Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study.

BACKGROUND: Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). METHODS: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. RESULTS: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200-380] vs. 250 [150-350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). CONCLUSIONS: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Procedural sedation in children for fractionated radiation treatment: Intranasal dexmedetomidine versus oral midazolam and ketamine.

Background and Aims: Sedation in paediatric cancer for fractionated radiation treatment (RT) is unique as the child has to be still for accurate delivery of RT, monitoring of the child is from a remote location and sedation is repeated for multiple sessions of RT. The present study was undertaken to compare the efficacy of intranasal dexmedetomidine with oral midazolam and ketamine combination for repeated sedation during fractionated RT in paediatric oncology. Methods: Ninety children aged between 3-6 years, planned for 21 fractions of RT, were randomised to receive intranasal dexmedetomidine 2 µg/kg (group D) or oral midazolam 0.2 mg/kg and ketamine 5 mg/kg (group MK). The 21 sessions of fractionated radiotherapy were divided into three subgroups of seven consecutive exposures 1-7, 8-14 and 15-21 for comparison. The primary endpoint was to determine the incidence of successful sedation. The sedation score achieved, time to satisfactory sedation and discharge, rescue ketamine required, and side effects were secondary endpoints. Results: The incidence of successful sedation in the three successive RT subgroups; sessions: 1-7, 8-14 and 15-21, was 82%, 75.6% and 66.7% in group D, as compared to 40%, 24.4% and 13.3% in group MK, respectively. (P < 0.001). A decrease in successful sedation was noted in the successive subgroups. Time to successful sedation and discharge was earlier in group D in comparison to MK (P = 0.000). More patients in group MK required rescue ketamine (P = 000). Conclusion: Intranasal dexmedetomidine produces more satisfactory sedation as compared to oral ketamine with midazolam for fractionated RT.

Steroid growth promoter modified glucose profile and liver morphology in broiler by altering the localization and expression pattern of hepatic glucocorticoid receptors.

This study explores the impact of dexamethasone (DEX) on the serum glucose profile, morphological attributes of the liver, and the expression of hepatic glucocorticoid receptors (GRs) in the broiler. To conduct this study, four homogenous groups of day-old chicks (DOCs) were used (n = 20 chicks per group); one control group (C), and three treatment groups (T1, T2, and T3). All the groups were maintained on a commercial feed with which 3, 5, and 7 mg DEX (per kg feed) were supplied to the T1, T2, and T3 groups, respectively. Samples were collected on days 7, 14, 21, and 28 of the experiment. The serum glucose profile was measured by spectrophotometry. The livers' morphometric attributes were recorded before being processed and stained with hematoxylin and eosin. The expression pattern of hepatic GR proteins was evaluated by immunohistochemical staining. DEX residue was detected in liver tissue using thin-layer chromatography. Increased serum glucose level was observed in the DEX groups. Fatty liver, hepatic congestion, and decreased morphometric attributes were the critical findings in the DEX groups. Congestion of the central veins, sinusoids, and accumulation of lipid droplets was also observed in the DEX groups. GR proteins were mostly localized in the central vein and cytoplasm of the hepatocytes, the expression of which was found to be upregulated with the increased dose of DEX. The residue of DEX was detected in the liver tissues in the higher dose groups. The findings imply that DEX can substantially alter the blood glucose profile and liver morphology.

Complete mitochondrial genome of freshwater pearl mussel Lamellidens marginalis (Lamarck, 1819) and its phylogenetic relation within unionidae family.

