Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions.

Background: Severe malaria is associated with impaired nitric oxide (NO) synthase (NOS)-dependent vasodilation, and reversal of this deficit improves survival in murine models. Malaria might have selected for genetic polymorphisms that increase endothelial NO signaling and now contribute to heterogeneity in vascular function among humans. One protein potentially selected for is alpha globin, which, in mouse models, interacts with endothelial NOS (eNOS) to negatively regulate NO signaling.

Systematic Review and Meta-Analysis of Endovascular Therapy Effectiveness for Unruptured Saccular Intracranial Aneurysms.

Background: Currently, endovascular treatment of intracranial aneurysms (ICAs) is limited by low complete occlusion rates. The advent of novel endovascular technology has expanded the applicability of endovascular therapy; however, the superiority of novel embolic devices over the traditional Guglielmi detachable coils (GDCs) is still debated. We performed a systematic review of literature that reported Raymond-Roy occlusion classification (RROC) rates of modern endovascular devices to determine their immediate and follow-up occlusion effectiveness for the treatment of unruptured saccular ICAs.

Management of Osteoporosis, Fracture and Falls in People with Multiple Sclerosis: Systematic Review of Guidelines.

People with multiple sclerosis (MS) have a higher prevalence of osteoporosis, falls and fractures. Guidelines for MS populations targeting the management of osteoporosis, fracture and falls risk may help reduce the burden of musculoskeletal disease in this population. We aimed to systematically review current guidelines regarding osteoporosis prevention, screening, diagnosis and management in people with MS.

Integrated genetic profiling of archival pediatric high-grade glial tumors and reassessment with 2021 WHO classification of paediatric CNS tumours.

Though rare, pediatric high-grade gliomas (pHGG) are a leading cause of cancer-related mortality in children. We wanted to determine whether our currently available clinical laboratory methods could better define diagnosis for pHGG that had been archived at our institution for the past 20 years (1998 to 2017). We investigated 33 formalin-fixed paraffin-embedded pHGG using ThermoFisher Oncoscan SNP microarray with somatic mutation analysis, Sanger sequencing, and whole genome sequencing.

Effects of enzyme-based removal of collagen and elastin constituents on the biaxial mechanical responses of porcine atrioventricular heart valve anterior leaflets.

The leaflets of the atrioventricular heart valves (AHVs) regulate the one-directional flow of blood through a coordination of the extracellular matrix components, including the collagen fibers, elastin, and glycosaminoglycans. Dysfunction of the AHVs, such as those caused by unfavorable microstructural remodeling, lead to valvular heart diseases and improper blood flow, which can ultimately cause heart failure. In order to better understand the mechanics and remodeling of the AHV leaflets and how therapeutics can inadvertently cause adverse microstructural changes, a systematic characterization of the role of each constituent in the biomechanical properties is appropriate.

Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers.

Purpose: Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging.

Occurrences of thermophilic Campylobacter in pigs slaughtered at Morogoro slaughter slabs, Tanzania.

Occurrences of thermophlic Campylobacter in pigs and pig carcasses was investigated in a cross-sectional study that was carried out in three selected slaughter slabs in Morogoro municipality, Tanzania. Before sampling, the slab hygiene, slaughter, carcass dressing, and meat handling was assessed. Fecal samples were collected from 66 slaughter pigs at the kill floor.

DNA polymorphisms and renal disease: a critical appraisal of studies presented at the annual ERA/EDTA and ASN conferences in 2004 and 2005.

Countless studies try to associate single DNA polymorphisms with disease, while there is growing evidence that many of these studies are of flawed design. Based on the Journal of the American Society of Nephrology (JASN) requirements for gene-disease association study quality, the abstracts presented at the two major international nephrology conferences in 2004 and 2005 organized by the European Renal Association/European Dialysis and Transplantation Association (ERA/EDTA) and American Society of Nephrology (ASN) are analysed to show how this problem affects nephrology. Over time, average sample numbers have increased, as have the numbers of abstracts compliant with the JASN requirements.

Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury.

Autophagy is known to be a feature of cardiomyopathies and chronic ischaemia. Here we demonstrate that autophagy is also induced by a single cycle of ischaemia/reperfusion (I/R in neonatal and adult rat cardiac myocytes). Consistent with the critical role for Beclin1 in autophagocytosis, reduction of Beclin1 expression in cardiac myocytes by RNAi reduces I/R-induced autophagy and this is associated with enhanced cell survival.

Heterogeneity of neural tube defects in Europe: the significance of site of defect and presence of other major anomalies in relation to geographic differences in prevalence.

In the period 1980-1987, neural tube defects were two to three times more prevalent in populations covered by EUROCAT registries in the United Kingdom and Ireland (UKI) than in Continental Europe and Malta (CEM). 1864 NTD cases in a total population of 580,000 births in UKI and 455 cases in a population of 380,000 births in CEM were analysed to find if there were differences in the ratio of prevalence rates between UKI and CEM according to site of the defect and association with non-central nervous system (CNS) anomalies. The prevalence rate ratio was high for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida, and low for encephalocele, lower spina bifida, and anencephaly without other neural tube defects.

The impact of supportive intervention after second trimester termination of pregnancy for fetal abnormality.

