RNAPII driven post-translational modifications of nucleosomal histones.

The current understanding of how specific distributions of histone post-translational modifications (PTMs) are achieved throughout the chromatin remains incomplete. This review focuses on the role of RNA polymerase II (RNAPII) in establishing H2BK120/K123 ubiquitination and H3K4/K36 methylation distribution. The rate of RNAPII transcription is mainly a function of the RNAPII elongation and recruitment rates. Two major mechanisms link RNAPII's transcription rate to the distribution of PTMs. First, the phosphorylation patterns of Ser2P/Ser5P in the C-terminal domain of RNAPII change as a function of time, since the start of elongation, linking them to the elongation rate. Ser2P/Ser5P recruits specific histone PTM enzymes/activators to the nucleosome. Second, multiple rounds of binding and catalysis by the enzymes are required to establish higher methylations (H3K4/36me3). Thus, methylation states are determined by the transcription rate. In summary, the first mechanism determines the location of methylations in the gene, while the second mechanism determines the methylation state.

Effect of different doses of dexmedetomidine as an adjuvant to lignocaine nebulization: A comparative study during awake flexible fiberoptic bronchoscopy.

Background and Aims: Mild to moderate sedation during bronchoscopy is essential for patient safety, comfort during and after the procedure, and to facilitate the performance of the bronchoscopist. Dexmedetomidine is a highly selective, centrally acting α-2 agonist used to provide conscious sedation during various procedures. The aim of this study was to compare the efficacy of three different doses of dexmedetomidine nebulization as an adjuvant to lignocaine during bronchoscopy. Material and Methods: Ninety American Society of Anesthesiologists physical status I/II patients, aged from 18 to 60 years, scheduled for an elective bronchoscopy, were recruited. They were divided into three groups: 30 patients in each group. Group I: The patient was nebulized with a mixture of 4 ml of 4% lignocaine and dexmedetomidine 0.5 µg/kg. Group II: The patient was nebulized with a mixture of 4% lignocaine, 4 ml, and dexmedetomidine, 1 µg/kg. Group III: The patient was nebulized with 4% lignocaine 4 ml and dexmedetomidine 1.5 µg/kg. Results: The mean cough score was (1.17 ± 0.37), (1.40 ± 0.49), and (1.70 ± 0.75) in group III, group II, and group I, respectively. A significant difference was found between the groups. Patients were more comfortable with a statistically significant difference in the comfort score in group III as compared to group II and group I. Conclusion: Dexmedetomidine nebulization in a dose of 1.5 µg/kg (compared to 1 µg/kg or 0.5 µg/kg) as an adjuvant to lignocaine, provides better bronchoscopy conditions and patient satisfaction.

The tetrameric structure of Plasmodium falciparum phosphoglycerate mutase is critical for optimal enzymatic activity.

The glycolytic enzyme phosphoglycerate mutase (PGM) is of utmost importance for overall cellular metabolism and has emerged as a novel therapeutic target in cancer cells. This enzyme is also conserved in the rapidly proliferating malarial parasite Plasmodium falciparum, which have a similar metabolic framework as cancer cells and rely on glycolysis as the sole energy-yielding process during intraerythrocytic development. There is no redundancy among the annotated PGM enzymes in Plasmodium, and PfPGM1 is absolutely required for the parasite survival as evidenced by conditional knockdown in our study. A detailed comparison of PfPGM1 with its counterparts followed by in-depth structure-function analysis revealed unique attributes of this parasitic protein. Here, we report for the first time the importance of oligomerization for the optimal functioning of the enzyme in vivo, as earlier studies in eukaryotes only focused on the effects in vitro. We show that single point mutation of the amino acid residue W68 led to complete loss of tetramerization and diminished catalytic activity in vitro. Additionally, ectopic expression of the WT PfPGM1 protein enhanced parasite growth, whereas the monomeric form of PfPGM1 failed to provide growth advantage. Furthermore, mutation of the evolutionarily conserved residue K100 led to a drastic reduction in enzymatic activity. The indispensable nature of this parasite enzyme highlights the potential of PfPGM1 as a therapeutic target against malaria, and targeting the interfacial residues critical for oligomerization can serve as a focal point for promising drug development strategies that may not be restricted to malaria only.

Drought stress in maize: stress perception to molecular response and strategies for its improvement.

