Traces of Human-Mediated Selection in the Gene Pool of Red Deer Populations.

In this study, we analysed the effect of human-mediated selection on the gene pool of wild and farmed red deer populations based on genotyping-by-sequencing data. The farmed red deer sample covered populations spread across seven countries and two continents (France, Germany, Hungary, Latvia, New Zealand, Poland, and Slovakia). The Slovak and Spain wild red deer populations (the latter one in a large game estate) were used as control outgroups. The gene flow intensity, relationship and admixture among populations were tested by the Bayesian approach and discriminant analysis of principal components (DAPC). The highest gene diversity (He = 0.19) and the lowest genomic inbreeding (FHOM = 0.04) found in Slovak wild population confirmed our hypothesis that artificial selection accompanied by bottlenecks has led to the increase in overall genomic homozygosity. The Bayesian approach and DAPC consistently identified three separate genetic groups. As expected, the farmed populations were clustered together, while the Slovak and Spanish populations formed two separate clusters. Identified traces of genetic admixture in the gene pool of farmed populations reflected a strong contemporary migration rate between them. This study suggests that even if the history of deer farming has been shorter than traditional livestock species, it may leave significant traces in the genome structure.

Efficiency of genotyping by sequencing in inferring genomic relatedness and molecular insights into fat tail selection in Tunisian sheep.

In developing countries, the use of simple and cost-efficient molecular technology is crucial for genetic characterization of local animal resources and better development of conservation strategies. The genotyping by sequencing (GBS) technique, also called restriction enzyme- reduced representational sequencing, is an efficient, cost-effective method for simultaneous discovery and genotyping of many markers. In the present study, we applied a two-enzyme GBS protocol (PstI/MspI) to discover and genotype SNP markers among 197 Tunisian sheep samples. A total of 100 333 bi-allelic SNPs were discovered and genotyped with an SNP call rate of 0.69 and mean sample depth 3.33. The genomic relatedness between 183 samples grouped the samples perfectly to their populations and pointed out a high genetic relatedness of inbred subpopulation reflecting the current adopted reproductive strategies. The genome-wide association study contrasting fat vs. thin-tailed breeds detected 41 significant variants including a peak positioned on OAR20. We identified FOXC1, GMDS, VEGFA, OXCT1, VRTN and BMP2 as the most promising for sheep tail-type trait. The GBS data have been useful to assess the population structure and improve our understanding of the genomic architecture of distinctive characteristics shaped by selection pressure in local sheep breeds. This study successfully investigates a cost-efficient method to discover genotypes, assign populations and understand insights into sheep adaptation to arid area. GBS could be of potential utility in livestock species in developing/emerging countries.

Preparatory stage of interventional extracardiac Fontan.

The extracardiac Fontan can be completed as an interventional procedure when the preparatory stage for Fontan completion is performed at the time of the bidirectional Glenn operation. In this video tutorial, we present the technique for the preparatory stage of an interventional extracardiac Fontan. The interventional aspect offers the advantage of avoiding a redo sternotomy, which involves the risk of cardiac injury, injury to the mediastinal collaterals due to the single-ventricle physiology, the acquired deranged coagulation that may incur morbidity associated with sternal re-entry, and the problems pertinent to cardiopulmonary bypass and/or cardioplegic arrest in this subset of patients.

Tetralogy of Fallot with pulmonary atresia and aortopulmonary window may mimic common arterial trunk.

Tetralogy of Fallot with pulmonary atresia is a group of congenital cardiac malformations, which is defined by the absence of luminal continuity between both ventricles and the pulmonary artery, and an interventricular communication. Pulmonary arterial supply in patients with tetralogy of Fallot with pulmonary atresia can be via the arterial duct or from collateral arteries arising directly or indirectly from the aorta (systemic-to-pulmonary artery collaterals), or rarely both. The rarest sources of pulmonary blood flow are aortopulmonary window and fistulous communication with the coronary artery.Herein, we describe an outflow tract malformation, tetralogy of Fallot with pulmonary atresia and aortopulmonary window, which was misdiagnosed as common arterial trunk. We emphasise the morphological differences.

