Modified NUTRIC Score as a Predictor of All-cause Mortality in Critically Ill Patients: A Systematic Review and Meta-analysis.

Purpose: The purpose of our meta-analysis was to look at the impact of modified nutrition risk in the critically ill (mNUTRIC) on mortality in patients with critical illness. Materials and methods: Literature relevant to this meta-analysis was searched in PubMed, Web of Science, and Cochrane Library till 26 August 2023. Prospective or retrospective studies, patients >18 years of age, studies that reported on mortality and mNUTRIC (mNUTRIC cut-off score) were included. The QUIPS tool was used to evaluate the risk for bias in prognostic factors. Results: A total of 31 studies on mNUTRIC score, involving 13,271 patients were included. The summary area under the curve (sAUC) of 0.80 (95% CI: 0.76-0.83) illustrates the mNUTRIC score's strong discrimination. The pooled sensitivity was 0.79 (95% CI: 0.74-0.84) and pooled specificity was 0.68 (95% CI: 0.63-0.73). We found no discernible variation in the mNUTRIC's prediction accuracy among cut-off values of <5 and >5 in our subgroup analysis and sAUC values were 0.82 (95% CI: 0.78-0.85) and 0.78 (95% CI: 0.74-0.81), respectively. Conclusion: We observed that mNUTRIC can discriminate between critically ill individuals and predict their mortality. Prospero: CRD42023460292. How to cite this article: Prakash J, Verma S, Shrivastava P, Saran K, Kumari A, Raj K, et al. Modified NUTRIC Score as a Predictor of All-cause Mortality in Critically Ill Patients: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2024;28(5):495-503.

Retrospective Analysis of Clinical Characteristics and Outcomes of Pregnant Women with SARS-CoV-2 Infections Admitted to Intensive Care Units in India (Preg-CoV): A Multicenter Study.

Aim: The aim was to examine the outcomes of pregnant women admitted to intensive care unit with coronavirus disease-2019 (COVID-19) infection during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in India. The primary outcome of the study was maternal mortality at day 30. The secondary outcomes were the intensive care unit (ICU) and hospital length of stay, fetal mortality and preterm delivery. Materials and methods: This was a retrospective multicentric cohort study. Ethical clearance was obtained. All pregnant women of the 15-45-year age admitted to ICUs with SARS-CoV-2 infection during 1st March 2020 to 31st October, 2021 were included. Results: Data were collected from nine centers and for 211 obstetric patients admitted to the ICU with a confirmed diagnosis of COVID-19. They were divided in to two groups as per their SpO2 (saturation of peripheral oxygen) level at admission on room air, that is, normal SpO2 group (SpO2 > 90%) and low SpO2 group (SpO2 < 90%). The mean age was (30.06 ± 4.25) years and the gestational age was 36 ± 8 weeks. The maternal mortality rate was10.53%. The rate of fetal death and preterm delivery was 7.17 and 28.22%, respectively. The average ICU and hospital length of stay (LOS) were 6.35 ± 8.56 and 6.78 ± 6.04 days, respectively. The maternal mortality (6.21 vs 43.48%, p < 0.001), preterm delivery (26.55 vs 52.17%, p = 0.011) and fetal death (5.08 vs 26.09%, p = 0.003) were significantly higher in the low SpO2 group. Conclusion: The overall maternal mortality among critically ill pregnant women affected with COVID-19 infection was 10.53%. The rate of preterm birth and fetal death were 28.22 and 7.17%, respectively. These adverse maternal and fetal outcomes were significantly higher in those admitted with low SpO2 (<90%) at admission compared with those with normal SpO2. How to cite this article: Sinha S, Paul G, Shah BA, Karmata T, Paliwal N, Dobariya J, et al. Retrospective Analysis of Clinical Characteristics and Outcomes of Pregnant Women with SARS-CoV-2 Infections Admitted to Intensive Care Units in India (Preg-CoV): A Multicenter Study. Indian J Crit Care Med 2024;28(3):265-272.

High-flow Nasal Oxygen Therapy in COVID-19 Critically Ill Patients with Acute Hypoxemic Respiratory Failure: A Prospective Observational Cohort Study.

