Human pegivirus infection after transplant: Is there an impact?

The microbiome's role in transplantation has received growing interest, but the role of virome remains understudied. Pegiviruses are single-stranded positive-sense RNA viruses, historically associated with liver disease, but their path-ogenicity is controversial. In the transplantation setting, pegivirus infection does not seem to have a negative impact on the outcomes of solid-organ and hematopoietic stem cell transplant recipients. However, the role of pegiviruses as proxies in immunosuppression monitoring brings novelty to the field of virome research in immunocompromised individuals. The possible immunomodulatory effect of pegivirus infections remains to be elucidated in further trials.     

Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome

Radonic T, de Witte P, Groenink M, de Bruin‐Bon RACM, Timmermans J, Scholte AJH, van den Berg MP, Baars MJH, van Tintelen JP, Kempers M, Zwinderman AH, Mulder BJM. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome. Marfan syndrome (MFS) is a connective tissue disorder with major features in cardiovascular, ocular and skeletal systems. Recently, diagnostic criteria were revised where more weight was given to the aortic root dilatation. We applied the revised Marfan nosology in an established adult Marfan population to define practical repercussions of novel criteria for clinical practice and individual patients. Out of 180 MFS patients, in 91% (n = 164) the diagnosis of MFS remained. Out of 16 patients with rejected diagnosis, four patients were diagnosed as MASS (myopia, mitral valve prolapse, borderline non‐progressive aortic root dilatation, skeletal findings and striae) phenotype, three as ectopia lentis syndrome and in nine patients no alternative diagnosis was established. In 13 patients, the diagnosis was rejected because the Z‐score of the aortic root was <2, although the aortic diameter was larger than 40 mm in six of them. In three other patients, the diagnosis of MFS was rejected because dural ectasia was given less weight in the revised nosology. Following the revised Marfan nosology, the diagnosis of MFS was rejected in 9% of patients, mostly because of the absence of aortic root dilatation defined as Z‐score ≥2. Currently used Z‐scores seem to underestimate aortic root dilatation, especially in patients with large body surface area (BSA). We recommend re‐evaluation of criteria for aortic root involvement in adult patients with a suspected diagnosis of MFS.     

Associations of the Interleukin‐1 Gene Locus Polymorphisms with Risk to Hip and Knee Osteoarthritis: Gender and Subpopulation Differences

Genetic predisposition to the complex hereditary disease like osteoarthritis (OA) of the large joints (hip and knee) includes the interleukin‐1 gene (IL‐1) cluster on chromosome 2. Using a case–control study with 500 OA patients (240 knee and 260 hip OA patients, all with joint replacement), we analysed frequencies of IL‐1 gene cluster polymorphisms in Croatian Caucasian population. The control samples came from 531 healthy individuals including blood donors. We genotyped two single nucleotide polymorphisms in the IL‐1 gene locus at IL‐1A (?889, C>T, rs1800587) and IL‐1B (+3594, C>T, rs1143634) and compared their frequencies between patients and controls. We predicted haplotypes by combining current data with our previous results on gene polymorphisms (IL‐1B, rs16944 and the IL‐1 receptor antagonist gene [IL‐1RN] variable number tandem repeat [VNTR]) for the same population. Haplotype analyses revealed gender disparities and showed that women carriers of the 1‐2‐1‐1 haplotype [IL‐1A(rs1800587) – IL‐1B(rs1143634) – IL‐1B(rs16944) – IL‐1RN(VNTR)] had sixfold lower risk to develop knee OA. However, carriers of the 1‐1‐1‐2 haplotype of both sexes had over twofold higher predisposition to hip OA. Our results differ from some earlier studies in Caucasian subpopulations, which may be due to the fact that this is the first study to separate genders in assessing the IL‐1‐locus genetic risk of OA. The results suggest that inflammatory mediators like IL‐1 might be implicated in the pathogenesis of primary OA in large joints and that as yet unidentified gender‐specific factors exist in a Croatian Caucasian population.     

Function after spinal treatment,exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery

Background  

The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period.     

Impact of obesity on female reproductive health: British Fertility Society, Policy and Practice Guidelines

Obesity has a significant adverse impact on reproductive outcome. It influences not only the chance of conception but also the response to fertility treatment, and increases the risk of miscarriage, congenital anomalies and pregnancy complications in addition to potential adverse effects on long term health of both mother and infant. Women should aim for a normal BMI before starting any form of fertility treatment. Treatment should be deferred until the BMI is less than 35 kg/m2, although in those with more time (e.g., less than 37 years; normal serum FSH concentration) a weight reduction to a BMI of less than 30 kg/m2 is preferable. Clinicians should consider deferring treatment to women outside these guidelines. Women should be provided with assistance to lose weight, including psychological support, dietary advice, exercise classes and where appropriate, weight reducing agents or bariatric surgery. Even a moderate weight loss of 5-10% of body weight can be sufficient to restore fertility and improve metabolic markers.     

