Advancing Evidence-based Palliative Care Research: Navigating Challenges and Proposing Solutions.

Amid the increasing demand for palliative care, driven by demographic shifts and medical progress, evidence-based practices face obstacles due to limited research. Complex patient conditions and ethical considerations challenge traditional methodologies, while the absence of comprehensive clinical trials hinders innovative interventions. Empowering practitioners with research skills and establishing a palliative care research network are efforts aimed at bridging these gaps. It is important to emphasise that these initiatives collectively aspire to enhance evidence-based practices, ensuring quality care for individuals facing severe illnesses.

Cannabinoids in anesthesia and chronic pain: Where do we stand?

Cannabis derivatives have been conventionally employed globally for their curative and restorative properties for various ailments. However, its recreational use and consequent legal restrictions have substantially cramped its scientific research. An emerging interest regarding the profound therapeutic potential of cannabinoids has been observed among clinicians. Despite a rich cultural background, high-quality research on cannabinoids is lacking in the Indian scenario. This review readdresses the challenges on this front and brings an insight into the current status of cannabinoids and their utility in scientific exploration. Cannabinoids have a significant medicinal value in various clinical disorders. Its use so far has been based on scarce resources and corroborations, as evidence-based substantiation is limited. Through this review article, we emphasize the remarkable role enacted by cannabinoids in the treatment of various clinical disorders and an utterly significant need to formulate stringent research methodologies to promote its systematic investigation.

Tomato Flu in the Time of COVID-19: Another Challenge for the Indian Health System.

Just as the country has recently dealt with the increase in COVID-19 and monkey pox cases, another dark cloud of "Tomato flu/ Tomato fever" loomed the skies of the nation. As of 24 august, 2022, 100 kids mainly below the age of 5 have been reported showing symptoms of the flu. Another state of Odisha, suspected similar infectious etiology in 36 cases out of which 26 Children were below the age of 10. This endemic viral illness has triggered an alert to the neighboring states of Tamil Nadu and Karnataka, along with the entire nation at large. The wrath of this disease is not just restricted to India but crossing borders. Tang, et al reported a case of a 13-month-old female child and her 5-year old brother based in United kingdom with similar etiology. Through this report, we aim to alert the frontline pediatricians, who are most likely to come across and manage such daunting cases with these non-specific clinical features in their routine clinical practice across the globe. Early and extreme preventive and surveillance measures must be undertaken to prevent substantial loss in public and private sector.

Exploring Potential Non-steroidal Aromatase Inhibitors for Therapeutic Application against Estrogen-dependent Breast Cancer.

BACKGROUND: Breast cancer is one of the most commonly diagnosed cancer types among women worldwide. Cytochrome P450 aromatase (CYP19A1) is an enzyme in vertebrates that selectively catalyzes the biosynthesis of estrogens from androgenic precursors. Researchers have increasingly focused on developing non-steroidal aromatase inhibitors (NSAIs) for their potential clinical use, avoiding steroidal side effects. OBJECTIVES: The objective of the present work is to search for potential lead compounds from the ZINC database through various in silico approaches. METHODS: In the present study, compounds from the ZINC database were initially screened through receptor independent-based pharmacophore virtual screening. These screened molecules were subjected to several assessments, such as Lipinski rule of 5, SMART filtration, ADME prediction using SwissADME and lead optimization. Molecular docking was further applied to study the interaction of the filtered compounds with the active site of aromatase. Finally, the obtained hit compounds, consequently represented to be ideal lead candidates, were escalated to the MD simulations. RESULTS: The results indicated that the lead compounds might be potential anti-aromatase drug candidate. CONCLUSION: The findings provided a valuable approach in developing novel anti-aromatase inhibitors for the treatment of ER+ breast cancer.

Effectiveness of Morphine in Managing Refractory Dyspnoea in Patients with Coronavirus Disease (COVID-19).