Background: Coronavirus disease-2019 (COVID-19) is prone to acute hypoxemic respiratory failure (AHRF). Because tracheal intubation is associated with a higher risk of death in these patients, AHRF employs high-flow nasal oxygen therapy (HFNOT). The goal of this study was to assess the effect of HFNOT on oxygenation status as well as different predictors of HFNOT failure. Methods: A prospective observational cohort study was conducted in COVID-positive critically ill adult patients (age >18 years) with AHRF, who were unable to maintain SpO2 >90% on a non-rebreathing face mask at an oxygen flow ≥15 L/minute. Respiratory variables (PaO2/FiO2, SpO2, and RR) before HFNOT (baseline) and then at 1 hour, 6 hours, 7th day, and 14th day after HFNOT application were recorded. Borg CR10 scale and visual analogue scale were used to evaluate the subjective sensation of dyspnea and comfort level, respectively. As needed, Student's t, Mann-Whitney U, or Wilcoxon signed-rank tests were performed. To find parameters linked to HFNOT failure, multivariate logistic regression and receiver operating characteristic (ROC) analysis were employed. Results: A total of 114 patients were enrolled in the study, with an HFNOT failure rate of 29%. The median PaO2/FiO2 ratio at baseline (before the initiation of HFNOT) was 99.5 (80-110) which significantly increased at various time points (1 hour, 6 hours, 7th day, and 14th day) after HFNOT initiation in the successful group. Patients reported significant improvement in sensation of breathlessness [9 (8-10), 3 (2-4); p <0.001] as well as in comfort level [2 (1-2), 8 (4-9); p <0.001]. Multivariate logistic regression analysis, sequential organ failure assessment (SOFA) score >7, acute physiology and chronic health evaluation (APACHE) II score >20, admission P/F ratio <100, D-dimer >2 mg/L, IL-6 >40 pg/mL, random blood sugar (RBS) >250 mg/dL, and 6 hours ROX Index <3.5 were independent prognostic factors of HFNOT failure. Conclusion: The use of HFNOT significantly increased the oxygenation levels in COVID-19 patients with AHRF at various time periods after HFNOT beginning. Age, SOFA score, APACHE II score, ROX score, admission P/F ratio, IL-6, D-dimer, and RBS were independent prognostic factors of HFNOT failure in this cohort. How to cite this article: Khan MS, Prakash J, Banerjee S, Bhattacharya PK, Kumar R, Nirala DK. High-flow Nasal Oxygen Therapy in COVID-19 Critically Ill Patients with Acute Hypoxemic Respiratory Failure: A Prospective Observational Cohort Study. Indian J Crit Care Med 2022;26(5):596-603.

Demographics and Clinical Characteristics of COVID-19-vaccinated Patients Admitted to ICU: A Multicenter Cohort Study from India (PostCoVac Study-COVID Group).

Background: Emergency authorization and approval were given for the coronavirus disease-19 (COVID-19) vaccines. The efficacy reported after phase III trials were 70.4% and 78% for Covishield and Covaxin, respectively.In this study, we aim to analyze the risk factors, which were associated with mortality in critically ill COVID-19-vaccinated patients admitted into intensive care unit (ICU). Materials and methods: This study was conducted from April 1, 2021 to December 31, 2021 across five centers in India. Patients who had received either one or two doses of any of the COVID vaccines and developed COVID-19 were included. The ICU mortality was a primary outcome. Results: A total of 174 patients with COVID-19 illness were included in the study. The mean age was 57 years standard deviation (SD 15). Acute physiology, age and chronic health evaluation (APACHE II) score and the sequential organ failure assessment (SOFA) score were 14 (8-24.5) and 6 (4-8), respectively. Multiple variable logistic regression showed patients who have received a single dose [odds ratio (OR): 2.89, confidence interval (CI): 1.18, 7.08], neutrophil:lymphocyte (NL) ratio (OR: 1.07, CI: 1.02,1.11), and SOFA score (OR: 1.18, CI: 1.03,1.36) were associated with higher mortality. Conclusion: The mortality in the vaccinated patients admitted to the ICU was 43.68% due to COVID illness. The mortality was lower in patients who had received two doses. How to cite this article: Havaldar AA, Prakash J, Kumar S, Sheshala K, Chennabasappa A, Thomas RR et al. Demographics and Clinical Characteristics of COVID-19-vaccinated Patients Admitted to ICU: A Multicenter Cohort Study from India (PostCoVac Study-COVID Group). Indian J Crit Care Med 2022;26(11):1184-1191.