Cardiovascular Safety and Sclerostin Inhibition.

Sclerostin, which is primarily produced by the osteocytes, inhibits the canonical Wnt pathway and thereby the osteoblasts and stimulates RANKL release by the osteocytes and thereby osteoclast recruitment. Inhibition of sclerostin therefore causes stimulation of bone formation and inhibition of resorption. In clinical trials, romosozumab, an antibody against sclerostin, increases bone mineral density and reduces the risk of fractures compared with placebo and alendronate. The cardiovascular safety of romosozumab was adjudicated in 2 large clinical osteoporosis trials in postmenopausal women. Compared with placebo, the incidence of cardiovascular events was similar in the 2 treatment groups. Compared with alendronate, the incidence of serious cardiovascular events was higher in women treated with romosozumab. The incidence of serious cardiovascular adverse events was low and post hoc analyses should therefore be interpreted with caution; however, the relative risk seemed unaffected by preexisting cardiovascular disease or risk factors. Sclerostin is expressed in the vasculature, predominantly in vascular smooth muscle cells in the media. However, preclinical and genetic studies have not demonstrated any increased cardiovascular risk with continuously low sclerostin levels or inhibition of sclerostin. Furthermore, no potential mechanisms for such an effect have been identified. In conclusion, while there is no preclinical or genetic evidence of a harmful effect of sclerostin inhibition on cardiovascular safety, the evidence from the large clinical trials in postmenopausal women is conflicting. Romosozumab should therefore be used for the treatment of postmenopausal women with osteoporosis at high risk of fracture after careful consideration of the cardiovascular risk and the balance between benefits and risks.

Valuation of Life With Disability: An International Comparison Study in Vietnam, Peru, and Haiti.

The authors measured perceived quality of life for 4 disabilities among 450 adults in 3 resource-limited countries, measuring mean utilities using time trade-off, and surveying participants on 35 sociocultural characteristics to compare utilities for disabilities by country and examine associated sociocultural characteristics. Mean utilities were >0 for mild and moderate, but <0 for severe and profound. Utilities differed across countries (P = .007, .000, .017, .000 for mild, moderate, severe, profound, respectively). Vietnamese utilities correlated with residence (P = .03, moderate), education (P = .03, severe), and number of children (P = .03, moderate). Peruvian utilities correlated with education (P = .05, mild; P = .05, severe), experience with disability (P = .001, mild), gender (P = .04, moderate; P = .03, profound), number of hospitalizations (P = .04, severe). In Haiti, the only correlate was rejection (P = .02, moderate). Culture-specific variables differentially shape perceptions of disability in developing countries, thereby affecting cost-effectiveness calculations. Given substantially negative perceptions, reducing major disability would improve cost-effectiveness of health-policy decisions more than reducing mortality.

Embryological basis of coarctation in cervical aortic arch: Ductus caroticus anomaly

Coarctation of the cervical aortic arch (CAA), though rare, is a clinical entity of embryological significance. Based on Rathke's aortic arch diagrams and Edward's concept of functioning double aortic arch, we are postulating that the coarctation in a CAA occurs due to partial involution of the dorsal aorta developed from the "ductus caroticus". Hence coarctation in CAA should be classified as a "clinically significant aortic arch anomaly of ductus caroticus origin". Conversely, location of coarctation in CAA substantiates the theory that embryogenesis of CAA is due to aortic arch development from the third or second branchial arch vessel, rather than the usual fourth arch vessel

No disponible

Anatomic classification of the right aortic arch.

The term right aortic arch is used for an aorta that arches over the right bronchus. Right aortic arch was classified into two types by Felson et al, based on branching patterns, with a proposed embryological explanation, and into three types by Shuford et al. Other anatomical variants of right aortic arch were described later, including isolated left brachiocephalic artery and aberrant left brachiocephalic artery. We have classified right aortic arch anatomy into 10 variants, supported by radiological evidence, and with reference to possible embryology. This classification will help in understanding the morphological basis for the formation of different types of right aortic arch and the course of the recurrent laryngeal nerve in such cases.