In rat B lymphocyte genesis sixty percent is lost from the bone marrow at the transition of nondividing pre-B cell to sIgM+ B lymphocyte, the stage of Ig light chain gene expression

The cycling B precursor cells in rat bone marrow (BM) that carry the B220 antigen and no surface Ig daily produce 780 million new cells. The pool of recirculating B lymphocytes in the rat, however, renew at a rate of only about 40 million cells/day. To analyze at which stages in B lymphocyte genesis the cell loss occurs, we identified post-mitotic cells in the rat BM B lineage, and determined their renewal rates. We used 5-bromo-deoxyuridine (BrdUrd) to label DNA-synthesizing cells, identifying incorporated BrdUrd with the mouse monoclonal antibody BU-1. B lineage cell subsets were identified by the markers HIS24 antigen (rat B220), terminal deoxynucleotidyl transferase (TdT), Ig mu heavy chain, and complete Ig. By use of double and triple immunocytology, we determined the extent of BrdUrd incorporation in the various B lineage compartments [HIS24+TdT-Ig-, TdT+, cytoplasmic mu chain (c mu)+ surface (s) IgM- pre-B, sIgM+ B]. Both sIgM+ B lymphocytes and all B precursors with cell diameters less than 11-12 microns were virtually devoid of DNA synthesis, as indicated by S-phase indices below 2%. In contrast, S-phase indices of large B precursors ranged between 43%-66%. We established the renewal rates of nondividing BM B lineage cells by placing osmotic minipumps containing BrdUrd subcutaneously in the flank of rats. The nondividing BM B lineage cells all renewed rapidly at rates between 2.4% and 5.6%/h, representing average half-lives of 29 to 12 h. In absolute numbers, the renewal/day/whole body BM was 165 X 10(6) for sIgM+ B lymphocytes, 422 X 10(6) for small c mu+ sIgM- pre-B cells, 89 X 10(6) for small TdT+ cells and 35 X 10(6) for small HIS24+TdT-Ig- cells. Assuming that recirculating B lymphocytes in the periphery are the descendants of BM sIgM+ B lymphocytes, which in their turn are the progeny of small pre-B cells, the renewal data indicate the following. Of the 165 million potentially available BM B lymphocytes, only 40 million cells become incorporated in the pool of recirculating B lymphocytes, representing a loss of 75%. BM B lymphocytes, in turn, use only (165/422 X 100% = ) 40% of the potential output from their immediate precursors. The 60% loss that occurs here may reflect the extent of aberrant Ig light chain gene rearrangement in normal B lymphocyte genesis.(ABSTRACT TRUNCATED AT 400 WORDS)     

The association of body mass index and biochemical hyperandrogenaemia in women with and without polycystic ovary syndrome

Objective

To investigate the association between BMI and different androgen parameters in women with PCOS and normal ovulatory women.

Study design

A cross sectional, observational study was carried out. A total of 286 patients aged 20–44 years were recruited. One hundred and sixty-five women had a diagnosis of PCOS and 121 women were ovulatory with no clinical or biochemical or ultrasound evidence of PCOS. The PCOS and non-PCOS groups were sub-divided into two subgroups based on BMI (BMI ≤ 30 kg/m² and BMI > 30 kg/m²). Androgen parameters measured were testosterone, androstenedione, free androgen index and sex hormone-binding globulin (SHBG). Testosterone and androstenedione were measured using tandem mass spectrometry. Free androgen index (FAI) was calculated using the formula: (testosterone/SHBG) × 100. Spearman rank correlations were used to determine relationship between BMI and androgens.

Results

The PCOS group had a higher BMI compared with the non-PCOS group (28.9 ± 5.8, 24.5 ± 4.1). Total testosterone, androstenedione, and FAI were significantly higher while SHBG was lower in the PCOS group. A correlation between BMI and total testosterone was not observed in either group. Positive correlations were observed between BMI and FAI in both PCOS (p < 0.001) and non-PCOS groups (p = 0.02) while a positive correlation was observed between BMI and androstenedione in the PCOS group (p = 0.001). SHBG correlated negatively with BMI in both groups.

Conclusion

A strong correlation exists between BMI and FAI but not with total testosterone, possibly due to the mediation of SHBG. Hyperandrogenaemia in the form of androstenedione seems to be augmented in PCOS with increasing BMI. A direct causal relationship between BMI and androgenaemia was not established.     

Instructions for authors of primary papers

Measurement of plasma prolactin frequently forms part of the routine investigation of infertile couples. In 315 consecutive women attending an infertility clinic in a university teaching hospital, all of those with increased plasma prolactin concentrations would have been detected from their symptoms. All women with prolactin concentrations in the range 500–800 miu l^?1 appeared to be ovulating. These data support previous proposals in guidelines published by both the European Society for Human Reproduction and Embryology (ESHRE, 1996) and the Royal College of Obstetricians and Gynaecologists (RCOG, 1998) that there is no benefit in measuring plasma prolactin in the investigation of infertility in women who are menstruating normally and have no other clinical indications.