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Introduction: Foot covering was one of the first things made by our primitive ancestors. Shoes have played an important role in human culture throughout history. Shoemakers and their health have attracted less attention than the shoes themselves. Musculo-skeletal problems were explored in this study to find out the prevalence and associated factors among the workers of the shoe making community in Kolkata, West Bengal. Methods: The study was done where shoemakers of the study area were considered and basic information on socio-economic status, demographic characteristics, pattern of musculo-skeletal morbidities. Community based cross-sectional study design was adopted and data collection was done through observation, interview and clinical examination. Results: This study found high prevalence (45.6%) of musculo-skeletal ailments among the shoe making workers and among all the ailments considered, most of them were suffering from ‘pain in limb joints’ (34.3%) followed by ‘low back pain’ (32.9%) and ‘neck pain’ (31.5%). Chi-square for linear trend analysis showed increasing odds ratio from 1 to 11.16 when the total duration of work for the shoemakers increased from less than 5 years to more than 21 years which was also statistically significant (χ2 = 21.82; p < 0.01). Similar trend was observed where odd ratio increased from 1 to 2.95 when daily working hours increased from less than 9 hours to more than 12 hours. (χ2 = 2.95; p < 0.09). Conclusion: Our study concluded high prevalence of musculo-skeletal ailments among shoe making workers and those are in increasing in linear trend analysis.

Background: During the recent pandemic, the number of patients with influenza-like symptoms had considerably increased in fever clinics of hospitals leading to queuing and increased patient dissatisfaction. Aims and Objectives: A time-motion study was therefore designed to evaluate the time taken at different service delivery points in the fever clinic and patient satisfaction regarding service delivery time. Materials and Methods: An institutional cross-sectional observational study was conducted at the fever clinic of Midnapore Medical College and Hospital for 1 month. A total of 200 patients were selected by systematic random sampling from the fever clinic outdoors and their movement was recorded and satisfaction assessed. Results: Most patients visited the clinic during the start of the week and in the first half of the day. The total mean time required from entry to exit was 9089 s±143.0. The maximum time was spent waiting time in the fever clinic entry queue followed by that at the pharmacy. The minimum time required was at the nursing table followed by a doctor’s consultation. The maximum meantime for movement between two stations was between station 5 (laboratory investigation station) and station 6 (pharmacy), that is, 1144 s±183.6. The majority of the study population was not satisfied with the time management in the fever clinic whereas only 18.0% of the participants were fully satisfied. Conclusion: Identifying the loopholes and formulating an effective time management strategy can help deliver better patient care as well as boost patient satisfaction.

Background: Effective vaccination is a successful tool for controlling COVID-19 pandemic, along with other preventive measures. Both intention to get vaccinated and barrier to vaccination played important role in COVID vaccination drive. Aims and Objectives: The present study was conducted to assess awareness, acceptance, and hesitancy about COVID-19 vaccine among the residents of rural and urban area and to assess the factors related to their attitude. Materials and Methods: A descriptive cross-sectional survey was conducted among the adult residents of urban and rural area over 6 months. Total sample size was 400. Simple random sampling technique was adopted to recruit the study participants after obtaining informed verbal consent. This process was continued until the desired number of sample size was attained. Data were compiled after collection and analysis was done. Results: Rural population had significantly higher knowledge of coronavirus and urban population knew prevention of coronavirus infection more. Correct knowledge of COVID vaccine availability was higher among rural people but higher knowledge of vaccine related information was among urban population. Sources of information were mainly from mass media. Vaccine acceptance was more among urban population, but apprehension was significantly higher among urban residents. Higher proportion of urban people was motivated significantly by the healthcare workers as well as self-motivated than their rural counterpart. Conclusion: Targeted interventions could be developed for increasing awareness of disease and availability of COVID-19 vaccines. Population-based vaccination program can decline the trend of the pandemic in long term.