Given the future demand for food crops, increasing crop productivity in drought-prone rainfed areas has become essential. Drought-tolerant varieties are warranted to solve this problem in major crops, with drought tolerance as a high-priority trait for future research. Maize is one such crop affected by drought stress, which limits production, resulting in substantial economic losses. It became a more serious issue due to global climate change. The most drought sensitive among all stages of maize is the reproductive stages and the most important for overall maize production. The exact molecular basis of reproductive drought sensitivity remains unclear due to genes' complex regulation of drought stress. Understanding the molecular biology and signaling of the unexplored area of reproductive drought tolerance will provide an opportunity to develop climate-smart drought-tolerant next-generation maize cultivars. In recent decades, significant progress has been made in maize to understand the drought tolerance mechanism. However, improving maize drought tolerance through breeding is ineffective due to the complex nature and multigenic control of drought traits. With the help of advanced breeding techniques, molecular genetics, and a precision genome editing approach like CRISPR-Cas, candidate genes for drought-tolerant maize can be identified and targeted. This review summarizes the effects of drought stress on each growth stage of maize, potential genes, and transcription factors that determine drought tolerance. In addition, we discussed drought stress sensing, its molecular mechanisms, different approaches to developing drought-resistant maize varieties, and how molecular breeding and genome editing will help with the current unpredictable climate change.

Perioperative role of oral gabapentin as an analgesic in paediatric patients: A randomised controlled trial.

Background and Aims: Surgical procedure commonly performed in the advanced pediatric age group includes urogenital surgery, adenotonsillectomy, etc., Aim: The aim of this study is to determine the effect of single-dose gabapentin 15 mg/kg on acute pain in the immediate postoperative period in patients aged 8-14 years undergoing surgeries under general anesthesia. Material and Methods: After the approval from the institutional ethical committee, 60 American Society of Anesthesiologists (ASA) I and II patients aged 8-14 years undergoing urogenital surgeries (orchidopexy/urethroplasty) under general anesthesia were included in this study. The patients were assigned into one of the two treatment groups. Patients in group I received oral gabapentin 15 mg/kg dissolved in 5 mL of honey 2 h before surgery, while patients in group II received 5 mL honey orally 2 h before surgery. Results: A total of 60 patients participated. Patients in group I had lower consumption of fentanyl perioperatively (intraoperatively: 1.36 ± 0.70 mcg/kg; postoperatively: 2.36 ± 0.795 mcg/kg) than group II (intraoperatively: 1.8 ± 0.6 mcg/kg; postoperatively: 2.9 ± 0.47 mcg/kg). The differences in the two groups were significant. The time to first rescue analgesia was greater in group I (3.03 ± 0.60 h) than in group II (2.26 ± 0.57 h). There was an increase in sedation score in the treatment group. Conclusion: Our clinical study demonstrates that a 15 mg/kg single preemptive oral dose of gabapentin might reduce the requirement of analgesics perioperatively in pediatric urogenital surgery but might also be associated with undesirable effects such as increased sedation.

Comparison of the oropharyngeal leak pressure between three second generation supraglottic airway devices during laparoscopic surgery in pediatric patients.

BACKGROUND: Previous studies have shown Proseal LMA and I gel similar to endotracheal intubation in ventilatory ability in pediatric laparoscopic surgeries. AIMS: The primary aim of this study was to assess whether there is a significant difference in the oropharyngeal leak pressure between Ambu Auragrain, I-gel, and Proseal LMA during pediatric laparoscopic surgery. METHODS: In this randomized controlled trial, 90 male patients of American Society of Anesthesiologists physical status I aged between 6 months and 10 years who were scheduled for laparoscopic single-sided inguinal hernia repair were recruited and randomly allocated to three groups in which airway was secured with Ambu Auragain, I gel, or Proseal LMA. The primary outcome was oropharyngeal leak pressure. The secondary outcomes were peak pressures before and after pneumoperitoneum, fiberoptic view, insertion attempts, insertion time, manipulations, perioperative and postoperative anesthesia-related problems. Continuous variables were compared using the one-way analysis of variance or the Kruskal-Wallis test with post hoc Turkey analysis. Categorical and ordinal data were compared using the chi-square test or Fisher's exact test. RESULTS: Oropharyngeal leak pressure before pneumoperitoneum was higher with I gel as compared to Ambu Auragain (27.36 ± 5.72 cm of H2 O vs 23.56 ± 5.72 cm of H2 O) (p = .021) and PLMA (27.36 ± 5.72 cm of H2 O vs 23.24 ± 4.35 cm of H2 O) (p = .011). Oropharyngeal leak pressure after pneumoperitoneum was also higher with I gel as compared to Ambu Auragain (31.58 ± 4.35 cm of H2 O vs 26.83 ± 5.00 cm of H2 O) (p = .001) and Proseal LMA (31.58 ± 4.35 cm of H2 O vs 27.03 ± 3.80 cm of H2 O) (p = .002). Oropharyngeal leak pressures of Ambu Auragain and Proseal LMA were comparable. Postoperative complications were similar in all the supraglottic airway devices. No regurgitation or aspiration-related problem was observed in our study. CONCLUSION: I gel had a higher oropharyngeal leak pressure than the other two supraglottic airway devices and therefore may represent a better choice in situations where higher ventilatory pressures may be necessary, for example, in extremes of weight trendelenburg position, etc. CLINICAL TRIAL IDENTIFIER: Clinical trial registry of India (CTRI/2018/11/016445).