Opiates are generally used to relieve dyspnoea in advanced diseases such as cancer and lung diseases. However, little is known regarding the safety and efficacy of morphine for refractory dyspnoea in coronavirus disease 2019 (COVID-19) patients. We retrospectively reviewed records of 18 COVID-19-positive patients who were administered morphine for refractory dyspnoea during hospitalisation between May 2021 and June 2021. Details of morphine usage, vital signs, an 11-point dyspnoea numeric rating scale (DNRS) and adverse events at baseline, 24 h and 72 h after the start of treatment were abstracted from records. The final clinical outcome in terms of death or discharge was noted. All patients had severe refractory dyspnoea (DNRS score ≥7) at the time of administration of morphine and had not been relieved from standard care for the past 3 days. In the results, the mean (standard deviation [SD]) age was 47.1 (12) years, male was 13 (72.20%) patients and modified Medical Research Council Grade 4 was present in all 18 patients. The mean (SD) 1st day dose of morphine was 7.03 (1.53) mg and the mean (SD) duration of morphine use was 5.22 (3.00) days. Significant decreases in DNRS, respiratory rate and oxygen saturation were observed 24 h and 72 h after the start of morphine administration. Meanwhile, blood pressure and heart rate were not significantly altered after treatment. The finding of this single-centre retrospective study indicates that morphine may be considered for use in the management of refractory dyspnoea among COVID-19 patients.

A Correlation Analysis of Peripheral Oxygen Saturation and Arterial Oxygen Saturation Among COVID-19 Patients.

Background and objective It has been observed that peripheral oxygen saturation (SpO2) measured by pulse oximeter is consistently lower than arterial oxygen saturation (SaO2) measured directly by blood gas analysis. In this study, we aimed to evaluate the correlation between SpO2 and SaO2, and SpO2 and partial pressure of oxygen (PaO2), and compare the SpO2/FiO2 (SF) and PaO2/FiO2 (PF) ratios in patients with coronavirus disease 2019 (COVID-19). Methods In this observational study, SpO2 was recorded and arterial blood gas analysis was performed among 70 COVID-19 patients presenting on room air (FiO2 = 0.21). SaO2 and PaO2 were recorded from arterial blood gas analysis. The SF and PF ratios were then calculated. Results The strength of correlations between SpO2 and SaO2, and SpO2 and PaO2, were significant (p<0.001) and moderately positive [Pearson coefficient (r) = 0.68, 0.53]. SpO2 value (85%), i.e., SF ratio (404.7 or below), was the best estimate for mild ARDS (acute respiratory distress syndrome) [PF ratio (300 or below)] with a sensitivity of 80.6% and specificity of 53%. Conclusion A pulse oximeter is a vital tool in the diagnosis and management of COVID-19. In our study, SpO2 was found to have a positive correlation with SaO2 and PaO2 with acceptable sensitivity but low specificity in estimating mild ARDS. Therefore, pulse oximetry can be used as a tool for the early diagnosis of mild COVID-19 ARDS as per the given considerations and clinical correlation.

Risk Assessment of Aerosol Generation During Vitreoretinal Surgery Using High Speed Imaging Amidst the COVID-19 Pandemic.

Purpose: The purpose of this study was to discuss the propensity of aerosol and droplet generation during vitreoretinal surgery using high speed imaging amidst the coronavirus disease 2019 (COVID-19) pandemic. Methods: In an experimental set up, various steps of vitreoretinal surgery were performed on enucleated goat eyes. The main outcome measures were visualization, quantification of size, and calculation of aerosol spread. Results: During intravitreal injection, insertion of cannulas, lensectomy, and vitrectomy with both 23 and 25-gauge instruments, with either valved or nonvalved cannulas, aerosols were not visualized which was confirmed on imaging. Although there was no aerosol generation during active fluid air exchange (FAE), there was bubbling and aerosol generation at the exit port of the handle during passive FAE. Under higher air pressure, with reused valved and fresh nonvalved cannulas, aerosol generation showed a trajectory 0.4 to 0.67 m with droplet size of 200 microns. Whereas removing cannulas or suturing under active air infusion (35 mm Hg and above) aerosols were noted. Conclusions: Based on the above experiments, we can formulate guidelines for safe vitrectomy during COVID-19. Some recommendations include the use of valved cannulas, avoiding passive FAE or to direct the exit port away from the surgeon and assistant, and to maintain the air pressure less than or equal to 30 mm Hg. Translational Relevance: In the setting of the COVID-19 pandemic, the risk from virus laden aerosols, as determined using an experimental setup, appears to be low for commonly performed vitreoretinal surgical procedures.

