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Background: In China, since 1989, an estimated 120 million children have been immunised with the SA 14-14-2 live-attenuated Japanese encephalitis (JE) vaccine at ages 1, 2, and 6 years. A case-control study of licensed vaccine found two doses to be 98% effective. Subsequently, researchers found that single-dose vaccine efficacy was high; we aimed to confirm this result.Methods: During July 11-24, 1999, 160000 doses of JE vaccine were given to children aged 1-15 years, resident in three districts of Nepal. Several cases of JE were admitted to hospital from early August. We obtained names and addresses of cases with serological evidence of a recent infection from Bheri Zonal Hospital, Nepalgunj. We did a matched case-control study and calculated the odds ratio of vaccination among JE cases and age-sex matched village controls.Findings: 20 children, aged 1-15 years, were identified whose illness conformed with the JE case definition and were resident in villages receiving the vaccine. None of 20 JE cases had received JE vaccine compared with 326 of 557 age-sex matched village controls. The efficacy of a single dose of JE vaccine was 99.3% (CI 94.9-100%).Interpretation: A single dose of JE vaccine is highly efficacious in preventing Japanese encephalitis when administered only days or weeks before exposure to infection. [ABSTRACT FROM AUTHOR]

PARP inhibitors have attracted considerable interest in drug discovery due to the clinical success of first-generation agents such as olaparib, niraparib, rucaparib, and talazoparib. Their success lies in their ability to trap PARP to DNA; however, first-generation PARP inhibitors were not strictly optimized for trapping nor for selectivity among the PARP enzyme family. Previously we described the discovery of the second-generation PARP inhibitor AZD5305, a selective PARP1-DNA trapper. AZD5305 maintained the antitumor efficacy of first-generation PARP inhibitors while exhibiting lower hematological toxicity. Recently, there has been interest in central nervous system (CNS)-penetrant PARP inhibitors for CNS malignancies and other neurological conditions; however, AZD5305 is not CNS penetrant. Herein we describe the discovery and optimization of a series of CNS-penetrant, PARP1-selective inhibitors and PARP1-DNA trappers, culminating in the discovery of AZD9574, a compound that maintains the PARP1 selectivity of AZD5305 with improved permeability, reduced efflux, and increased CNS penetration.

Carcinoid tumors (CT) are among the least studied tumors. It is a relatively rare and slow-growing tumor with good survival in its primary form. However, metastatic carcinoid tumor comes up with many different complications contributing to increased morbidity and mortality. Metastatic form of the disease has a wide spectrum of clinical manifestations and multisystem involvement including cardiovascular manifestations, neurological manifestations, and psychiatric manifestations and so on. In this review, we are centered towards the cardiovascular manifestations of the disease, which, by far, is one of the commonest causes of death in these patients. Being a neuroendocrine tumor, cardiovascular manifestations are mainly because of biologically active substances, produced by the tumor cells, remodeling the heart. Development of targeted therapies against carcinoid heart diseases is currently limited by lack of understanding of pathophysiology of the disease processes. In this review, we aim to figure out the spectrum of carcinoid heart diseases, along with the molecular biology of the changes going on, which, in turn, will not only pave a way to the development of targeted therapies but will also extend opportunities for molecular screening of the tumor and diagnosis at an early stage, thereby, reducing the morbidity and mortality., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Malignant atrophic papulosis sometimes known as Degos' disease is an idiopathic, uncommon condition with fewer than 200 occurrences documented. It is a chronic thrombo-obliterative vasculopathy characterised by papular skin lesions with a core porcelain-white atrophy and a surrounding telangiectatic border. We report a 15-year-old male patient with a recurrent history of hollow viscus perforation, which was managed on all the occasions with exploratory laparotomy and primary perforation repair. Additionally, the patient had a five month history of numerous, non-itchy, atrophic papules with a core porcelain-like area and hyperkeratotic margins, characteristic of Degos' disease. The only basis for diagnosis is the distinctive skin lesions with biopsy. Along with systemic lupus erythematosus and other connective tissue diseases, tuberculosis must also be taken into account while assessing the clinical presentation of malignant atrophic papulosis. There is currently no known treatment for malignant atrophic papulosis that has been effective., Keywords: case reports; intestinal perforation; malignant atrophic papulosis; ulcer; vasculitis.