BACKGROUND: Freshwater mussels play a key role in ecology and are often considered as ecological indicators. Conversely, these molluscs are one of the most threatened groups due to several anthropogenic factors. Knowledge of phylogenetic diversity would assist in formulating effective management and conservation measures. Lamellidens marginalis is one of the most widely used freshwater mussel for pearl production in India. The genomic resources for investigating its evolutionary relationship within the Unionidae family are lacking. METHODS AND RESULTS: In this study, the f-type mitochondrial genome of L. marginalis was sequenced using the Illumina sequencing platform. The length of the mitochondrial genome was 15,732 bp consisting of 23 tRNAs, 2 rRNAs and 13 protein coding genes. The arrangement of genes was UF1 type and gene overlap was observed between trnG and nad1. Comparative analysis with other Unionidae species showed a high divergence rate in nad6 followed by nad2 atp8 and nad5. The phylogenetic tree supported monophyly of the Unioninae subfamily and L. marginalis (Parreysiinae) formed a sister branch to this subfamily. The divergence time of the Parreysiinae from its most recent common ancestor (MRCA) was placed in the Mesozoic era. CONCLUSION: This information will be useful for the understanding the evolutionary pattern of the species of Parreysiinae subfamily.

Complexities in viral replication strategies as a potential explanation for prevalence of asymptomatic carriers in Covid-19 infections: analytical observation on SARS-Cov2 genome characteristics.

Analytical observations (in silico) indicate molecular features of SARS-Cov2 genome that potentially explains the high prevalence of asymptomatic cases in Covid-19 pandemic. We observed that the virus maintains a low preference for 'GGG' codon for glycine (3%) in its genome. We also observed multiple putative introns of 26-44 nucleotide (nt) length in the genomic region between the coding regions of Nsp10 and RPol in the viral ORF1ab, like several other beta-coronaviruses of similar infectivity levels. It appears that the virus employs a dual strategy to ensure unhindered replication within the host. One of the strategies employ a (- )1 frameshift translation event through programmed ribosomal slippage at the ribosomal slippage site in the ORF1ab. The alternate strategy relies on intron excision to generate a read through frame. The presence of 'GGG' in this conserved ribosomal slippage site ensures adequate tRNA in cytoplasm to match the codon, implying no additional frameshift translation due to ribosomal stalling. With fewer replication events, viral load remains low and resulting in asymptomatic cases. We suggest that this strategy is the primary reason for the prevalence of asymptomatic cases in the disease, enabling the virus to spread rapidly.

Optimising Cancer Surgery During COVID-19: Experience of Tertiary Cancer Centre in Eastern India.

PURPOSE: The timely management of cancer surgery suffered due to COVID-19 and nationwide lockdown. Continuing cancer surgery was a challenge faced by all. We present our experience on cancer surgery in a cancer centre with high volume of patients and limited resources during early pandemic. METHODS: We retrospectively analysed our operation theatre database on surgery and anaesthesia from 1st April to 30th June 2020. RESULTS: A total of 457 surgeries were done-complex major, major, intermediate and minor surgeries constituted 43%, 25%, 12% and 20%, respectively. Median age of patient was 50 years, and 76% were below 60. The median ASA class was I (I-IV), and 97% were ASA I and II. The median Eastern Cooperative Oncology Group score was 0 (0-3), and 92% had score 0 and 1. Major cases done under regional anaesthesia were 30.7%. Median length of intensive care unit stay was 1 (1-6) days, and length of hospital stay was 7 (7-15) days. Clavien-Dindo Grade II complication in patients above 60 years was 16.4% and below 60 years was 17.6% (p = 0.76). 10% in ASA I compared to 26% of ASA II (p = 0.00) and 15.9% with ECOG 0 and 1 compared to 30.9% with ECOG 3 and 4 (p = 0.01) had grade II complication. Four (1%) patients had Grade ≥ III CD complication. Covid testing was undertaken in 52% patients pre-operatively, and there was no positive case in post-operative period. CONCLUSIONS: Adopting and implementing institutional policy catering to limited resource available at our centre, we facilitated cancer surgery.

Role of dexmedetomidine as an anaesthetic adjuvant in breast cancer surgery as a day-care procedure: A randomised controlled study.

