Clinical and patient-reported outcome profile of patients with hepatitis B viral infection from the Global Liver Registry™.

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.

Post-malaria neurological syndrome (PMNS): a rare case report with brain biopsy findings.

Post-malaria neurological syndrome (PMNS) is a rare, self-limiting condition that presents with a wide range of neurological manifestations after clearance of malarial infection, especially 𝘗𝘭𝘢𝘴𝘮𝘰𝘥𝘪𝘶𝘮 f𝘢𝘭𝘤𝘪𝘱𝘢𝘳𝘶𝘮, most patients recover without residual deficits. Here we present a case of a 29-year-old, male with a recent history of malaria treated successfully, who presented due to a generalized tonic-clonic seizure, without any other neurological symptoms, the examination and labs were unremarkable, he underwent a computer tomography (CT) scan and Magnetic resonant imaging (MRI) which both showed two areas of vasogenic edema involving the subcortical white matter of left frontal and right posterior parasagittal regions, all autoimmune screens, infection workup from blood and CSF were negative, he underwent a brain biopsy that showed intense perivascular inflammation with neuronal loss and gliosis, findings are nonspecific and can be seen in a variety of condition. The patient's condition improved, and he was discharged without any complications.

Loss of Mitochondrial Protease CLPP Activates Type I IFN Responses through the Mitochondrial DNA-cGAS-STING Signaling Axis.

Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a serine protease that degrades damaged or misfolded mitochondrial proteins. CLPP-null mice exhibit growth retardation, deafness, and sterility, resembling human Perrault syndrome, but also display immune system alterations. However, the molecular mechanisms and signaling pathways underlying immunological changes in CLPP-null mice remain unclear. In this study, we report the steady-state activation of type I IFN signaling and antiviral gene expression in CLPP-deficient cells and tissues, resulting in marked resistance to RNA and DNA virus infection. Depletion of the cyclic GMP-AMP (cGAS)-stimulator of IFN genes (STING) DNA sensing pathway reduces steady-state IFN-I signaling and abrogates the broad antiviral phenotype of CLPP-null cells. Moreover, we report that CLPP deficiency leads to mitochondrial DNA (mtDNA) instability and packaging alterations. Pharmacological and genetic approaches to deplete mtDNA or inhibit cytosolic release markedly reduce antiviral gene expression, implicating mtDNA stress as the driver of IFN-I signaling in CLPP-null mice. Our work places the cGAS-STING-IFN-I innate immune pathway downstream of CLPP and may have implications for understanding Perrault syndrome and other human diseases involving CLPP dysregulation.

Hydrochar-nanoparticle integration for arsenic removal from wastewater: Challenges, possible solutions, and future horizon.

Arsenic (As) contamination poses a significant threat to human health, ecosystems, and agriculture, with levels ranging from 12 to 75% attributed to mine waste and stream sediments. This naturally element is abundant in Earth's crust and gets released into the environment through mining and rock processing, causing ≈363 million people to depend on As-contaminated groundwater. To combat this issue, introducing a sustainable hydrochar system has achieved a remarkable removal efficiency of over 92% for arsenic through adsorption. This comprehensive review presents an overview of As contamination in the environment, with a specific focus on its impact on drinking water and wastewater. It delves into the far-reaching effects of As on human health, ecosystems, aquatic systems, and agriculture, while also exploring the effectiveness of existing As treatment systems. Additionally, the study examines the potential of hydrochar as an efficient adsorbent for As removal from water/wastewater, along with other relevant adsorbents and biomass-based preparations of hydrochar. Notably, the fusion of hydrochar with nanoparticle-centric approaches presents a highly promising and environmentally friendly solution for achieving the removal of As from wastewater, exceeding >99% efficiency. This innovative approach holds immense potential for advancing the realms of green chemistry and environmental restoration. Various challenges associated with As contamination and treatment are highlighted, and proposed solutions are discussed. The review emphasizes the urgent need to advance treatment technologies, improve monitoring methods, and enhance regulatory frameworks. Looking outlook, the article underscores the importance of fostering research efforts, raising public awareness, and fostering interdisciplinary collaboration to address this critical environmental issue. Such efforts are vital for UN Sustainable Development Goals, especially clean water and sanitation (Goal 6) and climate action (Goal 13), crucial for global sustainability.