Background: Tonsillitis is defined as an inflammation of the tonsils characterized by signs of tonsillar erythema and exudates and recurrent tonsillitis is at least 7 episodes of acute tonsillitis in a year, or a minimum of 5 episodes in a year for 2 consecutive years, or at least 3 episodes in a year for 3 consecutive years. There are many research that have hypothesized the association of low level of Vitamin D and recurrent attacks of acute tonsillitis., Methods: A single centre prospective, cross sectional analytical study was conducted from 2021 June to 2022 March in Department of ENT and Head and Neck surgery in Kathmandu Medical College Teaching Hospital. The study participants were recruited from ENT Head and Neck OPD and the data on number of episodes of recurrent attacks of tonsillitis and serum level of Vitamin D were collected., Results: 78.8% of patients with tonsillitis had low level of serum Vitamin D (less than 30ng/ml) and 21.2% had optimal level of serum Vitamin D (more than 30ng/ml). The incidence of recurrent tonsillitis was 40.9% in patients with low level of Vitamin D where as the incidence of recurrent tonsillitis was 18.1% in patients with optimal level of Vitamin D., Conclusions: The low serum level of Vitamin D was found to be associated with recurrent episodes of tonsillitis.

Introduction: Coronavirus disease-19 infection is caused by the coronavirus and has taken a toll throughout the world. The aim of this study was to find the prevalence of coronavirus disease-19 infection among patients presenting to a tertiary care centre., Methods: A descriptive cross-sectional study was conducted at the fever clinic of a tertiary care centre between January 2021 to September 2021 after receiving ethical approval from the Institutional Review Committee (Reference number: 2011202001). Convenience sampling was done. Data were collected from the records of patients diagnosed with real-time polymerase chain reaction) test in the sample group. Point estimate and 95% Confidence Interval were calculated., Results: Among 230 patients presenting to the fever clinic, 130 (56.52%) (50.11-62.93, 95% Confidence Interval) were diagnosed with coronavirus disease-19., Conclusions: Our study found that the prevalence of coronavirus disease-19 was higher when compared to similar studies conducted in similar settings., Keywords: blood group; COVID-19; pandemic.

Efforts to mitigate the increasing emergence of antimicrobial resistance (AMR) will benefit from a One Health perspective, as over half of animal antimicrobials are also considered medically important in humans, and AMR can be maintained in the environment. This is especially pertinent to low- and middle-income countries and in community settings, where an estimated 80% of all antibiotics are used. This study features AMR genes found among humans, animals, and water at an urban informal settlement in Nepal with intensifying livestock production. We sampled humans, chickens, ducks, swine, and water clustered by household, as well as rodents and shrews near dwellings, concurrently in time in July 2017 in southeastern Kathmandu along the Manohara river. Real-time qualitative PCR was performed to screen for 88 genes. Our results characterize the animal-human-environmental interfaces related to the occurrence of specific resistance genes (bla SHV-1 (SHV(238G240E) strain), QnrS, ermC, tetA, tetB, aacC2, aadA1) associated with antibiotics of global health importance that comprise several drug classes, including aminoglycosides, beta-lactams, tetracyclines, macrolides, and fluoroquinolones. By characterizing risk factors across AMR genes of public health importance, this research highlights potential transmission pathways for further investigation and provides prioritization of community-based prevention and intervention efforts for disrupting AMR transmission of critically important antibiotics used in both humans and animals in Nepal., (© 2022. The Author(s).)

Background: To ameliorate the intra and post-op morbidities associated with newer techniques for tonsillectomy like coblation has been introduced in the recent past. This study was aimed to compare the cold steel dissection with the coblation technique with regards to its effectiveness and safety., Methods: An observational comparative study was carried out in 90 patients undergoing tonsillectomy between July 2018 to December 2019. Forty-five patients in each group of cold steel dissection and coblation were compared between the operative time, intraoperative blood loss, post-operative pain, post-operative bleeding and return to work. Intraoperative blood loss was measured using a standard sized gauge piece whereas post-operative pain was measured using a visual analogue scale (0-10) at first and third day of surgery., Results: The age and sex were comparable between the groups. The mean operation time (31.40±4.52 min versus 17.02±3.11 min), intraoperative blood loss (27.20±7.16 ml vs 9.73±5.52 ml), post-operative pain in day 1 (8.02±1.27 vs 4.98±1.03), post-operative pain in day 3 (4.80±0.89 vs 2.76±0.74) and time needed to return to work in days (10. 31±1.29 vs 6.76±1.20) were statistically significant in coblation group (p<0.000). Primary and secondary post-operative haemorrhage rates were similar in both the groups. There was no return to theatre for hemostasis., Conclusions: Coblation tonsillectomy significantly reduces operation time, intraoperative blood loss, post-operative pain (day1 and 3) and time required to return to work . This technique doesn't differ from cold steel dissection tonsillectomy in terms of primary and secondary post-operative hemorrhage.