The reactions of women who had had a termination of pregnancy for fetal abnormality in the second trimester have been studied retrospectively using a semi-structured questionnaire. The severity of the grief reaction was measured and the outcome at 6 months was compared with the findings from a previous study in South Wales which had led to the introduction of skilled support from genetic fieldworkers and formal genetic counselling after the termination. Of the 69 women interviewed, 55 (80 per cent) experienced an acute grief reaction and 17 (25 per cent) had not resolved their grief 6 months after the termination, compared with 37 (77 per cent) and 22 (46 per cent) out of 48 respectively in the previous study.

Factors affecting employability among young adults with spina bifida and hydrocephalus.

A sample of 98 young adults with spina bifida were interviewed. None had severe learning difficulties. All were resident in S.

Maternal serum alpha-fetoprotein screening for open neural tube defects in twin pregnancies.

Data on maternal serum alpha-fetoprotein (AFP) levels at 13-24 weeks' gestation in 46 twin pregnancies with open neural tube defects (22 with anencephaly, 24 with open spina bifida) and 169 unaffected twins were used to estimate the detection and false-positive rates associated with different cut-off levels. Using the conventional cut-off level of 2.5 multiples of the median (MoM) for unaffected singleton pregnancies of the same gestation and laboratory, the detection rate in twins was 99 per cent for anencephaly and 89 per cent for open spina bifida, with a false-positive rate of 30 per cent.

Relationship between fetal adrenal morphology and anterior pituitary function.

A comparative study of adrenal morphology between normal fetuses and those with anencephaly or congenital adrenal hyperplasia (CAH) was performed in order to examine the hypothesis that fetal adrenal mass and structure are adrenocorticotrophin (ACTH)-dependent throughout gestation. Combined adrenal weight in 102 normal fetuses was used to establish a reference range for the gestational ages of 15-27 weeks. During this period, mean adrenal weight showed a 6-fold linear increase.

Comparison of Corynebacterium parvum and Bordetella pertussis with Freund's complete adjuvant as immunopotentiators for beta-human chorionic gonadotropin linked to an atoxic fragment of tetanus toxin.

Corynebacterium parvum and Bordetella pertussis were compared with Freund's complete adjuvant (FCA) for their abilities to potentiate the immune response to haptenic beta-human chorionic gonadotropin covalently coupled to an atoxic 54,000-molecular-weight fragment of tetanus toxin (beta-hCG-TTII). The ability of each adjuvant to enhance production of antibodies to hCG in rabbits was measured by 125I-hCG radioimmunoassay. At sera dilutions of 1:10,000, analysis of variance for the 8-week postimmunization course showed that the mean 125I-hCG binding capacities of the C.

Interstitial deletion of 17p11.2: case report and review.

A child with mental retardation and multiple congenital abnormalities, including brachycephaly, an unusual facies, brachydactyly, clinodactyly and bilateral talipes valgus, was found to have a small interstitial deletion of the short arm of chromosome 17. The clinical features and cytogenetic observations are compared with those in previously reported cases.

Medical and social service provision for families of children with NTD.

The supply of services to the families of children with spina bifida participating in the South Wales longitudinal study was reviewed. Initially general information and contact with other mothers were the commonest needs; as the children grew older the need for practical, material and financial help took priority. Parents were, generally, very satisfied with support provided by hospital staff with whom they had frequent, regular contact.

Prenatal diagnosis of congenital adrenal hyperplasia: reliability of amniotic fluid steroid analysis.

The concentration of 170H-progesterone was measured in amniotic fluid samples collected from 55 mothers who had previously had a child with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. In eight pregnancies the levels of 170H-progesterone were raised; the parents elected to terminate in four and examinations of the fetus confirmed the diagnosis of congenital adrenal hyperplasia. In each case, the affected sib was a salt loser.

Homozygous paracentric inversion 12 in a mentally retarded boy: a case report and review of the literature.

A mentally retarded male was found to be homozygous for a paracentric inversion of the long arm of chromosome 12(inv(12)(q21.1q23.2].

Amniotic fluid steroid levels and fetal adrenal weight in congenital adrenal hyperplasia.

The concentration of 17-OH-progesterone was determined in second trimester amniotic fluid collected from 58 pregnancies at risk for fetal 21-hydroxylase deficiency. The prediction was incorrect in 1 male nonsalt-loser who had an increased plasma 17-OH-progesterone concentration at 3 months of age. All 11 infants predicted to be affected were salt-losers.

The fathers of children with spina bifida.

Health, employment, marital outcome and involvement with the child, of fathers with spina bifida (IF) and with "normal" controls (CF), were analysed at intervals from birth to 18 years. By 10 years IF had poorer reported health than did CF. By 18 years IF had more specific health problems, many being psychosomatic in nature, than CF or index and control mothers.

The apparently declining prevalence of neural tube defect in two counties in South Wales over three decades illustrating the need for continuing action and vigilance.

Neural tube defects, anencephaly and spina bifida (including encephalocele) have been the major malformation problem in South Wales. Births of affected offspring of residents of Mid and South Glamorgan between 1956 and June 1985 were ascertained from various sources. To these were added terminations following prenatal diagnosis and affected spontaneous abortions of 16 weeks gestation or more since 1973.