Incidence and risk factors of contrast-induced nephropathy in acute stroke patients undergoing computed tomography angiography: A single-center study.

OBJECTIVES: To investigate the prevalence and risk factors linked to contrast-induced nephropathy in this specific patient population, aiming to ensure the highest quality of clinical care. METHODS: In a retrospective analysis, all patients who presented with an acute stroke to King Fahad Hospital, Jeddah, Emergency Department from March until November 2022 and underwent Computed Tomography Angiography (CTA) brain, Inclusion criteria were as follows: a baseline creatinine results and CTA examination performed within 24 hours of symptom onset and an available early (<5 days after CTA) follow-up creatinine result. RESULTS: Among 246 stroke patients in the emergency, 182 underwent brain CTA and 8.24% had Contrast-Induced Nephropathy (CIN). intracerebral hemorrhage (ICH) increased CIN risk 7-fold (OR=6.7; 95% CI: 1.23-33.3). Abnormal baseline raised CIN risk 8-fold (OR=7.8; 95% CI: 1.74-35.1). hypertension doubled the risk for CIN (OR=2.1; 95% CI: 1.26-6.98) CONCLUSION: The incidence of CIN was 8.2%, particularly elevated in patients with ICH, hypertension, tissue plasminogen administration, and abnormal baseline, necessitating vigilance in managing acute stroke cases.

Power-efficient silicon nitride thermo-optic phase shifters for visible light.

We demonstrate power-efficient, thermo-optic, silicon nitride waveguide phase shifters for blue, green, and yellow wavelengths. The phase shifters operated with low power consumption due to a suspended structure and multi-pass waveguide design. The devices were fabricated on 200-mm silicon wafers using deep ultraviolet lithography as part of an active visible-light integrated photonics platform. The measured power consumption to achieve a π phase shift (averaged over multiple devices) was 0.78, 0.93, 1.09, and 1.20 mW at wavelengths of 445, 488, 532, and 561 nm, respectively. The phase shifters were integrated into Mach-Zehnder interferometer switches, and 10 - 90% rise(fall) times of about 570(590) µs were measured.

Neuroimmune mechanisms of cognitive impairment in a mouse model of Gulf War illness.

Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting approximately 30 percent of the nearly 700,000 Veterans of the 1991 Persian Gulf War. GWI-related chemical (GWIC) exposure promotes immune activation that correlates with cognitive impairment and other symptoms of GWI. However, the molecular mechanisms and signaling pathways linking GWIC to inflammation and neurological symptoms remain unclear. Here we show that acute exposure of murine macrophages to GWIC potentiates innate immune signaling and inflammatory cytokine production. Using an established mouse model of GWI, we report that neurobehavioral changes and neuroinflammation are attenuated in mice lacking the cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) and NOD-, LRR- or pyrin domain-containing protein 3 (NLRP3) innate immune pathways. In addition, we report sex differences in response to GWIC, with female mice showing more pronounced cognitive impairment and hippocampal astrocyte hypertrophy. In contrast, male mice display a GWIC-dependent upregulation of proinflammatory cytokines in the plasma that is not present in female mice. Our results indicate that STING and NLRP3 are key mediators of the cognitive impairment and inflammation observed in GWI and provide important new information on sex differences in this model.

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

Uniting the Global Gastroenterology Community to Meet the Challenge of Climate Change and Nonrecyclable Waste.

Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.

The utility of routine post-hospitalization CT imaging in patients with non-operative mild to moderate traumatic brain injury.