BACKGROUND AND AIMS: Breast cancer surgery can be carried out as day-care procedure to increase patient turnover, decrease disease progression and financial burden. The present study was carried out to assess the role of dexmedetomidine in breast cancer surgery as a day-care procedure. METHODS: This prospective randomised, double-blind study was carried out on 100 patients screened for day-care breast cancer surgery. They were divided into two groups of 50 each; who received either normal saline (Group NS) or 0.6 µg/kg/h dexmedetomidine (Group D) infusion from 10 min before induction until skin closure. All patients were given general anaesthesia. The incidence of discharge, post-operative pain (POP), average rescue analgesia (fentanyl) required and side effects were noted. Statistical analysis was performed using Student's t-test and Chi-square test. RESULTS: Incidence of discharge in group NS was 60% compared to 88% in Group D (P = 0.001). Average rescue analgesia requirement by group NS was 136.07 ± 43.06 µg, whereas it was 77.5 ± 29.86 µg in Group D (P = 0.01). The incidence of POP in 6 h and within 2 h of expected discharge time in Group NS was 56% and 28%, respectively, and in Group D, it was 8% in both the periods (P < 0.001 and 0.01). Side effects such as post-operative nausea, vomiting and bleeding were encountered in eight and two patients, respectively, in Group NS and two and one patients, respectively, in Group D. CONCLUSION: Dexmedetomidine as an anaesthetic adjuvant makes breast cancer surgery feasible on day-care basis.

Silencing and augmentation of IAG hormone transcripts in adult Macrobrachiumrosenbergii males affects morphotype transformation.

Morphotypic differentiation is the external manifestation of dominance hierarchy in Macrobrachium rosenbergii The intermediate morphotype orange claw (OC) male exhibits the highest growth rate and is subordinate in hierarchy to blue claw (BC) male while dominant on small male (SM). The present study was undertaken to examine the specific role of insulin-like androgenic gland (iag) hormone in morphotype differentiation of M. rosenbergii To achieve this, RNAi mediated knockdown as well as augmentation of iag transcripts were effected in ∼60 g OC males using plasmid-based constructs pcD-IAG-lh and pcD-IAGorf, respectively. The treatments were administered to animals maintained in isolation as well as in community. The knockdown plasmid construct that expresses iag-specific long hairpin RNA caused 16-fold reduction of iag transcripts in the SSN1 cell line in vitro When injected into OC males living in a community, 2.3-fold iag knockdown was recorded, while in isolated OC males it was 4.2-fold initially, but returned to normal subsequently. Compared with the respective controls, OC to BC transformations in the iag silenced animals were significantly lower in the community-reared group, while no difference was observed in the isolated animals. It is reported here for the first time that iag augmentation in OC males resulted in significantly higher OC to BC transformations, when animals were reared in community. This plasmid-based IAG knockdown approach could be developed into a low stress, feed or immersion treatment for controlling heterogeneous individual growth of M. rosenbergii males in aquaculture.

Analysis of variance, normal quantile-quantile correlation and effective expression support of pooled expression ratio of reference genes for defining expression stability.

Identification of a reference gene unaffected by the experimental conditions is obligatory for accurate measurement of gene expression through relative quantification. Most existing methods directly analyze variability in crossing point (Cp) values of reference genes and fail to account for template-independent factors that affect Cp values in their estimates. We describe the use of three simple statistical methods namely analysis of variance (ANOVA), normal quantile-quantile correlation (NQQC) and effective expression support (EES), on pooled expression ratios of reference genes in a panel to overcome this issue. The pooling of expression ratios across the genes in the panel nullify the sample specific effects uniformly affecting all genes that are falsely reflected as instability. Our methods also offer the flexibility to include sample specific PCR efficiencies in estimations, when available, for improved accuracy. Additionally, we describe a correction factor from the ANOVA method to correct the relative fold change of a target gene if no truly stable reference gene could be found in the analyzed panel. The analysis is described on a synthetic data set to simplify the explanation of the statistical treatment of data.

Emerging enteric fever due to switching biotype of Salmonella (paratyphi A) in Eastern Odisha.

