Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.     

The Performance of Upper Limb (PUL) module in limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy (LGMD) is a genetic muscle disorder causing weakness and wasting of the proximal limb musculature. When ambulation is lost, the attention must be shifted to the upper limb muscles’ function. We studied the upper limb muscle strength and the corresponding function in 15 LGMDR1/LGMD2A and 13 LGMDR2/LGMD2B, through the Performance of Upper Limb scale and the MRC score of upper limbs. The proximal item K and the distal items N and R were lower in LGMD2B/R2. The mean MRC score of all the muscles involved linearly correlated (r2 = 0.922) for item K in LGMD2B/R2. The functional worsening paralleled the muscles weakness in LGMD2B/R2. By contrast, at proximal level the function of LGMD2A/R1 was preserved despite muscle weakness was present, presumably due to compensatory strategies. Sometimes the combination of parameters might be more informative than considering them separately. PUL scale and MRC might be interesting outcome measures in non-ambulant patients.Key words: Performance of Upper Limb (PUL version 1.2) scale, limb-girdle muscular dystrophy, LGMD2A/R1, LGMD2B/R2, MRC score     

Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series

BackgroundTo evaluate the association between COVID-19 vaccination and retinal vein occlusion (RVO).MethodsThis multicentre self-controlled case series included patients with RVO seen in five tertiary referral centres in Italy. All adults who received at least one dose of the BNT162b2, ChAdOx1 nCoV-19, mRNA-1273 or Ad26.COV2.S vaccine and had a first diagnosis of RVO between January 01, 2021, and December 31, 2021 were included. Incidence rate ratios (IRRs) of RVO were estimated using Poisson regression, comparing rates of events in a 28-day period following each dose of vaccination and in the unexposed control periods.Results210 patients were included in the study. No increased risk of RVO was observed after the first dose (1–14 days IRR: 0.87, 95% CI: 0.41–1.85; 15–28 days IRR: 1.01, 95% CI: 0.50–2.04; 1–28 days IRR: 0.94, 95% CI: 0.55–1.58) and second dose of vaccination (1–14 days IRR: 1.21, 95% CI: 0.62–2.37; 15–28 days IRR: 1.08, 95% CI: 0.53–2.20; 1–28 days IRR: 1.16, 95% CI: 0.70–1.90). No association between RVO and vaccination was found in subgroup analyses by type of vaccine, gender and age.ConclusionsThis self-controlled case series found no evidence of an association between RVO and COVID-19 vaccination.Subject terms: Retinal diseases, Epidemiology     

Acquired von Willebrand syndrome in patients with monoclonal gammopathy of undetermined significance investigated using a mechanistic approach

BackgroundAcquired von Willebrand syndrome (AVWS) has been reported to occur in association with monoclonal gammopathy, usually of undetermined significance (MGUS). It may present as a type 1 or type 2 von Willebrand factor (VWF) defect depending on the patient’s representation of large VWF multimers.Materials and methodsThe mathematical model by Galvanin et al., already employed for studying inherited von Willebrand disease (VWD), was used to explore the pathogenic mechanisms behind MGUS-associated AVWS.ResultsThe patients studied showed significantly reduced VWF levels and function; an increased VWF propeptide to VWF antigen ratio; and all VWF multimers present but in reduced quantities, with the low-molecular-weight VWF forms being significantly more represented than those of higher molecular weight. Our mathematical model revealed a significantly increased VWF elimination rate constant, with values similar to those of type Vicenza VWD. An even more increased VWF proteolysis rate constant was observed, with values one order of magnitude higher than in type 2A VWD but, in contrast, no loss of large multimers. The model predicted the same elimination rate for high- and low-molecular-weight VWF multimers, but proteolysis of the high-molecular-weight forms also contributes to the pool of low-molecular-weight oligomers, which explains why they were relatively over-represented.DiscussionIn MGUS-associated AVWS the increase of both clearance and proteolysis contributes to the circulating levels and multimer pattern of VWF, with a phenotype that appears to be a combination of type Vicenza and type 2A VWD. Hence, the mechanisms behind the onset of AVWS seem to differ from those of inherited VWD.     

