Identification and understanding of pre-term birth at Kintampo Municipal Hospital: a qualitative cross-sectional study

Up to 42% of nearly 10 million under five deaths occur in neonates with prematurity being a principal cause. This paper presents the outcome of a cross sectional qualitative study conducted among 14 hospital staff engaged in infant care in Kintampo, Ghana. Confidential interviews were used to evaluate their knowledge and practice of preterm care. Critical steps in caring for normal and preterm infants were ranked as adequate, satisfactory or inadequate if 75% or more, 50% to 74%, or less than 50% of the health workers completed them respectively. For term infants, adequate care was provided in terms of cleaning and wrapping, weighing, and initiating early feeds. Knowledge and practice were inadequate in relation to preterm care. Educational interventions emphasizing preterm care are recommended as an essential package for rural health workers. A newborn assessment tool was designed to address the gap in data collection identified during the study.     

Human sperm express a functional androgen receptor: effects on PI3K/AKT pathway

BACKGROUND: Results from mice lacking the androgen receptor (AR) showed that it is critical for the proper development and function of the testes. The aim of this study was to investigate whether a functional AR is present in human sperm. METHODS: The expression of AR and its effects on sperm were evaluated by RT-PCR, Western Blot, Immunocytochemistry, PI3Kinase and DNA laddering assays. RESULTS: We showed in human sperm that AR is located at the head region. Dihydrotestosterone (DHT), in a dose-dependent manner, leads to the rapid phosphorylation of the AR on tyrosine, serine and threonine residues and this effect was reduced by the AR antagonist hydroxyflutamide (OH-Flut). The effects of AR were evaluated on the phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) pathway. Specifically, 0.1 and 1 nM DHT stimulated PI3K activity, whereas 10 nM DHT decreased PI3K activity and levels of p-AKT S473 and p-AKT T308, p-BCL2, and enhanced phosphatase and tensin homologue (PTEN) phosphorylation. In addition, 10 nM DHT was able to induce the cleavage of caspases 8, 9 and 3 and cause DNA laddering, and these effects were reversed either by casodex or OHFlut. By using wortmannin, a specific PI3K inhibitor, the cleavage of caspase 3 was reproduced, confirming that in sperm the PI3K/AKT pathway is involved in caspase activation. CONCLUSIONS: Human sperm express a functional AR that have the ability to modulate the PI3K/AKT pathway, on the basis of androgen concentration.     

Genotype distribution of clinical isolates of Trichosporon asahii based on sequencing of intergenic spacer 1

The sequence polymorphisms of intergenic transcribed spacer and the antifungal susceptibility profile of 18 Trichosporon asahii isolates from Spain, Argentina, and Brazil together with 43 intergenic transcribed spacer 1 sequences deposited in the GenBank were analyzed. Six genotypes were detected instead of 5 genotypes described previously. Genotype 1 was the most common found comprising 57.3% of all strains, followed by genotype 3 (14.7%) and genotype 5 (13.1%). Spanish strains had members in all genotypes except 2, whereas South American isolates were grouped with genotypes 1, 3, and 6. Our results indicate that all genotypes are present in at least 2 countries suggesting a worldwide distribution. On the other hand, genotype 6 was not previously described but was only composed of 2 South American strains isolated from a subcutaneous abscess and skin. All isolates showed amphotericin B MICs>or=2 mg/L supporting the in vitro resistance of this species to this antifungal. Three isolates from South America showed high MICs to all antifungals analyzed. The true epidemiologic usefulness of classifying T. asahii in genotypes should be ascertaining analyzing a high number of isolates from many countries.     

Are genetic variants of COMT associated with addiction?

The human catechol-O-methyl transferase (COMT) gene contains multiple single-nucleotide polymorphisms, some of which are postulated to have clinical significance. This article reviews human studies that have explored the association between COMT polymorphisms and addiction to drugs, alcohol or tobacco. Most studies concentrate on the Val108/158Met polymorphism. Although there are reports indicating a positive association with COMT polymorphisms and addiction, the majority of the studies failed to detect such a link between them with one exception, smoking. It is unlikely that there would be any single gene that could be designated as 'the addiction gene'. Rather, there seems to be a great number of genes that are associated with addiction, among which COMT seems to have a minor role. Environmental factors and genetic milieu have a great impact on whether the small effects of COMT polymorphisms on risk of addiction can be detected in a given population. Sex differences complicate the gene-environment interplay even further.     

