Dithionite-Mediated Tandem Nitro Reduction/Imine Formation/Intramolecular Cyclization for the Synthesis of Dihydro-benzothiadiazine-1,1-dioxides

A one-pot, tandem reductive annulation of 2-nitrobenzenesulfonamides with aldehydes to the synthesis of substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxides in the presence of sodium dithionite (Na2S2O4) is reported under mild conditions. The method involves in situ reduction of the nitro group followed by condensation with aldehydes to form an imine, which upon subsequent intramolecular cyclization forms the product under one-pot conditions. The protocol features use of inexpensive Na2S2O4 as the exclusive reagent, appreciable functional group tolerance, broad substrate scope, high product yields, and scalability

Recognition of Double-Stranded RNA by Guanidine-Modified Peptide Nucleic Acids

Double-helical RNA has become an attractive target for molecular recognition because many noncoding RNAs play important roles in the control of gene expression. Recently, we discovered that short peptide nucleic acids (PNA) bind strongly and sequence selectively to a homopurine tract of double-helical RNA via formation of a triple helix. Herein, we tested if the molecular recognition of RNA could be enhanced by α-guanidine modification of PNA. Our study was motivated by the discovery of Ly and co-workers that the guanidine modification greatly enhances the cellular delivery of PNA. Isothermal titration calorimetry showed that the guanidine-modified PNA (GPNA) had reduced affinity and sequence selectivity for triple-helical recognition of RNA. The data suggested that in contrast to unmodified PNA, which formed a 1:1 PNA–RNA triple helix, GPNA preferred a 2:1 GPNA–RNA triplex invasion complex. Nevertheless, promising results were obtained for recognition of biologically relevant double-helical RNA. Consistent with enhanced strand invasion ability, GPNA derived from d-arginine recognized the transactivation response element of HIV-1 with high affinity and sequence selectivity, presumably via Watson–Crick duplex formation. On the other hand, strong and sequence selective triple helices were formed by unmodified and nucelobase-modified PNA and the purine-rich strand of the bacterial A-site. These results suggest that appropriate chemical modifications of PNA may enhance molecular recognition of complex noncoding RNAs

Objective measures of non-adherence in cardiometabolic diseases: a review focused on urine biochemical screening

Cardiometabolic diseases are among the most prevalent and harmful conditions worldwide. They are complex, comorbid conditions that require polypharmacy – a known contributor to non-adherence in cardiovascular disease (CVD) and diabetes mellitus (DM). Suboptimal adherence is associated with poor disease control, which increases the risk of hospitalizations, mortality, and preventable financial implications. However, until recently, the lack of a gold standard for non-adherence testing in cardiometabolic diseases has been the major barrier for understanding true prevalence and mortality consequences. Recent European guidelines have endorsed biochemical testing as the preferred measure for non-adherence in CVD, with urinary screening methods being the most clinically widespread. The diagnostic and therapeutic benefits incurred to health service resources by use of biochemical non-adherence testing are vast, as hospitalizations and associated economic burdens are reduced, and tailored therapies are increased. However, biochemical testing can only signify a snap shot of adherence behavior, and true adherence may be skewed by pharmacokinetic factors. This review summarizes current literature regarding the prevalence, impact, and reasons of non-adherence in cardiometabolic disease. The benefits of current adherence diagnostic tools have been appraised, where urine in biochemical testing has been focused upon and evaluated against other matrices

The curious case of an invisible dog: a patient with non-psychiatric visual hallucinations.

A 74-year-old man reported experiencing hallucinations of a dog standing on his right side, following a recent episode of infective endocarditis. There was no history of reduced conscious level, psychosis or substance misuse. Neurological examination revealed an isolated right inferior quadrantopia, and the hallucinations were visible only in the area of the visual defect. A computed tomography scan confirmed a left occipital lobe infarct, congruent with the clinical signs. The infarct was deemed to be have originated from a septic embolus of his infected aortic valve and he was diagnosed with Charles Bonnet's syndrome (CBS). CBS is characterized by the presence of stereotyped visual hallucinations on a background of partial sight and in the absence of any psychotic illness. Early recognition can prevent wrongful diagnosis of a psychiatric condition, which may provide comfort to patients. Management is centred on reassurance and counselling, with medical therapies reserved only for patients experiencing distressing hallucinations

LDA classification results during wide path self-driving.

<p>LDA classification results during wide path self-driving.</p

Equipment used during experimentation.

<p>Jazzy wheelchair (left) for the autonomous riding, IMASEN wheelchair (right) for the self-driving, and sensors attached to the subjects for the both tasks.</p

Evaluation lever and GSR characterizations during autonomous riding.

<p>Evaluation lever and GSR characterizations during autonomous riding.</p

Reducing vitamin D requests in a primary care cohort: a quality improvement study.

BACKGROUND:Since 2000, vitamin D requests have increased 2-6 fold with no evidence of a corresponding improvement in the health of the population. The ease of vitamin D requesting may contribue to the rapid rise in its demand and, hence, pragmatic interventions to reduce vitamin D test ordering are warranted. AIM:To study the effect on vitamin D requests following a redesign of the electronic forms used in primary care. In addition, any potential harms were studied and the potential cost-savings associated with the intervention were evaluated. DESIGN & SETTING:An interventional study took place within primary care across Leicestershire, England. METHOD:The intervention was a redesign of the electronic laboratory request form for primary care practitioners across the county. Data were collected on vitamin D requests for a 6-month period prior to the change (October 2016 to March 2017) and the corresponding 6-month period post-intervention (October 2017 to March 2018), data were also collected on vitamin D, calcium, and phosphate levels. RESULTS:The number of requests for vitamin D decreased by 14 918 (36.2%) following the intervention. Changes in the median calcium and phosphate were not clinically significant. Cost-modelling suggested that if such an intervention was implemented across primary care in the UK, there would be a potential annual saving to the NHS of £38 712 606. CONCLUSION:A simple pragmatic redesign of the electronic request form for vitamin D test led to a significant reduction in vitamin D requests without any adverse effect on the quality of care

Short-term (left) and long-term (right) correlation maps during autonomous riding.

<p>Significant primary and secondary correlations with respect to lever evaluations are shown red and blue, respectively. The width of the connection line corresponds to the Spearman correlation <i>ρ</i> value, solid lines indicate significant correlations.</p

LDA classification results during wide path self-driving.

<p>LDA classification results during wide path self-driving.</p