We report a unique intraoperative finding of an additional double left atrial appendage (LAA) during an arterial switch operation with ventricular septal defect closure in a 4-month-old girl. Immediately after the procedure, a prolapsing mass within the left atrium (LA) on the transesophageal echocardiogram raised concerns of a possible thrombus. The LAA was clearly visible with a pressure monitoring line which was put intraoperatively. To investigate further, cardiopulmonary bypass was resumed, and the heart was arrested and explored. There was an appendage-like structure, separate from the one that had the pressure monitoring line, which was inverted inside. It was pulled out from outside clearly establishing a double LAA. This report illustrates an example of a diagnostic dilemma caused by a double atrial appendage which was invaginated into LA masquerading as a mass or thrombus.

Secondary erythrocytosis occurs in cyanotic heart disease as a physiological response to chronic hypoxia, and this leads to hyperviscosity and various complications of the same. Microvascular stasis due to hyperviscosity results in symptoms including headache, fatigue, paraesthesia, and loss of vision. An important and dreadful feature of hyperviscosity is overt thrombosis in organ systems, resulting in cerebrovascular accident and myocardial infarction. Limited body iron store in a state of secondary erythrocytosis brings forth iron-deficient microcytic red cells; these being more rigid and less deformable than normocytic cells, further aggravate vascular occlusion. The management of hyperviscosity syndrome starts with intravenous hydration and correction of latent iron deficiency. However, therapeutic phlebotomy may be employed as a rescue measure if symptoms persist despite correction of dehydration and anemia. We present a series of four patients with uncorrected cyanotic congenital heart disease who presented with a spectrum of features of hyperviscosity and discuss pathophysiology, clinical features, and management of hyperviscosity in detail.

Objective: The objective of this study is to delineate the characteristics and outcome of Pediatric Inflammatory Multisystem Syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection (PIMS-TS) in Eastern Indian settings. Materials and Methods: We conducted a prospective observational multicentric study from May 2020 to August 2020, collecting data on clinical profile, investigation findings, and outcome of the children aged 1 month–12 years admitted with the features of coronavirus disease 2019 (COVID-19) related hyperinflammation satisfying criteria for PIMS-TS from three tertiary care hospitals of Kolkata. Results: A total of 38 patients fulfilling the criteria of PIMS-TS were recruited. The median age of the study population was 5 years (1.9–8 years). Gastrointestinal symptoms were present in 33 (86.6%) of patients. Nasopharyngeal swab for COVID-19 reverse transcriptase-polymerase chain reaction was positive in 19 (50%) of patients, and immunoglobulin G antibody against COVID-19 was found in 12 (66.6%) of patients, whereas 19 (50%) of patients had a positive contact history of SARS-Co-V2 exposure. The features of Kawasaki, like illness with coronary changes, were seen in 12 (32%) cases, whereas myocarditis with ejection fraction

Transcatheter closure of patent ductus arteriosus (PDA) is now the standard of care with some exceptions. Best treatment for peripheral pulmonary artery (PA) stenosis in small children is still debatable. Surgical augmentation, balloon dilatation, and stenting are the available options with each having its own risks and limitations. Here, we are reporting complete transcatheter management of three cases of congenital rubella syndrome who had PDA and left branch PA stenosis by device closure and stent placement, with successful outcome in two cases and complication, leading to surgery in one. We also share our understanding of case selection for a better outcome.

The biosynthesis of cholesterol, an essential component of higher eukaryotic membranes, was worked out by Konrad Bloch (and Feodor Lynen) in the 1960s and they received the Nobel Prize around that time in recognition of their pioneering contributions. An elegant consequence of this was a hypothesis proposed by Konrad Bloch (the Bloch hypothesis) which suggests that each subsequent intermediate in the cholesterol biosynthesis pathway is superior in supporting membrane function in higher eukaryotes relative to its precursor. In this review, we discuss an autosomal recessive metabolic disorder, known as Smith-Lemli-Opitz syndrome (SLOS), associated with a defect in the Kandutsch-Russell pathway of cholesterol biosynthesis that results in accumulation of the immediate precursor of cholesterol in its biosynthetic pathway (7-dehydrocholesterol) and an altered cholesterol to total sterol ratio. Patients suffering from SLOS have several developmental, behavioral and cognitive abnormalities for which no drug is available yet. We characterize SLOS as a manifestation of the Bloch hypothesis and review its molecular etiology and current treatment. We further discuss defective Hedgehog signaling in SLOS and focus on the role of the serotonin1A receptor, a representative neurotransmitter receptor belonging to the GPCR family, in SLOS. Notably, ligand binding activity and cellular signaling of serotonin1A receptors are impaired in SLOS-like condition. Importantly, cellular localization and intracellular trafficking of the serotonin1A receptor (which constitute an important determinant of a GPCR cellular function) are compromised in SLOS. We highlight some of the recent developments and emerging concepts in SLOS pathobiology and suggest that novel therapies based on trafficking defects of target receptors could provide new insight into treatment of SLOS.

