Efficacy of Triglyceride Glucose Index-Neck Circumference and Triglyceride Glucose Index-Neck-to-Height Ratio in the Diagnosis of Cardiovascular Diseases and Metabolic Syndrome.

BACKGROUND: A group of characteristics known as metabolic syndrome raises the chance of developing diabetes and cardiovascular disease. Insulin resistance (IR) and obesity are regarded as critical metabolic syndrome pathophysiology. OBJECTIVES: The diagnostic accuracy of IR indicators, triglyceride (TG) glucose index-neck circumference (TyG-NC), and TG glucose index-neck-to-height ratio (TyG-NHtR) to be evaluated for the detection of cardiovascular diseases and metabolic syndrome in nondiabetic individuals. MATERIALS AND METHODS: A cross-sectional study was conducted and passed by the Ethics Committee of the institute. The age should be 18 years or older, and subjects should not have diabetes. Each patient's clinical information was gathered, and lab tests were run. The study was done for a period of 1 year. RESULTS: The study has 100 participants. Around 74% of the group was women. Only 26.5% of the group had an obesity diagnosis. Poor fasting plasma glucose levels were found in 19.4% of the research team. Receiver operating characteristic (ROC)-area under the curve (AUC) testing revealed that all examined IR indices can differentiate individuals with metabolic syndrome from those who are healthy. Our analysis laid out the soaring high area under the ROC curve for TyG index and the low stunted area under the ROC curve for TyG-NC. For obesity, all indices showed appreciable diagnostic efficacy, indicating the maximum achieved area under the ROC curve for TyG index and the minimum recorded metabolic score for IR. The AUC in the case of the metabolic score for IR (METS-IR) male sample population was found to be not statistically compelling. CONCLUSION: The exploration of indirect indices, the proposed ones, namely TyG-NC and TyG-NHtR, emphasized an intricate link between cardiovascular diseases and metabolic syndrome.

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.

Resistance analysis following sotrovimab treatment in participants with COVID-19 during the phase III COMET-ICE study.

Aim: Sotrovimab is an engineered human monoclonal antibody that binds a conserved region of the SARS-CoV-2 spike protein. The COMET-ICE phase III study evaluated sotrovimab for treatment of mild to moderate COVID-19 in nonhospitalized participants with ≥1 risk factor for severe disease progression. Materials & methods: We evaluated the presence of circulating SARS-CoV-2 variants of concern or interest (VOCs/VOIs) and characterized the presence of baseline, post-baseline and emergent amino acid substitutions detected in the epitope of sotrovimab in SARS-CoV-2. Results: None of the sotrovimab-treated participants with baseline epitope substitutions, and 1 of 48 sotrovimab-treated participants with post-baseline epitope substitutions, met the primary clinical endpoint for progression. Conclusion: Overall, progression was not associated with identified VOC/VOI or the presence of epitope substitutions in sotrovimab-treated participants.

Analysis of the genetics of the SARS-CoV-2 virus from participants in a clinical study for treatment of COVID-19 In a large clinical study, the ability of the monoclonal antibody sotrovimab to treat patients with mild to moderate COVID-19 was looked at. This paper focuses on the genetics of the SARS-CoV-2 viruses from participants in this clinical study. Overall, most participants in the study were infected with the original 'wild type' variant of SARS-CoV-2. We also looked for changes in the virus at the positions on the viral spike protein where sotrovimab binds. In participants treated with sotrovimab, changes in the virus at the site where sotrovimab binds on the viral surface protein were not associated with negative outcomes in participants. Clinical Trial Registration: NCT04545060 (ClinicalTrials.gov).

Quality of Life in People With Unilateral Lower Limb Amputation at a Tertiary Rehabilitation Centre in Northern India: A Cross-Sectional Study.