Primary Objective: The purpose of this study was to determine the utility of CT imaging in patients with non-operative mild-moderate TBI with respect to changes in management.Methods: We conducted a retrospective analysis for 191 patients over a 5-year interval to examine whether follow-up CT initiated a change in management. We created a logistic regression model to incorporate different variables contributing to change in management.Results: Of 191 patients, 31 (16.2%) underwent a change in management. Change in management was associated with older age (65 yo vs. 55 yo, p = .011), diagnosis of subdural hematoma (p = .041), antiplatelet/anticoagulant therapy (p = .009), imaging performed (p = .16), and increased blood products on CT (p = <0.0001). For patients on antiplatelet/anticoagulant therapy, only those with worsening findings on CT required a change in management (p = .0002, 0.039). Surgical intervention was indicated in two patients.Conclusions: Limited clinical value exists in repeat CT scans for patients with mild TBI. Most patients with traumatic SAH, contusions, or asymptomatic patients should not have repeat imaging, as our study revealed only 2% of patients with positive CT finding and 0.6% requiring surgical intervention.

Effect of Nitrogen Doping on the Optical Bandgap and Electrical Conductivity of Nitrogen-Doped Reduced Graphene Oxide.

Graphene as a material for optoelectronic design applications has been significantly restricted owing to zero bandgap and non-compatible handling procedures compared with regular microelectronic ones. In this work, nitrogen-doped reduced graphene oxide (N-rGO) with tunable optical bandgap and enhanced electrical conductivity was synthesized via a microwave-assisted hydrothermal method. The properties of the synthesized N-rGO were determined using XPS, FTIR and Raman spectroscopy, UV/vis, as well as FESEM techniques. The UV/vis spectroscopic analysis confirmed the narrowness of the optical bandgap from 3.4 to 3.1, 2.5, and 2.2 eV in N-rGO samples, where N-rGO samples were synthesized with a nitrogen doping concentration of 2.80, 4.53, and 5.51 at.%. Besides, an enhanced n-type electrical conductivity in N-rGO was observed in Hall effect measurement. The observed tunable optoelectrical characteristics of N-rGO make it a suitable material for developing future optoelectronic devices at the nanoscale.

Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility.

BACKGROUND: Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial. METHODS: Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL). RESULTS: A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3·1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was -111 ml (P = 0·456). Among patients at high risk of transfusion, the median EBL difference was -448 ml (P = 0·069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7·6(1·9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0·326). CONCLUSION: Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La resección hepática mayor se asocia con pérdida de sangre y necesidad de transfusión. Datos observacionales sugieren que la flebotomía hipovolémica (hypovolaemic phlebotomy, HP) puede reducir estos riesgos. Este ensayo clínico aleatorizado (randomised clinical trial, RCT) de factibilidad comparó HP con el tratamiento estándar con el fin de proporcionar información para un futuro ensayo multicéntrico. MÉTODOS: Se reclutaron pacientes sometidos a resecciones hepáticas mayores entre junio 2016 y enero 2018. La aleatorización se realizó durante el intraoperatorio y los cirujanos eran ciegos al resultado de la asignación. Para la HP, se extrajeron 7-10 mL/kg de sangre total, sin reposición de líquidos intravenosos. Los resultados primarios fueron la factibilidad y la pérdida de sangre estimada (estimated blood loss, EBL). RESULTADOS: Un total de 62 pacientes se aleatorizaron a HP (n = 31) y a tratamiento estándar (n = 31), a un ritmo de 3,1 pacientes/mes, cumpliendo el co-objetivo primario de la factibilidad. La mediana de la diferencia de EBL fue 11 mL (P = 0,46). Entre los pacientes con alto riesgo de transfusión, la mediana de la diferencia de EBL fue 448 mL (P = 0,069). Los objetivos secundarios de factibilidad se consiguieron: reclutamiento (89%), cegamiento (98%), y objetivo de la flebotomía (7,6 ± 1,9 mL/kg). Los cirujanos que fueron cegados percibieron que la resección fue más fácil con la HP (52% versus 32%) y acertaron el uso de HP con una exactitud del 65%. No hubo diferencia significativa en las complicaciones globales (32% versus 48%), complicaciones mayores y transfusión. Entre aquellos pacientes de alto riesgo, la trasfusión se realizó en un 13% versus 33% (P = 0,33). CONCLUSIÓN: Se cumplieron los objetivos, pero no se identificó diferencia en EBL en este estudio de factibilidad. Ello justifica un ensayo multicéntrico (PRICE-2) con poder estadístico para identificar una diferencia en la transfusión de sangre perioperatoria.