IFN-γ+ CD4+T cell-driven prophylactic potential of recombinant LDBPK_252400 hypothetical protein of Leishmania donovani against visceral leishmaniasis.

Visceral leishmaniasis (VL) is a potentially fatal parasitic disease causing high morbidity and mortality in developing countries. Vaccination is considered the most effective and powerful tool for blocking transmission and control of diseases. However, no vaccine is available so far in the market for humans. In the present study, we characterized the hypothetical protein LDBPK_252400 of Leishmania donovani (LdHyP) and explored its prophylactic behavior as a potential vaccine candidate against VL. We found reduced hepato-splenomegaly along with more than 50% parasite reduction in spleen and liver after vaccination in mice. Protection in vaccinated mice after the antigen challenge correlated with the stimulation of antigen specific IFN-γ expressing CD4+T cell (~4.6 fold) and CD8+T cells (~2.1 fold) in vaccinated mice in compared to infected mice, even after 2-3 months of immunization. Importantly, antigen-mediated humoral immunity correlated with high antigen specific IgG2/IgG1 responses in vaccinated mice. In vitro re-stimulation of splenocytes with LdHyP enhances the expression of TNF-α, IFN-γ, IL-12 and IL-10 cytokines along with lower IL-4 cytokine and IL-10/IFN-γ ratio in vaccinated mice. Importantly, we observed ~3.5 fold high NO production through activated macrophages validates antigen mediated cellular immunity induction, which is critical in controlling infection progression. These findings suggest that immunization with LdHyP mount a very robust immunity (from IL-10 towards TFN-γ mediated responses) against L. donovani infection and could be explored further as a putative vaccine candidate against VL.

Impact of COVID-19 on Psychological and Emotional Well-being of Healthcare Workers.

BACKGROUND: Coronavirus disease-2019 (COVID-19) in the last few months has disrupted the healthcare system globally. The objective of this study is to assess the impact of the COVID-19 pandemic on the psychological and emotional well-being of healthcare workers (HCWs). MATERIALS AND METHODS: We conducted an online, cross-sectional, multinational survey, assessing anxiety [using Generalized Anxiety Disorder (GAD) Scale: GAD-2 and GAD-7], depression (using Center for Epidemiologic Studies Depression Scale), and insomnia (using Insomnia Severity Index Scale), among HCWs across India, the Middle East, and North America. We used univariate and bivariate logistic regression to identify risk factors for psychological distress. RESULTS: The prevalence of clinically significant anxiety, depression, and insomnia was 41.4%, 48.0%, and 31.3%, respectively. On bivariate logistic regression, lack of social or emotional support to HCWs was independently associated with anxiety [odds ratio (OR), 3.81 (2.84-3.90)], depression [OR, 6.29 (4.50-8.79)], and insomnia [OR, 3.79 (2.81-5.110]. Female gender and self-COVID-19 were independent risk factors for anxiety [OR, 3.71 (1.53-9.03) and 1.71 (1.23-2.38)] and depression [OR, 1.72 (1.27-2.31) and 1.62 (1.14-2.30)], respectively. Frontliners were independently associated with insomnia [OR, 1.68 (1.23-2.29)]. CONCLUSION: COVID-19 pandemic has a high prevalence of anxiety, depression, and insomnia among HCWs. Female gender, frontliners, self-COVID-19, and absence of social or emotional support are the independent risk factors for psychological distress. HOW TO CITE THIS ARTICLE: Bhattacharya PK, Prakash J. Impact of COVID-19 on Psychological and Emotional Well-being of Healthcare Workers. Indian J Crit Care Med 2021;25(5):479-481.

Post-COVID-19 Pulmonary Fibrosis: A Lifesaving Challenge.