Background and purpose The patients after amputation undergo a sudden transformation in their quality of life. In India, amputation done at the appropriate time is a rare phenomenon because usually, the patients present themselves at the later stages. The surgeons, however, while performing amputation surgeries, primarily consider saving the life of a patient under adverse conditions when patients report to them very late that the surgeries are carried out urgently. Assessing the quality of life (QOL) and the various sociodemographic factors affecting the QOL paves the way for future rehabilitation programs. Aims and objectives To evaluate the quality of life of subjects with unilateral lower limb amputation among the North Indian population. Materials and methods This cross-sectional study was conducted in the tertiary rehabilitation center. A total of 106 Subjects were recruited. Informed consent was taken. WHOQOL-BREF contains 26 items covering four important aspects of QOL. The WHOQOL-BREF self-administered free questionnaire was used as a data collection tool, and the Hindi version downloaded from the WHO website was also used for those who can't understand English. Results The range of the physical domain, psychological domain, social domain, and environmental domain were 0 and 100. The mean score of different QOL transformed domain scores (on a scale of 100) were 47.91±20.12, 57.37±20.46, 59.36±25.32 and 51.50±21.96, respectively. Trauma was the leading cause of amputation, followed by diabetes mellitus, cancer, peripheral vascular disease, and other causes. Transtibial amputees were more in number compared to transfemoral. The percentage of male and female amputees was 78.30%, and 21.70%, respectively. Conclusion The physical domain was the most affected domain, followed by the psychological, social, and environmental domains. A delay in the prosthesis fitment aggravates the physical burden of amputees. Early prosthesis & psychological counseling will improve the QOL significantly.

Effect of Fluoroscopic-Guided Corticosteroid Injection in Patients With Sacroiliac Joint Dysfunction.

Background Sacroiliac joint dysfunction is a major cause of axial low back pain which can masquerade as pain from lumbar disc diseases. Treatment of axial back pain arising due to sacroiliac joint dysfunction remains a challenge. This study was conducted to evaluate the long and short-term effects of intra-articular corticosteroid injection in the relief of pain and disability caused by sacroiliac joint dysfunction. Methodology A total of 83 patients with sacroiliac joint dysfunction were included in this prospective randomized control study. Patients were randomized into two groups by a computer-generated randomization table. These two groups were treated with fluoroscopy-guided corticosteroid and local anesthetic injection (group A) and distilled water and local anesthetic injection (group B). Pre and post-intervention assessment of all patients was done based on the Numeric Pain Rating Scale (NPRS) for pain and Oswestry Disability Index (ODI) for disability. The outcome measures of the study were the NPRS and ODI assessed at the initial visit one (pre-injection), two weeks post-injection (visit 2), and four weeks post-injection (visit 3). Results Demographic data were comparable in both groups. There was no significant difference in pre-injection NPRS and ODI values in both groups. The changes in NPRS and ODI values were significant from pre-injection to two weeks to four weeks. Group A patients performed better in terms of a decrease in the perception of pain and a decrease in the perception of disability compared to group B patients in the second and fourth weeks of follow-up. Conclusions Fluoroscopy-guided corticosteroid injection is an effective measure for reducing pain and disability in patients with sacroiliac joint dysfunction.

Efficacy of Dry Needling Versus Transcutaneous Electrical Nerve Stimulation in Patients With Neck Pain Due to Myofascial Trigger Points: A Randomized Controlled Trial.