Autoimmunity in Membranous Nephropathy Targets Aldose Reductase and SOD2

Glomerular targets of autoimmunity in human membranous nephropathy are poorly understood. Here, we used a combined proteomic approach to identify specific antibodies against podocyte proteins in both serum and glomeruli of patients with membranous nephropathy (MN). We detected specific anti–aldose reductase (AR) and anti–manganese superoxide dismutase (SOD2) IgG₄ in sera of patients with MN. We also eluted high titers of anti-AR and anti-SOD2 IgG₄ from microdissected glomeruli of three biopsies of MN kidneys but not from biopsies of other glomerulonephritides characterized by IgG deposition (five lupus nephritis and two membranoproliferative glomerulonephritis). We identified both antigens in MN biopsies but not in other renal pathologies or normal kidney. Confocal and immunoelectron microscopy (IEM) showed co-localization of anti-AR and anti-SOD2 with IgG₄ and C5b-9 in electron-dense podocyte immune deposits. Preliminary in vitro experiments showed an increase of SOD2 expression on podocyte plasma membrane after treatment with hydrogen peroxide. In conclusion, our data support AR and SOD2 as renal antigens of human MN and suggest that oxidative stress may drive glomerular SOD2 expression.Primary membranous nephropathy (MN) is a common glomerular disease in humans with no universally effective clinical therapy. Treatments are entirely empirical, and the disease evolves toward renal failure in a significant number of patients.^1,2 The presence of glomerular subepithelial immune deposits is the distinctive pathologic feature of MN, thus supporting the concept of an immunologic origin. It is also known that inflammatory compounds such as complement, oxygen radicals,^3,4 or intracellular protein kinase Cβ⁵ may participate, having a key role in disease progression.In the past few decades, studies of experimental models, with a particular emphasis on the Heymann nephritis (HN) model,^6–8 have led to the identification of antigens of the autoantibody response in rats (megalin),⁷ mice (aminopeptidase A),⁹ and rabbits (neutral endopeptidase [NEP]),^10–12 but limited data are available for humans. Moreover, megalin, which is the target antigen in HN, is absent in human glomeruli, and the LDL receptor, its human homolog, is only partially co-localized with MN IgG deposits.^5,13–15 Seminal studies by Debiec et al.^11,12 support the formation of immune deposits against NEP, in particular, cases with metallomembrane endopeptidase mutations that lead to NEP deficiency and alloimmunization during pregnancy. More recently, Beck et al.¹⁶ reported the presence of specific IgG₄ against the M-type phospholipase A2 receptor (PLA2R) in glomerular eluates and in plasma of a significant percentage of patients with MN, suggesting PLA2R is a major antigen in this disease.Unequivocal identification of coexisting antigens in the podocyte membrane and in subepithelial deposits is essential for any progression in the understanding of the mechanisms of MN in humans. The aim of this study was to identify podocyte proteins recognized by circulating autoantibodies in patients with MN, to define their expression in glomeruli, and to quantify the levels of specific antibodies in sera and in renal biopsies. Results provide first evidence for de novo expression of specific autoantibodies against aldose reductase (AR) and superoxide dismutase 2 (SOD2) in sera and glomeruli of patients with MN.     

No evidence of association between BDNF gene variants and age-at-onset of Huntington's disease

Huntington's disease (HD) is a late-onset, autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion. The number of repeats on the HD chromosome explains most of the variability in age of onset, but genetic factors other than the HD gene are responsible for part of the residual variance. Based on the role played by the brain derived neurotrophic factor (BDNF) in neurodysfunction and neurodegeneration in HD, we searched for novel polymorphisms in the neuron restrictive silencer element located in the BDNF promoter. Then, the effect of the Val66Met variant in determining age of onset was tested in a large sample of HD carriers by using a multivariate regression approach. The CAG repeat number accounted for 62% of the variance. After correction for the predominant effect of the CAG expansion, no multiple regression model provided evidence of association between the Val66Met genotype and variation in age-at-onset. Additional studies are warranted to further investigate BDNF as genetic modifier of the HD phenotype.