Should Men who have sex with Men be allowed to donate blood in Israel?

Background

The present permanent deferral policy in Israel for MSM was established in 1977 and was based on the previous (now outdated) USA Food and Drug Administration standards. This study analyses epidemiological data regarding blood donations among MSM, in order to estimate the risk for HIV transfusion transmitted infection (TTI) if the policy is changed to allow at-risk MSM to donate blood.

Methods

An Excel based spreadsheet model integrated demographic, epidemiological data from the HIV National Register, laboratory, blood donation and testing data in order to calculate TTI due to false-negatives in known HIV+ donors, windows period donations, asymptomatic carriers and laboratory misclassification errors. A sensitivity analysis of our estimated TTIs for deferral periods for MSM was performed based on a literature review regarding this overall policy issue worldwide.

Results

MSM in Israel have a considerably higher relative risk (RR) of both prevalence (115) and incidence (143) of being HIV+ than persons without a risk factor. Allowing MSM to donate blood, without any deferral period, will add an additional five HIV TTI cases over the next decade. Imposition of a 1 or 5 years deferral of abstinence will increase the number of HIV TTI cases only by 0.10 and 0.05 cases, respectively.

Conclusion

A 1 year deferral period for blood donations from MSM in Israel is recommended.

     

Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function

Next‐generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co‐immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin‐488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway.     

The role of apoptosis in the early corneal wound healing after excimer laser keratectomy in the rat

Background: The potential role of apoptosis in corneal wound healing after excimer laser keratectomy was investigated in a rat model. Methods: Lewis rats underwent laser keratectomy using a 193-nm excimer laser. The central corneas were ablated in three depths: group A, epithelium; group B, superficial stroma; group C, deep stroma. Eyes were collected at 1, 12, 24, and 36 h and 1 week. Cellular markers associated with apoptosis – Fas, Fas ligand (FasL), Bcl-2, and Bax – were examined by immunohistochemistry. Keratocyte depletion and endothelial changes were evaluated histologically. In situ end labeling of double-stranded DNA breaks was used to demonstrate apoptosis in corneal sections. Results: Keratocyte depletion was observed in 6 (50%) of 12 rats (total from groups A, B, and C) at 12 h, 11 (73%) of 15 at 24 h, 3 (20%) of 15 at 36 h, and 2 (15%) of 13 at 1 week after laser surgery. Corneal endothelial edema was observed in the ablation zone. Expression of Fas, FasL, Bcl-2, and Bax in corneal cells showed dynamics similar to that of keratocyte depletion and endothelial changes. There was less expression of apoptotic molecules in newly generated epithelial cells and more in endothelial cells of the stromal ablation groups. Conclusions: Excimer laser keratectomy triggered apoptosis of corneal keratocytes and endothelial cells. More endothelial edema was observed in the stromal ablation than in the epithelial ablation group. The expression of apoptotic molecules coincided with the period of keratocyte depletion and regeneration and of endothelial recovery, suggesting that apoptosis is a dynamic part of corneal wound healing and remodeling after excimer laser keratectomy. Received: 9 November 1999 Revised: 18 May 2000 Accepted: 10 April 2000     

Inflammatory complications of CGRP monoclonal antibodies: a case series

BackgroundCalcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response.CasesWe present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy.ConclusionThis case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.     

Impaired T-lymphocyte function in B-chronic lymphocytic leukaemia as measured by the local xenogeneic graft-versus-host reaction.

The immunological dysfunction observed in B-chronic lymphocytic leukaemia (B-CLL) is often related to T-lymphocyte incompetence. The local xenogeneic graft-vs.-host reaction (XGVHR), an assay to evaluate T-lymphocyte function, was performed in 112 untreated B-CLL patients. The XGVHR results significantly correlated with clinical parameters: 37.1% of the patients in the stable phase (Rai stage 0-1-2) and only 13.3% of the patients in the progressive phase (Rai stage 3-4) had positive XGVHR results. Patients with negative results had a higher number and percentage of lymphocytes (25,247 vs. 17,071/microliter and 75.9% vs. 65.6%, respectively), much lower T/B lymphocyte ratio (0.37 vs. 0.93), higher WBC count (30,977 vs. 23,458/microliter), lower platelet count (158,068 vs. 181,684/microliter) and lower levels of IgA and IgM (115.6 vs. 200.5 mg/dl and 80.4 vs. 124.3 mg/dl, respectively) compared to those with positive results. Among those with negative XGVHR results, a higher mortality rate was found in those who had infections compared with those who did not (73.7% vs. 9.1%). In conclusion, the XGVHR assay significantly correlates with important characteristics of B-CLL and may be useful in the clinical evaluation of B-CLL patients.     

HIV Risk Behaviors Among Homeless Injection Drug Users of Different Ethnicities

The objectives of this study were to assess the prevalence of HIV risk behaviors among homeless injection drug users (IDUs) and to determine whether these risk behaviors vary by ethnicity. A face-to-face interview was administered to 769 homeless IDUs in Portland, Oregon, from 1993 to 1996. Homeless IDUs had a high prevalence of needle sharing and sexual intercourse with casual partners, and a low prevalence of condom use. African Americans had the lowest rate of needle sharing, and Hispanics the highest. Compared to Whites, African Americans and Hispanics were both more likely to have had sex with casual partners in the last 30 days. African Americans were most likely to have used a condom with casual partners. Results indicate the need for more effective and culturally tailored interventions. Special efforts are needed to reduce needle sharing and increase condom use among Hispanic homeless IDUs, who exhibited the highest rates of risk behaviors.Correspondence should be directed to Jin T. Song, Oregon Health, Division, 800 NE Oregon St., Suite 550, Portland, Oregon 97232     

Clustering of Pacinian corpuscle afferent fibres in the human median nerve

 To further study the functional organisation of human peripheral nerves, the intrafascicular arrangement of afferent fibres supplying Pacinian corpuscles (PCs) was explored by percutaneous microneurography using thin-calibre, concentric needle electrodes. In normal adults, 20 PC afferents were identified in 13 recording sites. Low-amplitude (less than 30 μm) vibratory stimuli to the skin were applied with tuning forks oscillating at 128 Hz or 256 Hz and response patterns of individual PC units were studied. In many recording sites, two, sometimes even three, PC afferents with adjacent or overlapping receptive fields in the hand were clustered in the nerve. The observed incidence in the records containing a certain number of PC units was compared with the expected probability calculated according to the hypothesis that all nerve fibres are randomly organised in peripheral nerves. The results suggested that PC afferents are partially segregated in the nerve. In addition, PC afferents were neighbouring on slowly adapting type II (SAII) units and skin sympathetic activity in individual fascicles. SAII units often innervated the same skin area as PC units, but did not respond to vibration. The data provided additional information regarding the functional organisation of the human peripheral nerve and the mechanisms underlying the sense of vibration in man with special regard to population behaviour of neighbouring PC mechanoreceptors. Received: 25 September 1998 / Accepted: 14 December 1998