Thomassenschofield3902

Multiple sclerosis is a chronic, demyelinating disease of the CNS. Cognitive impairment is a sometimes neglected, yet common, sign and symptom with a profound effect on instrumental activities of daily living. The prevalence of cognitive impairment in multiple sclerosis varies across the lifespan and might be difficult to distinguish from other causes in older age. MRI studies show that widespread changes to brain networks contribute to cognitive dysfunction, and grey matter atrophy is an early sign of potential future cognitive decline. Neuropsychological research suggests that cognitive processing speed and episodic memory are the most frequently affected cognitive domains. #link# Narrowing evaluation to these core areas permits brief, routine assessment in the clinical setting. Owing to its brevity, reliability, and sensitivity, the Symbol Digit Modalities Test, or its computer-based analogues, can be used to monitor episodes of acute disease activity. The Symbol Digit Modalities Test can also be used in clinical trials, and data increasingly show that cognitive processing speed and memory are amenable to cognitive training interventions.Dreams are experiences that occur during sleep, while we are disconnected from the environment. Thanks to recent progress in neuroimaging techniques, it is now becoming possible to relate dream features to specific patterns of brain activity. Some conditions occurring in patients with neurological disorders, such as lucid dreams and parasomnias, not only have diagnostic value, but also offer a window into the dream process. They show that dreaming is reflected in physiological signals, behaviours, and brain activity patterns, and that the body can enact dream content. Yet, the dream body can also be distinct from the real body; in their dreams, patients with congenital paraplegia can walk, those with sleep apnoea rarely suffocate, and phantom limb pain can disappear. These conditions provide valuable models for future studies investigating the mechanisms that underlie oneiric experiences.

Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms.

We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datrogressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders.

Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust.

Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust.

Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity.

We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF.paro a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research.

For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

find more who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories.

CONQUER was a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial done at 64 sites (hospitals, clinics, or research centres) in 12 countries (Belgium, Canada, Czech Republic, France, Germany, Hungary, Japan, the Netherlands, South Korea, Spain, the UK, and the USA). link2 Patients were 18-75 years of age, with episodic or chronic migraine, with migraine onset before the age of 50 years, who had a documented failure of preventive medications from two to four drug categories in the past 10 years owing to lack of efficacy or tolerability, or both. Patients were randomised 11 to receive subcutaneous placebo or galcanezumab 120 mg perbo in the preventive treatment of migraine and was safe and well tolerated in patients for whom multiple previous standard-of-care preventive treatments had failed. Galcanezumab might represent an important treatment option for patients who have not benefited from or tolerated previous standard-of-care treatments.

Eli Lilly.

Eli Lilly.Gene therapy involves the introduction of new genes into cells, to modify or manipulate the expression of a gene or to alter the biological properties, for the purpose of treating disease. It is designed to treat genetic diseases at their root, by correcting the mutation responsible, its success in treatment of blood cancers and rare diseases is encouraging, and it is also beginning to show promising effects against solid tumors. Here, we comprehensively analyze all the active clinical trials of gene therapy for solid tumors from January 2010 to April 2020. Our analysis highlights the increasing trends in gene therapy trials in China and elsewhere, as well as the potential of oncolytic viruses as gene therapy products for solid tumors in vivo.Organic synthesis is a vital process that is a mainstay of drug discovery. However, traditional manual-based approaches to organic synthesis might not be economical, especially in a research environment where budgets are increasingly restricted and the effective use of manpower and materials is crucial. Hence, there is a strong interest in automating the synthesis process, resulting in a growth in synthesis automation, especially of systems and configuration. Here, we systematically summarize recently developed automated systems for organic synthesis. This review will be useful for computational scientists aiming to develop novel tools and also for non-specialists and students to understand the frontier of automated synthesis.As a result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, a clinical complication can arise that is characterized by a hyperinflammatory cytokine profile, often termed a 'cytokine storm'. A protein complex (nuclear factor kappa-light-chain-enhancer of activated B cells; NF-κB) is intricately involved in regulating inflammation and the immune response following viral infections, with a reduction in cytokine production often observed following a decrease in NF-κB activity. An approved asthma drug, montelukast, has been found to modulate the activity of NF-κB, and result in a corresponding decrease in proinflammatory mediators. Herein, we hypothesize that repurposing montelukast to suppress NF-κB activation will result in an attenuation of proinflammatory mediators and a decrease in cytokine production, thereby leading to a reduction in symptom severity and to improved clinical outcomes in patients with Coronavirus 2019 (COVID-19).Mental illness and substance use disorders in the workplace have been increasingly recognised as a problem in most countries; however, evidence is scarce on which solutions provide the highest return on investment. We searched academic and grey literature databases and additional sources for studies that included a workplace intervention for mental health or substance abuse, or both, and that did an economic analysis. We analysed the papers we found to identify the highest yielding and most cost-effective interventions by disorder. On the basis of 56 studies, we found moderate strength of evidence that cognitive behavioural therapy is cost-saving (and in some cases cost-effective) to address depression. We observed strong evidence that regular and active involvement of occupational health professionals is cost-saving and cost-effective in reducing sick leave related to mental health and in encouraging return to work. We identified moderate evidence that coverage for pharmacotherapy and brief counselling for smoking cessation are both cost-saving and cost-effective. Addressing mental health and substance misuse in the workplace improves workers' wellbeing and productivity, and benefits employers' bottom line (ie, profit). Future economic analyses would benefit from the consideration of subgroup analyses, examination of longer follow-ups, inclusion of statistical and sensitivity analyses and discussion around uncertainty, and consideration of potential for bias.Natural, nonsurgical internal mammary artery (IMA) bypasses to the coronary circulation have been shown to function as extracardiac sources of myocardial blood supply. link3 The goal of this randomized, placebo-controlled, double-blind trial was to test the efficacy of permanent right IMA (RIMA) device occlusion on right coronary artery (RCA) occlusive blood supply and on clinical and electrocardiographic (ECG) signs of myocardial ischemia.

This was a prospective superiority trial in 100 patients with chronic coronary artery disease randomly allocated (11) to RIMA vascular device occlusion (verum group) or to RIMA sham procedure (placebo group). The primary study end point was RCA collateral flow index (CFI) as obtained during a 1-minute ostial RCA balloon occlusion at baseline before and at follow-up examination 6 weeks after the trial intervention. CFI is the ratio between simultaneous mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure. Simultaneously obtained secondary study end points were the registration of angina pectoris and quantitative intracoronary ECG ST-segment shift.