Does Long-term Oxygen Therapy and Noninvasive Ventilation Predispose Rhino-orbital-cerebral Mucormycosis in COVID-19 Patients?

How to cite this article: Kumar A, Kumar A, Kumar N, Kumar A, Sinha C, Singh PK. Does Long-term Oxygen Therapy and Noninvasive Ventilation Predispose Rhino-orbital-cerebral Mucormycosis in COVID-19 Patients? Indian J Crit Care Med 2022;26(9):1063-1064.

Endotracheal tube inflation tubing defect: an unusual cause of intraoperative volume leak.

Loss of endotracheal cuff pressure can lead to airway compromise and loss of volume delivery in mechanical ventilation requiring immediate intervention. A 40 years old male posted for bilateral interpositional arthroplasty was intubated nasally with 7.5 mm flexometallic endotracheal tube. In the intraoperative period airway leak was detected due to loss of cuff pressure even after repeated attempt of cuff inflation. After changing endotracheal tube, leak was detected from the inflation tubing distal to the cuff, which was apparent only when cuff pressure was increased above 30 cm of H2O.

Sympathetic storm or Cytokine storm: A diagnostic dilemma in patient of traumatic brain injury with COVID 19.

PURPOSE: Paroxysmal sympathetic hyperactivity (PSH) occurs in around 15-33% patients of traumatic brain injury. Due to presence of non-specific symptoms, it's always difficult to differentiate between paroxysmal sympathetic storm and cytokine storm syndrome and hence can delay specific treatment. CASE REPORT: We report a clinical case of 19-year-old male tested COVID 19 positive with diffuse axonal injury presented with features of paroxysmal sympathetic storm and cytokine storm syndrome. The patient showed the signs clinical improvement when we treated both these conditions. CONCLUSION: We suggest that clinicians need to have a high degree of suspicion of paroxysmal sympathetic storm in patients of traumatic brain injury and consider its diagnosis. Also, if patient is COVID 19 positive, early identification of signs of developing cytokine storm with monitoring of biomarkers is important for its timely management.

Painful Blisters of Left Hand Following Extravasation of Remdesivir Infusion in COVID-19.

How to cite this article: Kumar N, Kumar A, Pradhan S, Kumar A, Singh K. Painful Blisters of Left Hand Following Extravasation of Remdesivir Infusion in COVID-19. Indian J Crit Care Med 2021;25(2):240-241.

Multiple Peaked Cytokine Storm: Is Multiple Exposures to the COVID-19 Virus a Possible Cause?

Severe acute respiratory syndrome coronavirus 2 is the pathogen that causes coronavirus disease-2019 (COVID-19). Recent studies have shown that the "cytokine storm" (high concentration of proinflammatory cytokines) may contribute to the mortality of COVID-19. Repeated exposure to the virus can lead to a dose-dependent immune response that may be associated with more disease severity and higher mortality. Sudden deterioration/increased oxygen consumption after initial improvement may be due to multiple surges of cytokines storm within a short period, the possible cause may be due to multiple exposures within the incubation period. We hypothesize that multiple surges in cytokines storm in some patients may be due to multiple exposures of the same patient within the incubation period, sepsis, or other inflammatory lesions inside the body. In our cases, sepsis as a cause of cytokine storm was ruled out by doing the procalcitonin test, which was within the normal limit. HOW TO CITE THIS ARTICLE: Kumar A, Kumar A, Kumar A, Kumar N, Sinha C, Singh V. Multiple Peaked Cytokine Storm: Is Multiple Exposures to the COVID-19 Virus a Possible Cause? Indian J Crit Care Med 2021;25(4):463-464.

Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19.

How to cite this article: Kumar A, Kumar N, Lenin D, Kumar A, Ahmad S. Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19. Indian J Crit Care Med 2021;25(4):474-475.

Repackaging of Malfunctioning High-flow Nasal Cannula as a Rescue Oxygen Therapy: An Innovation amid COVID-19 Crisis.

