CANCER RISK IN MULTIPLE SCLEROSIS PATIENTS TAKING CLADRIBINE

J Neurol Neurosurg Psychiatry 2014;85(10):A1–A5

Leaching characteristics of the metal waste form from the electrometallurgical treatment process: Product consistency testing

Argonne National Laboratory is developing an electrometallurgical treatment for spent fuel from the experimental breeder reactor II. A product of this treatment process is a metal waste form that incorporates the stainless steel cladding hulls, zirconium from the fuel and the fission products that are noble to the process, i.e., Tc, Ru, Nb, Pd, Rh, Ag. The nominal composition of this waste form is stainless steel/15 wt% zirconium/1--4 wt% noble metal fission products/1--2 wt % U. Leaching results are presented from several tests and sample types: (1) 2 week monolithic immersion tests on actual metal waste forms produced from irradiated cladding hulls, (2) long term (>2 years) pulsed flow tests on samples containing technetium and uranium and (3) crushed sample immersion tests on cold simulated metal waste form samples. The test results will be compared and their relevance for waste form product consistency testing discussed

Neurologic complications of acute hepatitis E virus infection.

To assess the prevalence and clinical features of neurologic involvement in patients with acute hepatitis E virus (HEV) infection in Southern Switzerland. Among 1,940 consecutive patients investigated for acute hepatitis E, we identified 141 cases of acute of HEV infection (anti-HEV immunoglobulin M and immunoglobulin G both reactive and/or HEV RNA positive) between June 2014 and September 2017. Neurologic cases were followed up for 6 months. We compared patients with and without neurologic symptoms. Neurologic symptoms occurred in 43 acute HEV cases (30.4%) and consisted of neuralgic amyotrophy (NA, n = 15, 10.6%) and myalgia (n = 28, 19.8%). All NA cases were immunocompetent. Men had higher odds (OR = 5.2, CI 1.12-24.0, p = 0.03) of developing NA after infection with HEV, and in 3 couples simultaneously infected with HEV, only men developed NA. Bilateral involvement of NA was predominant (2:1) and occurred only in men. Seven NA cases were viremic (all genotype 3), but HEV was undetectable in their CSF. In the acute phase of NA, 9 patients were treated with intravenous immunoglobulin and 4 with prednisone, reporting no side effects and improvement in pain and strength. Myalgia occurred both without (n = 16) or with (n = 12) concomitant elevated serum creatinine kinase. Seven cases with myalgia in the shoulder girdle did not have muscle weakness ("forme fruste" of NA). Neurologic symptoms occurred in one-third of acute HEV infections and consisted of NA and myalgia. NA seems to occur more frequently in men infected by HEV and has a predominant (but not exclusive) bilateral involvement

How can we treat vulvar carcinoma in pregnancy? A systematic review of the literature

According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17\u201341 years). The tumor size range was 0.3\u201315 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before\u2010and\u2010after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV\u2010related features (condylomas/warts; HPV infection; high\u2010grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time\u2010to\u2010recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5\u201348 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease\u2010free at the end of follow\u2010up. Pregnant patients must be followed\u2010up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory

Seasonal Distribution of Psychiatric Births in England

There is general consensus that season of birth influences the risk of developing psychiatric conditions later in life. We aimed to investigate whether the risk of schizophrenia (SC), bipolar affective disorder (BAD) and recurrent depressive disorder (RDD) is influenced by month of birth in England to a similar extent as other countries using the largest cohort of English patients collected to date (n=57,971). When cases were compared to the general English population (n=29,183,034) all diseases showed a seasonal distribution of births (SC p=2.48E-05; BAD p=0.019; RDD p=0.015). This data has implications for future strategies of disease prevention

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Impact of month of birth on the development of autoimmune thyroid disease in the United Kingdom and Europe

