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Acute encephalitis syndrome (AES) outbreaks in children of Eastern Uttar Pradesh (E-UP) region of India have been a longstanding public health issue, with a significant case fatality rate of 20-25%. Since past decade, a rise in chikungunya (CHIK) cases has been occurring, which is a reported etiology of AES. However, the burden of chikungunya virus (CHIKV) among pediatric AES (pAES) is unknown from E-UP. We included 238 hospitalized pAES cases. The presence of IgM antibodies for CHIKV, and Dengue virus (DENV) was tested, and RT-PCR was performed for CHIKV and DENV in serologically confirmed CHIKV and DENV pAES cases. Positive samples were sequenced using Sangers sequencing. Further, to check for co-infection, IgM antibodies for other AES etiologies including Japanese encephalitis virus (JEV), Leptospira and Orientia tsutsugamushi (OT) in serum were also investigated. IgM ELISA demonstrated 5.04% (12) positivity for CHIKV. Among CHIKV IgM positive, 3 (25%, 3/12) pAES patients died. CHIKV genome was detected in 3 pAES specimens. Among which, 2 CHIKV cases were also positive for OT DNA. Partially sequenced CHIKV were genotyped as ECSA. The overall finding indicates evidence of CHIKV infection with high case fatality among pAES patients from E-UP. This study advocates constant serological and molecular surveillance of CHIKV in AES endemic regions of India., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As a part of novel discovery of drugs from natural resources, present study was undertaken to explore the antibacterial potential of chalcone Indl-2 in combination with different group of antibiotics. MIC of antibiotics was reduced up to eight folds against the different cultures of E. coli by both chalcones. Among the two compounds, the i. e. 1-(3', 4,'5'-trimethoxyphenyl)-3-(3-Indyl)-prop-2-enone (6, Indl-2), a chalcone derivative of gallic acid (Indl-2) was better along with tetracycline (TET) worked synergistically and was found to inhibit efflux transporters as obvious by ethidium bromide efflux confirmed by ATPase assays and docking studies. In combination, Indl-2 kills the MDREC-KG4 cells, post-antibiotic effect (PAE) of TET was prolonged and mutant prevention concentration (MPC) of TET was also decreased. In-vivo studies revealed that Indl-2 reduces the concentration of TNF-α. In acute oral toxicity study, Indl-2 was non-toxic and well tolerated up-to dose of 2000 mg/kg. Perhaps, the study is going to report gallic acid derived chalcone as synergistic agent acting via inhibiting the primary efflux pumps., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Introduction: Acute hemorrhagic conjunctivitis (AHC) outbreaks are caused mostly by viruses. During July-August 2023, there was a sudden spike in acute hemorrhage conjunctivitis cases in Eastern Uttar Pradesh, India. To identify the etiological and gain molecular epidemiology of the agent, the study was conducted., Methodology: Conjunctival swabs were collected from patients (n = 128) with presumed acute hemorrhage conjunctivitis visiting two tertiary care hospitals., Results: Enteroviruses infection was identified in 96 (75%) patients. In these patients, coxsackievirus A24 (CV-A24) infection was further confirmed by targeting the genetic regions of 3C protease and VP1. Furthermore, the study established the outbreak was caused by the genotype IV of CV-A24 with the highest genetic similarity with CV-A24 reported from Northeast India, China, and Pakistan circulating during the same period. The comparison of our study sequences with earlier Indian outbreak strains (2007) revealed four amino acid substitutions at the 3C region ("S21N," "V30I," "S66I," and "V75I") and three non-synonymous mutations at the VP1 region ("L16I," "P21S," and "N301D")., Conclusion: The study findings revealed that the AHC outbreak was caused by genotype IV of CV-A24 in this region. Molecular identification accompanied by phylogenetic analysis will be useful in studying the enterovirus epidemiology associated with AHC outbreaks., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Orientia tsutsugamushi is responsible for causing scrub typhus (ST) and is the leading cause of acute encephalitis syndrome (AES) in AES patients. A rapid and sensitive method to detect scrub typhus on-site is essential for the timely deployment of control measures. In the current study, we developed a rapid, sensitive, and instrument-free lateral flow assay (LFA) detection method based on CRISPR/Cas12a technology for diagnosing ST (named LoCIST). The method is completed in three steps: first, harnessing the ability of recombinase polymerase for isothermal amplification of the target gene; second, CRISPR/Cas12a-based recognition of the target; and third, end-point detection by LFA. The detection limit of LoCIST was found to be one gene copy of ST genomic DNA per reaction, and the process was complete within an hour. In 81 clinical samples, the assay showed no cross-reactivity with other rickettsial DNA and was 100% consistent with PCR detection of ST. LoCIST demonstrated 97.6% sensitivity and 100% specificity. Overall, the LoCIST offers a novel alternative for the portable, simple, sensitive, and specific detection of ST, and it may help prevent and control AES outbreaks due to ST. In conclusion, LoCIST does not require specialized equipment and poses a potential for future applications as a point-of-care diagnostic.