Oxygen supplementation is required for approximately 14% of the patients diagnosed of having COVID-19 infection. Despite the use of conventional oxygen therapy, 5% among these require treatment in the intensive care unit (ICU). Here, we are describing a situation in which oxygen therapy was delivered to the patients by making an assembly of oxygen tubing, three-way stopcock, and high-flow nasal cannula (HFNC) present in the hospital setting following the malfunction of air blender of HFNC machine (Fig. 1). This assembly might be useful as rescue oxygen therapy during a malfunction of HFNC machine and in resource-limited settings where HFNC machine is not available. The mechanisms of action could be (1) washout of anatomic dead space due to medium oxygen flow, (2) improved gas mixing in large airways, and (3) increased oxygen concentration inside the conducting airway. How to cite this article: Kumar A, Kumar A, Kumar N, Kumar A, Singh V, Kumar S, et al. Repackaging of Malfunctioning High-flow Nasal Cannula as a Rescue Oxygen Therapy: An Innovation amid COVID-19 Crisis. Indian J Crit Care Med 2021;25(8):948-949.

Dual Oxygen Therapy in COVID-19 Patient: A Method to Improve Oxygenation.

Approximately 5-6% of patients diagnosed to have COVID-19 infection present with severe hypoxemia requiring invasive ventilation or non-invasive ventilation (NIV). Additional oxygen to patients on NIV can be given by nasal prong or by connecting oxygen tubing directly to the O2 pick-off port of the NIV mask or by connecting oxygen tubing to the single-limb circuit in between ventilator and patient. Dual oxygen therapy improves oxygenation in COVID-19 patients on NIV. This method may make the patient more comfortable, increase tolerance to NIV, increase the usefulness of NIV for moderate and severe COVID-19 acute respiratory distress syndrome (ARDS). How to cite this article: Kumar A, Kumar A, Sinha C, Kumar N, Singh K, Singh PK. Dual Oxygen Therapy in COVID-19 Patient: A Method to Improve Oxygenation. Indian J Crit Care Med 2021;25(2):231-233.

Acute Exacerbation of Cough as a Precipitating Cause of Hypoxia in COVID-19 Patients.

Kumar A, Kumar A, Kumar A, Sinha C, Kumar N, Singh PK. Acute Exacerbation of Cough as a Precipitating Cause of Hypoxia in COVID-19 Patients. Indian J Crit Care Med 2021;25(11):1324-1325.

Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center.

Severe acute respiratory syndrome coronavirus 2 has affected millions of people worldwide. This pandemic requires newer medical management strategies to control the morbidity and mortality associated with the disease. Several approaches, including global targeting of inflammation or neutralizing a single key inflammatory mediator, are being employed to cope with cytokine storms in coronavirus disease-2019 (COVID-19). The role of anti-inflammatory biologics, such as acalabrutinib, tocilizumab, anakinra, and itolizumab can become relevant. Itolizumab is a humanized recombinant immunoglobulin G1 monoclonal antibody. It targets the extracellular, scavenger receptor cysteine-rich (SRCR) distal domain 1 of CD6 and is responsible for priming, activation, and differentiation of T-cells. Itolizumab has been approved by the Drug Controller General of India for the treatment of COVID-19 in India. Here, we shared our clinical experience of 20 patients having moderate acute respiratory distress syndrome (ARDS) due to COVID-19 on treatment with itolizumab. We observed the mortality benefit with single-dose itolizumab (1.6 mg/kg) in patients having moderate COVID-19 ARDS. HOW TO CITE THIS ARTICLE: Kumari P, Kumar A, Sinha C, Kumar A, Singh PK, Arun SK. Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center. Indian J Crit Care Med 2021;25(4):467-469.