Idiopathic dilated cardiomyopathy in children is a hopeless disease; most of the time, patients are destine to die or ultimately become transplant candidate. In our case series, on meticulous re-examination, treatable conditions such as obstructive disease (aortic stenosis, coarctation of aorta) or coronary artery abnormality (anomalous origin of the left coronary artery from the pulmonary artery and coronary artery occlusion by thrombus) or rhythm abnormality (supraventricular tachycardia) were diagnosed, and all patients were improved after successful correction of underlying cardiac disease.

In the midst of the COVID-19 pandemic, we report two cases of children presenting with typical diagnosis of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) who suffered from complete heart block requiring pacemaker placement which is an unusual presentation of PIMS-TS. We also compared it with the already existing data with similar manifestations. PIMS-TS is reported to occur in children with predominantly gastrointestinal symptoms, hemodynamic instability, and myocardial dysfunction. The implications of development of atrioventricular block during critical illness in PIMS-TS are yet unknown. Both patients had an otherwise normal cardiac structure and had no gastrointestinal symptoms but suffered complete heart block without any other identifiable etiology, both requiring temporary pacemaker placement. While one child recovered completely with medical management, the other child required permanent pacemaker placement. While we cannot be certain that COVID-19 was the cause, complete heart block appeared to be temporally related to COVID-19 infection in both patients, and hence, it is important for pediatricians to be aware of the potential manifestation of this disease.

Mid-term follow-up studies following modified Nikaidoh procedure done for Transposition of great arteries (TGA) with ventricular septal defect (VSD) with pulmonary stenosis (PS) showed that majority of the reoperations are in the form of conduit replacement either due to conduit stenosis or regurgitation. Bilateral branch pulmonary artery (PA) stenosis following Nikaidoh procedure is very rare. We are reporting a case of TGA, VSD with PS with borderline branch PAs who underwent modified Nikaidoh procedure and developed severe bilateral branch PA stenosis during early postoperative period. The patient was managed successfully with bilateral branch PA stenting.

Previous work from us and others has suggested that cholesterol is an important lipid in the context of the organization of the actin cytoskeleton. However, reorganization of the actin cytoskeleton upon modulation of membrane cholesterol is rarely addressed in the literature. In this work, we explored the signaling crosstalk between cholesterol and the actin cytoskeleton by using a high-resolution confocal microscopic approach to quantitatively measure changes in F-actin content upon cholesterol depletion. Our results show that F-actin content significantly increases upon chronic cholesterol depletion, but not during acute cholesterol depletion. In addition, utilizing inhibitors targeting the cholesterol biosynthetic pathway at different steps, we show that reorganization of the actin cytoskeleton could occur due to the synergistic effect of multiple pathways, including prenylated Rho GTPases and availability of membrane phosphatidylinositol 4,5-bisphosphate. These results constitute one of the first comprehensive dissections of the mechanistic basis underlying the interplay between cellular actin levels and cholesterol biosynthesis. We envision these results will be relevant for future understating of the remodeling of the actin cytoskeleton in pathological conditions with altered cholesterol.

