk in those with high body size in both childhood and adulthood (HR 4.05; 95% CI 3.84, 4.26). By contrast, cardiovascular disease risk was determined by adult body size, irrespective of childhood body size. CONCLUSIONS/INTERPRETATION: Low body size in childhood exacerbates the risk of type 2 diabetes associated with adult obesity but not the risk of cardiovascular disease. Thus, promoting healthy weight management from childhood to adulthood, among lean children, is crucial.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Obesidade Infantil , Adulto , Humanos , Criança , Adolescente , Adulto Jovem , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Índice de Massa Corporal , Fatores de Risco , Obesidade Infantil/complicações , Tamanho CorporalRESUMO
The sperm interacts with seminal plasma proteins during its transport through the female reproductive tract to reach the oocyte. Seminal plasma proteins have been associated as biomarkers of fertility in bovine males, while two-dimensional electrophoresis in polyacrylamide gels under denaturing conditions (2D-PAGE) is a useful technique for their separation, allowing their subsequent analysis with the aid of specialised software. Brahman bulls are known for their tolerance to tropical conditions such as low-quality pastures, high temperatures, and relative humidity as well as moderate resistance to infestations by parasites and insects. The present study describes the two-dimensional electrophoretic profiles of the seminal plasma proteins in the rainy and dry seasons, associating them with the fertility of Brahman bulls in the Colombian Orinoquía in a 90-days breeding season and a single-sire mating system (1 bull per 50 Brahman cows) with 60 consecutive days of rest. The fertility-related seminal plasma protein spots increased in the dry season. Likewise, a meaningful relationship was found between the protein spots that possibly coincide with the Binder of Sperm Proteins. It was also found that bulls with the highest percentages of pregnancy also had similarities in their 2D seminal plasma maps. We conclude that the seminal plasma protein profile of Brahman bulls raised in the Colombian low tropic changes between rainy and dry seasons, and such changes may influence the reproductive performance of those animals.
RESUMO
Machine learning force fields (MLFFs) are an increasingly popular choice for atomistic simulations due to their high fidelity and improvable nature. Here we propose a hybrid small-cell approach that combines attributes of both offline and active learning to systematically expand a quantum-mechanical (QM) database while constructing MLFFs with increasing model complexity. Our MLFFs employ the moment tensor potential formalism. During this process, we quantitatively assessed the structural properties, elastic properties, dimer potential energies, melting temperatures, phase stability, point defect formation energies, point defect migration energies, free surface energies, and generalized stacking fault (GSF) energies of Zr as predicted by our MLFFs. Unsurprisingly, the model complexity has a positive correlation with prediction accuracy. We also find that the MLFFs were able to predict the properties of out-of-sample configurations without directly including these specific configurations in the training dataset. Additionally, we generated 100 MLFFs of high complexity (1513 parameters each) that reached different local optima during training. Their predictions cluster around the benchmark DFT values, but subtle physical features such as the location of local minima on the GSF energy surface are washed out by statistical noise.
RESUMO
La Palma island is located in the NW of the Canary Islands and is one of the most volcanically active of the archipelago, therefore the existence of geothermal resources on the island is highly probable. The main objective of this work is to detect velocity anomalies potentially related to active geothermal reservoirs on La Palma island, by achieving a high-resolution seismic velocity model of the first few kilometres of the crust using Ambient Noise Tomography (ANT). The obtained ANT model is merged with a recent local earthquake tomography model. Our findings reveal two high-velocity zones in the island's northern and southern parts, that could be related to a plutonic intrusion and old oceanic crust materials. Conversely, four low-velocity zones are imaged in the southern part of the island. Two of them can be related to hydrothermal alteration zones located beneath the Cumbre Vieja volcanic complex. This hypothesis is reinforced by comparing the S-wave velocity model with the seismicity recorded during the pre-eruptive phase of the 2021 Tajogaite eruption, which revealed an aseismic volume coinciding with these low-velocity zones. Another low-velocity zone is observed in the southern part of the island, which we interpret as highly fractured rocks which could favour the ascent of hot fluids. A last low-velocity zone is observed in the central part of the island and associated with loose deposits generated by the Aridane valley mega landslide.
RESUMO
Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10% higher in African populations. Three ( SERPINA1, ZFP36L2 , and TLR10) signals contain predicted deleterious missense variants. Two loci, SOCS3 and HPN , each harbor two conditionally distinct, non-coding variants. The gene region encoding the protein chain subunits ( FGG;FGB;FGA ), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common (MAF=0.180) in African reference panels but extremely rare (MAF=0.008) in Europeans. Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation. Key Points: Largest and most diverse genetic study of plasma fibrinogen identifies 54 regions (18 novel), housing 69 conditionally distinct variants (20 novel).Sufficient power achieved to identify signal driven by African population variant.Links to (1) liver enzyme, blood cell and lipid genetic signals, (2) liver regulatory elements, and (3) thrombotic and inflammatory disease.
RESUMO
On Sept. 19th, 2021, a volcanic eruption began on the island of La Palma (Canary Islands, Spain). The pre-eruptive episode was characterized by seismicity and ground deformation that started only 9.5 days before the eruption. In this study, we applied seismic interferometry to the data recorded by six broadband seismic stations, allowing us to estimate velocity variations during the weeks preceding the eruption. About 9.5 days before the eruption, we observed a reduction in the seismic velocities is registered next to the eruptive centers that opened later. Furthermore, this zone overlaps with the epicenters of a cluster of volcano-tectonic earthquakes located at shallow depth (< 4 km) and detached from the main cluster of deeper seismicity. We interpret the decrease in seismic velocities and the occurrence of such a shallow earthquake cluster as the effect of hydrothermal fluid released by the ascending magma batch and reaching the surface faster than the magma itself.
