Transgenic mice for interleukin 3 develop motor neuron degeneration associated with autoimmune reaction against spinal cord motor neurons

Interleukin 3 (IL-3) stimulates the proliferation and differentiation of various haematopoietic progenitor cells. Recently, IL-3 and other cytokines were reported to exert a neurotrophic activity and to be associated with neurological disorders, suggesting their complex role in the central nervous system. We now show that overexpression of IL-3 in transgenic mice causes a motor neuron disease with several features of amyotrophic lateral sclerosis and progressive muscular atrophy. These animals exhibit hind limb paralysis at 7 months of age, associated with dendritic and axonal degeneration, loss of motor neurons in the spinal cord, and autoimmune reaction against these cells. We examined the effect of IL-3 on embryonic motor neurons survival in mixed spinal cord cultures. Our results suggest that motor neuronal degeneration is not directly triggered by the high level of expression of IL-3.     

Evaluation of VIASURE Sexually Transmitted Diseases Real Time PCR Detection kit (CerTest Biotec) for the diagnostic of sexually transmitted infections

IntroductionSexually transmitted infections (STIs) are common in our environment, and trends have been increasing in the last few years. Different methods for STIs diagnosis have been applied by microbiology laboratories over years, but real-time PCR has improved this process. Our objective was to evaluate VIASURE Sexually Transmitted Diseases Real-Time PCR Detection kit (CerTestBiotec, S.L.) comparing with the real-time PCR technique used in our laboratory (Allplex? STI7 Essential Assay, Seegene) which was considered as reference assay.MethodsA total of 948 samples from different sites (vaginal, endocervical, urethral, rectal, pharyngeal swabs and urine samples) were analyzed from July to September 2018.ResultsA discordant result was obtained in 4.5% (43 samples). These discrepancies were mainly observed in threshold cycle (Ct) value next to the limit of detection. The k coefficient obtained shows a very high agreement between both methods with k values from 0.92 to 0.99.ConclusionsVIASURE Sexually Transmitted Diseases Real-Time PCR Detection kit provides a very good correlation with Allplex STI7 and therefore, it's a good tool for the diagnostic of STIs. Positive results with Ct value obtained from 35 and low amplification signal should be applied with caution and should be interpreted based on the patient's clinical data.     

Lymphocytic myocarditis in an overlap syndrome of systemic sclerosis and polymyositis

Clinical Rheumatology -     

Parechovirus Genotype 3 Outbreak among Infants,New South Wales,Australia, 2013–2014

From October 2013 through February 2014, human parechovirus genotype 3 infection was identified in 183 infants in New South Wales, Australia. Of those infants, 57% were male and 95% required hospitalization. Common signs and symptoms were fever >38°C (86%), irritability (80%), tachycardia (68%), and rash (62%). Compared with affected infants in the Northern Hemisphere, infants in New South Wales were slightly older, both sexes were affected more equally, and rash occurred with considerably higher frequency. The New South Wales syndromic surveillance system, which uses near real-time emergency department and ambulance data, was useful for monitoring the outbreak. An alert distributed to clinicians reduced unnecessary hospitalization for patients with suspected sepsis.     

Utility of clinical comprehensive genomic characterization for diagnostic categorization in patients presenting with hypocellular bone marrow failure syndromes

Bone marrow failure (BMF) related to hypoplasia of hematopoietic elements in the bone marrow is a heterogeneous clinical entity with a broad differential diagnosis including both inherited and acquired causes. Accurate diagnostic categorization is critical to optimal patient care and detection of genomic variants in these patients may provide this important diagnostic and prognostic information. We performed real-time, accredited (ISO15189) comprehensive genomic characterization including targeted sequencing and whole exome sequencing in 115 patients with BMF syndromes (median age 24 years, range: 3 months - 81 years). In patients with clinical diagnoses of inherited BMF syndromes, acquired BMF syndromes or clinically unclassifiable BMF we detected variants in 52% (12 of 23), 53% (25 of 47) and 56% (25 of 45) respectively. Genomic characterization resulted in a change of diagnosis in 30 of 115 (26%) including the identification of germline causes for 3 of 47 and 16 of 45 cases with pre-test diagnoses of acquired and clinically unclassifiable BMF respectively. The observed clinical impact of accurate diagnostic categorization included choice to perform allogeneic stem cell transplantation, disease-specific targeted treatments, identification of at-risk family members and influence of sibling allogeneic stem cell donor choice. Multiple novel pathogenic variants and copy number changes were identified in our cohort including in TERT, FANCA, RPS7 and SAMD9. Whole exome sequence analysis facilitated the identification of variants in two genes not typically associated with a primary clinical manifestation of BMF but also demonstrated reduced sensitivity for detecting low level acquired variants. In conclusion, genomic characterization can improve diagnostic categorization of patients presenting with hypoplastic BMF syndromes and should be routinely performed in this group of patients.     