Introduction Myofascial pain is defined as pain arising primarily in muscles and associated with multiple trigger points. Among the non-pharmacological methods, trigger point injection and electrotherapy are effective methods to treat myofascial pain syndrome. This study compares the effectiveness of dry needling (DN) and transcutaneous electrical nerve stimulation (TENS) in reducing cervical pain intensity and improving cervical range of motion in patients with neck pain due to myofascial trigger points. Methods Fifty patients were enrolled and randomized into two groups. Patients in group A received dry needling, and those in group B received TENS. Patients were evaluated using the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Cervical Range of Motion (CROM) before the treatment and on days 14 and 28 after the treatment. The unpaired t-test was used to evaluate quantitative data, except for VAS, where the Mann-Whitney U test was used. All quantitative variables had a normal distribution with a standard deviation except for pain intensity (VAS), which deviated from the normal distribution. The significance level was set at a P-value=0.05. Results Both DN and TENS groups showed significant improvement in VAS, NDI, and CROM between days 0 and 28 (p=<0.001). The DN group showed greater improvements in pain intensity from day 0 to day 28 (p =<0.001). Between days 0 and 28, there was no discernible difference in NDI changes between the groups (p = 0.157 and p = 0.799, respectively). Mixed results were obtained for CROM, with significant improvement of cervical flexion in the dry needling group (p=<0.008) and significant improvement of cervical rotation to the painful side in the TENS group (<0.001). Conclusion Both dry needling and TENS are effective in reducing pain and improving NDI and CROM in patients with neck pain due to myofascial trigger points. However, as dry needling is more effective in pain reduction, a single session of dry needling is more beneficial and cost-effective as compared to multiple sessions of TENS.

Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection.

Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy.

Coupled atmosphere-ice-ocean dynamics during Heinrich Stadial 2.

Our understanding of climate dynamics during millennial-scale events is incomplete, partially due to the lack of their precise phase analyses under various boundary conditions. Here we present nine speleothem oxygen-isotope records from mid-to-low-latitude monsoon regimes with sub-centennial age precision and multi-annual resolution, spanning the Heinrich Stadial 2 (HS2) - a millennial-scale event that occurred at the Last Glacial Maximum. Our data suggests that the Greenland and Antarctic ice-core chronologies require +320- and +400-year adjustments, respectively, supported by extant volcanic evidence and radiocarbon ages. Our chronological framework shows a synchronous HS2 onset globally. Our records precisely characterize a centennial-scale abrupt "tropical atmospheric seesaw" superimposed on the conventional "bipolar seesaw" at the beginning of HS2, implying a unique response/feedback from low-latitude hydroclimate. Together with our observation of an early South American monsoon shift at the HS2 termination, we suggest a more active role of low-latitude hydroclimate dynamics underlying millennial events than previously thought.

Synthesis of Unsymmetrical Vicinal Diamines via Directed Hydroamination.

Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of substituted 1,2-diamines. Herein, the rhodium-catalyzed hydroamination of primary and secondary allylic amines using diverse amine nucleophiles, including primary, secondary, acyclic, and cyclic aliphatic amines to access a wide range of unsymmetrical vicinal diamines, is presented. The utility of this methodology is further demonstrated through the rapid synthesis of several bioactive molecules and analogs.

Targeted protein S-nitrosylation of ACE2 as potential treatment to prevent spread of SARS-CoV-2 infection.

Prevention of infection and propagation of SARS-CoV-2 is of high priority in the COVID-19 pandemic. Here, we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 Spike protein, thereby inhibiting viral entry, infectivity, and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and thus spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E-protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model, and thus provide a novel avenue for therapy.

Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase.

Toxoplasma gondii commonly infects humans and while most infections are controlled by the immune response, currently approved drugs are not capable of clearing chronic infection in humans. Hence, approximately one third of the world's human population is at risk of reactivation, potentially leading to severe sequelae. To identify new candidates for treating chronic infection, we investigated a series of compounds derived from diversity-oriented synthesis. Bicyclic azetidines are potent low nanomolar inhibitors of phenylalanine tRNA synthetase (PheRS) in T. gondii, with excellent selectivity. Biochemical and genetic studies validate PheRS as the primary target of bicyclic azetidines in T. gondii, providing a structural basis for rational design of improved analogs. Favorable pharmacokinetic properties of a lead compound provide excellent protection from acute infection and partial protection from chronic infection in an immunocompromised mouse model of toxoplasmosis. Collectively, PheRS inhibitors of the bicyclic azetidine series offer promise for treatment of chronic toxoplasmosis.

