Nocturnal variant of benign myoclonic epilepsy of infancy: a case series

Myoclonus is a brief, rapid, involuntary muscle jerk originating in the central nervous system that can be physiological or a symptom of disease. We report a group of five children with excessive myoclonic jerks, only during sleep, and abnormal EEG during the events. Although only one third of the events had EEG epileptiform correlate, the presence of myoclonus without epileptiform EEG correlate has been described in patients with benign myoclonic epilepsy of infancy. We hypothesize that these findings may represent a variant of benign myoclonic epilepsy of infancy.     

CCR9 signaling in dendritic cells drives the differentiation of Foxp3+ Tregs and suppresses the allergic IgE response in the gut

The chemokine receptor CCR9 and its only known ligand CCL25 play an important role in gut inflammation and autoimmune colitis. The function of CCR9-CCL25 in the migration of immune cells is well characterized. However, its role in the immune cell differentiation is mostly not known. Using dextran sodium sulfate (DSS)-induced gut inflammation model, we showed that CCR9⁺ dendritic cells (DCs) specifically CD11b⁻CD103⁺ DCs were significantly increased in the gut-associated lymphoid tissues (GALT) compared to control mice. These CCR9⁺ DCs express lower MHC II and CD86 molecules and had regulatory surface markers (FasL and latency-associated peptide, LAP) in the GALT. In the presence of CCL25, CCR9⁺ DCs promoted in vitro differentiation of Foxp3⁺ regulatory CD4⁺ T cells (Tregs). CCL25-induced differentiation of Tregs was due to intrinsic signaling in the DCs but not through CD4⁺ T cells, which was driven by the production of thymic stromal lymphopoietin (TSLP) and not IL-10. Furthermore, adoptive transfer of CCR9⁺ DCs in C57BL/6 mice promoted Tregs but reduced the Th17 cells in the GALT, and also suppressed the OVA-specific gut-allergic response. Our results suggest CCR9⁺ DCs have a regulatory function and may provide a new cellular therapeutic strategy to control gut inflammation and allergic immune reaction.     

Effect of S-methylisothiourea,an inducible nitric oxide synthase inhibitor,in joint pain and pathology in surgically induced model of osteoarthritis

The aim of the present study was to evaluate in vivo modulatory effect of S-methylisothiourea (SMT), a preferential inhibitor of inducible nitric oxide synthase (iNOS) on pain and pathology in the surgical model of osteoarthritis (OA) in rats. The OA was produced by the anterior cruciate ligament transection (ACLT) and medial meniscectomy (MMx) of right knee. SMT was administered 1 day prior to the production of OA and continued up to day 42 postoperation. Mechanical hyperalgesia, thermal hyperalgesia, tail flick latency after repeated flexion and extension of OA knee and knee diameter of right knee were determined at weekly intervals. Serum levels of IL-1β, TNF-α and nitrite concentration were determined at the end of the experiment. Glycosaminoglycan (GAG) content, collagen content and histopathological evaluation of articular cartilage were also determined at the end of the experiment. SMT reduced mechanical hyperalgesia and the serum levels of IL-1β, TNF-α and nitrite. Further, SMT reduced the loss of GAG from articular cartilage. Microscopically, SMT reduced the severity of the cartilage lesion. The results indicate the effectiveness of SMT in attenuating the pain and pathology of experimental OA phase by reducing the production of nitric oxide and interleukin-1β and tumor necrosis factor-α, which are known to play a major role in the pathophysiology of OA.     

Thrombotic microangiopathy following aortic surgery with hypothermic circulatory arrest: a single-centre experience of an underestimated cause of acute renal failure

 Open in a separate windowOBJECTIVESAcute kidney injury (AKI) following surgery involving the heart-lung-machine is associated with high mortality and morbidity. In addition to the known mechanisms, thrombotic microangiopathy (TMA) triggered by the dysregulation of complement activation was recently described as another pathophysiological pathway for AKI following aortic surgery. The aim of this retrospective study was to analyse incidence, predictors and outcome in these patients.METHODSBetween January 2018 and September 2019, consecutive patients undergoing aortic surgery requiring hypothermic circulatory arrest were retrospectively reviewed. If suspected, diagnostic algorithm was initiated to identify a TMA and its risk factors, and postoperative outcome parameters were comparably investigated.RESULTSThe incidence of TMA in the analysed cohort (n = 247) was 4.5%. Multivariable logistic regression indicated female gender {odds ratio (OR) 4.905 [95% confidence interval (CI) 1.234–19.495], P = 0.024} and aortic valve replacement [OR 8.886 (95% CI 1.030–76.660), P = 0.047] as independent predictors of TMA, while cardiopulmonary bypass, X-clamp and hypothermic circulatory arrest times showed no statistically significance. TMA resulted in postoperative AKI (82%), neurological disorders (73%) and thrombocytopaenia [31 (interquartile range 25–42) G/l], corresponding to the diagnostic criteria. Operative mortality and morbidity were equal to patients without postoperative TMA, despite a higher incidence of re-exploration for bleeding (27 vs 6%; P = 0.027). After 6 months, survival, laboratory parameters and need for dialysis were comparable between the groups.CONCLUSIONSTMA is a potential differential diagnosis for the cause of AKI following aortic surgery regardless of the hypothermic circulatory arrest time. Timely diagnosis and appropriate treatment resulted in a comparable outcome concerning mortality and renal function.     

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women

Background: Glyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure.Objective: We conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels.Methods: For 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography–tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate q<0.1 in ≥90% of 1,000 subsamples of the study population were considered differentially methylated. Differentially methylated sites from the probe-specific analysis were combined into a methylation index. Epigenetic age acceleration from three epigenetic clocks and an epigenetic measure of pace of aging were examined for associations with glyphosate and AMPA.Results: We identified 24 CpG sites whose methylation level was associated with urinary glyphosate concentration and two associated with AMPA. Four regions, within the promoters of the MSH4, KCNA6, ABAT, and NDUFAF2/ERCC8 genes, were associated with glyphosate levels, along with an association between ESR1 promoter hypomethylation and AMPA. The methylation index accurately predicted glyphosate levels in an internal validation cohort. AMPA, but not glyphosate, was associated with greater epigenetic age acceleration.Discussion: Glyphosate and AMPA exposure were associated with DNA methylation differences that could promote the development of cancer and other diseases. Further studies are warranted to replicate our results, determine the functional impact of glyphosate- and AMPA-associated differential DNA methylation, and further explore whether DNA methylation could serve as a biomarker of glyphosate exposure. https://doi.org/10.1289/EHP10174     

Improvement in Cardiovascular Risk Prediction with Electronic Health Records

The aim of this study was to compare the QRISKII, an electronic health data-based risk score, to the Framingham Risk Score (FRS) and atherosclerotic cardiovascular disease (ASCVD) score. Risk estimates were calculated for a cohort of 8783 patients, and the patients were followed up from November 29, 2012, through June 1, 2015, for a cardiovascular disease (CVD) event. During follow-up, 246 men and 247 women had a CVD event. Cohen’s kappa statistic for the comparison of the QRISKII and FRS was 0.22 for men and 0.23 for women, with the QRISKII classifying more patients in the higher-risk groups. The QRISKII and ASCVD were more similar with kappa statistics of 0.49 for men and 0.51 for women. The QRISKII shows increased discrimination with area under the curve (AUC) statistics of 0.65 and 0.71, respectively, compared to the FRS (0.59 and 0.66) and ASCVD (0.63 and 0.69). These results demonstrate that incorporating additional data from the electronic health record (EHR) may improve CVD risk stratification.