Pyridinium Ylide-Mediated Diastereoselective Synthesis of Spirocyclopropanyl-pyrazolones via Cascade Michael/Substitution Reaction.

We have devised a highly diastereoselective formal [2 + 1] annulation reaction of arylidene/alkylidine-pyrazolones with in situ-generated supported as well as standard pyridinium ylides to construct spirocyclopropanyl-pyrazolones. The cascade approach exhibits a wide range of functional group tolerance, gram-scale capability, and substrate versatility. A diverse range of spirocyclic cyclopropanes was synthesized extensively with both mediators, and the supported pyridine was reused in subsequent cycles. Density functional theory calculations confirmed the formation of spirocyclopropane as the lower energy pathway.

Diastereoselective synthesis of trans-2,3-dihydroindoles via formal [4 + 1] annulation reactions of a sulfonium ylide.

We have established an in situ generated sulfonium-ylide mediated annulation to construct 2,3-disubstituted-2,3-dihydroindoles. The [4 + 1] annulation approach relied on Michael addition/substitution reactions. These reactions were carried out at ambient temperature to deliver dihydroindoles with excellent yields and diastereoselectivities. Moreover, the versatility of this approach allows for the introduction of various functional groups, enabling further diversification of the dihydroindoles. Also, the cascade approach was broadened to synthesize dihydrobenzofurans.

Supported-amine-catalyzed cascade synthesis of spiro-thiazolone-tetrahydrothiophenes: assessing HSA binding activity.

We have devised a supported-amine-catalyzed efficient synthesis of spiro-thiazolone-tetrahydrothiophenes via a sulfa-Michael/aldol cascade approach. The catalyst demonstrated sustained efficacy over 21 cycles. These derivatives were found to exhibit excellent binding abilities with purified human serum albumin as indicated by both in silico and in vitro-based experiments.

Recyclable Polymer Supported DMAP Catalyzed Cascade Synthesis of α-Pyrones.

Polymer-supported catalysts have emerged as one of the sustainable and cost-effective alternatives in organic synthetic chemistry. We have developed the first polymer-supported DMAP catalyzed one-pot synthesis of diversely substituted α-pyrones. The cascade approach involves C5 conjugate addition of 5H-oxazol-4-ones to α,ß-unsaturated-ß-ketoesters followed by lactonization/elimination.

A reusable polymer anchored pyridine mediated formal [4 + 1] annulation reaction for the diastereoselective synthesis of 2,3-dihydrobenzofurans.

We have developed a highly stereoselective formal [4 + 1] annulation reaction to construct trans-2,3-dihydrobenzofurans utilising in situ generated supported pyridinium ylide. This approach has excellent substrate versatility and gram-scale synthesis capability. Moreover, the polymer-anchored pyridine has been recovered and reused multiple times. The product has been transformed into valuable molecules.

Severe cardiogenic shock and cardiac arrest due to fulminant cardiac sarcoidosis: a case report.

BACKGROUND: Cardiac sarcoidosis is found to occur in approximately 5% of patients with sarcoidosis. Its presentation can typically range from complete heart block to ventricular arrhythmias. This condition can rarely present with severe heart failure and cardiogenic shock requiring aggressive and timely management strategies. Advanced imaging techniques are usually required to assist with its diagnosis. CASE PRESENTATION: A 70-year-old woman with a history of pulmonary sarcoidosis presented with non-ST elevation myocardial infarction, congestive hepatopathy, and acute renal failure. Left heart catheterization showed evidence of non-obstructive coronary artery disease, and right heart catheterization revealed severely elevated filling pressures and depressed cardiac index. She underwent aggressive diuresis and placement of an intra-aortic balloon pump in addition to initiation of inotropic and vasopressor support. While in the cardiac intensive care unit, she experienced frequent episodes of ventricular tachycardia and went into cardiac arrest requiring cardiopulmonary resuscitation. High clinical suspicion for cardiac sarcoidosis was confirmed by cardiac magnetic resonance imaging findings. After starting immunosuppressive therapy for cardiac sarcoidosis, she demonstrated clinical improvement. CONCLUSION: Patients with cardiac sarcoidosis may remain asymptomatic or present with conduction abnormalities and arrhythmias. They rarely present with severe biventricular heart failure and cardiogenic shock, and in such cases, they require timely initiation of pharmacologic and device therapies, along with implementation of mechanical circulatory support.

Stereoselective synthesis of tri-substituted tetrahydrothiophenes and their in silico binding against mycobacterial protein tyrosine phosphatase B.