The aortic arch in tetralogy of Fallot: types of branching and clinical implications.

INTRODUCTION: Tetralogy of Fallot is the most common form of cyanotic CHD, with an incidence of 421 cases per million live births, constituting around 10% of CHD. Variations in aortic arch anatomy associated with tetralogy of Fallot, other than the incidence of right aortic arch (13-34%), are not frequently reported. A comprehensive analysis of a large number of tetralogy of Fallot cases is required to arrive at a compendious description of aortic arch anatomy. MATERIALS AND METHODS: All patients with a diagnosis of tetralogy of Fallot who had CT or MRI either pre or post procedures between 1 January 2010 and 31 December 2019 at our hospital were included in the study. Using radiology consultants' reports and analysis of individual images, we identified the various morphological patterns of aortic arches prevalent in these patients. RESULT: Out of 2684 patients who met the inclusion criteria, 1983 patients had left aortic arch (73.9%), 688 patients had right aortic arch (25.7%), four patients had cervical aortic arch (0.15%), eight patients had double aortic arch (0.3%), one patient had an aorto-pulmonary window (0.04%), and none of the patients had interrupted aortic arch. Sub-classification and clinical implications of the arch variations are described. CONCLUSION: Up to 10% of tetralogy of Fallot patients may have significant anatomical variations of aortic arch that would necessitate changes or additional steps in their surgical or interventional procedures.

Genetic Connectedness Between Norwegian White Sheep and New Zealand Composite Sheep Populations With Similar Development History.

The Norwegian White sheep (NWS) and New Zealand Terminal Sire Composite (NZC) sheep breeds have been developed based on crossing of multiple breeds, mainly of Northern European origin. A close genetic relationship between these populations could enable across-country genomic evaluations. The main objectives of this study were to assess the genetic connectedness between Norwegian and New Zealand sheep populations and estimate numerous genetic diversity metrics for these two populations. A total of 792 NWS and 16,912 NZC animals were genotyped using a high-density Illumina SNP chip panel (∼606K SNPs). The NZC animals were grouped based on their breed composition as: Finn, Lamb Supreme, Primera, Texel, "Other Dual Purpose", and "Other Terminal Sire". The average level of linkage disequilibrium ranged from 0.156 (for Primera) to 0.231 (for Finn). The lowest consistency of gametic phase was estimated between NWS and Finn (0.397), and between NWS and Texel (0.443), respectively. Similar consistency of gametic phase was estimated between NWS and the other NZC populations (∼ 0.52). For all composite sheep populations analyzed in this study, the majority of runs of homozygosity (ROH) segments identified had short length (<2,500 kb), indicating ancient (instead of recent) inbreeding. The variation in the number of ROH segments observed in the NWS was similar to the variation observed in Primera and Lamb Supreme. There was no clear discrimination between NWS and NZC based on the first few principal components. In addition, based on admixture analyses, there seems to be a significant overlap of the ancestral populations that contributed to the development of both NWS and NZC. There were no evident signatures of selection in these populations, which might be due to recent crossbreeding. In conclusion, the NWS composite breed was shown to be moderately related to NZC populations, especially Primera and Lamb Supreme. The findings reported here indicate a promising opportunity for collaborative genomic analyses involving NWS and NZC sheep populations.

Cardiac Perivascular Epithelioid Cell Tumor: Report of a Child and Review of the Literature.

Cardiac tumors presenting as mediastinal masses in childhood are rare. This report describes the case of a 6-year-old girl who presented to us after a failed attempt at resection of a mass arising from the left atrial appendage. Computed tomography-guided biopsy suggested a perivascular epithelioid cell tumor (PEComa). Sirolimus was started in order to reduce the mass size. She subsequently underwent resection of the mass by midline sternotomy approach and cardiopulmonary bypass. Recovery was uneventful and the child is doing well at two-year follow-up. Contemporary literature is reviewed. Only seven cases, including two children, with mediastinal PEComa have been reported. Pathology and treatment options are discussed.

Profusion of G-quadruplexes on both subunits of metazoan ribosomes.

Mammalian and bird ribosomes are nearly twice the mass of prokaryotic ribosomes in part because of their extraordinarily long rRNA tentacles. Human rRNA tentacles are not fully observable in current three-dimensional structures and their conformations remain to be fully resolved. In previous work we identified sequences that favor G-quadruplexes in silico and in vitro in rRNA tentacles of the human large ribosomal subunit. We demonstrated by experiment that these sequences form G-quadruplexes in vitro. Here, using a more recent motif definition, we report additional G-quadruplex sequences on surfaces of both subunits of the human ribosome. The revised sequence definition reveals expansive arrays of potential G-quadruplex sequences on LSU tentacles. In addition, we demonstrate by a variety of experimental methods that fragments of the small subunit rRNA form G-quadruplexes in vitro. Prior to this report rRNA sequences that form G-quadruplexes were confined to the large ribosomal subunit. Our combined results indicate that the surface of the assembled human ribosome contains numerous sequences capable of forming G-quadruplexes on both ribosomal subunits. The data suggest conversion between duplexes and G-quadruplexes in response to association with proteins, ions, or other RNAs. In some systems it seems likely that the integrated population of RNA G-quadruplexes may be dominated by rRNA, which is the most abundant cellular RNA.

Communal metabolism by Methylococcaceae and Methylophilaceae is driving rapid aerobic methane oxidation in sediments of a shallow seep near Elba, Italy.

The release of abiotic methane from marine seeps into the atmosphere is a major source of this potent greenhouse gas. Methanotrophic microorganisms in methane seeps use methane as carbon and energy source, thus significantly mitigating global methane emissions. Here, we investigated microbial methane oxidation at the sediment-water interface of a shallow marine methane seep. Metagenomics and metaproteomics, combined with 13 C-methane stable isotope probing, demonstrated that various members of the gammaproteobacterial family Methylococcaceae were the key players for methane oxidation, catalysing the first reaction step to methanol. We observed a transfer of carbon to methanol-oxidizing methylotrophs of the betaproteobacterial family Methylophilaceae, suggesting an interaction between methanotrophic and methylotrophic microorganisms that allowed for rapid methane oxidation. From our microcosms, we estimated methane oxidation rates of up to 871 nmol of methane per gram sediment per day. This implies that more than 50% of methane at the seep is removed by microbial oxidation at the sediment-water interface, based on previously reported in situ methane fluxes. The organic carbon produced was further assimilated by different heterotrophic microbes, demonstrating that the methane-oxidizing community supported a complex trophic network. Our results provide valuable eco-physiological insights into this specialized microbial community performing an ecosystem function of global relevance.

Valuation of Quality of Life in Pediatric Disability in a Developing Country.

This article assessed how Indian providers and mothers value quality of life in pediatric disabilities, hypothesizing lower values with increasing disability, lower values among providers than mothers, and lower values among mothers with versus mothers without a disabled child. We asked 175 participants: "If born tomorrow, how many years of a disabled life ( y) would you trade to avoid life-long disability" for 4 hypothetical disabilities, calculating "utility" scores as: (life span - y) / life span, where death = 0 and full life without disability = 1. Providers' utilities were 0.67 (mild), 0.18 (moderate), -0.70 (severe), and -0.60 (profound); 0.67, 0, -0.77, and -0.88 for mothers without and 0.38, -0.49, -0.86, and -0.87 for mothers with a disabled child. Mothers without reported lower utilities than providers (severe and profound disability [ P ≤ .03]), and higher utilities than mothers (for mild and moderate disability [ P < .001]). Major disability is valued as a fate worse than death in India.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

This corrects the article DOI: 10.1038/pr.2014.47.