Aim & objective: To report mid-term follow-up result of transcatheter closure of perimembranous Ventricular septal defect (VSD) in children weighing less than 10 kg using Amplatzer Duct Occlude-I (ADO-I) by left ventricular (LV) mid-cavity approach. Material & method: This is retrospective review of 35 children weighing less than 10 kg with moderate to large perimembranous VSD who were selected for transcatheter closure of VSD using ADO-I in between October 2016 to September 2018. Mean age was 2.08 ± 0.67 years (mean ± SD) and mean weight was 7.2 ± 1.2 kg (mean ± SD). Procedure was done by crossing the VSD from right ventricular side instead of using the standard approach by forming arterio-venous loop. Average fluoroscopic time was 9.2 ± 2.9 min (mean ± SD) and mean procedure time was 34.1 ± 13.1 min (mean ± SD). Mean follow-up period was 8.7 months (3–12 months) Result: Device closure was successfully done in 32 patients. There was device induced aortic regurgitation (AR) in one case who was sent for surgery. One child was found to have complete heart block on first post-procedure day requiring permanent pace-maker implantation. During follow up none of them had any residual VSD, rhythm disturbance, AR and left or right ventricular outflow obstruction. Conclusion: Device closure can be successfully done in moderate to large perimembranous VSD using left ventricular mid cavity approach in small children. LV mid-cavity approach has advantages in terms of lesser hemodynamic instability, lesser fluoroscopy and lesser chance of device induced AR than standard technique particularly in smaller children.

Abstract Background In majority of children bidirectional Glenn shunt is a safe and efficacious procedure with minimal post-operative issues. Rarely, there may be dysfunction in the Glenn pathway due loss of anatomical integrity or derangements in normal physiological or hemodynamic milieu. We report 4 cases in the last 3 years (2016-2019) where complications in the Glenn circuit led to serious consequences requiring transcatheter interventions. Case presentation Two of our patients presented with frank features of superior vena cava syndrome. One of them had right Glenn anastomotic site narrowing leading to severe obstruction along with significant left pulmonary artery origin stenosis. The other child had excessive antegrade flow impeding normal Glenn flow leading to superior vena cava syndrome. The next child in our series was initially lost to follow-up after bidirectional Glenn surgery. Later on, this child was noted to have discontinuous left pulmonary artery with perfusion only to the right lung from the Glenn. The remaining child described in this series had developed a large tortuous venous collateral post Glenn shunt leading to severe cyanosis. All the above children needed prompt percutaneous interventions to revert back to their basal state. On follow-up, the benefit was sustained in all. Conclusions Percutaneous intervention procedures often provide a successful bailout option in various complicated situations post Glenn surgery with reasonable efficacy and safety.

Unexplained cyanosis without any complex congenital heart disease needs further diagnostic work up. We present an adolescent child presenting with unexplained cyanosis who was found to have diffuse pulmonary arteriovenous malformations (PAVMs) due to abernethy malformation type 2, a variety of congenital extrahepatic portosystemic shunt (CEPS). This malformation was successfully closed by endovascular occlusion.

Kawasaki disease (KD) is a vasculitis of medium-sized arteries of which coronary artery involvement is of particular concern. Here, we are presenting three cases of KD with coronary artery aneurysm. One patient was treated with oral antiplatelet and anticoagulant, another one with impending coronary artery occlusion was managed by infusion of thrombolytic medication and last one, neglected KD patient needed coronary artery bypass grafting.

We report a case of 8-year-old boy with unexplained desaturation and clubbing. Echocardiography showed anomalous drainage of right superior vena cava into left atrium. He did not have any neurological symptoms preoperatively. Some perioperative observations and subtle postoperative behavioral changes prompted us to investigate him further. He was found to have extensive cerebral arteriovenous malformations and hemiatrophy of brain.

Congenital ventricular diverticulum is a rare congenital malformation of the heart. It remains mostly asymptomatic unless associated with other congenital cardiac defects. We present a case of a 4-month-old child who had dextrocardia, large inlet ventricular septal defect, amounting to single ventricle, and severe pulmonary artery hypertension. There was a right ventricular diverticulum which passed through the foramina of Morgagni to give rise to a pulsating lump in the epigastrium. Right ventricular diverticulum presenting with a pulsating mass in the abdomen is a rare entity. The confirmation of diverticulum was made with histopathology.

Complete sternal cleft is a very rare congenital midline defect of the sternum. It is not uncommonly associated with intracardiac defects. We report a case of a 2-year-old child with complete sternal cleft and tetralogy of Fallot who presented with cyanotic spells. The child underwent total correction, followed by chest wall reconstruction on the next day.

