Public Awareness and Attitude towards COVID-19 Infection and Vaccines: A cross-sectional national survey in Nepal.

Background To combat COVID-19, high vaccination rates are essential. However, challenges such as vaccine denial, lack of knowledge, and negative attitudes hinder progress. Assessing public understanding of vaccination is crucial to promote acceptance and reducing reluctance. Objective To understand people's awareness and attitude regarding COVID-19 infection and vaccines in Nepal. Method A cross-sectional web-based survey was conducted among the Nepali population of age 18 years and above in April 2021 during the early phase of vaccination deployment. A structured questionnaire was used to collect awareness data, and a five-point Likert scale was employed to assess participants' attitudes. The survey categorized participants into two groups based on whether their awareness level or attitude score was above or below the mean. The secondary outcome was the association between socio-demographic factors and COVID-19 awareness or attitude. Result Of 475 eligible participants, 46% had a low level of awareness on COVID-19 infection whereas 56% had low awareness on COVID-19 vaccines. Every six out of ten participants had a positive attitude towards the national COVID-19 vaccination program. Most of the participants had high awareness of COVID-19 symptoms and preventive measures (hand hygiene, physical distancing, mask), but two-thirds had a false perception of vaccine safety and contraindications. People's education status, occupation, province, and current/prior COVID-19 infection status were found to be significantly associated with their awareness regarding COVID-19 disease or vaccines. Conclusion The study revealed limited COVID-19 awareness among the Nepali population but a positive attitude toward the national vaccination program. Regular updates on COVID-19 and vaccines are important as new variants and vaccines emerge.

Management of Different Types of Pneumothorax at Dhulikhel Hospital, Kathmandu University Hospital.

Background Pneumothorax is defined as the presence of air in the pleural cavity. Pneumothorax can be classified as Spontaneous and Traumatic according to the etiology. Spontaneous pneumothorax is further classified as Primary and Secondary. Objective This study was conducted to know the management of different types of pneumothorax at Dhulikhel Hospital, Kathmandu University Hospital. Method This was a hospital based retrospective study conducted at Dhulikhel Hospital, Kathmandu University Hospital. Patients admitted in Surgery Ward with diagnosis of Pneumothorax from January 2018 to December 2019 were included in this study. Result This study included 144 patients with pneumothorax age ranging from 14 years to 94 years. Most of the patients were male with male:female ratio of 3.8:1. Eighty-four (58.03%) patients had Traumatic pneumothorax followed by Secondary spontaneous pneumothorax in 53(36.08%) patients and Primary spontaneous pneumothorax in seven (4.86%) patients. Among 144 patients, chest tube drain was required in 135 patients and nine patients were managed conservatively. One patient underwent Video Assisted Thoracoscopic Surgery (VATS) with Bullectomy and mechanical pleurodesis. Sixteen patients had persistent pneumothorax, among which six patients required chemical pleurodesis, two patients required negative suction therapy and five patients required both chemical pleurodesis and negative suction therapy. Conclusion This study showed pneumothorax to be more common in male population. Traumatic pneumothorax was the most common type followed by Secondary spontaneous pneumothorax and Primary spontaneous pneumothorax.

Neuropsychiatric manifestations in General Paralysis of Insane (GPI).

General paralysis of insane is a form of neurosyphilis which brings parenchymatous changes in the central nervous system. Its manifestations include a variety of neuropsychiatric symptoms ranging from cognitive impairment to overt psychosis. Clinicians face difficulties in proper diagnosis as variety of symptoms changes from one form to other within a short period of time. Rarity of the disease at this modern era of penicillin is also another factor in timely diagnosis and management of such cases. Here we present a case of general paralysis of insane who presented with variety of neuropsychiatric symptoms and have had great difficulties to reach into the diagnosis.

Sensitivity and Specificity of Lateral Flow Antigen Test Kits for COVID-19 in Asymptomatic Population of Quarantine Centre of Province 3.

