Dosimetric comparison of O-ring versus conventional C-arm linear accelerator for volumetric modulated arc therapy (VMAT) of head and neck cancer and carcinoma cervix patients.

The objective of this study is dosimetric comparison between the O-ring Halcyon and C-arm Clinac iX linac for volumetric modulated arc therapy (VMAT) plans for head & neck (H&N) cancer and carcinoma cervix patients. Total 60 patients of H&N cancer and carcinoma cervix were enrolled prospectively from March 2021 to March 2023. VMAT plans with 6 MV photons for Halcyon and Clinac iX were generated and compared for each patient by dose volume histogram for planning target volume coverage and organ at risk (OAR) sparing. There were no differences in between both the linacs for PTV D2% and D98%, homogeneity index, conformity index, Dmax (maximum dose) and Dmean (mean dose) of OAR. Halcyon had significantly shorter treatment time compared to Clinac iX. Halcyon delivered higher integral dose and monitor units. O-ring Halcyon produces VMAT plans comparable to other C-arm linacs for H&N and carcinoma cervix patients.

Ribosomal protein control of hematopoietic stem cell transformation through direct, non-canonical regulation of metabolism.

We report here that expression of the ribosomal protein, RPL22, is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML); reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from increased expression of the Rpl22 target, ALOX12, an upstream regulator of fatty acid oxidation (FAO). The increased FAO mediated by Rpl22-deficiency also persists in leukemia cells and promotes their survival. Altogether, these findings reveal that Rpl22 insufficiency enhances the leukemia potential of HSC via non-canonical de-repression of its target, ALOX12, which enhances FAO, a process that may serve as a therapeutic vulnerability of Rpl22 low MDS and AML leukemia cells. Highlights: RPL22 insufficiency is observed in MDS/AML and is associated with reduced survivalRpl22-deficiency produces an MDS-like syndrome and facilitates leukemogenesisRpl22-deficiency does not impair global protein synthesis by HSCRpl22 controls leukemia cell survival by non-canonical regulation of lipid oxidation eTOC: Rpl22 controls the function and transformation potential of hematopoietic stem cells through effects on ALOX12 expression, a regulator of fatty acid oxidation.

India's Multi-Sectoral Response to Oxygen Surge Demand during COVID-19 Pandemic: A Scoping Review.

Oxygen support became one of the rate-limiting steps for medical care during COVID-19 pandemic in India. The primary aim of this study was to appraise the manufacturing, supply, and distribution of medical oxygen during the pandemic. The secondary objectives were to highlight the coordination of various stakeholders to mitigate the oxygen surge and to present a critical analysis of India's response to the emergent situation. Using an analytic approach, we have delineated India's response to mitigate the medical oxygen surge during the distressing second peak between March-May 2021. In the pre-COVID-19 era, of the total 6900 MT of oxygen produced in India, only 1000 MT was available for medical usage, which was increased up to 19940 MT through the strengthening of in-house oxygen manufacturing, low-cost innovations, and enhanced storage facilities. High-burden states were identified, and transport was facilitated through departments of railways, defence and civil aviation. Real-time scrutiny of the oxygen supply was provided. Essential customs duties on importing oxygen and vital equipment were exempted, along with other swift decisions. National Oxygen Stewardship Program' was initiated to build the capacity of health care workers in oxygen therapy and rational use of surplus oxygen. The pandemic overwhelmed the health system. But a coordinated multi-stakeholder approach facilitated the fight against oxygen surge. However, a comprehensive pandemic response will need more than just oxygen. This resourceful utilization offers a silver lining and facilitates the improvement of health systems and health outcomes in the long term.

Selection and application of biological safety cabinets in diagnostic and research laboratories with special emphasis on COVID-19.

The ongoing coronavirus disease (COVID-19) pandemic is a global public health emergency. Adherence to biosafety practices is mandatory to protect the user as well as the environment, while handling infectious agents. A biological safety cabinet (BSC) is the most important equipment used in diagnostic and research laboratories in order to safeguard the product, the person, and the environment. The World Health Organization has emphasized the use of validated BSCs in order to ensure quality of the results. There are different classes of BSCs that are used in various work environments based on the need. It is imperative to use appropriate levels of biosafety and types of BSCs in laboratories based on the risk assessment of the pathogen used. During the development of COVID-19 laboratories and training of laboratory staff, we came across several queries about the functions and selection of BSCs and realized that the knowledge about the detailed information on selections and applications of BSCs is scanty. There are several guidelines regarding the biosafety aspects for diagnostic and research laboratories handling infectious pathogens from national and international agencies. However, there is no detailed information on the use of appropriate types of BSCs and their functions in the context of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In view of this, the present paper describes in detail the selection and applications of BSCs, which could be useful for laboratories handling or planning to handle SARS-CoV-2 and suspected samples.