A facile approach to tri-substituted tetrahydrothiophenes via thia-Michael/aldol has been developed. The cascade reaction was carried out in the presence of 5 mol% of DABCO in ethyl acetate to afford diversely functionalized tetrahydrothiophenes (THTs) with excellent diastereoselectivity. The present methodology has broad substrate tolerance. Gram-scale reaction proceeds with equal efficiency. Functional group transformations further highlight the synthetic potential of the THTs. An asymmetric version of the cascade reaction has also been investigated and a maximum of 72% ee was observed with cinchonidine derived squaramide. Moreover, in silico based molecular docking followed by deep learning based affinity prediction and molecular dynamics simulation analysis indicate the synthesized THT derivatives can act as potent competitive inhibitors of MptpB at low micromolar to nanomolar concentrations. In silico ADME analysis further suggests the plausibility of these compounds to act as future anti-mycobacterial therapeutic leads.

Prevalence, risk factors and effects of restless legs syndrome in COPD patients.

Restless legs syndrome (RLS), a sensory motor disorder, is commonly seen amongst chronic obstructive pulmonary disease (COPD) patients. We conducted a study to know its prevalence in COPD and analyse the possible cause and effect of RLS. It is an analytical cross-sectional study conducted between July 2016-December 2020.The prevalence of RLS was evaluated in patients of COPD using RLS diagnostic criteria. Spirometry, iron profile and arterial blood gas analysis was performed in all the patients to evaluate the cause of RLS. The effect was evaluated with diagnostic criteria for insomnia and patient health questionnaire (PHQ2) for depression. There were 205 participants with a mean age of 59±8 years, 182 (88.7%) men and 23 (11.2%) women. The mean body mass index (BMI) was 29±3.9 kg/m2. The prevalence of RLS was 31.2%. RLS was more common amongst women compared to men (60.8% vs 27.4%). RLS was more prevalent among hypoxemic (PaO2<60 mm Hg) and hypercapnic (PaCO2>45 mm Hg) patients (p<0.016; p<0.017). The ROC curve plotted between PaO2 and RLS occurrence showed that the patients having PaO2 less than 76 mm of Hg were more prone to develop RLS. RLS patients had a higher incidence of insomnia as compared to those without RLS (68.8% vs 36.8%, p<0.001). COPD with RLS patients had more depressive symptoms with a higher patient health questionnaire 2 (PHQ2) score (35.9% vs 14.2%, p<0.001) compared to non-RLS COPD patients. The multiple regression analysis also confirmed that RLS led to insomnia and depressive symptoms in COPD patients. To conclude, RLS is common in COPD patients. RLS leads to insomnia and depression, thus should be identified and treated.

Vascular compression of Duodenum: A case report of superior mesenteric artery syndrome.

Superior mesenteric artery (SMA) passes over the third part of duodenum and can cause its obstruction when the aorto-mesenteric angle is hyper acute. Although the condition is rare, the diagnosis can be made using radiography and the treatment consists of division of ligament of Treitz and duodenojejunostomy. We present a case of SMA syndrome in an elderly lady, who was managed successfully with surgery.

Impact of the initial phase of COVID-19 pandemic on surgical oncology services at a tertiary care center in Eastern India.

BACKGROUND: The COVID-19 pandemic has caused a global health emergency and affected the resources in both the public and private health sectors significantly. The present study aims to assess the impact of the pandemic on the services by the department in the first 3 months since the first COVID case in the region. METHODS: The study period was from 16 March to 15 June 2020. We queried the database for data on site of the tumor, diagnosis, stage, tumor board decisions and planning, surgical procedures, adjuvant treatment, and follow-up details. The change in tumor board decision and actual treatment taken by the patient were all recorded, taking into consideration the COVID-19 pandemic. RESULTS: Among the 1567 patient contacts, 1306 were out-patient visits and 261 teleconsultations. Fifty-four patients underwent surgery from the 87 admitted to the hospital. Ten preoperative patients and two postoperative patients were tested for COVID and reported to be negative. CONCLUSIONS: The dilemma of providing cancer surgery services to the patients in this pandemic has been global. Strict measures and guidelines can help to overcome the COVID pandemic time, keeping in mind the locoregional logistics.

Enhancing cooperation during pediatric ultrasound: Oral midazolam versus conventional techniques.

BACKGROUND AND AIMS: Ultrasound is a safe and non-invasive method for detecting numerous pathologies. Pediatric patients are often uncooperative which leads to decreased quality and increased time of scan. We compared the conventional means alone and combination of oral midazolam for the above cited purpose. MATERIAL AND METHODS: This double blind prospective study (CTRI/2016/06/007030) was conducted after obtaining due approval from institutional ethical committee. One hundred Children aged 2-6 years belonging to ASA class 1 or 2, posted for high resolution ultrasonography of abdomen were included in the study. They were randomised to receive midazolam 0.3 mg/kg mixed in 20 mL of apple juice (Group I) or 20 mL of apple juice alone (Group II) 20 minutes prior to the procedure. The parameters assessed were level of cooperation, sonologist's satisfaction, total scan time, heart rate and SpO2. RESULTS: Out of 100 patients, 44 patients of group I and 42 of group II were analysed. The cooperation score was significantly higher in Group I (35%) than Group II (19%). Likert scale revealed very satisfied and satisfied rating in 61.3% (Group I) and 21.4% (Group II). The time taken by sonologist and number of attempts were significantly less in Group I than Group II. There was no difference in discharge time between the groups. There was no reportable adverse event in either group. CONCLUSION: Oral midazolam is a safe and effective agent to aid routine abdominal ultrasonography in pediatric patients.

Arterial spin labeling magnetic resonance perfusion study to evaluate the effects of age and gender on normal cerebral blood flow.

PURPOSE: Arterial spin labeling (ASL) is a noninvasive magnetic resonance (MR) perfusion technique to detect changes in blood flow. This study was undertaken to obtain a reference set of normal values of cerebral blood flow (CBF) in different age groups using three-dimensional pseudocontinuous ASL (3D PCASL) technique. The existence of an age-related decline in the gray matter (GM) and white matter (WM) CBF was evaluated. The gender-related CBF was also analyzed. MATERIALS AND METHODS: One hundred and sixty normal volunteers of varying age (6-72 years), arranged in 4 age groups, underwent MR perfusion imaging using 3D PCASL technique at 3 Tesla (T). Mean CBF values in global and regional GM and WM in different age groups were extracted from the quantitative perfusion map. RESULTS: A significant negative correlation was observed between the age and mean GM and WM CBF values (r = -0.80, P = 0.001; r = -0.59, P = 0.001, respectively). Similar results were also observed between age and various regional mean GM and WM CBF values (P = 0.001). No significant effect of gender on the GM CBF and WM CBF was found in any age group (P > 0.05). CONCLUSION: PCASL technique provides reliable quantitative parameters for the precise mapping of age-related perfusion changes occurring in the normal brain.

Discerning nonrigid 3D shapes from motion cues.

Many organisms and objects deform nonrigidly when moving, requiring perceivers to separate shape changes from object motions. Surprisingly, the abilities of observers to correctly infer nonrigid volumetric shapes from motion cues have not been measured, and structure from motion models predominantly use variants of rigidity assumptions. We show that observers are equally sensitive at discriminating cross-sections of flexing and rigid cylinders based on motion cues, when the cylinders are rotated simultaneously around the vertical and depth axes. A computational model based on motion perspective (i.e., assuming perceived depth is inversely proportional to local velocity) predicted the psychometric curves better than shape from motion factorization models using shape or trajectory basis functions. Asymmetric percepts of symmetric cylinders, arising because of asymmetric velocity profiles, provided additional evidence for the dominant role of relative velocity in shape perception. Finally, we show that inexperienced observers are generally incapable of using motion cues to detect inflation/deflation of rigid and flexing cylinders, but this handicap can be overcome with practice for both nonrigid and rigid shapes. The empirical and computational results of this study argue against the use of rigidity assumptions in extracting 3D shape from motion and for the primacy of motion deformations computed from motion shears.

An upcycled fraction of Melaleuca alternifolia essential oil regenerates the skin through the skin melatonin pathway and improves sleep quality.

BACKGROUND: Sleep is one of the most important factors affecting overall health. During the night, the skin repairs damage caused by daily stresses. Melatonin plays a key role in this process. Toxins are removed, and cellular repair and growth hormone production are increased. Inter alia, this also decreases signs of intrinsic aging. AIMS: The current study was intended to demonstrate the impact of a unique fraction of Melaleuca alternifolia (FMA) essential oil, on sleep and skin quality. METHODS: The effect of FMA was investigated in vitro on skin cells, evaluating its antioxidant and anti-inflammatory properties, and in an ex-vivo study on human skin biopsies treated with FMA following stress induction. In addition, two clinical studies were performed on volunteers with life-style-related sleep complaints. In one study, sleep was measured using a noncontact monitoring device (SleepScore Labs, Max). A second study was conducted to assess skin anti-aging effects. RESULTS: In vitro application of FMA reduced IL-8 and reactive oxygen species (ROS) generation in skin cells. This was confirmed ex vivo through a decrease in inflammatory markers and an increase in antioxidant enzymes after stress induction. Interestingly, FMA also upregulated melatonin-associated genes. Real-world sleep tracking revealed that FMA significantly improved sleep quality, relative to unscented control. In vivo applications also showed a reduction in signs of aging. CONCLUSION: These results provide initial data to suggest that this unique FMA delivers skin anti-aging benefits via a two-pronged mode of action, improving sleep quality, and reducing skin inflammatory and oxidative stress.

