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.

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.

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.

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.

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.

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.

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.

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.

Reusable Supported Pyridine-Mediated Cascade Synthesis of trans-2,3-Dihydroindoles via In Situ-Generated N-Ylide.

Merrifield resin-anchored pyridines were prepared and applied as reusable mediators for trans-selective cascade synthesis of 2,3-dihydroindoles. The developed approach relied on in situ N-ylide formation followed by Michael substitution reactions. The cascade reaction was also carried out efficiently with simple pyridine. The products were further transformed into synthetically valuable compounds, and supported pyridine was reused for multiple cycles. Density functional theory calculations confirmed the trans-selectivity as the lower-energy pathway.

Long-term quality of life and work ability among severe COVID-19 survivors: A multicenter study.

Background: Coronavirus disease 2019 (COVID-19), is known for its variable severity and high infectivity. Though fewer than 15% of infected cases develop severe disease, a major proportion had prolonged stay in the intensive care unit (ICU). Prolonged ICU stay is known to have a long-term impact on behavior and quality of life.8 Therefore, it is likely that patients discharged after severe COVID-19 have issues that persist for long term. The current study aimed to assess the long-term impact of severe COVID-19 on the Quality of life (QOL), sleep pattern, behavior, and workability. Methods: The current multicenter study adopted a cross-sectional design to analyze data from two tertiary care COVID-19 dedicated hospitals. All experimental procedures were approved by the ethics committee of the M.L.B Medical College. Participants were 20-60 age group who had been admitted to the ICU because of severe COVID-19 and had elapsed at least one and a half year since their discharge. After informed written consent the participants were assessed for: EUROHIS-QOL 8-item index; Workability Score; Quality of sleep; The major depression inventory (MDI) questionnaire; Generalized anxiety disorder 7 item scale (GAD-7); Current global health status score: an innovative subjective scale (1 -10) to determine the current global health status when 5 is the status before COVID-19. Findings: 491 participants were assessed, the median follow-up time after discharge from the hospital was 561·0 days (range, 548-580 days). The mean duration of ICU stay was 8.72 ± 2.85 days. There was significant reduction in the prevalence of obesity, diabetes, and hypertension as compared with discharge time. The mean of EUROHIS-QOL score, workability score, current global health status score was 3.28 ± 0.98, 6.87 ± 0.85, 4.53 ± 1.36 respectively. The mean MDI and anxiety scores were 4.12 ± 1.45 and 18.63 ± 3.28, respectively. Interpretation: Severe COVID-19 survivors have new-onset psychological disorders and sleep disturbances. Long term quality of life and work ability remains poor after prolong ICU admission secondary to severe COVID-19.

Privacy Enhancing and Scalable Federated Learning to Accelerate AI Implementation in Cross-Silo and IoMT Environments.

Federated Learning (FL) is a machine learning technique that enables to collaboratively learn valuable information across devices or sites without moving the data. In FL, the model is trained and shared across decentralized locations where data are privately owned. After local training, model updates are sent back to a central server, thus enabling access to distributed data on a large scale while maintaining privacy, security, and data access rights. Although FL is a well-studied topic, existing frameworks are still at an early stage of development. They encounter challenges with respect to scalability, data security, aggregation methodologies, data provenance, and production readiness. In this paper, we propose a novel FL framework that supports functionalities like scalable processing with respect of data, devices, sites and collaborators, monitoring services, privacy, and support for use cases. Furthermore, we integrate multi party computation (MPC) within the FL setup, preventing reverse engineering attacks. The proposed framework has been evaluated in diverse use cases both in cross-device and cross-silo settings. In the former case, in-device FL is leveraged in the context of an AI-driven internet of medical things (IoMT) environment. We demonstrate the framework suitability for a range of AI techniques while benchmarking with conventional centralized training. Furthermore, we prove the feasibility of developing a user-friendly pipeline that enables an efficient implementation of FL in diverse clinical use cases.

A Curious Case of White Out Lung.

CASE PRESENTATION: A 40-year-old Asian man with COPD presented to the ER with an acute exacerbation and type 2 respiratory failure. He was intubated and placed on the mechanical ventilator. He had a tobacco smoking history of 30 pack-years. Otherwise, he had no other significant medical or social history. The family history was non contributory. His physical development was normal.

Use of Multimodal Therapies to Treat Severe Orthostatic Hypotension From Autonomic Failure.

Orthostatic hypotension is one of the most debilitating features of autonomic failure. Presentations tend to be diverse and non-specific, ranging from dizziness and lightheadedness to loss of consciousness. Early recognition of this illness may prove to be difficult, and control of symptoms typically requires a multidisciplinary approach with patient education, pharmacologic, and device therapies. This condition tends to be associated with significant patient morbidity and poor quality of life, and treatment regimens typically require frequent adjustments before optimal symptom control is achieved. However, with a multidisciplinary approach, utilization of multimodal therapies, and proper identification of underlying pathophysiologic mechanisms, symptom improvement may be achieved. An 81-year-old male was admitted to our hospital following a syncopal episode. While hospitalized, he experienced severe syncope and was treated with physical therapy, midodrine, fludrocortisone, octreotide, erythropoietin, and intravenous iron infusions. He displayed minimal improvement and then had a biventricular pacemaker placed and had a resolution of all postural symptoms.

Comparative Evaluation of Intrathecal Dexmedetomidine and Fentanyl as an Adjuvant for Combined Spinal-Epidural Analgesia for Labor.

Background: Combined spinal-epidural technique is a widely accepted and popular modality for labor analgesia. Opioids are being used as adjuvants since long time. Dexmedetomidine is a new drug that is being used as an intrathecal adjuvant. Aim: The study aims to compare the safety and efficacy of fentanyl and dexmedetomidine as intrathecal adjuvants in labor analgesia. Settings and Design: This was a continuous, prospective, randomized controlled trial with 120 parturients. Materials and Methods: After ethical approval and written consent, participants were divided randomly into two groups: Group A - bupivacaine 2.5 mg (0.5 mL diluted to 2 mL) + 20 µg of dexmedetomidine in 1 mL saline intrathecally (total volume: 3 mL) and Group B - bupivacaine 2.5 mg (0.5 mL diluted to 2 mL) + 15 µg of fentanyl in 1 mL saline intrathecally (total volume: 3 mL). Primary outcomes were satisfactory analgesia, mode of delivery, and neonatal outcome. Participants were monitored for the onset and duration of analgesia, degree of motor block, and maternal and fetal side effects. Results: A total of 108 parturients reported sufficient analgesia (Group A: 57; Group B: 51), and 74 patients delivered vaginally (Group A: 41; Group B: 44). The rates of normal vaginal delivery were higher in Group B. Group A reported earlier onset of analgesia (61.26 ± 18.23 s) that lasted for longer duration (124.16 ± 26.23 min) than in Group B. There were no serious side effects in any of the groups. Fetal ultrasound revealed attenuation of fetal heart rate variability. The heart rate of newborns was also found to be low in Group A. Conclusion: Chances of vaginal delivery are higher with intrathecal fentanyl as an adjuvant. Intensity and duration of analgesia are better with intrathecal dexmedetomidine.

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.

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.