BACKGROUND: Typhoid fever is classically caused by Salmonella enterica serotype typhi.Recently the frequency of isolation of S. paratyphi A (SPA) has been increased in comparison to S. typhi in Indian scenario. AIM: To observe the rate of isolation and antimicrobial susceptibility pattern of SPA from suspected enteric fever cases attending tertiary care centres of Eastern Orissa. SETTINGS AND DESIGN: Retrospective study Materials and Methods: 1488 blood samples were collected during different duration of fever and cultured in BACTEC blood culture system and bottles showing signal for growth were subcultured and identified as Salmonella spp. by standard procedure and mini API (Biomeriux) and antimicrobial susceptibility by disc diffusion method. STATISTICAL ANALYSIS: Chi square test. RESULTS: 167 Salmonella spp. were isolated including 83.8% Salmonella paratyphi A and 16.6% S. typhi. Among them 102 were males and 65 were females with mean age of 22.7 yrs. S. paratyphi A was the predominant spp. each year but during 2008 - 2011, there was a dramatic rise (significant P value- 0.034). Multidrug resistance was noticed in 10.2% of the isolates. 98% of S. paratyphi A were resistant to nalidixic acid and 41% to ciprofloxacin, but the MIC of ciprofloxacin was raised between 1-2 µgm/dl showing the relation between nalidixic acid resistance and raised MIC of ciprofloxacin. CONCLUSION: Nalidixic acid should be tested along with ciprofloxacin disc while testing for susceptibility and MIC of ciprofloxacin is mandatory before advocating therapy to prevent treatment failure.

Validation of the EuroQol Five-dimensions - Three-Level Quality of Life Instrument in a Classical Indian Language (Odia) and Its Use to Assess Quality of Life and Health Status of Cancer Patients in Eastern India.

BACKGROUND AND OBJECTIVES: The EuroQol five-dimensions - 3-level (EQ5D) is a versatile quality of life (QOL) instrument with five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analog scale. It can be used to calculate quality-adjusted life years. We aimed to evaluate the validity, reliability, and responsiveness of an Odia version of EQ5D and to study the QOL of cancer patients in our part of the country as cancer treatment in India still focuses largely on longevity due to scarcity of resources. MATERIALS AND METHODS: The EQ5D tool was translated into Odia language in collaboration with the EQ group. This tool and the World Health Organization-5 (WHO-5) questionnaires were administered to 155 surgical outpatients and 150 cancer patients in two hospitals of Eastern India. The convergent and discriminant validities (construct validity), concurrent validity, reliability (test-retest method of administering the tool to a part of the population after 7-14 days), and the internal consistency (Cronbach's alpha) were measured using preestablished hypotheses. The data from the cancer patients were analyzed separately. RESULTS: The QOL worsened with age and was worse in cancer patients proved that the tool had good construct validity. The Anxiety Depression dimension had good correlation with all the dimensions WHO-5 (rho > 0.4) indicating a good concurrent validity. Internal consistency and reliability of the tool were good (Cronbach's alpha > 0.7). Cancer patients had a poor QOL (mean EQ5D index 0.37SD 0.4) with male patients, patients with Grade II cancer or referred for pain care services and those with living spouses reporting worse QOL. CONCLUSIONS: The Odia version of the EQ5D has good reliability and validity for the measurement of health status in cancer and outpatient department patients. Cancer patients in this part of the country have a poor QOL and may need a closer look at pain management and improved societal support systems.

Transfusion transmitted diseases in perioperative and intensive care settings.

Patients in the perioperative period and intensive care unit are commonly exposed to blood transfusion (BT). They are at increased risk of transfusion transmitted bacterial, viral and protozoal diseases. The risk of viral transmission has decreased steadily, but the risk of bacterial transmission remains same. Bacterial contamination is more in platelet concentrates than in red cells and least in plasma. The chances of sepsis, morbidity and mortality depend on the number of transfusions and underlying condition of the patient. Challenges to safe BT continue due to new emerging pathogens and various management problems. Strategies to restrict BT, optimal surgical and anaesthetic techniques to reduce blood loss and efforts to develop transfusion alternatives should be made. Literature search was performed using search words/phrases blood transfusion, transfusion, transfusion transmitted diseases, transfusion transmitted bacterial diseases, transfusion transmitted viral diseases, transfusion transmitted protozoal diseases or combinations, on PubMed and Google Scholar from 1990 to 2014.