CONTEXT: Viral/bacterial infection is proposed as a trigger for the autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies in European Caucasian AITD subjects found higher birth rates in the autumn/winter, suggesting those born in the autumn/winter experience increased viral/bacterial exposure after birth, impacting upon immune system development and predisposing to AITD later in life. OBJECTIVE: Month of birth effects were investigated in three independent European Caucasian AITD datasets. DESIGN: Variation in GD and HT onset was compared across months and seasons, with fluctuations across all 12 months analyzed using a Walter-Elwood test. SETTING: The study was conducted at a research laboratory. PATIENTS: National UK Caucasian AITD Case Control Collection (2746 GD and 502 HT compared with 1 423 716 UK births), National UK Caucasian GD Family Collection (239 GD and 227 unaffected siblings), and OXAGEN AITD Caucasian Family Collection (885 GD, 717 HT, and 794 unaffected siblings of European Caucasian decent). MAIN OUTCOME MEASURES: Case-control and family-based association studies were measured. RESULTS: No consistent month of birth effects were detected in GD females or males across all three collections. In HT females from the OXAGEN AITD Caucasian Family Collection, slightly higher birth rates were detected in autumn (Walter's test statistic = 7.47, P = .024) however, this was not seen in the HT females from the case-control cohort. CONCLUSION: Our results suggest in UK/Northern European Caucasian GD subjects, month of birth does not impact on AITD development. Although some month of birth effects for HT females in one collection cannot be excluded, only further work in larger European Caucasian AITD collections can confirm these effects

Plutonium-238 Alpha-Decay Damage Study of the Ceramic Waste Form.

An accelerated alpha-decay damage study of a glass-bonded sodalite ceramic waste form has recently been completed. The purpose of this study was to investigate the physical and chemical durability of the waste form after significant exposure to alpha decay. This accelerated alpha-decay study was performed by doping the ceramic waste form with {sup 238}Pu which has a much greater specific activity than {sup 239}Pu that is normally present in the waste form. The alpha-decay dose at the end of the four year study was approximately 1 x 10{sup 18} alpha-decays/gram of material. An equivalent time period for a similar dose of {sup 239}Pu would require approximately 1100 years. After four years of exposure to {sup 238}Pu alpha decay, the investigation observed little change to the physical or chemical durability of the ceramic waste form (CWF). Specifically, the {sup 238}Pu-loaded CWF maintained it's physical integrity, namely that the density remained constant and no cracking or phase de-bonding was observed. The materials chemical durability and phase stability also did not change significantly over the duration of the study. The only significant measured change was an increase of the unit-cell lattice parameters of the plutonium oxide and sodalite phases of the material and an increase in the release of salt components and plutonium of the waste form during leaching tests, but, as mentioned, these did not lead to any overall loss of waste form durability. The principal findings from this study are: (1) {sup 238}Pu-loaded CWF is similar in microstructure and phase composition to referenced waste form. (2) Pu was observed primarily as oxide comprised of aggregates of nano crystals with aggregates ranging in size from submicron to twenty microns in diameter. (3) Pu phases were primarily found in the intergranular glassy regions. (4) PuO phase shows expected unit cell volume expansion due to alpha decay damage of approximately 0.7%, and the sodalite phase unit cell volume has expanded slightly by 0.3% again, presumably due to alpha-decay damage. (5) No bulk sample swelling was observed. (6) No amorphization of sodalite or actinide bearing phases was observed after four years of alpha-decay damage. (7) No microcracks or phase de-bonding were observed in waste form samples aged for four years. (8) In some areas of the {sup 238}Pu doped ceramic waste form material bubbles and voids were found. Bubbles and voids with similar size and density were also found in ceramic waste form samples without actinide. These bubbles and voids are interpreted as pre-existing defects. However, some contribution to these bubbles and voids from helium gas can not be ruled out. (9) Chemical durability of {sup 238}Pu CWF has not changed significantly after four years of alpha-decay exposure except for an increase in the release of salt components and Pu. Still, the plutonium release from CWF is very low at less than 0.005 g/m{sup 2}

The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects