Cytomegalovirus seropositivity is negatively associated with multiple sclerosis.

BACKGROUND: Epidemiological data suggest a role for common viruses in the pathogenesis of multiple sclerosis (MS), and recent data showed a negative association of past cytomegalovirus (CMV) infection on pediatric MS risk. OBJECTIVE: Our aim was to analyze the association of CMV infection with MS risk in an adult case-control material. A meta-analysis was performed to validate our findings. METHODS: Epidemiological Investigation in MS (EIMS) is a case-control study with incident cases and population-based controls. Anti-CMV antibody titers were measured with ELISA, and HLA-A and DRB1 genotyping was performed with SSP-PCR, in 658 MS cases, who all fulfilled the McDonald criteria for MS, and 786 controls. RESULTS: CMV seropositivity was associated with a decreased MS risk, OR = 0.73 (0.58-0.92 95% CI), p = 0.005, adjusted for index age, gender, smoking, sun exposure, EBNA1 IgG titer and HLA-A*02 and DRB1*15. When we removed all cases and controls younger than 18 years at index, the protective effect was still apparent. CONCLUSIONS: CMV is negatively associated with adult-onset MS pathology, consistent with results from a study on pediatric MS cases. It remains to be shown whether this negative association is due to a true protective effect of CMV infection on MS risk.

Evaluation of the quality and impact of online learning through the SAFE EUROPE webinars.

INTRODUCTION: The SAFE EUROPE project, a European-funded project, addressed educational gaps of Therapeutic Radiographers/Radiation Therapists (TR/RTTs) by offering a series of free webinars. This study aimed to assess the quality of these webinars and their impact on professional practice. METHODS: Data collection involved two methods: an automated feedback form administered after each webinar, supplemented by a survey disseminated through social media. The collected data encompassed attendance statistics, participants' professions and geographic locations, webinar quality assessment, the acquisition of new knowledge and skills, the application of this newfound knowledge in practice, and the likelihood of recommending these webinars. Descriptive statistics and thematic analysis were used to analyse the quantitative and qualitative data, respectively. Ethical approval for the study was obtained. RESULTS: 11,286 individuals from 107 countries participated in 18 webinars. Despite 72.7% being radiographers, a diverse array of professionals attended the webinars, including medical physicists, oncologists, radiologists, and academics. Remarkably, 98.7% of respondents rated the webinar quality as either good or excellent. The average rating for the likelihood of recommending these webinars to colleagues was 8.96/10. A substantial proportion of respondents expressed agreement or strong agreement that the webinars enhanced their knowledge (85%) and skills (73%). Furthermore, 79% of participants indicated that the webinars motivated them to change practice, with 65% having already implemented these changes. The insights from open-ended questions corroborated these findings. CONCLUSION: The webinars effectively achieved the aim of the SAFE EUROPE project to enhance practice by increasing knowledge and skills. Participants overwhelmingly endorsed the quality of these webinars. IMPLICATIONS FOR PRACTICE: Webinars represent a cost-efficient training tool that reaches a global audience and various radiography/radiotherapy professions. The development of additional webinars is strongly recommended.

Epstein-Barr virus and multiple sclerosis: interaction with HLA.

Epstein-Barr virus (EBV) infection, history of infectious mononucleosis (IM) and HLA-A and DRB1 have all been proposed as risk factors for multiple sclerosis (MS). Our aim was to analyse possible interactions between antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA1) or EBNA1 fragments, presence of DRB1*15 and absence of A*02. The study population includes newly diagnosed cases and matched controls. Interaction on the additive scale was calculated using attributable proportion due to interaction (AP), which is the proportion of the incidence among individuals exposed to two interacting factors that is attributable to the interaction per se. IM showed association with MS, odds ratio (OR)=1.89 (1.45-2.48% confidence interval (CI)), as did raised EBNA1 IgG OR=1.74 (1.38-2.18 95%CI). All EBNA1 fragment IgGs were associated with MS risk. However, EBNA1 fragment 385-420 IgG levels were more strongly associated to MS than total EBNA1 IgG, OR=3.60 (2.75-4.72 95%CI), and also interacted with both DRB1*15 and absence of A*02, AP 0.60 (0.45-0.76 95%CI) and AP 0.39 (0.18-0.61 95%CI), respectively. The observed interaction between HLA class I and II genotype and reactivity to EBV-related epitopes suggest that the mechanism through which HLA genes influence the risk of MS may, at least in part, involve the immune control of EBV infection.

Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta.

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish-Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.

Sunlight is associated with decreased multiple sclerosis risk: no interaction with human leukocyte antigen-DRB1*15.

BACKGROUND: Both insufficient exposure to sunlight and vitamin D deficiency have been associated with an increased risk for multiple sclerosis (MS). An interaction between human leukocyte antigen HLA-DRB1*15 and vitamin D in MS was recently proposed. We investigated the association between previous exposure to ultraviolet radiation (UVR), vitamin D status at inclusion in the study, and MS risk including the interaction of these factors with HLA-DRB1*15. METHODS: A population-based case-control study involving 1013 incident cases of MS and 1194 controls was performed in Sweden during 2005-2010. Subjects were classified according to their UVR exposure habits, vitamin D status, and HLA genotypes. The associations between different sun exposure habits/vitamin D levels and MS were calculated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. Potential interaction was evaluated by calculating the attributable proportion due to interaction. RESULTS: Subjects with low UVR exposure had a significantly increased risk of MS compared with those who reported the highest exposure (OR 2.2, 95% CI 1.5-3.3). Similarly, subjects who had 25-hydroxy-vitamin D levels less than 50 nM/l had an increased risk for MS (OR 1.4, 95% CI 1.2-1.7). The association between UVR exposure and MS risk persisted after adjustment for vitamin D status. There was no interaction with HLA-DRB1*15 carriage. CONCLUSIONS: UVR and vitamin D seem to affect MS risk in adults independently of HLA-DRB1*15 status. UVR exposure may also exert a protective effect against developing MS via other pathways than those involving vitamin D.

No evidence of IL21 association with multiple sclerosis in a Swedish population.

Multiple sclerosis (MS) patients, with a second autoimmune disease after lymphocyte depletion, had elevated serum IL-21 before and after treatment which correlated to IL21 genotypes. In addition, the IL21 gene has been associated to several other autoimmune diseases. However, in a Spanish population there was no association to MS. Here, in a Swedish cohort (2090 MS cases and 1732 controls) 12 single nucleotide polymorphisms (SNPs) tagging IL21 were not associated to disease. There was no interaction with risk alleles of IL21R and HLA-DRB1*15. Lack of genetic association was confirmed in a meta-analysis with pooled data from the present study and the Spanish study. In conclusion, IL21 has not been shown to be a major risk gene for MS.

RGMA and IL21R show association with experimental inflammation and multiple sclerosis.

Rat chromosome 1 harbors overlapping quantitative trait loci (QTL) for cytokine production and experimental models of inflammatory diseases. We fine-dissected this region that regulated cytokine production, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), anti-MOG antibodies and pristane-induced arthritis (PIA) in advanced intercross lines (AILs). Analysis in the tenth and twelfth generation of AILs resolved the region in two narrow QTL, Eae30 and Eae31. Eae30 showed linkage to MOG-EAE, anti-MOG antibodies and levels of interleukin-6 (IL-6). Eae31 showed linkage to EAE, PIA, anti-MOG antibodies and levels of tumor necrosis factor (TNF) and IL-6. Confidence intervals defined a limited set of potential candidate genes, with the most interesting being RGMA, IL21R and IL4R. We tested the association with multiple sclerosis (MS) in a Nordic case-control material. A single nucleotide polymorphism in RGMA associated with MS in males (odds ratio (OR)=1.33). Polymorphisms of RGMA also correlated with changes in the expression of interferon-gamma (IFN-gamma) and TNF in cerebrospinal fluid of MS patients. In IL21R, there was one positively associated (OR=1.14) and two protective (OR=0.87 and 0.68) haplotypes. One of the protective haplotypes correlated to lower IFN-gamma expression in peripheral blood mononuclear cells of MS patients. We conclude that RGMA and IL21R and their pathways are crucial in MS pathogenesis and warrant further studies as potential biomarkers and therapeutic targets.

Transmission of infection from non-isolated patients with COVID-19 to healthcare workers.