Fine Grained Tensor Network Methods.

We develop a strategy for tensor network algorithms that allows to deal very efficiently with lattices of high connectivity. The basic idea is to fine grain the physical degrees of freedom, i.e., decompose them into more fundamental units which, after a suitable coarse graining, provide the original ones. Thanks to this procedure, the original lattice with high connectivity is transformed by an isometry into a simpler structure, which is easier to simulate via usual tensor network methods. In particular this enables the use of standard schemes to contract infinite 2D tensor networks-such as corner transfer matrix renormalization schemes-which are more involved on complex lattice structures. We prove the validity of our approach by numerically computing the ground-state properties of the ferromagnetic spin-1 transverse-field Ising model on the 2D triangular and 3D stacked triangular lattice, as well as of the hardcore and softcore Bose-Hubbard models on the triangular lattice. Our results are benchmarked against those obtained with other techniques, such as perturbative continuous unitary transformations and graph projected entangled pair states, showing excellent agreement and also improved performance in several regimes.

Haemorrhoidectomy under local anaesthesia versus spinal anaesthesia: a systematic review and meta-analysis.

AIMS: To evaluate comparative outcomes of local anaesthesia (LA) and spinal anaesthesia (SA) in patients undergoing haemorrhoidectomy. METHODS: A systematic online search was conducted using the following databases: PubMed, Scopus, Cochrane Database, The Virtual Health Library, Clinical trials.gov , and Science Direct. Only randomised controlled trials (RCTs) comparing excisional haemorrhoidectomy under LA and SA were included. Post-operative pain score, need for rescue analgesia, urinary retention, headache, rectal bleeding, and operative time were the evaluated outcome parameters. RESULTS: Seven RCTs reporting a total number of 440 patients of whom 222 patients underwent haemorrhoidectomy under LA and 218 patients had the procedure under SA were included. LA was associated with significantly lower post-operative pain at 6 h (mean difference (MD) - 2.25, P = 0.0001) and at 24 h (MD - 0.87, P = 0.0002), need for a rescue analgesia (risk ratio (RR) 0.18, P = 0.002), urinary retention (RR 0.17, P = 0.0001), and headache (RR 0.09, P = 0.0003) compared with SA. However, there was no significant difference in rectal bleeding (RR 0.89, P = 0.70) and operative time (MD 1.15, P = 0.19) between LA and SA. CONCLUSION: Compared with SA, LA may be associated with significantly lower post-operative pain, need for rescue analgesia, urinary retention, and headache making it an attractive choice of anaesthesia in day-case surgery for those who are not either fit for GA or refuse such anaesthetic modality.

Prevalence of Hemoglobinopathies (ß-Thalassemia and Sickle Cell Trait) in the Adult Population of Al Majma'ah, Saudi Arabia.