How to cite this article: Prakash J, Bhattacharya PK, Priye S, Kumar N. Post-COVID-19 Pulmonary Fibrosis: A Lifesaving Challenge. Indian J Crit Care Med 2021;25(1):104-105.

Structure-guided approach to identify a novel class of anti-leishmaniasis diaryl sulfide compounds targeting the trypanothione metabolism.

Leishmania protozoans are the causative agent of leishmaniasis, a neglected tropical disease consisting of three major clinical forms: visceral leishmaniasis (VL), cutaneous leishmaniasis, and mucocutaneous leishmaniasis. VL is caused by Leishmania donovani in East Africa and the Indian subcontinent and by Leishmania infantum in Europe, North Africa, and Latin America, and causes an estimated 60,000 deaths per year. Trypanothione reductase (TR) is considered to be one of the best targets to find new drugs against leishmaniasis. This enzyme is fundamental for parasite survival in the human host since it reduces trypanothione, a molecule used by the tryparedoxin/tryparedoxin peroxidase system of Leishmania to neutralize the hydrogen peroxide produced by host macrophages during infection. Recently, we solved the X-ray structure of TR in complex with the diaryl sulfide compound RDS 777 (6-(sec-butoxy)-2-((3-chlorophenyl)thio)pyrimidin-4-amine), which impairs the parasite defense against the reactive oxygen species by inhibiting TR with high efficiency. The compound binds to the catalytic site and engages in hydrogen bonds the residues more involved in the catalysis, namely Glu466', Cys57 and Cys52, thereby inhibiting the trypanothione binding. On the basis of the RDS 777-TR complex, we synthesized structurally related diaryl sulfide analogs as TR inhibitors able to compete for trypanothione binding to the enzyme and to kill the promastigote in the micromolar range. One of the most active among these compounds (RDS 562) was able to reduce the trypanothione concentration in cell of about 33% via TR inhibition. RDS 562 inhibits selectively Leishmania TR, while it does not inhibit the human homolog glutathione reductase.

Modified directed self-learning sessions in physiology with prereading assignments and Pecha Kucha talks: perceptions of students.

The present study reports perceptions of first-year undergraduate medical students ( n = 120), regarding modified directed self-learning (DSL) sessions in physiology. Students were provided with prereading assignments (faculty developed PowerPoint slides containing diagrams with incomplete labeling/flowcharts with missing steps) pertaining to the DSL topic 1 wk before the scheduled small-group DSL presentations. During DSL presentation sessions, which were facilitated by teachers, a few students individually presented learning objectives in the specified topic. Apart from that, students discussed answers for the questions in the prereading assignment. Students were also given an opportunity to use technology to support DSL, by way of involving them in Pecha Kucha (PK) talks. The impact of the modified DSL method was determined by requesting students to respond to a validated questionnaire. Frequency analysis of the responses revealed that >60% of students were positive about the modified DSL sessions improving their DSL, presentation, collaborative learning, and information retrieving skills. Students agreed that PK talks helped them to learn how to organize content (65%), present concise information (65.8%), and apply creativity (72.5%). Even though small in number, there were comments that the prereading assignments were useful for learning. The present study revealed that, even though students actively participated in modified DSL sessions, their perceptions on satisfaction and usefulness of the same toward achievement of various skills were not encouraging. The study generated significant results, which implies that undergraduate medical students should be oriented on the relevance of active learning strategies in their future studies.

2,3-Dihydro-3ß-methoxy Withaferin-A Protects Normal Cells against Stress: Molecular Evidence of Its Potent Cytoprotective Activity.

2,3-Dihydro-3ß-methoxy withaferin-A (3ßmWi-A) is a natural withanolide that is structurally close to withaferin-A (Wi-A), is cytotoxic to human cancer cells, and is a candidate anticancer natural compound. Using cell-based biochemical, molecular, and imaging assays, we report that Wi-A and 3ßmWi-A possess contrasting activities. Whereas Wi-A caused oxidative stress to normal cells, 3ßmWi-A was well tolerated at even 10-fold higher concentrations. Furthermore, it promoted survival and protected normal cells against oxidative, UV radiation, and chemical stresses. We provide molecular evidence that 3ßmWi-A induces antistress and pro-survival signaling through activation of the pAkt/MAPK pathway. We demonstrate that 3ßmWi-A (i) contrary to Wi-A is safe and possesses stress-relieving activity, (ii) when given subsequent to a variety of stress factors including Wi-A, protects normal cells against their toxicity, and (iii) is a vital compound that may guard normal cells against the toxicity associated with various targeted therapeutic regimes in clinical practice.

Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons.

Maneb (MB) and paraquat (PQ) are environmental toxins that have been experimentally used to induce selective damage of dopaminergic neurons leading to the development of Parkinson's disease (PD). Although the mechanism of this selective neuronal toxicity in not fully understood, oxidative stress has been linked to the pathogenesis of PD. The present study investigates the mechanisms of neuroprotection elicited by Withania somnifera (Ws), a herb traditionally recognized by the Indian system of medicine, Ayurveda. An ethanolic root extract of Ws was co-treated with the MB-PQ induced mouse model of PD and was shown to significantly rescue canonical indicators of PD including compromised locomotor activity, reduced dopamine in the substantia nigra and various aspects of oxidative damage. In particular, Ws reduced the expression of iNOS, a measure of oxidative stress. Ws also significantly improved the MB + PQ mediated induction of a pro-apoptotic state by reducing Bax and inducing Bcl-2 protein expression, respectively. Finally, Ws reduced expression of the pro-inflammatory marker of astrocyte activation, GFAP. Altogether, the present study suggests that Ws treatment provides nigrostriatal dopaminergic neuroprotection against MB-PQ induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects.

Clinical Assessment of the Ambu® Aura-i™ as an Independent Ventilatory Device and Conduit for Fiberoptic-Guided Endotracheal Intubation in Adults.

Background and aim A novel supraglottic airway device of the second generation is the Ambu® Aura-i™. It is designed to accommodate standard cuffed tracheal tubes and is phthalate-free and compatible with MRI. The primary objectives of the research were to examine the properties and efficiency of Ambu® Aura-i™ as a means of enabling fiberoptic-guided intubation, the view of the glottis during fiber optic examination, the duration of intubation in fiber optic bronchoscopy, the ease of intubation, the success rate of intubation, and the duration for device removal from the tracheal tube. Methodology A hospital-based descriptive observational study was conducted with 80 patients. An adequately sized Ambu® Aura-i™ was placed after general anesthesia was induced. Following a fiberoptic examination of the view of the glottis through the Ambu® Aura-i™, the trachea was intubated under fiberoptic guidance. The Ambu® Aura-i™ insertion time, glottic view grading, ease of intubation, and time required for fiberoptic-guided intubation were recorded. Also, the time taken to remove the Ambu® Aura-i™ was documented. Results Similar levels of ease were experienced by both groups after inserting the Ambu® Aura-i™, being easy in both group 1 (37/40) and in group 2 (38/40). In group 1, the average time taken to insert the Ambu® Aura-i™ was 13.53±1.91 seconds, while in group 2, it was 13.98±2.4 seconds. The average time required for fiberoptic-guided intubation was found to be 14.95±1.85 seconds in group 1 and 14.15±1.37 seconds in group 2, indicating a statistically negligible variation. Conclusion The low cost of Ambu® Aura-i™, size suitability and availability for almost all age groups, compatibility with MRI machines, and availability in phthalate-free versions contribute to it being a more appealing and useful ventilatory device, as well as an intubation tool for both normal and emergency airway management.

Effects of Local Wound Infiltration Post-Mastectomy Using Bupivacaine Alone, Bupivacaine With Ketamine, and Bupivacaine With Dexmedetomidine: A Randomized Double-Blind Study.