RESUMO
This research aimed to evaluate the impact of temperature and energy status on the thermal indices, physiological parameters, and ruminal papilla mRNA expression levels of Zebu beef heifers (Bos taurus indicus). In this trial, we used six ruminal-cannulated Nellore females. The experimental design was a 6 × 6 Latin square, with six treatments and six periods. The research used a 2 × 2 + 2 factorial scheme. The arrangement comprised: two thermal conditions [thermoneutrality (TN; 21.6 °C) or heat stress (HS, 34 °C)]; two dietary energy levels (low or high-energy); and two additional treatments, with heifers exposed to the TN, but pair-fed with females exposed to HS (PFTN). For our purposes, body temperature, heart and respiratory rates were measured and the relative mRNA expression was quantified using the PCR-RT technique. Compared to TN or PFTN, the HS increased the body temperature measurements in the morning and evening (p ≤ 0.04). Heart rate was 22% greater for heifers under HS than for TN (p < 0.01) and 13% higher for those under HS than PFTN (p = 0.03) in the morning. Respiratory rates increased with HS exposure compared to TN or PFTN (p < 0.01). Heifers submitted to HS and fed low-energy diets had and tended to have lower caspase 3 (CASP3, p 0.001) and sodium-glucose cotransporter type 1 (SGLT1; p = 0.17) mRNA expressions, respectively. Heat-stressed heifers fed low-energy diets also increased the putative anion transporter (PAT1; p ≤ 0.01) mRNA expressions by 60%. Heifers under HS-fed high-energy diets had greater kallikrein-related peptidase (KLK) 9 expressions (p = 0.02), while KLK10 (p = 0.11) tended to be up-regulated in heifers in TN-fed a low-energy diets. In conclusion, heat stress down-regulated the mRNA expression of rumen markers related to short-chain fatty acids transport and pH modulation.
Assuntos
Dieta , Temperatura Alta , Bovinos , Animais , Feminino , Dieta/veterinária , Resposta ao Choque Térmico , Epitélio , RNA Mensageiro , Ração Animal/análise , Rúmen/fisiologiaRESUMO
INTRODUCTION: Atopic dermatitis (AD) is a chronic, relapsing-remitting illness. In moderate-to-severe instances, recommendations urge patient-centered systemic therapy. Existing standards lack long-term treatment success requirements. A treat-to-target methodology was proposed for systemic therapy patients that requires global improvements to prompt decisions about treatment. METHODS: We conducted an observational study between May 2021 and June 2022 in three Ecuadorian patients with severe AD who were treated with dupilumab to assess the clinical evolution and behavior of the subdomains evaluated by clinimetric tools. RESULTS: Patients A and C satisfied disease-domain response criteria to dupilumab at 12 and 24 weeks, but B did not complete the algorithm objectives. Nonetheless, patient A improved AD severity, itching, bleeding, desquamation, sleep, daily activities, mood, emotions, sexual troubles, clothing, and sports subdomains. Patient B experienced reduced symptomatology, AD aggravation, daily activities impact, and work/study impairment. Patient C improved from severe to mild desquamation, itching, exudate, lichenification, and rough/dry skin. Sleep, shame, and study subdomains improved the most. CONCLUSION: We provide a new operational construct for analyzing current patient-reported outcome measures (PROMs) and clinician-reported outcome measures (CROMs) based on subdomains to widen our understanding of the state of disease activity and make clinical decisions when the treat-to-target strategy is not attained.
RESUMO
Monitoring aeroallergens has a long history within the American Academy of Allergy, Asthma & Immunology. The Aeroallergen Network of the National Allergy Bureau is composed mainly of members of the American Academy of Allergy, Asthma & Immunology, whose objectives are to enhance the knowledge of aerobiology and its relationship to allergy, increase the number of certified stations, maintain the standardization and quality of aerobiology data, improve the alert and forecast reporting system, and increase ties with other scientific entities inside and outside the United States. The public has a keen interest in pollen counts and pollen forecasts, as do many health professionals in the allergy community. In this review, we explore the past, present, and future of allergen monitoring with a focus on methods used for sampling, the training of those performing the analysis, and emerging technologies in the field. Although the development of automated samplers with machine intelligence offers great promise for meeting the goal of a fully automated system, there is still progress to be made regarding reliability and affordability.
Assuntos
Asma , Hipersensibilidade , Humanos , Estados Unidos/epidemiologia , Reprodutibilidade dos Testes , Alérgenos , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , PólenRESUMO
On January 12, 2020, Taal volcano in Philippines erupted, 43 years after its previous eruption in 1977. This eruption was preceded by diffuse CO2 degassing precursory signals. Significant temporal variations in diffuse CO2 emission from Taal Main Crater Lake (TMLC) were observed across the ~ 12 years reaching high CO2 degassing rates in 2011 and 2017, with values typical of plume degassing volcanoes. In addition to these CO2 surveys at the TCML, soil CO2 efflux continuous monitoring was implemented at Taal volcano since 2016 and a clear increasing trend of the soil CO2 efflux in 2017 was observed. These geochemical observations are most simply explained by magma recharge to the system, and represent the earliest warning precursor signals to the January 2020 eruptive activity.