Introduction: Septoplasty without turbinoplasty is one of the main reasons for failure of procedure in case of deviated nasal septum with inferior turbinate hypertrophy. Septoturbinoplasty is the procedure of choice for complete treatment. The main objective is to find out the prevalence of endoscopic septoturbinoplasty among patients undergoing surgery in Department of Otolaryngology-Head and Neck of a tertiary care hospital., Methods: This was a descriptive cross-sectional study in Department of Otolaryngology-Head and Neck Surgery done over a period of 1 year duration from 1st August 2020 to 31st July 2021 among 1248 patients who underwent surgery in the department. Ethical Approval was taken from Institutional Review Committee of Kathmandu Medical College and Teaching Hospital (Reference number: 2207202004). A convenience sampling technique was used. Two different techniques, Microdebrider Assisted Turbinoplasty and Outfracture with Submucosal Diathermy were used in surgery. Nasal Obstruction and Symptom Evaluation Scale questionnaire was used pre and postoperatively for data collection. Data were analyzed in Statistical Package for the Social Sciences version 16. Point estimate at 95% Confidence Interval was calculated, with frequency, percentage, mean and standard deviations., Results: Out of 1248 patients, about 92 (7.37%) patients (4.95-10.14 at 95% Confidence Interval) underwent septoturbinoplasty. The mean Nasal Obstruction and Symptom Evaluation Scale before surgery was 75.21±6.19., Conclusions: The prevalence of septoturbinoplasty in our study is similar to other studies done in similar settings. We found almost complete resolution of breathing problems following endoscopic septoturbinoplasty, hence improving quality of life.

Background: In thyroid surgery, it is essential to identify and preserve recurrent laryngeal nerve to avoid injury to the nerve which will lead to nerve paralysis or paresis. The meticulous dissection of recurrent laryngeal nerve is important for careful identification and preservation of the nerve to prevent post operative vocal cord paresis and hoarseness., Methods: A single centre prospective, cross sectional study was conducted from May 2019 to January 2021 in Department of ENT and Head and Neck surgery in Kathmandu Medical College Teaching Hospital. The data on distance between recurrent laryngeal nerve and superior parathyroid gland during thyroidectomy were collected., Results: The mean distance of recurrent laryngeal nerve in relation to superior parathyroid gland during thyroid surgery was 5.03±1.79 millimeters. The recurrent laryngeal nerve lies within 5mm of superior parathyroid gland in 83.05% cases and between 6 and 10mm in 15.25 % of cases., Conclusions: The recurrent laryngeal nerve is found in the close proximity to the superior parathyroid gland. The visual method of identification of recurrent laryngeal nerve can be widely adopted in thyroid surgery to prevent recurrent laryngeal nerve injury.

Introduction: Tonsillectomy is one of the most common surgical procedures performed by Otolaryngologists world-wide. There are various techniques for tonsillectomy, but none of the techniques has been accepted as the best one universally. Despite the efforts of all the surgeon and use of recent techniques, some post-tonsillectomy morbidity is unavoidable. The main objective of our study is to find out the mean duration for cessation of pain among the patients following tonsillectomy operation in a tertiary care hospital., Methods: This is a descriptive cross-sectional study of 104 patients who underwent tonsillectomy in department of otolaryngology of Kathmandu Medical College from 1st August 2020 to 31st July 2021. Convenient sampling technique was used. Ethical Approval was taken from Ethical Clearance Committee of hospital (Reference number: 2207202005). Proforma containing visual analog score was given to every patient for scoring the severity of postoperative pain. The scoring of pain was done from 1st postoperative day till 14th postoperative day. Descriptive statistical analysis was done., Results: One hundred four patients had undergone tonsillectomy in our hospital. The mean duration for cessation of pain was 10 (9.75±1.97) days with mean duration of analgesia taken of 11 (10.84±2.15) days. The mean duration after tonsillectomy operation for cessation of pain on drinking was 8 (7.51±1.19) days and on eating solids 12 (11.59±2.56) days. Patients reported the first normal night of sleep at seven (6.90±1.41) days and return to normal daily activities 11 (11.18±2.53) days., Conclusions: From the study concluded that the mean duration for cessation of pain after tonsillectomy is slightly lower than other similar study.

Poly-ADP-ribose-polymerase (PARP) inhibitors have achieved regulatory approval in oncology for homologous recombination repair deficient tumors including BRCA mutation. However, some have failed in combination with first-line chemotherapies, usually due to overlapping hematological toxicities. Currently approved PARP inhibitors lack selectivity for PARP1 over PARP2 and some other 16 PARP family members, and we hypothesized that this could contribute to toxicity. Recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for driving efficacy in a BRCA mutant background. Herein, we describe the structure- and property-based design of 25 (AZD5305), a potent and selective PARP1 inhibitor and PARP1-DNA trapper with excellent in vivo efficacy in a BRCA mutant HBCx-17 PDX model. Compound 25 is highly selective for PARP1 over other PARP family members, with good secondary pharmacology and physicochemical properties and excellent pharmacokinetics in preclinical species, with reduced effects on human bone marrow progenitor cells in vitro.