Background and aim While the infiltration of surgical incisions with local anesthetics is not a new practice, it remains a crucial component of contemporary multimodal analgesia protocols. This study aimed to evaluate the efficacy and safety of using adjuvants in combination with local anesthetic wound infiltration for pain management in patients undergoing mastectomy surgery. Methods Eighty-one patients aged 18-60 years, classified as American Society of Anesthesiologists (ASA) grade I or II, were scheduled for unilateral mastectomy and randomly assigned to three groups of 27 each. The groups were designated as Group C (bupivacaine alone), Group D (bupivacaine with dexmedetomidine), and Group K (bupivacaine with ketamine). Group C received 0.25% bupivacaine alone, Group D received 0.25% bupivacaine with 1 mcg/kg dexmedetomidine, and Group K received 0.25% bupivacaine with 1 mg/kg ketamine. The time to achieve a Visual Analogue Scale (VAS) score of 3 following local wound infiltration was recorded for each group. Additionally, total postoperative fentanyl intake during the first 24 hours, as measured by the patient-controlled analgesia (PCA) pump, was compared among the groups. Sedation levels were assessed using the Ramsay Sedation Scale (RSS). Data were analyzed using the Chi-Square test and one-way ANOVA in IBM SPSS Statistics for Windows, Version 28.0 (Released 2021; IBM Corp., Armonk, NY, USA). Results Demographic factors were similar across the three groups. Analysis of the VAS scores revealed that the ketamine group provided better postoperative pain control than the dexmedetomidine group (p < 0.001). Groups D (71.72 ± 71.73) and K (3.53 ± 13.42) had significantly lower 24-hour fentanyl intake (in mcg) compared to Group C (the control group), as measured by PCA. Additionally, Group C had a significantly lower RSS at the sixth hour (p = 0.003) compared to both Groups D and K. Conclusion Ketamine, when used as an adjuvant to bupivacaine for local infiltration, enhances the effectiveness and prolongs postoperative analgesia more effectively than dexmedetomidine in patients undergoing mastectomy.

Adverse Effects Related to Corticosteroid Use in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis.

OBJECTIVES: We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness. DATA SOURCES: We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials. STUDY SELECTION: We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP. DATA EXTRACTION: We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia, superinfections/secondary infections, neuropsychiatric effects, and neuromuscular weakness. DATA SYNTHESIS: We included 47 RCTs (n = 13,893 patients). Corticosteroids probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95% CI, 0.87-1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or secondary infections (RR, 0.97; 95% CI, 0.89-1.05; absolute risk reduction, 0.5%; moderate certainty) and may have no effect on neuromuscular weakness (RR, 1.22; 95% CI, 1.03-1.45; ARI, 1.4%; low certainty) or neuropsychiatric events (RR, 1.19; 95% CI, 0.82-1.74; ARI, 0.5%; low certainty). Conversely, they increase the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11-1.31; ARI, 5.4%; high certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI, 1.29-1.96; ARI, 2.3%; moderate certainty). CONCLUSIONS: In ARDS, sepsis, and CAP, corticosteroids are associated with hyperglycemia and probably with hypernatremia but likely have no effect on gastrointestinal bleeding or secondary infections. More data examining effects of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular weakness, would clarify the safety of this class of drugs in critical illness.

Neuroprotective role of Withania somnifera root extract in maneb-paraquat induced mouse model of parkinsonism.

Parkinson's disease (PD) is a neurodegenerative disorder and these days a lot of emphasis is given on the treatment of this disease using herbal medicines. The present study evaluates the neuroprotective effect of Withania somnifera (Ws) root extract on Parkinsonian mice. The mice were divided into three groups; the first group served as control, the second group was given maneb (MB) and paraquat (PQ) and the last group was administered MB-PQ along with Ws root extract for 3, 6 and 9 weeks. The behavioral studies showed a significant improvement in the motor movement patterns and gripping ability of Ws root extract exposed Parkinsonian mice. Tyrosine hydroxylase (TH) immunostaining was reduced in the substantia nigra of MB-PQ exposed mice, while Ws co-exposure restored TH immunostaining significantly. Additionally, our results also demonstrate generation of oxidative stress in the nigrostriatal region of MB-PQ exposed mice. There was a marked decline in the level of catalase and a simultaneous increase in the level of nitrite and lipid peroxidation in Parkinsonian mice. Thus, the Ws root extract have shown to counteract the pro-oxidants and their associated oxidative stress in the PD model studied here. Our results clearly indicate the usefulness of Ws root extract in providing protection against MB-PQ induced nigrostriatal dopaminergic neurodegeneration and marked improvement in the behavioral, anatomical and the biochemical deformities.