The dynamic interactions between G protein-coupled receptors (GPCRs) and their cognate protein partners are central to several cell signaling pathways. For example, the association of CXC chemokine receptor 1 (CXCR1) with its cognate chemokine, interleukin-8 (IL8 or CXCL8) initiates pathways leading to neutrophil-mediated immune responses. The N-terminal domain of chemokine receptors confers ligand selectivity, but unfortunately the conformational dynamics of this intrinsically disordered region remains unresolved. In this work, we have explored the interaction of CXCR1 with IL8 by microsecond time scale coarse-grain simulations, complemented by atomistic models and NMR chemical shift predictions. We show that the conformational plasticity of the apo-receptor N-terminal domain is restricted upon ligand binding, driving it to an open C-shaped conformation. Importantly, we corroborated the dynamic complex sampled in our simulations against chemical shift perturbations reported by previous NMR studies and show that the trends are similar. Our results indicate that chemical shift perturbation is often not a reporter of residue contacts in such dynamic associations. We believe our results represent a step forward in devising a strategy to understand intrinsically disordered regions in GPCRs and how they acquire functionally important conformational ensembles in dynamic protein-protein interfaces.

In this study, we have specifically blocked a key step of sphingolipid (SL) biosynthesis in Candida glabrata by disruption of the orthologs of ScIpt1 and ScSkn1. Based on their close homology with S. cerevisiae counterparts, the proteins are predicted to catalyze the addition of a phosphorylinositol group onto mannosyl inositolphosphoryl ceramide (MIPC) to form mannosyl diinositolphosphoryl ceramide (M(IP)2C), which accounts for the majority of complex SL structures in S. cerevisiae membranes. High throughput lipidome analysis confirmed the accumulation of MIPC structures in ΔCgipt1 and ΔCgskn1 cells, albeit to lesser extent in the latter. Noticeably, ΔCgipt1 cells showed an increased susceptibility to azoles; however, ΔCgskn1 cells showed no significant changes in the drug susceptibility profiles. Interestingly, the azole susceptible phenotype of ΔCgipt1 cells seems to be independent of the ergosterol content. ΔCgipt1 cells displayed altered lipid homeostasis, increased membrane fluidity as well as high diffusion of radiolabeled fluconazole (3H-FLC), which could together influence the azole susceptibility of C. glabrata. Furthermore, in vivo experiments also confirmed compromised virulence of the ΔCgipt1 strain. Contrarily, specific functions of CgSkn1 remain unclear.

Abstract Cholesterol plays a crucial role in cell membrane organization, dynamics and function. Depletion of cholesterol represents a popular approach to explore cholesterol-sensitivity of membrane proteins. An emerging body of literature shows that the consequence of membrane cholesterol depletion often depends on the actual process (acute or chronic), although the molecular mechanism underlying the difference is not clear. Acute depletion, using cyclodextrin-type carriers, is faster relative to chronic depletion, in which inhibitors of cholesterol biosynthesis are used. With the overall goal of addressing molecular differences underlying these processes, we monitored membrane dipole potential under conditions of acute and chronic cholesterol depletion in CHO-K1 cells, using a voltage-sensitive fluorescent dye in dual wavelength ratiometric mode. Our results show that the observed membrane dipole potential exhibits difference under acute and chronic cholesterol depletion conditions, even when cholesterol content was identical. To the best of our knowledge, these results provide, for the first time, molecular insight highlighting differences in dipolar reorganization in these processes. A comprehensive understanding of processes in which membrane cholesterol gets modulated would provide novel insight in its interaction with membrane proteins and receptors, thereby allowing us to understand the role of cholesterol in cellular physiology associated with health and disease.