Vitamin D levels in paediatric intensive care unit patients and its relation to severity of illness: An Indian experience.

Vitamin D deficiency is a common disorder that is associated with morbidity and mortality in the general population. We conducted a cross-sectional study of 384 children admitted to paediatric intensive care to determine its prevalence and association with severity of illness and outcome in critically ill children. The severity of illness was evaluated using the paediatric risk of mortality score (PRISM III), on admission, at 24 and 48 h. Vitamin D deficiency was observed in 175 children (45.6%) and was associated with higher severity of illness, need for mechanical ventilation and increased mortality.

A novel reassortant avian influenza H4N6 virus isolated from an environmental sample during a surveillance in Maharashtra, India.

Background & objectives: Low pathogenic avian influenza (LPAI) viruses cause mild clinical illness in domestic birds. Migratory birds are a known reservoir for all subtypes of avian influenza (AI) viruses. The objective of the study was to characterize AI H4N6 virus isolated from an environmental sample during surveillance in Maharashtra, India. Methods: AI surveillance in wild migratory birds was conducted during the winter migratory bird season (2016-2017) in Pune, India. AI H4N6 virus was isolated from the faecal droppings of a wild migratory waterbird. Virological and molecular characterization of the isolated virus was carried out. Virus titration, haemagglutination inhibition assay, receptor specificity assay, intravenous pathogenicity index and neuraminidase inhibition assays were performed. Full genome sequencing, molecular and phylogenetic analyses were also conducted. Results: The virus was found to be of low pathogenicity, with avian type receptor specificity, and was susceptible to neuraminidase inhibitors. Phylogenetic and molecular analysis revealed that the present virus is a result of extensive reassortment with AI H8N4, H6N2, H4N3 and H3N6, predominantly as donor viruses among others. Interpretation & conclusions: This is the first report of the isolation and characterization of an LPAI H4N6 virus from an environmental sample from India. The present study showed that the H4N6 virus is a novel reassortant and divergent as compared with the reported H4N6 viruses from poultry in India, indicating independent introduction. This highlights the role of wild and migratory birds in the transmission of AI viruses and necessity of such studies at the human-animal interface.

Morphological and Biochemical Characteristics of Avian Faecal Droppings and Their Impact on Survival of Avian Influenza Virus.

Environmental specimens such as faecal droppings are considered important for the detection of avian influenza viruses (AIV). In view of lower rates of AIV isolation from avian faecal droppings, characterization of droppings is imperative to elucidate contributing factors. However, there are no reports on morphological and biochemical characteristics of droppings. The objective of the present study was the characterization of droppings from different avian species and their impact on the AIV detection and isolation. A total of 373 droppings belonging to 61 avian species from 22 families of apparently healthy wild migratory, resident, domestic birds and poultry were studied during five winter migratory bird seasons between 2007 to 2012 and 2016-2017. The colour, morphology and size of the droppings varied from species-to-species. These data could be useful for the identification of avian species. Droppings from 67% of the avian species showed acidic pH (4.5-6.5); nine species showed neutral pH (7.0), and 11 species showed alkaline pH (7.5). The infectious titers of AIV in droppings with acidic pH were significantly lower (p < 0.05) than those of the droppings with neutral and alkaline pH. However, acidic pH did not hamper AIV detection by real-time RT-PCR. In order to avoid the impact of acidic pH, collecting fresh droppings into viral transport medium (pH 7.0-7.5) would help improve the rate of AIV isolation.

Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma.

Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc-finger E-box binding homeobox 1 (ZEB1), which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

Vancomycin-resistance Enterococcal Colonization in Hospitalized Patients in Relation to Antibiotic Usage in a Tertiary Care Hospital of North India.