Background: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection., Methods: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated., Results: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 -25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29-1.73), being male (aRR:1.26; 95%CI: 1.18-1.34), residing in urban location (aRR:1.58; 95%CI: 1.03-2.43) and past history of TB (aRR:1.49; 95%CI: 1.26-1.76)., Conclusion: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To estimate the frequency distribution of different anatomical positions, and to measure the diameter, wall thickness, and length of appendix in patients with non-appendicular symptoms., Material and Methods: This retrospective observational study was conducted among 1,575 patients, who had undergone computed tomography (CT) scan of abdomen for various non-appendicular signs and symptoms. Frequency of distribution of different anatomic locations and measurements of various morphologic parameters were recorded., Results: The most common location of appendix was retrocecal, followed by sub-cecal, post-ileal, and pelvic locations. The mean length of appendix was 66.7 mm (range, 6.3-123 mm), and the diameter was 6.3 mm (range, 2.8-11.3 mm). Diameter of > 6 mm was noted in 48.12% patients. The mean wall thickness was 2.37 mm, ranging 1.2-4.2 mm. The most common intra-luminal content was air-mixed with hypodense or hyperdense material observed in 70.5% of cases., Conclusions: Although an appendix with diameter less than 6 mm may be considered normal, a diameter above 6 mm has an overlap between a normal and inflamed appendix. Therefore, it should be considered in association with clinical and secondary findings to avoid overdiagnosis and unnecessary appendicectomies. We strongly recommend that diameter-based CT criteria to diagnose appendicitis should be revised and standardized., Competing Interests: The authors report no conflict of interest., (© Pol J Radiol 2023.)

Introduction Cavitary lung disease has a wide range of differential diagnoses, which include both benign and malignant lesions. Imaging differentiation of benign from malignant cavitary lesions has always been a challenge due to overlapping imaging findings. The present study describes the most accurate multidetector computed tomography (MDCT) findings that could help in differentiating benign from malignant conditions in correlation with the histopathological reports. Methods This retrospective study was carried out on diagnosed cases of cavitary lung lesions on MDCT from January 2022 to February 2023. We evaluated the number of cavitary lung lesions, their location with respect to lung segment/lobe, the maximum diameter of the largest lesion, the maximum wall thickness of the largest cavity, and additional findings associated with these lesions. Measurements of the maximum wall thickness were plotted on a graph. Statistical analysis was done, and a receiver operating characteristic curve (ROC) was calculated to find the accurate cut-off wall thickness for malignant and non-malignant lesions. These findings were then correlated with the histopathological report. Results A review of the MDCT scans of 47 patients was done; 30 (63.8%) of those were male with a mean age of 47.93±14.68 (SD) years while 17 (36.2%) were female with a mean age of 52.53 ±18.38 (SD) years. Out of 47 patients, 27 (57.4%) had benign lesions and 20 (42.5%) had malignant lesions. Significant differences (p<0.05) were found between benign and malignant lesions while comparing the averages of maximum wall thickness (8.1 mm and 14.5 mm, respectively) and the irregular inner margin of the largest cavitary lesions. The presence of consolidation and centrilobular nodules correlated significantly (p<0.05) with the benign nature of cavitary lung lesions. The maximum cut-off wall thickness was <6 mm and >17 mm for the differentiation of benign from malignant lung lesions, respectively. Conclusions The maximum wall thickness and irregular inner margin of cavitary lung lesions was a good indicator for the differentiation of benign and malignant etiologies on MDCT while consolidation and centrilobular nodules favoured the benign etiology more., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lal et al.)

