Iodine-Catalyzed Claisen-Rearrangements of Allyl Aryl Ethers and Subsequent Iodocyclizations.

Iodine can be considered as the simplest halogen-bond donor. Previous investigations have revealed its remarkable catalytic effect in various reactions. The catalytic activity of iodine can often even compete with that of traditional Lewis acids. So far, iodine was typically used to activate carbonyl derivatives like Michael acceptors. We now demonstrate that iodine can also be used to activate allyl aryl ethers in Claisen rearrangements. The formed ortho-allylic phenols rapidly undergo iodocyclizations to afford dihydrobenzofurans, which are important building blocks for medicinal applications. A comparison with different catalysts further highlights the potential of iodine catalysis for this reaction. Computational and mechanistic investigations provide deeper insights into the underlying non-covalent interactions and their role for the catalysis.

Anxiety and depression are common in rheumatoid arthritis and correlate with poor quality of life in Indian patients.

OBJECTIVES: We planned this study to assess the prevalence of anxiety and depression in rheumatoid arthritis (RA) patients and its correlation with quality of life (QOL) in these patients. MATERIAL AND METHODS: Eighty-eight patients (76 females) were included in this cross-sectional study. The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression. Quality of life was measured using the World Health Organization WHOQOL-BREF. The severity of pain was measured by 100-millimetre-long Visual Analogue Scale (VAS), and functional disability was measured by using the Indian version of the Health Assessment Questionnaire (HAQ). The disease activity was measured by Disease Activity Score for 28 joints with 3 variables. RESULTS: Probable anxiety and depression were seen in 61 (69%) and 68 (77%) of the patients, respectively. Patients with anxiety had more severe pain (VAS 53.8 ±26.4 vs. 39.7 ±26.1, p < 0.05), and significantly lower scores in all the 4 domains of the WHOQOL-BREF. Patients with depression had more pain (VAS 54.2 ±25.2 vs. 33.5 ±27.3, p < 0.01), higher HAQ scores (1.0 ±0.7 vs. 0.5 ±0.7, p < 0.01), and lower QOL scores. Both anxiety and depression scores had a negative correlation with all the 4 domains of the WHOQOL-BREF. Anxiety had a significant negative effect on psychological (ß = -0.58, p < 0.001) and environmental domains (ß = -0.39, p < 0.001), while depression had a significant negative effect on psychological (ß = -0.57, p < 0.001) and environmental domains (ß = -0.53, p < 0.001). Both anxiety and depression predicted more pain in RA patients (ß = 0.24, p < 0.001 and ß = 0.44, p < 0.001, respectively). CONCLUSIONS: Anxiety and depression correlated with poor QOL in all 4 domains of the WHOQOL-BREF. Higher HADS scores had a negative effect on all the domains of the WHOQOL-BREF and predicted more severe pain in RA patients. Thus, patients with RA need to be screened and treated for underlying anxiety and depression to improve their QOL, pain, and functional status.

Temporal sustainability of guideline based door-to-needle times for intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: Door to needle (DTN) time provides valuable insight into stroke care workflow and is a performance indicator of an acute stroke unit. The aim of the current study was to ascertain whether a door to needle time of less than 60 min can be achieved for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) and maintained long term in a comprehensive stroke unit. METHODS: Patients with AIS treated with IVT in the stroke unit formed the study group. Demographic and clinical characteristics including door to imaging (DTI) time, DTN time, and 3 month functional outcome were abstracted. Pairwise comparison was done of yearly median DTI and DTN times with Bonferroni correction. RESULTS: Over a period of 6 years a total of 196 patients with mean age of 61.5 ± 13.1 years and median (IQR) NIHSS 11 (8-16) underwent IVT. The median DTI time and DTN time over the study period was 15 (12-21) minutes and 40 (30-50) minutes respectively. A total of 90.1%, 69.4% and 29.1% patients received IVT within 60 min, 45 min and 30 min respectively. On pairwise comparison of the median yearly DTN Year 2016 and 2017 were lower compared to most of the earlier years (p < 0.0001). Good functional outcome (mRS ≤ 2) was noted in 68.7% patients at 3 months follow-up. CONCLUSION: It is possible to sustainably reduce DTN time for IVT in AIS to well below the current 60 min benchmark with hospital system training and teamwork.

Electroneurography and Advanced Neuroimaging Profile in Pediatric-onset Metachromatic Leukodystrophy.

CONTEXT: Metachromatic leukodystrophy (MLD) is a rare autosomal-recessive disorder characterized by demyelination of central and peripheral nervous system. There is scarcity of literature on the electrophysiological aspects of peripheral nerves and the advanced neuroimaging findings in MLD. AIM: The aim was to study the nerve conduction parameters and advanced neuroimaging findings in patients with MLD. MATERIALS AND METHODS: This study is a retrospective analysis conducted, between 2005 and 2016, of 12 patients who had biochemical, histopathological, or genetic confirmation of MLD and disease onset before 18 years of age. The clinical, electroneurography, and the advanced neuroimaging findings were reviewed and analyzed. STATISTICAL ANALYSIS: The data were presented as percentages or mean ± standard deviation as defined appropriate for qualitative and quantitative variables. RESULTS: Mean age of onset was 4.84 (±4.60) years and seven patients were males. Eight patients had juvenile MLD and four had late infantile MLD. Clinical presentation of psychomotor regression was more common in infantile MLD (75%), whereas gait difficulty (62.5%) and cognitive impairment (37.5%) were more frequent in juvenile MLD. Nerve conduction study (NCS) revealed diffuse demyelinating sensorimotor peripheral neuropathy in 9 (75%) patients. One patient had a rare presentation with conduction blocks in multiple nerves with contrast enhancement of cauda equina. Diffusion restriction involving periventricular and central white matter was seen in five patients and bilateral globus pallidi blooming was noted in three patients. CONCLUSION: This study highlights the utility of NCS and advanced magnetic resonance imaging sequences in the diagnosis of MLD.

Conformational switching via an intramolecular H-bond modulates the fluorescence lifetime in a novel coumarin-imidazole conjugate.

Achieving synthetic control over light-driven molecular dynamics is essential for designing complex molecule-based devices. Here we design a novel coumarin-imidazole conjugate (1) whose excited state structural dynamics are primarily controlled by a distant intramolecular H-bonding interaction within the backbone. The coumarin conjugate is based on a 1,2,4,5-aryl substituted imidazole framework (aryl = -Ph and -PhOH) covalently connected to the coumarin moiety via a C-N bond. A carefully positioned OH group in the aryl part of the imidazole fragment resulted in achieving two dissimilar O-HN and O-HO distal intramolecular hydrogen bonding interactions. NMR studies in conjunction with density functional theory (DFT) at the B3LYP/6-311G(d,p) level of theory show the existence of two ground state conformers with a rotational barrier of 6.12 kcal mol-1. Due to the presence of conformational isomers of 1, the local excited state dynamics of the parent coumarin get biased towards a long-lived fluorescence state with diminished non-radiative decay channels. Time-resolved emission studies show an ∼4-5 times increase in the excited state lifetime in 1 when compared to coumarin-imidazole conjugates, 2 and 3, without the OH group. Solvent dependent studies show that solvent polarity, the H-bond donating ability and viscosity dictate the conformational distribution in the ground state and the dynamical evolution to the final emissive state. Our studies highlight the importance of rotamerism around the C1-C4 single bond, which leads to rigidification along the coumarin-imidazole backbone through a combination of distal H-bonding and solvent interactions. The concept of new emission signaling pathways caused by conformational switching between two states offers a new paradigm to introduce functional allostery in macromolecular backbones.