The COSEVAST Study Outcome: Evidence of COVID-19 Severity Proportionate to Surge in Arterial Stiffness.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the cardiovascular system at many levels. It initially infects endothelial cells, inducing marked endothelial damage and inflammation. However, there was no empirical evidence of functional compromise of arterial walls. AIMS AND OBJECTIVE: Our primary objective was to study functional arterial damage in coronavirus disease 2019 (COVID-19) and establish the noninvasive measurement of arterial stiffness as an independent marker of disease severity. MATERIALS AND METHODS: We recorded the arterial stiffness of 23 mild, 21 moderate, and 20 severe COVID-19 patients grouped on the latest National Institute of Health (NIH) severity criteria. We observed arterial stiffness of COVID-19 patients with standard parameters like noninvasive estimated carotid-femoral pulse wave velocity (cfPWV), age-normalized increase in cfPWV (ANI_cfPWV), age-normalized increase in aortic augmentation pressure (ANI_AugP), and heart rate-normalized augmentation index (HRN_ AIx). All the parameters were also corrected for statistically significant confounding factors. RESULTS: Moderate and severe COVID-19 patients have extremely significantly elevated arterial stiffness than mild patients. In mild patients, cfPWV (829.1 ± 139.2 cm/second) was significantly lower than both moderate (1067 ± 152.5 cm/second, p <0.0001) and severe (1416 ± 253.9 cm/second, p <0.0001) patients. ANI_cfPWV in moderate and severe patients was significantly higher than mild patients (mild: 101.2 ± 126.1 cm/second; moderate: 279 ± 114.4 cm/second; severe: 580.1 ± 216.4 cm/second; intergroup p <0.0001). The results even after correction for significant confounding factors did not show any considerable change in the increasing trend of arterial stiffness. CONCLUSION: This study establishes the functional deterioration of arteries in proportion to the severity of COVID-19. HOW TO CITE THIS ARTICLE: Kumar N, Kumar S, Kumar A, Bhushan D, Kumar A, Kumar A, et al. The COSEVAST Study Outcome: Evidence of COVID-19 Severity Proportionate to Surge in Arterial Stiffness. Indian J Crit Care Med 2021;25(10):1113-1119.

Modified Negative Airflow Aerosol Prevention Box for COVID-19 Patients.

The importance of this intubation box has come to light recently in view of the coronavirus disease-2019 (COVID-19) pandemic and the fact that intubation is an aerosol-generating procedure (AGP). Risks of the healthcare worker attending to the airway of COVID-19 patients is high and the intubation box aims to minimize that and reduce contamination of the environment. To address this objective of decreasing transmission during AGP, we created a negative airflow aerosol box with a leak-proof airway handling system using readily available and affordable materials. The dimension of this box was 24 × 17.5 × 17.5 cm and it was made of high-quality 4 mm transparent acrylic sheet with two arm holes of 10 cm diameter. The caudal end of the negative airflow aerosol prevention box is wrapped with disposable plastic sheet and the both hand slots are sealed using camera cover and latex hand gloves and it decreases the risk of contamination. How to cite this article: Kumar N, Kumar A, Kumar A, Sinha C. Modified Negative Airflow Aerosol Prevention Box for COVID-19 Patients. Indian J Crit Care Med 2020;24(10):981-982.

Prolonged Use of Supraglottic Airway Device for Mechanical Ventilation in the Intensive Care Unit.

How to cite this article: Naaz S, Sahay N, Kumar R, Kumar A, Asghar A. Prolonged Use of Supraglottic Airway Device for Mechanical Ventilation in the Intensive Care Unit. Indian J Crit Care Med 2020;24(10):1001-1002.

Acute Necrotizing Encephalitis as a Probable Association of COVID-19.

BACKGROUND: Meanwhile, over 50 lakh people have now been affected by coronavirus disease-2019 (COVID-19) across the globe. There are various reports on neurological manifestations of COVID-19, which have attracted broad attention. Acute necrotizing encephalopathy (ANE) is a rare complication of influenza and other viral infections and has been related to intracranial cytokine storm, which results in breach in blood-brain barrier leading to encephalitis like presentation. We report an unusual case of acute necrotizing encephalitis as a solitary presentation of COVID-19. CASE DESCRIPTION: We report a case of 35-year-old man from Bihar, presented to our emergency department in unconscious state, with high-grade fever and vomiting since last 5 days. Previous magnetic resonance imaging (MRI) brain showed a left parasellar-middle cranial fossa mass looks most likely like an invasive meningioma. Urgent noncontrast computed tomography scan (NCCT) brain showed that mass as well as hypodensities in both thalami and left caudate nucleus. As per our institutional protocol, clinical management of raised intracranial pressure was initiated. As there is no current evidence from any randomized control trails (RCTs) to recommend any specific treatment for suspected or confirmed patients with COVID-19 with acute necrotizing encephalitis. CONCLUSION: Our case highlights the importance of identifying encephalitis as a presenting sign of COVID-19 based on NCCT findings with normal cerebrospinal fluid (CSF) and normal chest X-ray (CXR) findings. HOW TO CITE THIS ARTICLE: Kumar N, Kumar S, Kumar A, Pati BK, Kumar A, Singh C, et al. Acute Necrotizing Encephalitis as a Probable Association of COVID-19. Indian J Crit Care Med 2020;24(10):991-994.