ABO antibody titres: a multisite comparative study of equivalency and reproducibility for automated solid-phase and haemagglutination titration,and manual dilution with gel column agglutination technology

BackgroundABO antibody titres are important in many clinical decisions; however, much variability is observed in titre results. For reliable and reproducible titre results, automated ABO titration methods have been developed. In this 10-site study, we evaluated the equivalency of the automated ABO titration assays on the Galileo NEO, a fully automated blood bank analyzer (Immucor, Inc.) to manual titration with gel Column Agglutination Technology (CAT), as well as the reproducibility of both methods.Materials and methodsTen different locations participated in this study. The equivalency study included 70 random samples at each site. The reproducibility study tested the same blinded 30-sample panel at each study site. Anti-A and anti-B IgM and IgG antibody titres were tested with both the automated and manual methods; additionally, dithiothreitol (DTT) treatment was used to inactivate IgM antibodies in the manual CAT method.ResultsThe equivalency between CAT manual method and Galileo NEO automated titres at each site ranged from 38 to 88%; equivalency for each isotype was 66.2% for IgM, 60.6% for IgG, and 88.5% for DTT-treated IgG. The reproducibility study evaluated the titre variation of each sample obtained from the 10 sites. The average titre ranges (in doubling dilutions) for the automated and manual methods, respectively, were 2.15±1.0 and 4.03±1.8 for IgM, and 1.53±0.7 and 4.10±1.9 for IgG; for the manual DTT-treated IgG, the average titre range was 3.45±1.8 doubling dilutions.DiscussionThe results demonstrated that the Galileo NEO automated and manual CAT ABO titres are not equivalent. However, the study also demonstrated that titre reproducibility is enhanced with the Galileo NEO automated ABO titration assays relative to the manual CAT ABO titration method. Therefore, to improve management of patients receiving care across multiple institutions, our study supports the use of automated ABO titration.     

Long-term genotoxic effects in the hematopoietic system of prenatally X-irradiated mice

Purpose: To investigate the genotoxic effects of prenatal X-irradiation in mice and the possible presence of late genomic instability.

Materials and methods: Pregnant mice were exposed to 0, 1 or 2?Gy at embryonic day 11.5. Blood smears were obtained from pups at birth and on post-natal day 11, 21, 42 and 140. Hematological data (diameter of erythrocytes, percentage of reticulocytes and Granulocyte-to-Lymphocyte ratio [GLR]) and genotoxicity (micronucleated erythrocytes, micronucleated reticulocytes, CREST-positive and negative micronuclei) were assessed.

Results: Prenatal irradiation caused perinatal reticulocytosis (which ended on postnatal day 11) and a dose-dependent increase of GLR (indicative of myeloid skewing) on postnatal days 42 and 140. Two temporally distinct genotoxic effects were observed: an early, acute damage (still detectable at birth and soon after) and a late, long-term damage.

Conclusions: Increases in micronuclei frequencies and GLR observed from day 42 on are both ascribable to DNA damage. Time of appearance of this late effect may be linked to the shift of hematopoiesis from spleen to bone marrow and to cell-extrinsic factor such as the microenvironment. This study confirms that ionizing radiation can induce long-term genotoxic effects in the hematopoietic system and shows that prenatal irradiation determines genomic instability in blood-forming tissues of adult mice.     

Well-Being and Perceived Quality of Life in Elderly People Displaced After the Earthquake in L’Aquila,Italy

On 6 April 2009, the city of L’Aquila was hit by a violent earthquake that destroyed almost all of its medieval centre, and the surviving inhabitants were evacuated and relocated in temporary quarters or undamaged homes. The aim of this study was to investigate the perceived quality of life of the elderly population 3 years after the earthquake in relation to the social and logistic issues of new housing. The study was carried out between October 2011 and March 2012, and involved 571 subjects aged over 65 years living in the municipality of L’Aquila. The interviews took place in the surgeries of general practitioners and the city’s Department of Prevention and Vaccination in the anti-influenza immunisation period. The instrument used was a 36-item questionnaire with closed, multiple choice answers divided into the following sections: demographics, everyday activities, health and perceived health, and the quality of life in the city. The results show that, 3 years after the earthquake, the elderly population living in the new towns and temporary housing of L’Aquila have a worse perception of their quality of life than the others. They feel a certain social isolation and wish to live elsewhere. Governments faced with the problems arising from a natural calamity should take into account all of the elements making up a good quality of life and, before making choices whose impact cannot be changed, consider both their immediate and long-term social consequences.