Despite the high prevalence of hemoglobinopathies in Saudi Arabia, the prevalence data in some regions are lacking. Updating the epidemiological survey of hemoglobinopathies at regular intervals is necessary to develop effective prevention and control strategies. Therefore, the primary aim of this study was to determine the prevalence of selected hemoglobinopathies in Saudi adults attending premarital screening at the King Khaled General Hospital (KKGH), Al Majma'ah, Saudi Arabia. The current retrospective study was approved by the Central Institutional Review Board (IRB) of the Ministry of Health (with central IRB log #2019-0039E) and was carried out at the above hospital. The data of the premarital couples, who attended the premarital screening center at KKGH from 1 October 2016 to 30 September 2019, was included in this study. A cation exchange high performance liquid chromatography (HPLC) system was used for screening of the selected hemoglobinopathies. In total, 3755 cases including 1953 (52.01%) males and 1802 (47.99%) females, were screened for hemoglobinopathies. Abnormal hemoglobin (Hb) fractions were observed in 38 (1.01%) cases. The prevalence of ß-thalassemia (ß-thal) trait was 0.69% (26/3755) and that of sickle cell trait 0.32% (12/3755). Our results showed that the prevalence of ß-thal trait is higher than that of sickle cell trait in the adult population of Al Majma'ah. Further comprehensive programs should be carried out to determine the prevalence of hemoglobinopathies in various provinces and cities of Saudi Arabia and other countries. This will help to maintain the updated records of the disease incidence for improving the control measures.

Genetic structure of Iranian indigenous sheep breeds: insights for conservation.

Genetic structure and genetic diversity levels of indigenous Iranian sheep breeds are not clear, despite the interest this region has in itself as an important center for domestication of livestock. Early population genetic studies have reported high levels of diversity among Iranian sheep breeds until recently, when high admixture levels and genetic homogeneity have been detected. The rapid reduction of diversity observed in Iranian breeds might be due to an increasing trend of intensive crossbreeding practices or even total replacement of native breeds by highly specialized and productive ones. From a conservative perspective, this situation is highly concerning; thus, it might be wise to consider a conservation program in Iran to preserve the original genetic diversity in native sheep breeds. In this study, a total of 1065 animals with the purest morphological features representing 24 Iranian indigenous sheep breeds were sampled, corresponding to ancestral breed diversity. These samples were genotyped for 17 microsatellite loci in order to (1) determine the native ancestral diversity of Iranian breeds, (2) define the degree of genetic relationship among studied breeds, and (3) assess conservation priorities among defined groups. Our results showed no recent loss of diversity, but high genetic diversity levels for indigenous sheep breeds in Iran. Indeed, the analysis of conservation priorities pointed out the importance of 8 breeds for maintaining Iranian sheep breeds' maximum genetic diversity. Thus, under a genetic perspective, these 8 breeds should be the ones included into conservation programs for restocking endangered areas.

Out of Southern East Asia of the Brown Rat Revealed by Large-Scale Genome Sequencing.

The geographic origin and migration of the brown rat (Rattus norvegicus) remain subjects of considerable debate. In this study, we sequenced whole genomes of 110 wild brown rats with a diverse world-wide representation. We reveal that brown rats migrated out of southern East Asia, rather than northern Asia as formerly suggested, into the Middle East and then to Europe and Africa, thousands of years ago. Comparison of genomes from different geographical populations reveals that many genes involved in the immune system experienced positive selection in the wild brown rat.

Effect of fitness on cardiac structure and function in overweight and obesity (the FATCOR study).