Histologic Analysis of Porcine Dermal Graft Augmentation in Treatment of Rotator Cuff Tears.

BACKGROUND: Biologic augmentation via extracellular matrix (ECM) scaffolds has been utilized to address rotator cuff tears with poor-quality tissue. PURPOSE: To evaluate the cellular changes in graft explants taken from patients treated with porcine dermal grafts for rotator cuff tears. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Four graft biopsy specimens were obtained from patients treated with porcine dermal grafts in an interposition technique for rotator cuff tears and compared with a nonimplanted graft and a normal rotator cuff specimen. Biopsy of the graft site was performed at 18 days, 3 months, 7 months, and 10.5 months after implantation. Hematoxylin and eosin staining was used to evaluate for cellular and vascular changes. Picrosirius red (PSR) stain with 90° polarized light was performed to evaluate collagen fibril size and orientation. All biopsy specimens were analyzed by a pathologist. RESULTS: There was evidence of progressive remodeling of the porcine dermal grafts. The most mature grafts demonstrated vessel infiltration and extensive remodeling without evidence of inflammation, foreign body reaction, or tissue rejection. PSR demonstrated increased organization of collagen domains, resembling normal tendon by 10.5 months postoperatively. CONCLUSION: This series suggests that ECM grafts may serve as an effective scaffold for host cell infiltration, collagen reorganization, and vascularization as a result of histologic changes demonstrated with retrieval of specimens from patients with rotator cuff tears that were augmented with porcine dermal grafts.

Drug repurposing screens identify chemical entities for the development of COVID-19 interventions.

The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.

Cross-sectional study on the role of public awareness in preventing the spread of COVID-19 outbreak in India.

BACKGROUND: WHO has recommended personal hygiene (respiratory hygiene, using face masks, washing hands with warm water and soap, use of alcohol-based hand sanitizers, avoid touching mouth, eyes & nose, cleanliness), social distancing and careful handling of purchased products as an effective preventive measure for COVID-19 disease. The growing pandemic of COVID-19 disease requires social distancing and personal hygiene measures to protect public health. But this message is not clear and well understood among people. The aim of this study is to determine the awareness, knowledge and attitude about COVID-19 and relate the behaviour of Indian society, especially when the country is restarting all its economic activities, after the complete lockdown. METHOD: The present paper is based on an extensive survey among 21 406 adult participants of various sections of Indian society with different age groups between 18 and 80 years to introspect the level of public awareness with respect to cause, spread, prevention and treatment of disease caused by spread of COVID-19 viral outbreak, which will be automatically reflected in the societal behavioural response of rigorous precautionary measures. CONCLUSIONS: There is a need to extend the knowledge base among individuals to enhance their active participation in the prevention mechanisms with respect to the spread of the pandemic. There is a need to elaborate the Indian socio-cultural aspects, so that society starts appreciating and voluntarily following social distancing. This should improve the adaptability of people with livelihood resilience to let them protect themselves not only from the present pandemic but also from all other unforeseen infections, and to provide care to patients.

Evaluating CO2 flux and recharge source in geothermal springs, Garhwal Himalaya, India: stable isotope systematics and geochemical proxies.