BACKGROUND: Alarming rise of vancomycin-resistant enterococci (VRE) is a global cause of concern. Several factors have been held responsible for such rise, of which antibiotic usage is a prominent one. OBJECTIVE: This study was undertaken to determine the intestinal VRE colonization rate amongst hospitalized patients in relation to use of various antibiotics in the Intensive Care Unit (ICU) of a tertiary care university hospital, India. MATERIALS AND METHODS: Stool samples were collected weekly from all the patients in the adult ICU for a period of 6 months and processed for isolation and phenotypic and genotypic characterization of VRE isolates. Patient and treatment details were noted and cases (those with VRE in stool) and controls (those without VRE in stool) were compared statistically. Further, a multivariate analysis was done to identify those antibiotics as independent risk factors for VRE colonization. RESULTS: VRE colonization was found in 34.56% (28/81) of the patients studied, with the majority 75% (21/28) carrying the vanA gene. The cases had significantly more (P < 0.05) duration of hospital stay and antibiotic exposure. Intake of metronidazole, vancomycin, and piperacillin-tazobactam were identified as significant risk factors both in univariate and multivariate analysis. CONCLUSION: A potential reservoir of VRE was thus revealed even in low VRE prevalence setting. Based on this high colonization status, restriction of empirical antibiotic use, reviewing of the ongoing antibiotic policy, and active VRE surveillance as an integral part of infection control strategy were suggested.

Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.

The nuclear receptor peroxisome-proliferation-activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers, including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell-cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or ß-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell-cycle progression of cancer cells by altering ROS levels.

Evaluating the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium: a prospective, randomized, double blind, placebo-controlled study.

BACKGROUND: Patients undergoing craniotomy, experience moderate to severe pain in postoperative period. Flupirtine does not have side effects like sedation and increase postoperative bleeding, so it may be a useful analgesic in neurosurgical patients. We designed this prospective, randomized, double blind, placebo-controlled study to evaluate the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium. MATERIALS AND METHODS: A total of 390 adults (18 to 70 y), American Society of Anaesthesiologists I and II, of either sex, undergoing elective craniotomy, were randomly divided into 3 equal groups of 130 each. Group 1 (control) received placebo, group 2 (diclofenac) received tablet diclofenac 50 mg, and group 3 (flupirtine) received capsule flupirtine 100 mg. All medications were given 8 hourly on second postoperative day for 48 hours. Visual Analogue Scale score, level of sedation and incidence of side effects were observed. RESULTS: Nineteen patients were dropped from the study and therefore subsequent analysis was carried out for 371 patients only. There was significant reduction of Visual Analogue Scale score in flupirtine and diclofenac group when compared to control (P<0.0001). Pain relief observed in control, flupirtine, and diclofenac group was 69.8%, 90.2%, and 90.5%, respectively. Need of rescue analgesia was significantly less in flupirtine and diclofenac group as compared to control (P<0.0001). No significant difference was observed among the groups in regards to adverse effects. CONCLUSION: We conclude that oral flupirtine 100 mg is safe and as effective as oral diclofenac sodium 50 mg in reducing postcraniotomy pain.

Poor compliance with the antibiotic policy in the intensive care unit (ICU) of a tertiary care hospital in India.

INTRODUCTION: Most developing countries are adopting antibiotic policies to contain the acute problem of drug resistance; however, several obstacles prevent their fulfillment. This study was undertaken to prospectively determine the compliance with the antibiotic policy in the intensive care unit (ICU) of a tertiary care hospital and possible reasons for non-compliance. METHODOLOGY: Compliance with the newly introduced antibiotic policy was studied for a period of six months. A total of 170 cases from the ICU were included. Relevant information regarding patient characteristics, treatment details, infection control, and antibiotic prescribing practices in the ICU with reference to the antibiotic policy was collected. Reasons for non-compliance were studied. RESULTS: The rate of compliance with the antibiotic policy was 21.18%. Heavy use of antibiotics prior to the time of admission in the ICU was the major cause of non-compliance. Microbiological investigation had been sent in only 51.17% of the cases and change in treatment protocol based on culture report was done in 53.3%. The rate of use of third-generation cephalosporins was 76.78%. CONCLUSIONS: We found non-compliance with the antibiotic policy in the ICU mainly due to improper and inappropriate antibiotic usage in other indoor units of the hospital. In our case, a policy covering the entire hospital is required to meet the goals of antibiotic usage restriction. An effective surveillance, review, and evaluation process should be an integral part of the policy, even in developing countries, to measure the effects of such policies.

Establishment of cell line from embryonic tissue of Pipistrellus ceylonicus bat species from India & its susceptibility to different viruses.