Where you Live in Nova Scotia Can Significantly Impact Your Access to Lifesaving Cardiac Care: Access to Invasive Care Influences Survival.

BACKGROUND: Invasive cardiac care is the preferred method of treatment for patients with acute coronary syndromes (ACS) complicated by cardiogenic shock (CS). In Nova Scotia, invasive cardiac care is only available in Halifax at the Queen Elizabeth II Health Sciences Centre (QEII-HSC). METHODS: All consecutive patients diagnosed with ACS and CS in 2009-2013 in Nova Scotia were included. Data were obtained from the clinical database of Cardiovascular Health Nova Scotia. The primary outcome was in-hospital mortality. RESULTS: A total of 418 patients with ACS and CS were admitted to the hospital. Access to invasive care was limited to 309 (73.9%) of these patients. For those who presented elsewhere in the province, 64.2% were transferred to the QEII-HSC. The mortality rate among the 309 patients with access to invasive care was significantly lower than that among the 109 patients who did not have access (41.7% vs 83.5%; P < 0.0001). Unadjusted mortality was lowest among patients undergoing primary percutaneous coronary intervention (33.1%). After adjustment for clinical differences, access to cardiac catheterization remained an independent predictor of survival (odds ratio, 0.2; 95% confidence interval, 0.11-0.36). Heat map analysis revealed that access was lowest in regions furthest from Halifax. CONCLUSIONS: ACS complicated by CS has a high mortality rate. We demonstrate that access to health care centres offering cardiac catheterization is independently associated with survival, and public health initiatives that improve access should be considered. Patients presenting furthest from Halifax were the least likely to be transferred, suggesting that geography remains an important barrier to livesaving care.

Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns.

OBJECTIVE: To determine the association of antenatal magnesium sulfate with cerebellar hemorrhage in a prospective cohort of premature newborns evaluated by magnetic resonance imaging (MRI). STUDY DESIGN: Cross-sectional analysis of baseline characteristics from a prospective cohort of preterm newborns (<33 weeks gestation) evaluated with 3T-MRI shortly after birth. Exclusion criteria were clinical evidence of a congenital syndrome, congenital infection, or clinical status too unstable for transport to MRI. Antenatal magnesium sulfate exposure was abstracted from the medical records and the indication was classified as obstetric or neuroprotection. Two pediatric neuroradiologists, blinded to the clinical history, scored axial T2-weighted and iron susceptibility MRI sequences for cerebellar hemorrhage. The association of antenatal magnesium sulfate with cerebellar hemorrhage was evaluated using multivariable logistic regression, adjusting for postmenstrual age at MRI and known predictors of cerebellar hemorrhage. RESULTS: Cerebellar hemorrhage was present in 27 of 73 newborns (37%) imaged at a mean ± SD postmenstrual age of 32.4 ± 2 weeks. Antenatal magnesium sulfate exposure was associated with a significantly reduced risk of cerebellar hemorrhage. Adjusting for postmenstrual age at MRI, and predictors of cerebellar hemorrhage, antenatal magnesium sulfate was independently associated in our cohort with decreased cerebellar hemorrhage (OR, 0.18; 95% CI, 0.049-0.65; P = .009). CONCLUSION: Antenatal magnesium sulfate exposure is independently associated with a decreased risk of MRI-detected cerebellar hemorrhage in premature newborns, which could explain some of the reported neuroprotective effects of magnesium sulfate.

Preoperative Sildenafil administration in children undergoing cardiac surgery: a randomized controlled preconditioning study.