On-Arrival Lumbar Epidural Analgesia for Lower Limb Trauma Pain in Emergency Care: A Superiority Randomized Controlled Trial.

BACKGROUND: Lower limb trauma in emergency settings often leads to pain management challenges. Traditional methods, primarily non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, have limitations. This study explores the efficacy of epidural analgesia in emergency for lower limb trauma patients (ELETRA) as an alternative for managing pain in lower limb trauma patients upon arrival in emergency care. OBJECTIVES:  This study primarily focuses on determining ELETRA's effectiveness in reducing pain for patients with lower limb trauma upon arrival. It also aims to evaluate ELETRA's influence on decreasing stress and shortening hospital stays compared to traditional pain management approaches. METHODS: This study was executed as a prospective, parallel-design, randomized controlled trial in the emergency department of a tertiary care teaching hospital. The interventions were performed in a dedicated induction room adjacent to the emergency operating theater. The trial was registered in the Clinical Trial Registry of India with registration number CTRI/2022/08/044699 dated 16/08/2022. Participants were 18- to 50-year-old patients with lower limb injuries, classified under American Society of Anesthesiologists (ASA) class 1 or 2. Participants were randomized into two groups: one receiving ELETRA and the other standard pain control treatment. The effectiveness of pain relief was measured through a visual analog scale (VAS), and hemodynamic parameters, adverse effects, levels of acute phase reactants, and stress hormones were also measured along with patient satisfaction. RESULTS: The study enrolled 356 participants with lower limb injuries. After excluding participants lost following the intervention, data from 157 individuals in Group A and 160 in Group B were analyzed. Group A's success rate for analgesia (VAS < 2) was 92.35% (n = 145), significantly higher than Group B's 75.62% (n = 121) (p < 0.001). The commonest side effect was hypotension (5.73%) in Group A and nausea in Group B (7.5%). C-reactive protein (CRP) levels rose to 104.71 ± 8.99 mg/dL in Group A and 192.58 ± 9.23 mg/dL in Group B; the difference was statistically significant. Serum cortisol levels were also higher in Group B (67.18 ± 9.21) compared to Group A (44.72 ± 6.14) at one week. Group B had a longer hospital stay, averaging 12.24 ± 4.81 days, against Group A's 10.19 ± 4.91 days. CONCLUSION: ELETRA is a safe and effective alternative for pain management in lower limb trauma patients in emergency settings. It reduces pain, improves patient satisfaction, and has a favorable impact on stress responses.

Follow-up study of COVID-19 sequelae (FOSCO study).

INTRODUCTION: We undertook the first study from India to evaluate the long-term health effects of coronavirus disease 2019 (COVID-19). METHODS: The patients enrolled in our post-COVID-19 clinic were followed up for assessment at 1, 3, 6 and 12 months after recovery from acute disease prospectively. RESULTS: 200 patients with mean age of 50.72 years and 57.5% males were analysed. 42.5% had severe and 17% had moderate disease at the time of diagnosis. The persistence of symptoms beyond 1 month of diagnosis was seen in 72.5% (145/200) patients. 8% (16/200) of the patients had post-COVID-19 complications that required rehospitalisation after discharge or recovery from acute COVID-19. The complications included respiratory failure (2%), lung cavities (3.5%), fungal infection, pericardial effusion, pneumothorax and death. The symptoms were persistent beyond 3 months in 51% (102/200) and beyond 6 months in 17.5% (35/200) of cases. The patients with persistent symptoms beyond 3 months and 6 months had significantly higher intensive care unit (ICU) admission during acute COVID-19, severe disease during acute COVID-19, and higher prevalence of comorbidities compared to the recovered patients. The clinical recovery was attained in 95.5% (91/200) patients, and the radiological recovery was attained in 97.92% patients at 1 year. The mean duration to clinical recovery was 174.2 days. CONCLUSIONS: COVID-19 recovery takes longer time. However, clinico-radiological recovery is attained in >95% cases by one year.

Efficiency of extracting stereo-driven object motions.

