Neuroinflammation in neurological disorders: pharmacotherapeutic targets from bench to bedside

Metabolic Brain Disease - Neuroinflammation is one of the host defensive mechanisms through which the nervous system protects itself from pathogenic and or infectious insults. Moreover,...     

Anomalous origin of coronary artery from the opposite aortic sinus of Valsalva-a single center experience with a therapeutic conundrum

Background: Coronary artery anomalies are rare congenital abnormalities, most often found incidentally on conventional coronary angiography and CT angiography (CTA). CTA better delineates the origin and course of anomalous coronaries. Anomalous origin of coronary artery from the opposite aortic sinus of Valsalva (ACAOS) has a prevalence of 1% with a very few having an interarterial (malignant) course. There is limited literature, especially in the Indian population, dealing with this topic.Methods: In this retrospective observational study, angiographic data of 8500 consecutive patients from June 2011 to December 2019 at a large tertiary care hospital in western India was analyzed. Patients diagnosed with ACAOS underwent CTA for delineation of the exact anatomy. Those with a non-malignant course with evidence of ischemia clinically or on stress myocardial perfusion imaging (MPI), underwent PCI. Others with a non-malignant course were medically managed. Patients with malignant (interarterial) course were revascularized by coronary artery bypass graft (CABG) surgery in case of LCA involvement or positive MPI test. Asymptomatic patients with negative MPI were managed medically. Clinical follow-up over 12 months of patients undergoing PCI and those with a malignant course showed no major adverse cardiovascular events (MACE).Results: Of the 8500 patients studied, 74 (0.87%) had ACAOS. Of these, 51 (68.9%) patients had anomalous origin of right coronary artery (RCA) from the left aortic sinus, 21 (28.4%) had anomalous origin of the circumflex artery (Cx) from the right aortic sinus and two patients (2.7%) had an anomalous origin of the left main coronary artery (LCA) from the right aortic sinus. Interarterial course was found in five (6.7%) patients. Of these, four patients underwent CABG-one asymptomatic patient with LCA from right aortic sinus and three with positive MPI in anomalous RCA. All five patients with malignant course and ten patients who underwent PCI were free of MACE over 12 months’ clinical follow up.Conclusions: ACAOS is a rare anomaly and if interarterial course is excluded, then PCI is feasible in selected cases with significant stenosis. Patients with malignant course with inducible ischemia or LCA involvement should undergo surgical revascularisation.     

Design and rationale of an intelligent algorithm to detect BuRnoUt in HeaLthcare workers in COVID era using ECG and artificiaL intelligence: The BRUCEE-LI study

BackgroundThere is no large contemporary data from India to see the prevalence of burnout in HCWs in covid era. Burnout and mental stress is associated with electrocardiographic changes detectable by artificial intelligence (AI).ObjectiveThe present study aims to estimate the prevalence of burnout in HCWs in COVID-19 era using Mini Z-scale and to develop predictive AI model to detect burnout in HCWs in COVID-19 era.MethodsThis is an observational and cross-sectional study to evaluate the presence of burnout in HCWs in academic tertiary care centres of North India in the COVID-19 era. At least 900 participants will be enrolled in this study from four leading premier government-funded/public-private centres of North India. Each study centre will be asked to recruit HCWs by approaching them through various listed ways for participation in the study. Interested participants after initial screening and meeting the eligibility criteria, will be asked to fill the questionnaire (having demographic and work related with Mini Z questionnaire) to assess burnout. The healthcare workers will include physicians at all levels of training, nursing staff and paramedical staff who are involved directly or indirectly in COVID-19 care. The analysis of the raw electrocardiogram (ECG) data and development of algorithm using convolutional neural networks (CNN) will be done by experts.ConclusionsIn Summary, we propose that ECG data generated from the people with burnout can be utilized to develop AI-enabled model to predict the presence of stress and burnout in HCWs in COVID-19 era.     

Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases

GeroScience - Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated...     

Design,Synthesis and Characterization of HIV-1 CA-Targeting Small Molecules: Conformational Restriction of PF74

Small molecules targeting the PF74 binding site of the HIV-1 capsid protein (CA) confer potent and mechanistically unique antiviral activities. Structural modifications of PF74 could further the understanding of ligand binding modes, diversify ligand chemical classes, and allow identification of new variants with balanced antiviral activity and metabolic stability. In the current work, we designed and synthesized three series of PF74-like analogs featuring conformational constraints at the aniline terminus or the phenylalanine carboxamide moiety, and characterized them using a biophysical thermal shift assay (TSA), cell-based antiviral and cytotoxicity assays, and in vitro metabolic stability assays in human and mouse liver microsomes. These studies showed that the two series with the phenylalanine carboxamide moiety replaced by a pyridine or imidazole ring can provide viable hits. Subsequent SAR identified an improved analog 15 which effectively inhibited HIV-1 (EC₅₀ = 0.31 μM), strongly stabilized CA hexamer (ΔTm = 8.7 °C), and exhibited substantially enhanced metabolic stability (t_1/2 = 27 min for 15 vs. 0.7 min for PF74). Metabolic profiles from the microsomal stability assay also indicate that blocking the C5 position of the indole ring could lead to increased resistance to oxidative metabolism.     

Epileptiform activity in the electroencephalogram of 6-year-old children of women with epilepsy

Purpose:To study the epileptiform discharges (EDs) in the electroencephalogram (EEG) of 6-8-year-old children of women with epilepsy (WWE).Results:Of the 185 children examined, 37 (20%) children (19 males, 18 females) had ED in their EEG. The EDs were generalized in 7 children, and focal in 30 children. The EDs were present in the sleep record only of 16 (43%) children and in the awake record only of 6 (16%) children. Out of the 94 children for whom seizure history was available, 7 children (7.4%) had seizures (neonatal seizures: 4, febrile seizure: 1, and single nonfebrile seizure: 2) and none had history of epilepsy or recurrent nonfebrile seizures. The odds ratio (OR) for occurrence of ED in the EEG was significantly higher for children of WWE [OR = 3.5, 95% confidence interval (CI) 2.3-6.0] when compared to the published data for age-matched children of mothers without epilepsy. There was no association between the occurrence of ED and the children''s maternal characteristics [epilepsy syndrome, seizures during pregnancy, maternal intelligence quotient (IQ)] or the children''s characteristics [antenatal exposure to specific antiepileptic drugs (AEDs), birth weight, malformations, IQ].Conclusion:Children of WWE have a higher risk of epileptiform activity in their EEG when compared to healthy children in the community though none had recurrent seizures.     

Clinical significance of “positive” cervical spine MRI findings following a negative CT

Emergency Radiology - To review and analyze the clinical significance of positive acute traumatic findings seen on MRI of the cervical spine (MRCS) following a negative CT of the cervical spine...     

Twenty-first century tobacco use: it is not just a risk factor anymore

Despite availability of effective treatments for nicotine addiction, smoking remains prevalent with serious health consequences. Most smokers recognize the ill effects of smoking but are unable to quit. Nicotine addiction may be viewed as any other chronic illness that results from exposure to a recognizable agent (tobacco) and manifests with a well-documented set of signs and symptoms. Much like any chronic disease, both environmental and genetic factors determine the occurrence and severity of this affliction. There has been recent focus on uncovering the genetic basis of nicotine addiction. In this article, we have attempted to briefly review the current evidence for the role of genetics in smoking as well as comment on available pharmacotherapeutic options for treating nicotine dependence.