BACKGROUND & OBJECTIVES: Pipistrellus ceylonicus bat species is widely distributed in South Asia, with additional populations recorded in China and Southeast Asia. Bats are the natural reservoir hosts for a number of emerging zoonotic diseases. Attempts to isolate bat-borne viruses in various terrestrial mammalian cell lines have sometimes been unsuccessful. The bat cell lines are useful in isolation and propagation of many of the viruses harboured by bats. New stable bat cell lines are needed to help such investigations and to assist in the study of bat immunology and virus-host interactions. In this study we made an attempt to develop a cell line from P. ceylonicus bats. METHODS: An effort was made to establish cell line from embryo of P. ceylonicus species of bat after seeding to Dulbecco's modified eagle medium (DMEM) supplemented with 10 per cent foetal bovine serum; a primary cell line was established and designated as NIV-BtEPC. Mitochondrial DNA profile analysis was done using cyt-b and ND-1 gene sequences from the cell line. Phylogenetic tree was constructed using neighbour-joining algorithm for cyt-b and ND-1 genes with 1000-bootstrap replicates. RESULTS: NIV-BtEPC cell line was susceptible to Chandipura (CHPV) and novel adenovirus (BtAdv-RLM) isolated from Rousettus leschenaulti from India but did not support multiplication of a number of Bunyaviruses, Alphaviruses and Flavivirus. This might be useful for isolation of a range of viruses and investigation of unknown aetiological agents. INTERPRETATION & CONCLUSIONS: In this study, a new bat cell line was developed from P. ceylonicus. This cell line was successfully tested for the susceptibility to Chandipura and BtAdv-RLM virus isolated from bats. The approach developed and optimised in this study may be applicable to the other species of bats and this established cell line can be used to facilitate virus isolation and basic research into virus-host interaction.

CHARACTERIZATION OF MOLLUSCICIDAL COMPONENT OF Moringa oleifera LEAF AND Momordica charantia FRUITS AND THEIR MODES OF ACTION IN SNAIL Lymnaea acuminata / Caracterização do componente moluscicida das folhas da Moringa oleifera e das frutas da Momordica charantia e seus modos de ação sobre o caramujo Lymnaea acuminata

SUMMARY The molluscicidal activity of the leaf powder of Moringa oleifera and lyophilized fruit powder of Momordica charantia against the snail Lymnaea acuminata was time and concentration dependent. M. oleifera leaf powder (96 h LC50: 197.59 ppm) was more toxic than M. charantia lyophilized fruit powder (96 h LC50: 318.29 ppm). The ethanolic extracts of M. oleifera leaf powder and Momordica charantia lyophilized fruit powder were more toxic than other organic solvent extracts. The 96 h LC50 of the column purified fraction of M. oleifera leaf powder was 22.52 ppm, while that of M. charantia lyophilized fruit powder was 6.21 ppm. Column, thin layer and high performance liquid chromatography analysis show that the active molluscicidal components in M. oleifera leaf powder and lyophilized fruit of M. charantia are benzylamine (96 h LC50: 2.3 ppm) and momordicine (96 h LC50: 1.2 ppm), respectively. Benzylamine and momordicine significantly inhibited, in vivo and in vitro, the acetylcholinesterase (AChE), acid and alkaline phosphatase (ACP/ALP) activities in the nervous tissues of L. acuminata. Inhibition of AChE, ACP and ALP activity in the nervous tissues of L. acuminata by benzylamine and momordicine may be responsible for the molluscicidal activity of M. oleifera and M. charantia fruits, respectively. .

RESUMO A atividade moluscicida do pó das folhas de Moringa oleifera e do pó liofilizado das frutas da Momordica charantia contra o caramujo Lymnaea acuminata é dependente do tempo e da sua concentração. O pó da folha da M. oleifera (96 h LC50: 197.59 ppm) foi mais tóxico do que o pó liofilizado da fruta da M. charantia (96 h LC50: 318.29 ppm). Os extratos etanólicos do pó de folha da M. oleifera e do pó liofilizado da fruta da M. charantia foram mais tóxicos do que outros extratos orgânicos solventes. O 96 h LC50 da fração purificada por coluna do pó das folhas da M. oleifera foi 22.52 ppm enquanto que o pó liofilizado do fruto da M. charantia foi 6.21 ppm. Coluna, camada fina e a alta performance da análise da cromatografia líquida mostram que os componentes ativos moluscicidas do pó da folha da M. oleifera e do liofiliizado da fruta da M. charantia são a benzilamina (96 h LC50: 22.3 ppm) e a momordicina (96 h LC50: 1.2 ppm), respectivamente. A benzilamina e a momordicina inibiram de maneira significante in vivo e in vitro a acetilcolinesterase (AChE), as atividades das fosfatases alcalina e ácida (ACP/ALP) nos tecidos nervosos da L. acuminata. A inibição da atividade da AChE, ACP e ALP nos tecidos nervosos da L. acuminata pela benzilamina e momordicina podem ser responsáveis pela atividade moluscicida da M. oleifera e dos frutos da M. charantia, respectivamente. .

Anesthetic management of emergency laparotomy in a case of ischemic cardiomyopathy with COPD.