Background Nearly after 6 months of the spread of Corona Virus Disease 19, along with the world Nepal is still trying to control the spread and prevent general population from acquiring it. With limited resources in manpower, technology and evidence it has been a difficult battle. But with time and more understanding of the virus new technology to detect the virus are coming up. It is a major breakthrough in the diagnostic field as this helps us in not only detecting the virus but also helps us to mobilize our human resources. This comes in a time where the cases are increasing at an alarming rate. Although numbers of Polymerase Chain Reaction testing have increased but due to the time consuming and the cost wise, we need a faster and equally reliable alternative. Antigen test approved by different countries can be used for point of care, screening and surveillance depending upon the requirements after calculating its sensitivity, specificity and accuracy. Objective To find out sensitivity and specificity of the Antigen test kit for COVID-19. Method Antigen tests were compared with Reverse Transcription Polymerase Chain Reaction as a reference standard in calculated sample size of 113 subjects in a high risk population. Both Reverse Transcription Polymerase Chain Reaction and antigen test were performed in a same subject with in maximum of 2 days' interval. Convenience sampling technique was used to select the subjects. Ethical approval was taken from Nepal Health Research Council before data collection. Study was done from August to September 2020 from Quarantine center of Province 3. Result There were total of 113 test carried out, among those 47 were positive and 66 were negative in Reverse Transcription Polymerase Chain Reaction. After preparing two by two table, Sensitivity and specificity of the tested was calculated which came out to be 85% and 100% respectively, with accuracy of 93.80%. Conclusion Even though the sensitivity and specificity came to be higher, this test should be interpreted cautiously depending upon the prevalence of Corona Virus Disease 19 in that particular community and the clinical and epidemiological context of the person who has been tested. When in doubt by clinical correlation should be confirmed with Reverse Transcription Polymerase Chain Reaction.

Analysis of porcine body size variation using re-sequencing data of miniature and large pigs.

BACKGROUND: Domestication has led to substantial phenotypic and genetic variation in domestic animals. In pigs, the size of so called minipigs differs by one order of magnitude compared to breeds of large body size. We used biallelic SNPs identified from re-sequencing data to compare various publicly available wild and domestic populations against two minipig breeds to gain better understanding of the genetic background of the extensive body size variation. We combined two complementary measures, expected heterozygosity and the composite likelihood ratio test implemented in "SweepFinder", to identify signatures of selection in Minipigs. We intersected these sweep regions with a measure of differentiation, namely FST, to remove regions of low variation across pigs. An extraordinary large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on SNP-array data of F2 individuals from a cross of Goettingen Minipigs and large pigs. RESULTS: Selective sweep analysis identified putative sweep regions for growth and subsequent gene annotation provided a comprehensive set of putative candidate genes. A long swept haplotype on chromosome X, descending from the Goettingen Minipig founders was associated with a reduction of adult body length by 3% in F2 cross-breds. CONCLUSION: The resulting set of genes in putative sweep regions implies that the genetic background of body size variation in pigs is polygenic rather than mono- or oligogenic. Identified genes suggest alterations in metabolic functions and a possible insulin resistance to contribute to miniaturization. A size QTL located within the sweep on chromosome X, with an estimated effect of 3% on body length, is comparable to the largest known in pigs or other species. The androgen receptor AR, previously known to influence pig performance and carcass traits, is the most obvious potential candidate gene within this region.

Conserved roles of Osiris genes in insect development, polymorphism and protection.