Evaluation of geogenic carbon fluxes between solid Earth and its atmosphere is essential to understand the global geological carbon cycle. Some of the key geogenic CO2 suppliers are the magmatic mantle and metamorphic degassing from active and quiescent volcanoes, fault zones, geothermal systems and CO2 rich groundwater. Indian Himalayan geothermal field hosts about 340 geothermal springs in natural as well as artesian condition that eject hot waters and volatiles with varied temperature and chemical composition. These sites provide an opportunity to analyse tectonically driven gas emissions and their impact on regional and global climate. Here we adopt a method for direct measurement of Dissolved Inorganic Carbon (DIC ≈ HCO3) concentration in the geothermal springs to estimate geogenic CO2 flux from an active region based on water discharge and area of geothermal system between the tectonic boundaries of the Main Central Thrust (MCT) and Main Boundary Thrust (MBT) of the Garhwal (Northwest) Himalaya. In the study area, geothermal spring water contain high δ13CDIC ratio (- 8.5‰ to + 4.0‰ VPDB), and among the major ions, bicarbonate (HCO3-) varies by an order of magnitude from 1697 to 21,553 µEq/L; chloride and sodium vary from 90 to 19,171 µEq/L and 436 to 23181 µEq/L. The elevated concentration of Cl- and Na+ in geothermal spring waters suggests affinity towards their deeper origin. These geothermal springs cover a large area of nearly 10,000 km2 of the Garhwal region showing a significant discharge of CO2 rich water with an estimated carbon dioxide degassing flux of ~7.2 × 106 mol/year to the atmosphere. Considering widespread occurrences of geothermal springs in tectonically active areas worldwide, the proposed direct measurement of DIC may be used as a reliable tool to estimate CO2 fluxes in different active orogenic settings within the Earth system. Results of stable isotopes of δ18O (VSMOW) and δD (VSMOW) in these geothermal spring waters follow the Global Meteoric Water Line (GMWL), suggesting affinity of their recharge through the meteoric origin.

Genome based safety assessment for Bacillus coagulans strain LBSC (DSM 17654) for probiotic application.

The present study on Bacillus coagulans strain LBSC (DSM 17654) describes the use of whole genome sequencing, in correlation with the phenotypic properties to assess the safety of the strain. Analysis of the 16S rRNA sequence of the B. coagulans strain LBSC (DSM 17654), showed 100% homology with 99% coverage with B. coagulans strain HM-08. BLAT (BLAST Like Analysis Tool) analysis for whole genome comparison with B. coagulans ATCC 7050, B. coagulans HM-08 and B. coagulans Slac showed 96%, 99% and 99% sequence identity respectively. Whole genome sequencing results demonstrated a single scaffold of 36,35,902 bp and 3331 coding sequences. Gene ontology segregated the proteins as those with molecular function, cellular component and biological process of the predicted genes from assembled genome. Risk associated sequences like antibiotic resistance genes, biogenic amine producing genes, virulence factor genes and other safety related genes were identified with focus on horizontal gene transfer and its non-functionality. The absence of mobile elements in the vicinity of the genes, render it non-transferable and non-toxic phenotypic properties confirm the non-functionality of the genes. Absence of functional genes of concern and confirmation of absence of mobile elements in the vicinity of other non-clinically significant genes indicated no safety concern. The absence of complete and functional prophage sequences which are deleterious for the genome stability and presence of CRISPR system which are advantageous for genome stability by acting as a barrier to entry of foreign DNA elements indicated the stability of the genome. The molecular approach used in this study satisfies the requirements for the safety assessment of the probiotic strain which could indicate it to be potentially safe.

A Randomized Controlled Trial to Evaluate the Role and Efficacy of Oral Glutamine in the Treatment of Chemo-radiotherapy-induced Oral Mucositis and Dysphagia in Patients with Oropharynx and Larynx Carcinoma.