Integrated computational and experimental approach for novel anti-leishmanial molecules by targeting Dephospho-coenzyme A kinase.

Coenzyme A acts as a necessary cofactor for many enzymes and is a part of many biochemical processes. One of the critical enzymes involved in Coenzyme A synthesis is Dephospho-coenzyme A-kinase (DPCK). In this study, we have used integrated computational and experimental approaches for promising inhibitors of DPCK using the natural products available in the ZINC database for anti-leishmanial drug development. The top hit compounds chosen after molecular docking were Veratramine, Azulene, Hupehenine, and Hederagenin. The free binding energy of Veratramine, Azulene, Hupehenine, and Hederagenin was estimated. Besides the favourable binding point, the ligands also showed good hydrogen bonding and other interactions with key residues of the enzyme's active site. The natural compounds were also experimentally investigated for their effect on the L. donovani promastigotes and murine macrophage (J774A.1). A good antileishmanial activity by the compounds on the promastigotes was observed as estimated by the MTT assay. The in-vitro experiments revealed that Hupehenine (IC50 = 7.34 ± 0.37 µM) and Veratramine (IC50 = 12.46 ± 2.28 µM) exhibited better inhibition than Hederagenin (IC50 = 23.36 ± 0.54 µM) and Azulene (IC50 = 24.42 ± 3.28 µM). This work has identified novel anti-leishmanial molecules possibly acting through the inhibition of DPCK.

Preemptive Levetiracetam Decreases Postoperative Pain: A Double-Blind, Randomised, Control Trial.

Background Previously many studies have found the use of anti-epileptic drugs such as pregabalin, carbamazepine, and gabapentin in pain management. In addition, levetiracetam (LEV), an effective anti-epileptic drug, has shown analgesic effects in animal models. We aimed to evaluate the effect of oral LEV as pre-emptive analgesia in patients who underwent laparoscopic cholecystectomy under general anaesthesia and postoperative fentanyl requirements. Material and methods Forty-two patients of the American Society of Anaesthesiologists (ASA) grade I and II of either gender posted for elective laparoscopic cholecystectomy surgery were included in this double-blind, randomised, placebo-controlled study. Patients were divided into two equal groups of 21 each to receive either tablet LEV 500 mg or a matching placebo tablet, given 1 hour before surgery. Postoperative pain was assessed by a visual analogue scale (0-100 mm), where 0 meant no pain and 100, worst pain. In addition, patients received IV fentanyl as rescue analgesia during the first 24 hours of the postoperative period. Results Nineteen patients in the LEV group and 20 in the placebo group completed the study. Patients in the LEV group had significantly lower pain scores at all time intervals except 0 hours and reduced fentanyl consumption postoperatively in the first 24 hours (p<0.05). Side effects were comparable in both groups. Conclusion A single, preoperative dose of oral LEV 500 mg significantly decreases post-surgical pain and fentanyl demand as rescue analgesia in elective laparoscopic cholecystectomy.

Tracking collective emotions in 16 countries during COVID-19: a novel methodology for identifying major emotional events using Twitter.

Using messages posted on Twitter, this study develops a new approach to estimating collective emotions (CEs) within countries. It applies time series methodology to develop and demonstrate a novel application of CEs to identify emotional events that are significant at the societal level. The study analyzes over 200 million words from over 10 million Twitter messages posted in 16 countries during the first 120 days of the COVID-19 pandemic. Daily levels of collective anxiety and positive emotions were estimated using Linguistic Inquiry and Word Count's (LIWC) psychologically validated lexicon. The time series estimates of the two collective emotions were analyzed for structural breaks, which mark a significant change in a series due to an external shock. External shocks to collective emotions come from events that are of shared emotional relevance, and this study develops a new approach to identifying them. In the COVID-19 Twitter posts used in the study, analysis of structural breaks showed that in all 16 countries, a reduction in collective anxiety and an increase in positive emotions followed the WHO's declaration of COVID-19 as a global pandemic. Announcements of economic support packages and social restrictions also had similar impacts in some countries. This indicates that the reduction of uncertainty around the evolving COVID-19 situation had a positive emotional impact on people in all the countries in the study. The study contributes to the field of CEs and applied research in collective psychological phenomena.