In Silico Exploration of Phytoconstituents From Phyllanthus emblica and Aegle marmelos as Potential Therapeutics Against SARS-CoV-2 RdRp.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide has increased the importance of computational tools to design a drug or vaccine in reduced time with minimum risk. Earlier studies have emphasized the important role of RNA-dependent RNA polymerase (RdRp) in SARS-CoV-2 replication as a potential drug target. In our study, comprehensive computational approaches were applied to identify potential compounds targeting RdRp of SARS-CoV-2. To study the binding affinity and stability of the phytocompounds from Phyllanthus emblica and Aegel marmelos within the defined binding site of SARS-CoV-2 RdRp, they were subjected to molecular docking, 100 ns molecular dynamics (MD) simulation followed by post-simulation analysis. Furthermore, to assess the importance of features involved in the strong binding affinity, molecular field-based similarity analysis was performed. Based on comparative molecular docking and simulation studies of the selected phytocompounds with SARS-CoV-2 RdRp revealed that EBDGp possesses a stronger binding affinity (-23.32 kcal/mol) and stability than other phytocompounds and reference compound, Remdesivir (-19.36 kcal/mol). Molecular field-based similarity profiling has supported our study in the validation of the importance of the presence of hydroxyl groups in EBDGp, involved in increasing its binding affinity toward SARS-CoV-2 RdRp. Molecular docking and dynamic simulation results confirmed that EBDGp has better inhibitory potential than Remdesivir and can be an effective novel drug for SARS-CoV-2 RdRp. Furthermore, binding free energy calculations confirmed the higher stability of the SARS-CoV-2 RdRp-EBDGp complex. These results suggest that the EBDGp compound may emerge as a promising drug against SARS-CoV-2 and hence requires further experimental validation.

Propensity of aerosol and droplet creation during oculoplastic procedures: A risk assessment with high-speed imaging amidst COVID-19 pandemic.

PURPOSE: The study uses principles of liquid and gas mechanics to verify and quantify the generation of aerosols in oculoplastic procedures, namely surgery using a scalpel, electrosurgical device, and a mechanized drill. METHODS: Surgical techniques were performed ex vivo using the electrosurgical device, scalpel, and mechanized drill on the muscle and bone of commercially available chicken. The liquid and gas dynamics were observed using a high-speed high-resolution Photron SA5 camera (0.125 to 8 ms temporal resolution, 0.016 to 0.054 mm/pixel spatial resolution) and stroboscopic lighting (Veritas 120 E LED Constellation). The analysis was performed using in-house algorithms and ImageJ software. RESULTS: The use of a mechanized drill at 35000 rpm and a 3 mm fluted burr generated aerosol with particle size 50 to 550 microns with a spread of 1.8 m radius. Surgical smoke was generated by an electrosurgical device in both cutting and coagulation modes. Dispersion of the smoke could be controlled significantly by the use of suction, mean smoke spread ratio being 0.065 without suction and 0.002 with use of suction within 2 cm. CONCLUSION: The quantification of the aerosol generation will help surgeons take practical decisions in their surgical techniques in the pandemic era.

Cooperative evaporation in two-dimensional droplet arrays.