AIM: To determine the role and efficacy of oral glutamine in the treatment of chemo-radiotherapy-induced oral mucositis and dysphagia in patients with carcinoma of the oropharynx and larynx. The primary objective of this study was to compare the incidence and severity of oral mucositis and dysphagia between the glutamine group (oral glutamine, along with concurrent chemo-radiotherapy) and the control group (concurrent chemo-radiotherapy alone, no glutamine). Secondary objectives were to compare the time to onset of oral mucositis and dysphagia, the incidence of treatment breaks (more than three consecutive radiation fractions missed), and significant weight loss (more than 3 kilograms of weight loss from the baseline) between the two groups. METHOD: A total of 60 patients with locally advanced carcinoma of the oropharynx and larynx (Stage III - IV) who were receiving concurrent chemo-radiotherapy were randomised to the glutamine group (study arm, n = 30) and the non-glutamine group (control arm, n = 30). All patients were treated by radiotherapy to a total dose of 70 Gy in 35 fractions, along with concurrent weekly injections of cisplatin (40 mg/m2) chemotherapy. Patients in the study arm received 10 gm of oral glutamine two hours before radiotherapy (five days a week during the seven-week course of radiotherapy). In the control arm, glutamine was not given to patients during the chemo-radiotherapy treatment. All patients were assessed for oral mucositis, dysphagia, weight loss, and compliance/gap in the treatment (greater than three consecutive days of radiation missed) until the completion of chemo-radiotherapy. Grading of oral mucositis and dysphagia was done as per the National Cancer Institute, Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Out of 60 patients, 56 patients (93.33%) completed the full course of chemo-radiotherapy treatment. Twenty-seven patients (96.43%) in the control arm developed Grade III oral mucositis compared to only 12 patients (42.83%) in the glutamine arm (p < 0.001). Twenty-six patients (93%) in the control arm developed Grade III dysphagia compared to only 11 patients (39%) in the glutamine arm (p < 0.001). Glutamine significantly decreased the incidence and severity of mucositis and dysphagia. Glutamine delayed the onset of mucositis and dysphagia. As severe dysphagia was more prevalent in the control arm, feeding by Ryle's tube was required in 17 patients (56.67%) in the control arm versus only in eight patients (26.67%) in the glutamine arm (p = 0.03). Significant weight loss during the treatment was seen in all patients of the control arm (100% patients) compared to only 71% of the patients in the glutamine arm (p = 0.004). In the control arm, 46.67% patients had treatment interruption (gap) compared to 16.67% in the glutamine arm (p = 0.025). Sixteen patients (53%) from the control arm required admission (inpatient care) in the hospital to manage the treatment-toxicity (mucositis and dysphagia) compared to seven patients (23%) from the glutamine arm (p = 0.03). CONCLUSION: Glutamine significantly decreased the incidence and severity of chemo-radiotherapy-induced oral mucositis and dysphagia. It delayed the onset of oral mucositis and dysphagia, improved the compliance to the chemo-radiotherapy treatment, and reduced the requirement for hospitalization for the management of treatment-induced toxicities in patients with locally advanced carcinoma of the oropharynx and larynx.

Characterization of a class III peroxidase from Artemisia annua: relevance to artemisinin metabolism and beyond.

KEY MESSAGE: A class III peroxidase from Artemisia annua has been shown to indicate the possibility of cellular localization-based role diversity, which may have implications in artemisinin catabolism as well as lignification. Artemisia annua derives its importance from the antimalarial artemisinin. The -O-O- linkage in artemisinin makes peroxidases relevant to its metabolism. Earlier, we identified three peroxidase-coding genes from A. annua, whereby Aa547 showed higher expression in the low-artemisinin plant stage whereas Aa528 and Aa540 showed higher expression in the artemisinin-rich plant stage. Here we carried out tertiary structure homology modelling of the peroxidases for docking studies. Maximum binding affinity for artemisinin was shown by Aa547. Further, Aa547 showed greater binding affinity for post-artemisinin metabolite, deoxyartemisinin, as compared to pre-artemisinin metabolites (dihydroartemisinic hydroperoxide, artemisinic acid, dihydroartemisinic acid). It also showed significant binding affinity for the monolignol, coniferyl alcohol. Moreover, Aa547 expression was related inversely to artemisinin content and directly to total lignin content as indicated by its transient silencing and overexpression in A. annua. Artemisinin reduction assay also indicated inverse relationship between Aa547 expression and artemisinin content. Subcellular localization using GFP fusion suggested that Aa547 is peroxisomal. Nevertheless, dual localization (intracellular/extracellular) of Aa547 could not be ruled out due to its effect on both, artemisinin and lignin. Taken together, this indicates possibility of localization-based role diversity for Aa547, which may have implications in artemisinin catabolism as well as lignification in A. annua.