Much of the variation among insects is derived from the different ways that chitin has been moulded to form rigid structures, both internal and external. In this study, we identify a highly conserved expression pattern in an insect-only gene family, the Osiris genes, that is essential for development, but also plays a significant role in phenotypic plasticity and in immunity/toxicity responses. The majority of Osiris genes exist in a highly syntenic cluster, and the cluster itself appears to have arisen very early in the evolution of insects. We used developmental gene expression in the fruit fly, Drosophila melanogaster, the bumble bee, Bombus terrestris, the harvester ant, Pogonomyrmex barbatus, and the wood ant, Formica exsecta, to compare patterns of Osiris gene expression both during development and between alternate caste phenotypes in the polymorphic social insects. Developmental gene expression of Osiris genes is highly conserved across species and correlated with gene location and evolutionary history. The social insect castes are highly divergent in pupal Osiris gene expression. Sets of co-expressed genes that include Osiris genes are enriched in gene ontology terms related to chitin/cuticle and peptidase activity. Osiris genes are essential for cuticle formation in both embryos and pupae, and genes co-expressed with Osiris genes affect wing development. Additionally, Osiris genes and those co-expressed seem to play a conserved role in insect toxicology defences and digestion. Given their role in development, plasticity, and protection, we propose that the Osiris genes play a central role in insect adaptive evolution.

Short communication: Uncovering quantitative trait loci associated with resistance to Mycobacterium avium ssp. paratuberculosis infection in Holstein cattle using a high-density single nucleotide polymorphism panel.

Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of Johne's disease in cattle. Johne's disease is a disease of significant economic, animal welfare, and public health concern around the globe. Therefore, understanding the genetic architecture of resistance to MAP infection has great relevance to advance genetic selection methods to breed more resistant animals. The objectives of this study were to perform a genome-wide association study of previously analyzed 50K genotypes now imputed to a high-density single nucleotide polymorphism panel (777K), aiming to validate previously reported associations and potentially identify additional single nucleotide polymorphisms associated with antibody response to MAP infection. A principal component regression-based genome-wide association study revealed 15 putative quantitative trait loci (QTL) associated with the MAP infection phenotype (serum or milk ELISA tests) on 9 different chromosomes (Bos taurus autosomes 5, 6, 7, 10, 14, 15, 16, 20, and 21). These results validated previous findings and identified new QTL on Bos taurus autosomes 15, 16, 20, and 21. The positional candidate genes NLRP3, IFi47, TRIM41, TNFRSF18, and TNFRSF4 lying within these QTL were identified. Further functional validation of these genes is now warranted to investigate their roles in regulating the immune response and, consequently, cattle resistance to MAP infection.

Prophylactic efficacy of S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07) against sulfur mustard induced lung toxicity in mice.

OBJECTIVE: The present study was planned to investigate the prophylactic efficacy of S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07), against topically applied SM induced pulmonary toxicity in mouse. MATERIALS AND METHODS: Animals were pretreated with S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07) (249.4 mg/kg by oral gavage) 30 minutes before SM exposure. The SM (6.48 mg/kg) was applied on hair clipped dorsocaudal region (percutaneous) of the animal. The animals were sacrificed on day 1, 3, 5 and 7. The biochemical changes those were observed in the bronchoalveolar lavage (BAL) fluid and lung tissue included protein, LDH, MPO, ß-glucuronidase, MMP-2, MMP-9, activated macrophages, reduced glutathione and lipid peroxidation level. RESULTS AND DISCUSSION: Pretreatment with DRDE-07 (0.2 LD50) attenuated SM-induced changes at all time point tested. BAL fluid biochemical endpoints indicated epithelial and endothelial cell damages as evidenced by increase in BAL protein, LDH level and increased number of activated macrophages. The increased myeloperoxidase activity and ß-glucuronidase level exhibited the degranulation of neutrophils due to SM toxicity in lung. The zymogrphy analysis of BAL fluid showed a significant increase in matrix metalloproteases (MMP) activity due to inflammatory cells accumulation. CONCLUSION: Thirty minutes pretreatment with DRDE-07 decreased vascular permeability reduced the inflammation and oxidative stress, hence may be recommended as a potential prophylactic agent for SM intoxication.