OBJECTIVES: Sildenafil has strong cardiac preconditioning properties in animal studies and has a safe side-effect profile in children. Therefore, we evaluated the application of Sildenafil preconditioning to reduce myocardial ischaemia/reperfusion injury in children undergoing surgical ventricular septal defect (VSD) closure. METHODS: This is a randomized, double-blind study. Children (1-17 years) undergoing VSD closure were randomized into three groups: placebo (Control group), preconditioning with 0.06 mg/kg (Sild-L group) and 0.6 mg/kg Sildenafil (Sild-H group). PRIMARY ENDPOINT: troponin release. CK-MB, Troponin I, inflammatory response (IL-6 and TNF-α), bypass and ventilation weaning times, inotropy score and echocardiographic function were assessed. Data expressed as median (range), and a value of P < 0.05 was considered significant. RESULTS: Thirty-nine patients were studied (13/group). Aortic cross-clamp time was similar [27 (18-85) and 27 (12-39) min] in the Control and Sild-L groups, respectively, but significantly longer [39 (20-96) min] in the Sild-H group when compared with the Control group. Area under the curve of CK-MB release was 1105 (620-1855) h ng/ml in the Control group, 1672 (564-2767) h ng/ml in the Sild-L group and was significantly higher in the Sild-H group [1695 (1252-3377) h ng/ml] when compared with the Control group. There were no significant differences in inflammatory response markers, cardiopulmonary bypass and ventilation weaning times, inotropy scores and echocardiographic function between the groups. CONCLUSIONS: In this small study, Sildenafil failed to reduce myocardial injury in children undergoing cardiac surgery, nor does it alter cardiac function, inotropic needs or postoperative course. A subclinical increase in cardiac enzyme release after Sildenafil preconditioning cannot be excluded. CLINICAL TRIALS REGISTRY: CTRI/2014/03/004468.

RECURRENT MYXOMA ARISING FROM MULTIPLE CARDIAC CHAMBERS WITH SYSTEMIC EMBOLIZATION:A CASE REPORT.

Myxomas occupying multiple chambers of the heart are extremely rare, being more common in familial cases. Recurrence of these tumors after surgical excision is also a rare condition, observed in about 3% of patients in sporadic cases. Systemic embolization especially to the brain is one of the common presentations of cardiac myxomas apart from intracardiac obstruction and systemic symptoms. We report an adolescent girl presenting with recurrent myxoma arising from multiple cardiac chambers with systemic embolization. As a diagnostic and preventive measure of recurrence and chronic systemic embolization, we recommend a regular follow up of such patients with echocardiographic evaluation following surgical resection.

Care practices and traditional beliefs related to neonatal jaundice in northern Vietnam: a population-based, cross-sectional descriptive study.

BACKGROUND: The National Hospital of Pediatrics in Vietnam performed >200 exchange transfusions annually (2006-08), often on infants presenting encephalopathic from lower-level hospitals. As factors delaying care-seeking are not known, we sought to study care practices and traditional beliefs relating to neonatal jaundice in northern Vietnam. METHODS: We conducted a prospective, cross-sectional, population-based, descriptive study from November 2008 through February 2010. We prospectively identified mothers of newborns through an on-going regional cohort study. Trained research assistants administered a 78-item questionnaire to mothers during home visits 14-28 days after birth except those we could not contact or whose babies remained hospitalized at 28 days. RESULTS: We enrolled 979 mothers; 99% delivered at a health facility. Infants were discharged at a median age of 1.35 days. Only 11% received jaundice education; only 27% thought jaundice could be harmful. During the first week, 77% of newborns were kept in dark rooms. Only 2.5% had routine follow-up before 14 days. Among 118 mothers who were worried by their infant's jaundice but did not seek care, 40% held non-medical beliefs about its cause or used traditional therapies instead of seeking care. Phototherapy was uncommon: 6 (0.6%) were treated before discharge and 3 (0.3%) on readmission. However, there were no exchange transfusions, kernicterus cases, or deaths. CONCLUSIONS: Early discharge without follow-up, low maternal knowledge, cultural practices, and use of traditional treatments may limit or delay detection or care-seeking for jaundice. However, in spite of the high prevalence of these practices and the low frequency of treatment, no bad outcomes were seen in this study of nearly 1,000 newborns.