Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Influence of Gender and Age on the Willingness to Reduce Nicotine Consumption—Results of a Survey in Urological Cancer Patients (KRAUT Study)

Although it is well-known that smoking can cause lung cancer, the relationship between smoking and urologic cancers seems not as obvious and awareness is not widespread in the general population. For the KRAUT (knowledge of the relation between smoking and urological tumors among patients with a urological tumor disease) study, 258 patients with the diagnosis of urological cancer were interviewed using a questionnaire. Most (72.1%) stated that they never had a conversation regarding this topic with any doctor. Educational work in this field should be intensified to reduce the development and progression of urologic cancer. Purpose: Our objective was to investigate whether patients with urologic tumors were aware of smoking as a risk factor for the development and progression of several urologic cancers and the extent of the medical education they had received. Another aim was to investigate whether gender or age influenced patients' willingness to change their smoking habits. Materials and Methods: Patients with histologically malignant urologic tumors were enrolled in our questionnaire-based study from September 2013 to December 2014 in 2 urology departments. Patients were asked about their smoking habits and their general understanding of the relationship between smoking and the onset of cancer (urologic cancer and lung cancer). Also, the extent of information they had acquired from a physician was assessed. The descriptive and oncologic data of the patients were recorded. Results: Of 258 enrolled patients, 186 (72.1%) had never had an informational discussion with a doctor about smoking and their urologic tumor disease. Of the 160 active and former smokers, only 45 (28.1%) were planning to stop or reduce smoking because of their tumor disease. The willingness to change smoking habits was greater for women, with a statistically significant difference (odds ratio, 5.59; P = .002). Younger patients aged <58 years were also more willing to reduce or stop smoking. Conclusion: In our study, most patients with urologic cancer were unaware of smoking as the most probable cause of tumor development. The patients had not received proper counseling from doctors on smoking and the risk it poses for tumor progression. Efforts to balance compliance among the genders and age groups through risk-adapted counseling should be undertaken. (C) 2018 Elsevier Inc. All rights reserved

What do patients with urothelial cancer know about the association of their tumor disease with smoking habits? Results of a German survey study

Purpose: Smoking represents a primary risk factor for the development of urothelial carcinoma (UC) and a relevant factor impacting UC-specific prognosis. Data on the accordant knowledge of UC-patients in this regard and the significance of physicians in the education of UC-patients is limited. Materials and Methods: Eighty-eight UC-patients were enrolled in a 23-items-survey-study aimed to analyse patient knowledge and awareness of their tumor disease with smoking along with physician smoking cessation counselling. Results: The median age of the study patients was 69 years; 26.1% (n=23), 46.6% (n=41), and 27.3% (n=24), respectively, were non-smokers, previous, and active smokers. Exactly 50% of active smokers reported a previous communication with a physician about the association of smoking and their tumor disease; however, only 25.0% were aware of smoking as main risk factor for UC development. Merely 33% of the active smokers had been prompted directly by their physicians to quit smoking. About 42% of active smokers had received the information that maintaining smoking could result in a tumor-specific impairment of their prognosis. Closely 29% of active and about 5% of previous smokers (during the time-period of active smoking) had been offered support from physicians for smoking cessation. No association was found between smoking anamnesis (p=0.574) and pack-years (p=0.912), respectively, and tumor stage of UC. Conclusions: The results of this study suggest that the medical conversation of physicians with UC-patients about the adverse significance of smoking is limited. Implementation of structured educational programs for smoking cessation may be an opportunity to further enhance comprehensive cancer care