A minimum data set prevalence of pain quality indicator: is it accurate and does it reflect differences in care processes?

BACKGROUND: A new prevalence of pain quality indicator based on the Minimum Data Set (MDS) has been developed for the purpose of providing nursing home (NH) consumers with information that would allow them to compare the quality of pain care between facilities. The purpose of this study was to compare pain-related care processes between NHs that scored in the lower 25th percentile (low pain prevalence) or upper 75th percentile (high pain prevalence) based on this indicator. METHODS: Care processes related to pain assessment, documentation, and treatment were independently evaluated using standardized resident interview and medical record review protocols for 255 residents in 16 NHs that reported MDS pain prevalence of less than 15% (8 NHs in lower 25th percentile) or greater than 30% (8 NHs in upper 75th percentile). RESULTS: A significantly greater proportion of participants in the high pain prevalence NHs reported symptoms indicative of chronic pain during interview. The standardized pain interview revealed a significantly higher prevalence of pain among participants in the lowest quartile NH group compared to the MDS pain prevalence quality indicator, but the pain prevalence according to both MDS and interview were comparable in the higher quartile NHs. Medical record review showed that a significantly greater proportion of participants in upper quartile NHs had pain assessments documented by licensed nurses and physicians, received pain medication, and had documentation of treatment response. CONCLUSIONS: An MDS pain quality indicator accurately discriminates prevalence of pain between facilities. However, interpretation of the pain indicator requires caution. Rather than reflecting poor quality, a high prevalence of pain according to the MDS was associated with better pain assessment and treatment care processes.     

How often is a positive faecal occult blood test the result of coeliac disease?

BACKGROUND AND AIMS: It has been reported that occult gastrointestinal bleeding as detected by faecal occult blood (FOB) testing can occur in coeliac disease. This study examines whether a positive FOB is a feature of coeliac disease and whether FOB-positive subjects need investigation for coeliac disease. METHODS: First, the records of patients on the Nottingham Register for Coeliac Disease were reviewed for positive FOB testing. Second, the Nottingham colorectal cancer screening trial database was also reviewed to examine how many coeliac patients on the Register had participated and to examine their FOB results. Finally, sera from 309 screening trial participants who were FOB-positive but had no colonic abnormality were screened for immunoglobulin A (IgA) gliadin and IgA endomysial and human tissue transglutaminase (tTG) IgA antibodies. RESULTS: Five of 590 patients on the Register had had FOB tests at the time of diagnosis; four had positive tests during investigation of diarrhoea and/or anaemia. Of 21 patients on the Register who had participated in the colorectal cancer screening trial, one had a positive FOB test and was found to have a rectal tubulo-villous adenoma. Of the 309 FOB-positive patients, 7% (22 subjects) were positive for IgA gliadin antibodies, but none had IgA endomysial antibodies detected and two subjects had positive human tTG antibody assays for coeliac disease. CONCLUSIONS: Occult gastrointestinal bleeding occurs in a small number of symptomatic coeliac disease patients before diagnosis, but is no more frequent in treated and undetected coeliac disease patients than in the general population. Unless there are other indications, coeliac disease does not need to be considered in the investigation of a positive FOB test.     

Hepatitis B virus DNA in patients with HBsAg in south western Nigeria

There are about 400 million people with chronic hepatitis B virus (HBV) infection worldwide with a potential of adverse sequelae including hepatocellular carcinoma. Recent data have shown that the level of HBV DNA in serum or plasma of an infected person probably reflects more accurately the replicative activity of the virus and therefore may serve as a better maker for management of the infection. This study was designed to determine the rate of detection of HBV DNA in blood samples of patients with HBsAg positive in Nigeria in comparison with the HBe and anti‐HBe used widely as serological markers of infectivity. Plasma samples from 105 patients with HBsAg positive were tested for the presence of HBeAg and anti‐HBe using a commercial enzyme‐linked immunosorbent assay while plasma HBV DNA was quantified using the COBAS Amplicor HBV Monitor assay. Of the 105 HBsAg samples, 17 (16.2%) and 85 (81%) were positive for HBeAg and anti‐HBe, respectively, while 8 (7.6%) were negative for both HBeAg and anti‐HBe. HBV DNA was detected in 86 (81.9%) of the samples, out of which 15 (18.1%) and 67 (80.7%) were positive for HBeAg and anti‐HBe, respectively. HBV DNA was detected in 78.4% of the HBeAg negative samples and in all the eight samples that were negative for both HBeAg and anti‐HBe. The implication of these findings in the management of patients with HBV infection is compelling. J. Med. Virol. 85:214–218, 2013. © 2012 Wiley Periodicals, Inc.     

RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary

Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under‐described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild‐type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.