Most living things and many nonliving things deform as they move, requiring observers to separate object motions from object deformations. When the object is partially occluded, the task becomes more difficult because it is not possible to use two-dimensional (2-D) contour correlations (Cohen, Jain, & Zaidi, 2010). That leaves dynamic depth matching across the unoccluded views as the main possibility. We examined the role of stereo cues in extracting motion of partially occluded and deforming three-dimensional (3-D) objects, simulated by disk-shaped random-dot stereograms set at randomly assigned depths and placed uniformly around a circle. The stereo-disparities of the disks were temporally oscillated to simulate clockwise or counterclockwise rotation of the global shape. To dynamically deform the global shape, random disparity perturbation was added to each disk's depth on each stimulus frame. At low perturbation, observers reported rotation directions consistent with the global shape, even against local motion cues, but performance deteriorated at high perturbation. Using 3-D global shape correlations, we formulated an optimal Bayesian discriminator for rotation direction. Based on rotation discrimination thresholds, human observers were 75% as efficient as the optimal model, demonstrating that global shapes derived from stereo cues facilitate inferences of object motions. To complement reports of stereo and motion integration in extrastriate cortex, our results suggest the possibilities that disparity selectivity and feature tracking are linked, or that global motion selective neurons can be driven purely from disparity cues.

Prevalence and spectrum of haemoglobinopathies in females of reproductive age group- A first tertiary care center experience in Punjab, North India.

Background: Thalassemia and hemoglobinopathies are a group of inherited conditions characterized by abnormalities in the synthesis or structure of hemoglobin (Hb). According to estimates, approximately 7% of the world population is a carrier of Hb disorders, leading to high morbidity and mortality. To reduce the burden of these highly prevalent monogenic disorders, detecting them in the carrier stage is crucial to prevent disease progression. Aim: We aimed to estimate the prevalence and spectrum of hemoglobinopathies in females in the reproductive (20-40 years) age group. Settings and Design: It was a retrospective observational study carried out for 2.5 years (from January 2018 till June 2020). Materials and Methods: All the females in the age group of 20-40 years age whose blood samples were received in the department for High-Performance Liquid Chromatography (HPLC) were included. The cases with abnormal HPLC findings were analyzed for hematological parameters including hemoglobin, RBC count, and RBC indices [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), & red cell distribution width - coefficient of variation (RDW-CV)]. Statistical Analysis: Statistical package for social science (SPSS) statistics 21 version for Microsoft Windows (Chicago, USA) was used for statistical analysis of data. The data were described in terms of range, mean ± standard deviation (SD), frequencies (number of cases), and relative frequencies (percentage) as appropriate. Results: During the study period, 72.2% of the females were affected with ß-thalassemia trait, followed by HbD Punjab trait (17.8%), HbQ India trait (2.9%), ß-thalassemia major (1.8%), and two cases (1.2%) each of HbS trait, HbD Iran trait, and compound heterozygous of HbD Punjab and ß-thalassaemia, whereas HbE trait, compound heterozygous of HbQ and ß-thalassemia, compound heterozygous of HbJ-variant and ß-thalassemia had one case each (0.6%). Conclusion: Preventive strategies are cost-effective and include population screening, premarital screening, screening of spouses, genetic counseling, and prenatal diagnosis. Educating the carrier females about the potential risk and various screening methods may help in controlling the disease.

Differential Radiographic Chest Findings in COVID-19 Positive Patients with and Without Comorbidities.

Background: The pandemic of Covid-19 resulted in significant morbidity and mortality, especially in those with pre-existing diseases like diabetes mellitus, cardiovascular diseases, etc., primarily due to extensive pulmonary involvement. The chest radiograph is the first imaging tool used in all Covid-19 patients. Hence, in this study, we attempt to understand and evaluate the role of the chest radiograph in Covid-19 patients with and without coexisting diseases. Materials and Methods: Our study included RTPCR-positive Covid-19 patients with comorbidities (560 cases) and without comorbidities (145 controls), viz. diabetes mellitus, hypertension, coronary artery disease, or thyroid disease. All controls and cases had chest radiographs with simple fractional zonal scores in a predesigned proforma. Statistical evaluation of chest radiograph scores was compared with and within groups. Results: Among the controls, approximately 63.5% revealed pulmonary findings on chest radiographs contrary to 77% among cases. No statistical differences were noted among controls and cases based on age and gender. The presence of pleural effusion was noted as a significant factor affecting the score and hence the prognosis in both controls and cases. Statistically significant differences were noted in SFZ scores between controls and various case groups. Conclusion: Chest radiograph scores in Covid-19 disease are higher in patients with comorbidities at the time of presentation, most marked in those with both hypertension and thyroid disease followed by those with hypertension and coronary artery disease. Lower zone predominance is seen in all patients including those with and without comorbidities. The chest radiograph scores become statistically significant with more than one existing comorbidity.