Prenatal developmental toxicity study of n-heneicosane in Wistar rats.

n-Heneicosane (C21) is one of the vital pheromone for attracting mosquitoes of Aedes spp to lay their eggs in areas of stagnant fresh water, for their subsequent destruction, thus controlling spread of dangerous disease transmission by the vectors. As part of a safety evaluation, we have investigated embryo toxic and teratogenic potential, if any, of C21 following OECD Test Guideline 414. C21 was offered at a dose of 1 g/kg body weight mixed in the standard rat pellet diet to treated rats, whereas the control group received only standard rat pellet diet. There were no mortalities and animals did not show any clinical signs of toxicity. A similar pattern of body weight gain, feed and water intake was observed in treated and control groups. Analysis of maternal toxic response, maternal end points of development of the foetus and developmental end points for litters did not show any gross structural abnormality in dams or foetus of treated group compared to that of the control group. Thus, it was concluded that C21 at a dose of 1 g/kg was neither embryo toxic nor teratogenic in Wister rats. Furthermore, the no observed adverse effect level for teratogenicity for C21 in rats may be considered as 1 g/kg body weight under the present experimental conditions.

Prevalence of Sensory Neuropathy in Type 2 Diabetes Mellitus and Its Correlation with Duration of Disease.

Background Peripheral neuropathy is one of the most common and distressing late complication of diabetes mellitus. Ignorance of the complications may develop foot ulcers and gangrene requiring amputation. Objective The main objective of this study is to find out the prevalence of sensory neuropathy in type 2 diabetes mellitus and to compare it with the duration of disease. Method Two hundred seventy one patients with type 2 diabetes mellitus of both gender age 30 years and above willing to participate were included in this study. Patients having hypothyroidism, rheumatoid arthritis, B12 deficiency, cerebrovascular disease, chronic musculoskeletal disease, Parkinson's disease, alcohol abuse, chronic renal or liver failure and cancer were excluded from the study. Touch, pin prick and vibration sensation were tested. Vibration perception threshold was recorded from six different sites of the sole of each foot using Biothesiometer. Result Two hundreds seventy one type 2 diabetic outpatients were studied. The mean age was 59.81±22.85 years. The overall prevalence of diabetic sensory neuropathy in the study population was 58.70%. A rising trend of diabetic sensory neuropathy with increasing age and duration of diabetes was observed. Neuropathy was found more in patients having urinary microalbuminuria. Burning and pins and needles sensation were most common symptoms. Conclusion The overall prevalence of diabetic sensory neuropathy in the study population was 58.70% (mean age 59.81±22.85 yrs), and its prevalence increased with duration of diabetes and increasing age. Its prevalence was found more in patients having microalbuminuria.

Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins.

Mycobacterium avium ssp. paratuberculosis (MAP) causes chronic enteritis in cattle that results in substantial financial losses to the cattle industry worldwide. Given that susceptibility to MAP infection is determined in part by genetics, marker-assisted selection may help in the breeding of animals that are more resistant to MAP infection. The toll-like receptor 4 gene (TLR4) was selected as a potential candidate gene because of its role in innate immunity and its involvement in MAP recognition and infection. The objective of this study, therefore, was to identify associations between TLR4 polymorphisms and susceptibility to MAP infection in Canadian Holstein cows. Two biologically relevant SNPs, including c.-226G>C in the 5'-untranslated region and the non-synonymous SNP c.2021C>T in the potential TIR domain, were selected for an association analysis with MAP infection status in 409 Canadian Holsteins. The haplotype C-T from these combined SNPs yielded significant association with susceptibility to MAP infection, supporting the involvement of TLR4 in susceptibility to MAP infection.

A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in combination with gemcitabine in patients with solid tumors.