Serotonin is a neurotransmitter that plays a crucial role in the regulation of several behavioral and cognitive functions by binding to a number of different serotonin receptors present on the cell surface. We report here the synthesis and characterization of several novel fluorescent analogs of serotonin in which the fluorescent NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) group is covalently attached to serotonin. The fluorescent ligands compete with the serotonin1A receptor specific radiolabeled agonist for binding to the receptor. Interestingly, these fluorescent ligands display a high environmental sensitivity of their fluorescence. Importantly, the human serotonin1A receptor stably expressed in CHO-K1 cells could be specifically labeled with one of the fluorescent ligands with minimal nonspecific labeling. Interestingly, we show by spectral imaging that the NBD-labeled ligand exhibits a red edge excitation shift (REES) of 29 nm when bound to the receptor, implying that it is localized in a restricted microenvironment. Taken together, our results show that NBD-labeled serotonin analogs offer an attractive fluorescent approach for elucidating the molecular environment of the serotonin binding site in serotonin receptors. In view of the multiple roles played by the serotonergic systems in the central and peripheral nervous systems, these fluorescent ligands would be useful in future studies involving serotonin receptors.

Background: A time and motion study is used to determine the amount of time required for a specific activity, work function, or mechanical process. Few such studies have been reported in the outpatient department of institutions, and such studies based exclusively on immunization clinic of an institute is a rarity. Materials and Methods: This was an observational cross sectional study done in the immunization clinic of R.G. Kar Medical College, Kolkata, over a period of 1 month (September 2010). The study population included mother/caregivers attending the immunization clinics with their children. The total sample was 482. Pre-synchronized stopwatches were used to record service delivery time at the different activity points. Results: Median time was the same for both initial registration table and nutrition and health education table (120 seconds), but the vaccination and post vaccination advice table took the highest percentage of overall time (46.3%). Maximum time spent on the vaccination and post vaccination advice table was on Monday (538.1 s) and nutritional assessment and health assessment table took maximum time on Friday (217.1 s). Time taken in the first half of immunization session was more in most of the tables. Conclusion: The goal for achieving universal immunization against vaccine-preventable diseases requires multifaceted collated response from many stakeholders. Efficient functioning of immunization clinics is therefore required to achieve the prescribed goals. This study aims to initiate an effort to study the utilization of time at a certain health care unit with the invitation of much more in depth analysis in future.

The cell cycle is a ubiquitous, multi-step process that is essential for growth and proliferation of cells. The role of membrane lipids in cell cycle regulation is not explored well, although a large number of cytoplasmic and nuclear regulators have been identified. We focus in this work on the role of membrane cholesterol in cell cycle regulation. In particular, we have explored the stringency of the requirement of cholesterol in the regulation of cell cycle progression. For this purpose, we utilized distal and proximal inhibitors of cholesterol biosynthesis, and monitored their effect on cell cycle progression. We show that cholesterol content increases in S phase and inhibition of cholesterol biosynthesis results in cell cycle arrest in G1 phase under certain conditions. Interestingly, G1 arrest mediated by cholesterol biosynthesis inhibitors could be reversed upon metabolic replenishment of cholesterol. Importantly, our results show that the requirement of cholesterol for G1 to S transition is absolute, and even immediate biosynthetic precursors of cholesterol, differing with cholesterol merely in a double bond, could not replace cholesterol for reversing the cell cycle arrest. These results are useful in the context of diseases, such as cancer and Alzheimer's disease, that are associated with impaired cholesterol biosynthesis and homeostasis.

Calcium signaling represents one of the most important signaling cascades in cells and regulates diverse processes such as exocytosis, muscle contraction and relaxation, gene expression and cell growth. G protein-coupled receptors (GPCRs) are the most important family of receptors that activate calcium signaling. Since calcium signaling regulates a large number of physiological responses, it is intriguing that how changes in cytosolic calcium levels by a wide range of stimuli lead to signal-specific physiological responses in the cellular interior. In order to address this issue, we have analyzed temporal calcium profiles induced by two GPCRs, the serotonin(1A) and purinergic receptors. In this work, we have described a set of parameters for the analysis of calcium transients that could provide novel insight into mechanisms responsible for maintaining signal specificity by shaping calcium transients. An interesting feature of calcium signaling that has emerged from our analysis is that the profile of individual transients in a calcium response could play an important role in maintaining downstream signal specificity. In summary, our analysis offers a novel approach to identify differences in calcium response patterns induced by various stimuli.