The evaporation of a sessile drop in a gaseous environment may be critical to many practical applications. Evaporation dynamics of interacting sessile droplets is strongly influenced by the proximity of adjacent droplets. We study the effects of droplet-droplet vapor-mediated interactions on the evaporation lifetime of two-dimensional arrays of sessile water droplets. We observe that the presence of neighboring droplets acts as a mode of vapor accumulation which slows down the evaporation process. By considering an arbitrarily configured two-dimensional array of droplets, here we provide a simple generalized theoretical limit to their lifetime in an evaporating state. Using a scaling analysis, we put forward that the sessile droplet lifetime in a two-dimensional array is a linear function of the extent of confinement for various surface wettability and droplet geometric parameters (contact angle and contact radius). Notwithstanding the geometrical and physical complexity of the effective confinement generated due to their cooperative interactions, we show that the consequent evaporation characteristics may be remarkably insensitive to the topographical details of the overall droplet organization for a wide range of droplet-substrate combinations. With subsequent deployment of particle-laden droplets, however, our results lead to the discovery of a unique pathway towards tailoring the internal flows within the collective system by harnessing an exclusive topologically driven symmetry-breaking phenomenon, yielding a strategy of patterning particulate matters around the droplet array.

Dynamics of droplet impingement on bioinspired surface: insights into spreading, anomalous stickiness and break-up.

Inspired by the self-cleaning ability of lotus leaves and stickiness (towards water) of rose petals, we investigate the droplet impact dynamics on such bioinspired substrates. Impact studies are carried out with water droplets for a range of impact velocities on glass, PDMS and soft lithographically fabricated replicas of the lotus leaf and rose petals, which exhibit near identical wetting properties as that of the original biological entities. In this work, we investigate the spreading, dewetting and droplet break-up mechanisms subsequent to impact. Surprisingly, the rose petal and lotus leaf replicas manifest similar impact dynamics. The observation is extremely intriguing and counterintuitive, as rose petal and its replicas are sticky in contrast to lotus leaves. However, these observations are based on experiments performed with sessile water droplets. By contrast, in the current study, we find that rose petal replicas exhibit non-sticky behaviour at the short time scale ∼ ( O ( 10 - 3 ) ) s similar to that exhibited by lotus leaf replicas. Air entrapment in the micrometre features of bioinspired surfaces prevent frictional dissipation of droplet kinetic energy, leading to contact edge recession. We have also unveiled interesting universal physics that govern the spreading, recession of the contact edge and subsequent break-up modes (ligament or bulb-ligament) of the droplet.

Evaluation of analgesic efficacy of dexmedetomidine as adjuvant with ropivacaine in ultrasound-guided adductor canal block in patients following anterior cruciate ligament reconstruction surgeries.

INTRODUCTION: Local anaesthetic (LA) with highly selective alpha-2 agonist dexmedetomidine has not been evaluated in adductor canal block (ACB) for arthroscopic anterior cruciate ligament (ACL) reconstruction surgeries. The study evaluates postoperative analgesic effect of ropivacaine with adjuvant dexmedetomidine following postoperative ultrasound-guided ACB. METHODS: 105 randomized subjects received ultrasound-guided ACB using 15 mL of 0.5% ropivacaine, with 0.5 µg kg-1 of dexmedetomidine administered perineurally (Group II), intravenously (Group III) or none (Group I). Primary outcome included 24 hours' total morphine consumption postoperatively. Secondary outcomes included haemodynamics and adverse effects. RESULTS: The postoperative total morphine consumption was significantly reduced till 4 hours in II 0.57 mg (0.98 (0-3)) (p = 0.011) and up to 6 hours in Group III 0.77 mg (1.00 (0-4)) (p = 0.004) compared to Group I. The postoperative total morphine consumption was comparable at 24 hours in Group III 3.57 mg (1.73 (0-8)) and Group II 3.34 mg (1.92 (07)) (p = 1.000). The visual analogue scale (VAS) scores were comparable in all the three groups at all the time intervals studied (p > 0.05). There were no adverse effects observed during the study. CONCLUSION: Use of perineural dexmedetomidine with LA for ACB in the postoperative period resulted in significant reduction in total morphine consumption in initial 4 hours as compared to 6 hours with intravenous (IV) dexmedetomidine.