BACKGROUND: Tivantinib (ARQ 197) is an orally available, non-adenosine triphosphate competitive, selective c-MET inhibitor. The primary objective of this study was to evaluate the safety, tolerability and to establish the recommended phase II dose (RP2D) of tivantinib and gemcitabine combination. PATIENTS AND METHODS: Patients with advanced or metastatic solid tumors were treated with escalating doses of tivantinib (120-360 mg capsules) in combination with gemcitabine (1000 mg/m(2) weekly for 3 of 4 weeks). Different schedules of administration were tested and modified based on emerging preclinical data. Tivantinib was given continuously, twice a day (b.i.d.) for 2, 3 or 4 weeks of a 28-day cycle or on a 5-day on, 2-day off schedule (the day before and day of gemcitabine administration). RESULTS: Twenty-nine patients were treated with gemcitabine and escalating doses of tivantinib: 120 mg b.i.d. (n = 4), 240 mg b.i.d. (n = 6) and 360 mg b.i.d. (n = 19). No dose-limiting toxicities were observed in escalation. The RP2D was 360 mg b.i.d. daily, and 45 additional patients were enrolled in the expansion cohort. Grade ≥3 treatment-related toxicities were observed in 54 of 74 (73%) patients with the most common being neutropenia (43%), anemia (30%), thrombocytopenia (28%) and fatigue (15%). There was one treatment-related death due to neutropenia. Administration of gemcitabine did not affect tivantinib concentration. Fifty-six patients were assessable for response. Eleven (20%) patients achieved a partial response and 26 (46%) had stable disease (SD), including 15 (27%) who achieved SD for over 4 months. Ten of 37 patients with clinical benefit had prior exposure to gemcitabine. CONCLUSION: The combination of tivantinib at its monotherapy dose and standard dose gemcitabine was safe and tolerable. Early signs of antitumor activity may warrant further development of this combination in nonsmall-cell lung cancer, ovarian, pancreatic and cholangiocarcinoma. CLINICALTRIALSGOV IDENTIFIER: NCT00874042.

A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression.

BACKGROUND: Nucleotide transporters such as human equilibrative nucleoside transporter-1 (hENT1) play a major role in transporting gemcitabine into cells. CO-1.01 (gemcitabine-5'-elaidate) is a novel cytotoxic agent consisting of a fatty acid derivative of gemcitabine, which is transported intracellularly independent of hENT1. CO-1.01 was postulated to have efficacy as a second-line treatment in gemcitabine-refractory pancreatic adenocarcinoma in patients with negative tumor hENT1 expression. METHODS: Eligibility criteria included patients with either a newly procured or archival biopsy tumor confirming the absence of hENT1 and either gemcitabine-refractory metastatic pancreas adenocarcinoma or with progression of disease following resection during or within 3 months of adjuvant gemcitabine therapy. Patients were treated with intravenous infusion of CO-1.01 dosed at 1250 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle. The primary end point was disease control rate (DCR). RESULTS: Nineteen patients were enrolled of which 18 patients were evaluable for efficacy assessment. Thirteen patients (68%) had liver metastases, 6 (32%) had lymph node metastases, and 10 (53%) had lung metastases. Two of 18 patients (11%) achieved disease control. The median survival time was 4.3 (95% CI 2.1-8.1) months. All patients experienced at least one treatment-related adverse event with the majority of events being mild or moderate. CONCLUSION: This study did not meet its primary endpoint and no efficacy signal was identified for CO-1.01 in treating progressive metastatic pancreas adenocarcinoma.

Development of freeze dried synbiotic formulation using a probiotic strain of Lactobacillus plantarum.

Synbiotics offer potential in the prophylactic management of gastrointestinal disorders. Therefore, present study evaluates the effect of prebiotics (inulin and gum acacia) on Lactocaillus plantarum for developing a freeze-dried synbiotic product from the selected culture. L. plantarum exhibited the highest specific growth rate (0.23/h) in presence of inulin followed by gum acacia (0.22/h) and glucose (0.22/h). Preparation of the lyophilized synbiotic powder incorporating inulin or gum acacia and using non fat dry milk as base material was standardized. Throughout refrigerated storage for 90 days, viable counts (i. e. 8 to 9 log cfu/g) of the probiotic bacteria in the product remained high, while a considerable reduction in the counts was observed in the product stored at room temperature (25 ± 1 °C).