BACKGROUND AND AIMS: Obesity is associated with reduced left ventricular (LV) systolic myocardial function. We aimed to explore by means of a cross-sectional study whether this effect is offset in the presence of good fitness. METHODS AND RESULTS: We studied clinical and echocardiographic data from 469 overweight (body mass index [BMI] >27 kg/m2) and obese (BMI ≥30 kg/m2) women and men without known cardiovascular (CV) disease in the FAT associated CardiOvasculaR dysfunction (FATCOR) study. The participants were grouped according to obesity and sex- and age adjusted peak oxygen uptake, obtained by ergospirometry. LV systolic myocardial function was assessed by peak systolic global longitudinal strain (GLS) measured by speckle tracking echocardiography. The association of fitness with GLS was tested in logistic regression analyses and reported as odds ratio (OR) with 95% confidence interval (CI). In the total study population, participants were 47 years old, 60% were women, and mean BMI was 32.0 kg/m2. GLS did not differ between fit and unfit subjects within the overweight and obese groups (both p > 0.05), but the overweight fit group had higher GLS (more negative value) compared to the obese unfit group (-20.1 ± 2.6 vs. -19.0 ± 3.0, p < 0.05). In obese subjects, fitness was associated with higher GLS (OR 0.88 [95% CI 0.79-0.99, p < 0.05) in multivariable logistic regression analysis, independent of significant associations with higher arterial stiffness and lower fat percentage (all p < 0.05). In the overweight group, fitness was not significantly associated with GLS. CONCLUSION: In obesity, fitness was independently associated with higher GLS, while no association was found in overweight. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.govNCT02805478.

Detection of breed-specific copy number variations in domestic chicken genome.

Copy number variations (CNVs) are important large-scale variants. They are widespread in the genome and may contribute to phenotypic variation. Detection and characterization of CNVs can provide new insights into the genetic basis of important traits. Here, we perform whole-genome short read sequence analysis to identify CNVs in two indigenous and commercial chicken breeds to evaluate the impact of the identified CNVs on breed-specific traits. After filtration, a total of 12 955 CNVs spanning (on average) about 9.42% of the chicken genome were found that made up 5467 CNV regions (CNVRs). Chicken quantitative trait loci (QTL) datasets and Ensembl gene annotations were used as resources for the estimation of potential phenotypic effects of our CNVRs on breed-specific traits. In total, 34% of our detected CNVRs were also detected in earlier CNV studies. These CNVRs partly overlap several previously reported QTL and gene ontology terms associated with some important traits, including shank length QTL in Creeper-specific CNVRs and body weight and egg production characteristics, as well as muscle and body organ growth, in the Arian commercial breed. Our findings provide new insights into the genomic structure of the chicken genome for an improved understanding of the potential roles of CNVRs in differentiating between breeds or lines.

Sex differences in subclinical cardiac disease in overweight and obesity (the FATCOR study).

BACKGROUND AND AIMS: Subclinical cardiac disease, like abnormal left ventricular (LV) geometry or left atrial (LA) dilatation, is common in obesity. Less is known about sex differences in the prevalence and type of subclinical cardiac disease in obesity. METHODS AND RESULTS: Clinical and echocardiographic data from 581 women and men without established cardiovascular disease and body mass index (BMI) > 27.0 kg/m2 participating in the FAT associated CardiOvasculaR dysfunction (FATCOR) study was analyzed. LA dilatation was recognized as LA volume indexed for height2 ≥16.5 ml/m2 in women and ≥18.5 ml/m2 in men, and abnormal LV geometry as LV hypertrophy and/or increased relative wall thickness. On average, the participants were 48 years old, 60% women and mean BMI was 32.1 kg/m2. Overall, the prevalence of subclinical cardiac disease was higher in women than men (77% vs. 62%, p < 0.001). Women had a higher prevalence of LA dilatation than men (74% vs. 56%, p < 0.001), while men had a higher prevalence of abnormal LV geometry (30% vs. 21%, p = 0.011). After adjusting for confounders in multivariable logistic regression analysis, female sex was associated with a 2-fold higher risk of subclinical cardiac disease, in particular LA dilatation (confidence interval [CI] 1.67-3.49, p < 0.001), while male sex was associated with a 2-fold higher risk of abnormal LV geometry (CI 1.30-3.01, p = 0.001). CONCLUSION: The majority of overweight and obese participants in the FATCOR study had subclinical cardiac disease, which may contribute to the impaired prognosis observed in obesity. Women had a higher prevalence of subclinical cardiac disease than men. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.govNCT02805478.