Insufficiently protected healthcare workers (HCWs), defined as high-risk contacts of patients with coronavirus disease 2019 (COVID-19), are routinely quarantined. This study evaluated the transmission of infection from a symptomatic patient with COVID-19 to 60 HCWs exposed at ≤2 m for ≥15 min or during aerosol-generating procedures. Following ≥106 unique high-risk contacts, none of the HCWs tested positive for severe acute respiratory syndrome coronavirus-2 RNA or developed antibodies. The HCWs reported adherence to basic infection control procedures. These results are in accordance with other reports, and should reassure HCWs and further stimulate broader evaluation of the foundation for the current practice of home quarantining non-symptomatic HCWs.

The European core curriculum for radiotherapy technologists.

BACKGROUND: The Radiotherapy Technologist is the third member of the team responsible for the accurate delivery of radiotherapy to the cancer patient. Educational standards have been established for both radiotherapists and medical physicists and our group recognised the need to also standardise the education of radiotherapy technologists. MATERIALS AND METHODS: The project commenced in 1990 and was completed by 1994 when an agreed core curriculum was presented at a consensus conference. All aspects of curriculum development and education delivery were reviewed during this four year period. RESULTS: Core topics were identified. educational entry standards described and a duration of three years, consistent with European Union mobility regulations, agreed. CONCLUSIONS: The core curriculum describes the standard necessary to be achieved for entry into the profession to ensure the optimum treatment is offered to all patients throughout the European Union. Regular review of the core curriculum should be carried out to ensure the defined standards are maintained.

Boys with undescended testes: endocrine, volumetric and morphometric studies on testicular function before and after orchidopexy at nine months or three years of age.

CONTEXT: A randomized controlled study was conducted comparing the outcome of surgery for congenital cryptorchidism at 9 months or 3 yr of age. OBJECTIVE: The aim of the study was to investigate whether surgery at 9 months is more beneficial than at 3 yr and to identify early endocrine markers of importance for testicular development. PATIENTS AND METHODS: A total of 213 biopsies were taken at orchidopexy, and the number of germ and Sertoli cells per 100 seminiferous cord cross-sections and the surface area of seminiferous tubules and interstitial tissue were analyzed. Inhibin B, FSH, LH, and testosterone were determined. Testicular volume was assessed by ultrasonography and by a ruler. RESULTS: The number of germ and Sertoli cells and testicular volume at 9 months were significantly larger than at 3 yr. The intraabdominal testes showed the largest germ cell depletion at 3 yr. At both ages, testicular volume correlated to the number of germ and Sertoli cells. None of the hormones measured during the first 6 months of life (LH, FSH, testosterone, and inhibin B) could predict the number of germ or Sertoli cells at either 9 or 36 months of age, nor could hormone levels predict whether spontaneous descent would occur or not. CONCLUSION: Morphometric and volumetric data show that orchidopexy at 9 months is more beneficial for testicular development than an operation at 3 yr of age. Testicular volume was furthermore shown to reflect germ cell numbers in early childhood, whereas endocrine parameters could not predict cellular structure of the testis or its spontaneous descent.

HLA-DRB1 and month of birth in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) displays a month-of-birth effect, with an excess of individuals being born in the spring and a deficit in the winter. This effect was shown to be more pronounced in familial cases of MS. In the present study, we investigated whether this month-of-birth association has any relation to the principal MS susceptibility gene, HLA-DRB1. METHODS: A total of 4,834 patients with MS, 4,056 controls, and 659 unaffected siblings from Canada, Sweden, and Norway were genotyped for the HLA-DRB1 gene. Month of birth was compared for patients, controls, and unaffected siblings with and without the MS risk allele HLA-DRB1*15. RESULTS: Significantly fewer patients with MS carrying the HLA-DRB1*15 risk allele were born in November compared with patients not carrying this allele (p = 0.02). Additionally, patients with MS carrying HLA-DRB1*15 had a higher number of April births compared with patients with MS not carrying HLA-DRB1*15 (p = 0.004). These differences were not present in controls or unaffected siblings. CONCLUSIONS: Month of birth, HLA-DRB1 genotype, and risk of multiple sclerosis are associated. The interaction of a seasonal risk factor with loci at or near HLA-DRB1 during gestation or shortly after birth is implicated.