Determinants of COVID-19-related lethality in multiple sclerosis: a meta-regression of observational studies

Journal of Neurology - To identify risk factors for an increased lethality of COVID-19 in patients with multiple sclerosis (MS). We searched scientific databases to identify cohort studies with the...     

A proposal for classifying peristomal skin disorders: results of a multicenter observational study

The challenges of caring for abdominal ostomy disorders have grown over the years. Because the literature shows no evidence of a tool to classify peristomal skin disorders, a study group comprised of seven enterostomal therapy nurses and four surgeons sought to provide an objective, reproducible, standardized classification instrument. A prospective, observational study was conducted among eight ostomy centers across Italy. The 339 patient participants (272 men, 67 women, average age 63 [25 to 85] years) were divided into two groups according to onset of complications (less than or greater than 1 year); 800 digital photographs were taken to enhance observation and blood samples were drawn for additional data. From the data obtained, a classification scheme was created and subsequently tested using four non-study group experts. The resulting instrument facilitated lesion interpretation and detection, including topography. Thus far, this is the first validated classification attempt not based on assessments of lesions attributable to entirely different etiopathogenetic factors. Further research to refine the tool and to correlate the additional data obtained from blood samples with the classification system is underway.     

Reproductive male-mediated risk: Spontaneous abortion among wives of pesticide applicators

This study was conducted among 32 pesticide applicators occupationally exposed to pesticides to determine whether paternal exposure is associated with an increased risk of spontaneous abortion. The ratio of abortion was compared between applicators and a group of 51 food retailers (control population). The ratio of abortions/pregnancies for applicators was 0.27 and for retailers 0.07. OR for spontaneous abortion adjusted for age of wife and smoking of parents is 3.8 times greater than for the control population in the multiple logistic regression model and 7.6 times with interaction effects model.     

Modelling MRI enhancing lesion counts in multiple sclerosis using a negative binomial model: implications for clinical trials

In multiple sclerosis (MS) the number of new enhancing lesions seen on monthly magnetic resonance imaging (MRI) scans is the most widely used response variable in MRI-monitored studies of experimental treatments. However, no statistical model has been proposed to describe the distribution of the number of such lesions across MS patients. This article briefly summarizes the statistical models for counted data. The negative binomial (NB) model is proposed to fit the number of new enhancing lesions counted in a set of 56 untreated MS patients followed for 9 months. It is shown that the large variability present in this data set is better addressed by the NB model (residual deviance=66.6, 54 degrees of freedom) than by the Poisson model (residual deviance=1830.1, 55 degrees of freedom). Applications of the parametrization of lesion counts are discussed, and an example related to computer simulations for the sample size estimation is presented.     

Homer expression in the Xenopus tadpole nervous system

Homer proteins are integral components of the postsynaptic density and are thought to function in synaptogenesis and plasticity. In addition, overexpression of Homer in the developing Xenopus retinotectal system results in axonal pathfinding errors. Here we report that Xenopus contains the homer1 gene, expressed as the isoform, xhomer1b, which is highly homologous to the mammalian homer1b. The mammalian homer1 gene is expressed as three isoforms, the truncated or short form homer1a and the long forms homer1b and -1c. For Xenopus, we cloned three very similar variants of homer1b, identified as Xenopus xhomer1b.1, xhomer1b.2, and xhomer1b.3, which display up to 98% homology with each other and 90% similarity to mammalian homer1b. Furthermore, we demonstrate that Xenopus also contains a truncated form of the Homer1 protein, which could be induced by kainic acid injection and is likely homologous to the mammalian Homer1a. xHomer1b expression was unaffected by neuronal activity levels but was developmentally regulated. Within the brain, the spatial and temporal distributions of both Homer isoforms were similar in the neuropil and cell body regions. Homer1 was detected in motor axons. Differential distribution of the two isoforms was apparent: Homer1b immunoreactivity was prominent at junctions between soma and the ventricular surface; in the retina, the Mueller radial glia were immunoreactive for Homer1, but not Homer1b, suggesting the retinal glia contain only the Homer1a isoform. Homer1b expression in muscle was prominent throughout development and was aligned with the actin striations in skeletal muscle. The high level of conservation of the xhomer1 gene and the protein expression in the developing nervous system suggest that Homer1 expression may be important for normal neuronal circuit development.     

MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a

The aim of this study was to investigate changes of brain volume as measured by magnetic resonance imaging (MRI) in relapsing-remitting multiple sclerosis (MS) patients under treatment with interferon beta-1a. Moreover, the relationship between brain volume changes and standard MR or clinical outcome variables was determined. After a 6-month pretreatment period, 52 patients with relapsing-remitting MS were assigned to receive interferon beta-1a (Rebif-Serono) during a 24-month treatment period MRI scans were performed monthly during the 6-month pretreatment period and for the first 9 months of the treatment period. A final MRI scan was also performed at the end of the 12- and 24-month treatment period. Over 24 months of IFNbeta-1a treatment, a significant decrease of hyperintense lesion volume was found (-18.0%; p<0.0001) compared to the last pretreatment scan, while T1 hypointense volume showed a slight nonsignificant increase (+2.2%), and brain volume showed a significant decrease (-2.2%; p<0.0001). The mean volume of enhancing lesions over the 6-month pretreatment period was significantly related to absolute (p=0.02; r=-0.32) and per cent change (p=0.03; r=-0.30) of brain volume during 24-month treatment period. No correlations between changes in brain volume and changes in T2 hyperintense volume or T1 hypointense volume were observed. Neither was there a relationship between brain volume and changes of Expanded Disability Status Scale (EDSS) or frequency in clinical relapses. Of the group in whom was detected a significant decrease of brain volume, 13 out of 26 (50%) had a sustained change in EDSS while in the group that did not have a significant decrease of brain volume, only 3 out of 26 (11.5%) had a sustained EDSS change (p=0.02). In this study a decrease of brain volume was found in relapsing-remitting MS patients treated with IFNbeta-1a over 2 years. The only parameter that predicted brain volume decrease by 2 years of IFNbeta-1a treatment was the mean volume of enhancing lesions over the 6-month pretreatment period.     

Interleukin-12 production by human polymorphonuclear leukocytes

Human polymorphonuclear leukocytes (PMN) stimulated by lipopolysaccharide (LPS) produce interleukin-12 (IL-12). Both the free IL-12 p40 chain and minute amounts of the biologically active IL-12 p70 heterodimers are produced by PMN. Interferon-γ (IFN-γ) enhanced the LPS-induced secretion of both the free IL-12 p40 chain and the p70 heterodimer by approximately fivefold. As observed for other IL-12-producing cell types, the ratio of free p40 chain to p70 heterodimer secreted by LPS-stimulated PMN was approximately 20:1. LPS induced a 100-fold increase of IL-12 p40 mRNA, but had minimal effect on p35 mRNA accumulation, IFN-γ enhanced the LPS-induced accumulation of p40 mRNA and directly induced a several-fold increase in the accumulation of p35 mRNA. Therefore, the combined effect of LPS and IFN-γ induced sufficient expression of both p40 and p35 to attain production of the biologically active p70 heterodimer at physiologically relevant concentrations. The ratio between p40 and p35 mRNA abundance in PMN stimulated with both LPS and IFN-γ was approximately 200:1, explaining the secretion of the free p40 chain in much higher concentrations than the p70 heterodimer. IL-10, an inhibitor of the production of various cytokines in PMN, also suppressed IL-12 mRNA accumulation and secretion by PMN. Because of the important immunoregulatory function of IL-12, in particular induction of IFN-γ production and facilitation of T helper cell type 1 response, the ability of PMN to produce IL-12 suggests that neutrophils may play an active role in the regulatory interaction between innate resistance and adaptive immunity.     

Tumors of the excretory urinary tract in workers of the textile industry in the Prato area]

A hospital-based case-control study on bladder and lower urinary tract cancers was conducted in the Prato area, where the textile industry is the main manufacturing sector (about 50,000 employees). "Cases" were male subjects, aged over 15 years in whom urothelial cancer had been diagnosed in the period 1980-1985; controls (two for each case) were subjects of the same sex and age with other urological diseases or cancer of the prostate or testis. Cases and controls were interviewed via a questionnaire on occupational history and personal habits. A positive association was found for subjects who had worked in the textile industry (O.R. = 1.42; C.I. = 1.0-2.0). Analysis by job titles showed positive association for "rag selectors" (O.R. = 4.09; C.I. = 1.39-11.96), whereas no association was found for dyers (O.R. = 0.74; C.I. = 0.29-1.87).