A GFP-based bacterial biosensor with chromosomally integrated sensing cassette for quantitative detection of Hg(II) in environment.

A mercury biosensor was constructed by integrating biosensor genetic elements into E. coli JM109 chromosome in a single copy number, using the attP/attB recombination mechanism of lambda phage. The genetic elements used include a regulatory protein gene (merR) along with operator/promoter (O/P) derived from the mercury resistance operon from pDU1358 plasmid of Serratia marcescens. The expression of reporter gene gfp is also controlled by merR/O/P. Integration of the construct into the chromosome was done to increase the stability and precision of the biosensor. This biosensor could detect Hg(II) ions in the concentration range of 100-1700 nmol/L, and manifest the result as the expression of GFP. The GFP expression was significantly different (P < or = 0.05) for each concentration of inducing Hg(II) ions in the detection range, which reduces the chances of misinterpretation of results. A model using regression method was also derived for the quantification of the concentration of Hg(II) in water samples.

Culture and the role of choice in agency.

Three cross-cultural studies conducted among U.S. and Indian adults compared perceptions of helping friends in strongly versus weakly expected cases, views of helping family versus strangers, and responses to a self-determination motivation scale. Expectations to help family and friends were positively correlated with satisfaction and choice only among Indians and not among Americans. Also, whereas U.S. respondents associated lesser satisfaction and choice with strongly versus weakly socially expected helping, Indian respondents associated equal satisfaction and choice with the 2 types of cases. Providing evidence of the importance of choice in collectivist cultures, the results indicate that social expectations to meet the needs of family and friends tend to be more fully internalized among Indians than among Americans. Methodologically, the results also highlight the need to incorporate items that tap more internalized meanings of role-related social expectations on measures of motivation in the tradition of self-determination theory.

Protection of Penaeus monodon from Infection of White spot syndrome virus by DNA Construct Expressing Long Hairpin-RNA Against ICP11 Gene.

A plasmid construct (pICP11-LH) was designed to constitutively express long-hairpin RNA (lhRNA) against icp11 gene, which is reportedly the most highly expressed gene of White spot syndrome virus (WSSV) and likely to have an important role in viral pathogenesis. The construct was used singly and in combination with other similar constructs designed against vp28 and vp19. A total of 6 treatments, T1 (pICP11-LH; 35 µg), T2 (pVP28-LH; 35 µg), T3 (pVP28-LH and pVP19-LH; 17.5 µg each), T4 (pVP28-LH and pVP19-LH; 25 µg:10 µg), T5 (pICP11-LH, pVP28-LH and pVP19-LH; 11.5 µg each) and T6 (pGFP-LH; 35 µg) were injected intramuscularly into 20 g Penaeus monodon specimens. The shrimp were challenged with WSSV 24 hpi and protection efficacy was measured in terms of survival and viral load 15 days after challenge. Appropriate negative and positive controls were used. T2 and T3 offered highest protection (75%) followed by T1 (67%) and T4 and T5 groups (58%), while T6 showed 25% protection. In all the target specific treatments, the viral load as estimated by single tube WSSV kit was kept in check (10-100 copies), whereas in the unimmunized challenged controls it progressed to severe infection (>10(5) copies). In spite of over 3 times higher expression of ICP11 compared to VP28, its knockdown by pICP11-LH did not offer any protective advantage over pVP28-LH, either singly or in combination. Moreover, none of the combinations bettered the protection efficacy of pVP28-LH administered alone. To investigate concerns about deleterious effect of plasmid persistence and constitutive expression on shrimp growth, a lab-scale 1 month growth study was conducted with 4 treatments T2, T3, T4 and T6, where no difference in specific growth rate was observed compared to controls.