Measurement of right atrial volume and diameters in healthy Nepalese with normal echocardiogram.

BACKGROUND: The size of right atrium is expected to be different in diverse healthy ethnic groups. It is important to know the normal size of right atrium in our healthy population. OBJECTIVE: The study aimed to find out the normal values of right atrial volume, right atrial short axis diameter and right atrial long axis diameter in healthy Nepalese population with normal echocardiographic findings. It also looked at correlations between right atrial dimensions and the right atrial volume. METHOD: Verbal consent was taken from all the participants. One hundred participants between the age of 18 and 60 years with normal echocardiographic findings and without any chronic disease were included in this study. Right atrial volume was measured by using area length method. Right atrial short axis diameter and Right atrial long axis diameter were measured in the four chamber view. RESULT: The mean right atrial volume was 23.64±5.36 ml (range 11.30-40.00 ml).The range of right atrial short axis diameter and right atrial long axis diameter were 1.34-3.80 cm and 2.4-4.7 cm respectively. CONCLUSION: The size of right atrium in the Nepalese population is smaller compared to western population. Male right atrial volume size is greater than female in Nepalese population similar to western population. The findings of normal value of right atrial volume and right atrial diameter in Nepalese population will help the physician to assess patients with various conditions affecting the right atrium.

Binding of Nucleotide Inhibitors to the NS5 RdRp of the ZIKA Virus in the Replication Initiation State.

INTRODUCTION: The bindings of several ribonucleoside triphosphate (NTP) inhibitors to the RNA-dependent RNA polymerase (RdRp) of the Zika virus (ZIKV) are studied herein to identify potential drug-like candidates that can inhibit the replication of the viral genome by RdRp. METHOD: In this study, a guanosine triphosphate (GTP) bound RdRp structure is generated to model the replication initiation state of RdRp. Subsequently, the bindings of 30 NTP inhibitors to the GTP binding site of RdRp are studied in detail by using the molecular docking method. Based on the docking scores, four NTP inhibitors, such as 2'-Cmethyl- adenosine-5'-triphosphate (mATP), 7-deaza-2'-C-methyladenosine-TP (daza-- mATP), 1-N6-Ethenoadenosine-5'-triphosphate (eATP), and Remdesivir-5'-triphosphate (RTP) are shortlisted for further analysis by employing molecular dynamics simulations and binding free-energy methods. RESULTS: These inhibitors are found to bind to RdRp quite strongly, as evident from their relative binding free energies that lie between -31.54±4.54 to -89.46±4.58 kcal/- mol. As the binding of RTP to the GTP site of RdRp generates the most stable complex, which is about 45 kcal/mol more stable than the binding of GTP to RdRp, it is most likely that RTP may inhibit the replication of the Zika viral genome efficiently. CONCLUSION: However, experimental studies are required to measure the potency of RTP and other drugs before their clinical use.

Repurposing of antiparasitic drugs against the NS2B-NS3 protease of the Zika virus.

To date, no approved drugs are available to treat the Zika virus (ZIKV) infection. Therefore, it is necessary to urgently identify potential drugs against the ZIKV infection. Here, the repurposing of 30 antiparasitic drugs against the NS2B-NS3 protease of the ZIKV has been carried out by using combined docking and molecular dynamics- (MD) simulations. Based on the docking results, 5 drugs, such as Amodiaquine, Primaquine, Paromomycin, Dichlorophene, and Ivermectin were screened for further analysis by MD simulations and free energy calculations. Among these drugs, Amodiaquine and Dichlorophen are found to produce the most stable complexes and possess relative binding free energies of about -44.3 ± 3.7 kcal/mol and -41.1 ± 5.3 kcal/mol respectively. Therefore, they would act as potent small-molecule inhibitors of the ZIKV protease.However, evaluations of biological and safety activities of these drugs against the ZIKV protease are required before their clinical use.Communicated by Ramaswamy H. Sarma.