Anesthesia for non-cardiac surgeries in patients with ischemic cardiomyopathy with other co-morbidities is a challenging situation for anesthetists. The choice of anesthesia and anesthetic agents should be judicious and balanced to maintain optimum cardiac output and to avoid myocardial depression for a successful postoperative outcome. Here, we describe the anesthetic management for emergency exploratory laparotomy in a patient who was suffering from ischemic cardiomyopathy along with chronic obstructive pulmonary disease and was presented to the emergency operation theater for gastrointestinal tract perforation.

Effect of the perioperative infusion of dexmedetomidine on chronic pain after breast surgery.

BACKGROUND: This prospective double-blind trial was undertaken to analyze the role of perioperatively administered dexmedetomidine on the occurrence of chronic pain in cases undergoing surgery for breast cancer. SUBJECTS AND METHODS: Eighty-six cases were randomly assigned to two groups to receive either dexmedetomidine (2 µg/ml) in group D or saline in group C, in a loading dose of 0.5 ml/kg, intravenous (IV), 30 min prior to induction, followed by a continuous infusion of 0.25 ml/kg/h IV till the completion of surgery, and then the dose tapered to 0.1 ml/kg/h for up to 24 h. The standardized questionnaires that measured chronic pain (Brief Pain Inventory, BPI; Short Form McGill Pain Questionnaire, SF-MPQ2) and quality of life (Quality of Life Scale, QOLS) were gathered after 3 months of surgery as a primary outcome. Pain (verbal numerical score, VNS), sedation scores (Ramsay scoring), and analgesic requirements were also assessed for 72 h postoperatively. RESULTS: In total, 84 cases (n=42) were analyzed for acute pain and 69 (34 in group D and 35 in group C) for chronic pain. The consumption of isoflurane/fentanyl intra-operatively and paracetamol postoperatively was significantly lower in Group D. The sedation scores were non-significant between the groups. The VNS at rest and after movement was significantly lower in group D at corresponding times (except at 60 min) throughout the assessment period. The BPI and SF-MPQ2 scores were significantly lower in group D in most of the factors. The QOLS score was significantly better in group D in all items except for relationships, friends, and learning. CONCLUSION: The perioperative infusion of dexmedetomidine has a pivotal role in attenuating the incidence and severity of chronic pain and improving the quality of life in cases undergoing breast cancer surgery.

Malignant hyperthermia in endosulfan poisoning.

We are reporting a case of endosulfan poisoning, admitted in a state of altered consciousness, vomiting, and seizure. The diagnosis was based on history, physical examination and positive reports from toxicological screening. After 8 hrs of admission, a sudden rise in EtCO(2), respiratory rate, heart rate, blood pressure, and body temperature was noted. Masseter spasm was there and patient's elbow/knees could not be bent upon manipulation. Caffeine halothane contraction test later confirmed it to be malignant hyperthermia (MH). We suggest that if there is a sudden rise in body temperature, stiffness in limbs or massater spasm in a case of endosulfan poisoning, the diagnosis of MH should be considered as one possibility when etiology is not certain.

Comparison of three different formulations of local anaesthetics for cervical epidural anaesthesia during thyroid surgery.

BACKGROUND: To compare the efficacy and safety of local anaesthetics under cervical epidural anaesthesia (CEA) using lignocaine (1%), bupivacaine (0.25%) and ropivacaine (0.5%) for thyroid surgery. METHODS: In a prospective, randomized fashion, 81 patients were selected for thyroid surgery under CEA. They were assigned to one of three groups: Group L, B and R to receive 10 mL of 1% lignocaine, 0.25% bupivacaine and 0.5% ropivacaine, respectively. We compared their efficacy in terms of pulmonary and haemodynamic parameters, blockade quality and complications. RESULTS: Of the total, 74 patients completed the study successfully. Sensory block attained the median dermatomal range of C2-T4/T5 in all the groups. Motor block was more pronounced in the ropivacaine group. Cardiorespiratory parameters decreased significantly in all the groups; however, none of the patients had any major complications except for bradycardia in two patients. Among the measured variables, the decrease in heart rate and peak expiratory force was more in the lignocaine group while forced vital capacity and forced expiratory volume at 1 sec declined to a greater extent in the ropivacaine group. The lignocaine group required significantly more epidural top-ups compared with the other two groups. CONCLUSION: We conclude that cervical epidural route can be safely used for surgery on thyroid gland in patients with normal cardiorespiratory reserve, using either of local anaesthetics chosen for our study. Under the selected dose and concentrations, the decrease in cardiorespiratory parameters was lesser with bupivacaine.