Structures and dynamics of peptide and peptidomimetic inhibitors bound to the NS2B-NS3 protease of the ZIKA virus.

Infections caused by the Zika virus (ZIKV) have detrimental effects on human health, in particular on infants. As no potent drug or vaccine is available to date to contain this viral disease, it is necessary to design inhibitors that can target the NS2B-NS3 protease of the ZIKV, which is mainly responsible for the proliferation of the virus inside the host cells . Here, molecular dynamics (MD) simulation and molecular mechanics energies combined with the generalized Born and surface area continuum solvation model (MM/GBSA) are used to understand the binding modes and stabilities of R, KR, KKR, WKR, WKKR, YKKR, and FKKR peptide inhibitors bound to the NS3-NS2B protease. The results are compared with the corresponding results obtained for covalent (compound 1) and non-covalent (compound 4*) peptidomimetic inhibitors . It is revealed that peptide inhibitors can bind strongly with the ZIKV protease with the ΔGbind ranging from -12 kcal/mol to -73 kcal/mol. Among these peptides, YKKR is found to make the most stable complex with the protease and fully occupy the electrostatically active substrate binding site. Hence, it would inhibit the protease activities of ZIKV strongly. The residue-wise decomposition of ΔGbind indicates that Asp75, Asp129, Tyr130, Ser135, Gly151, Asn152, Glys153, and Tyr161 of NS3 and Ser81, Asp83, and Phe84 of NS2B play a prominent role in the inhibitor binding. Therefore, any future design of inhibitors should be aimed to target these residues.

Short-course Palliative Hypofractionated Radiotherapy in Patients with Poor-prognosis High-grade Glioma: Survival and Quality of Life Outcomes from a Prospective Phase II Study.

AIMS: To report longitudinal quality of life (QoL) outcomes and survival in patients with poor-prognosis high-grade glioma (HGG) treated with palliative hypofractionated radiotherapy. MATERIALS AND METHODS: Patients with poor-prognosis HGG were accrued on a prospective study of short-course palliative hypofractionated radiotherapy (35 Gy/10 fractions/2 weeks). The European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and brain cancer module (BN20) were used in English or validated Indian vernacular languages (Hindi and Marathi) for QoL assessment at baseline (before radiotherapy), the conclusion of radiotherapy, 1 month post-radiotherapy and subsequently at 3-monthly intervals until disease progression/death. Baseline QoL scores were compared with corresponding scores from a historical HGG cohort. Summary QoL scores were compared longitudinally over time by related samples Friedman's two-way test. Progression-free survival and overall survival were calculated using the Kaplan-Meier method and reported as 1-year estimates with 95% confidence intervals. RESULTS: Forty-nine (89%) of 55 patients completed the planned course of hypofractionated radiotherapy. Longitudinal QoL data were available in 42 (86%) of 49 patients completing radiotherapy, comprising the present cohort. The median age of included patients, comprised mainly of glioblastoma patients (81%), was 57 years, with an interquartile range (IQR) of 50-66 years and a median baseline Karnofsky score of 60 (IQR = 50-60). Baseline QoL scores were significantly worse for several domains compared with a historical institutional cohort of HGG patients treated previously with conventionally fractionated radiotherapy, indicating negative selection bias. QoL scores remained stable for most domains after palliative hypofractionated radiotherapy, with statistically significant improvements in fatigue (P = 0.032), dyspnoea (P = 0.042) and motor dysfunction (P = 0.036) over time. At a median follow-up of 8 months, Kaplan-Meier estimates of 1-year progression-free survival and overall survival were 33.3% (95% confidence interval 21.7-51.1%) and 38.1% (95% confidence interval 25.9-56%), respectively. CONCLUSION: Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis HGG is associated with stable and/or improved QoL scores in several domains, making it a viable resource-sparing regimen.