Background: Urinary bladder cancer is more common in geriatric population. Transurethral resection of bladder tumor remains the mainstay of treatment. It is usually performed under subarachnoid block. However, obturator nerve is spared in subarachnoid block that can produce adductor jerk, which is associated with bladder injury, rupture, incomplete resection of tumor and hematoma. To overcome this jerk, selective obturator nerve block is commonly performed. Thus, we conducted this study to compare the efficacy of ultrasound and nerve stimulator-guided techniques for obturator nerve block., Methods: This is a prospective, comparative study conducted at a tertiary care hospital in Nepal. Sixty patients, scheduled to undergo Transurethral Resection of Bladder Tumor for lateral and posterolateral wall bladder cancer under subarachnoid block were enrolled and divided into two group having thirty patients in each groups. Group I received 15 ml of 0.25% Bupivacaine to block obturator nerve by using peripheral nerve stimulator. Group II received the same amount of Bupivacaine to block obturator nerve under ultrasound guidance. We evaluated the success of the block, ease of the procedure and complications., Results: The adductor reflex was present in 23.33% of cases with nerve stimulator guided obturator nerve block, whereas, it was16.66% in ultrasound guided technique (p=0.75). The success rate of obturator nerve block was 76.66% in nerve stimulator guided technique, whereas 83.33% in ultrasound guided technique (p= 0.21). 83.33% of obturator nerve block was found to be easy in nerve stimulator guided technique, whereas 66.66 % in ultrasound guided technique (p = 0.14). There were no major complications noted., Conclusions: The findings of this study conclude that both ultrasound and nerve stimulator guided techniques equally abolished the adductor reflexes. Both techniques are easy to perform and safe.

Scrub typhus (ST) caused by Orientia tsutsugamushi (OT), has long been known to cause acute encephalitis syndrome (AES) and acute febrile illness (AFI). The immunodominant 56 kDa protein of OT, which is encoded by the 56 kDa gene (1600 bp encoding 516-541 amino acids) is a commonly studied antigen for genotype and serotype assignment. Previous studies from India have utilized partial type specific antigen (TSA) 56 kDa sequences for OT strain characterisation. On the other hand, understanding the antigenic diversity of current OT strains, is critical for developing specific diagnostic tests and vaccines against ST. As a result, the current study analyses antigenic variants using the entire TSA56 ORF of OT from AES cases. Phylogenetic investigation using complete TSA56 ORF sequences revealed Karp and Gilliam were the circulating predominant strains of OT. Furthermore, Immuno-informatical analysis demonstrated that the majority of high-binding affinity CD4 TCEs against the most prevalent Indian human leukocyte antigen alleles were present in the S-VDIII/IV and S-VDIV spacer regions of TSA56 ORF. TSA56 conserved spacer is crucial for OT immunological response investigations. Further, the pathophysiological effects of spacer domains in ST require further investigation. Furthermore, the characterization of the TSA56 spacer region of the OT from different parts of India is critical for developing region-specific ST diagnostic assays and vaccines., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/objectives: Globally, the COVID-19 pandemic and its prevention and control policies have impacted maternal and child health (MCH) services. This study documents the challenges faced by patients in accessing MCH services, and the experiences of health care providers in delivering those services during the COVID-19 outbreak, explicitly focusing on the lockdown period in India., Methods: A cross-sectional study (rapid survey) was conducted in 18 districts from 6 states of India during March to June, 2020. The sample size included 540 MCH patients, 18 gynaecologists, 18 paediatricians, 18 district immunisation officers and 108 frontline health workers. Bivariate analysis and multivariable analysis were used to assess the association between sociodemographic characteristics, and challenges faced by the patients., Results: More than one-third of patients (n = 212; 39%) reported that accessing MCH services was a challenge during the lockdown period, with major challenges being transportation-related difficulties (n = 99; 46%) unavailability of hospital-based services (n = 54; 23%) and interrupted outreach health services (n = 39; 18.4%). The supply-side challenges mainly included lack of infrastructural preparedness for outbreak situations, and a shortage of human resources., Conclusions/recommendations: A holistic approach is required that focuses on both preparedness and response to the outbreak, as well reassignment and reinforcement of health care professionals to continue catering to and maintaining essential MCH services during the pandemic.

There are several bacteria called superbugs that are resistant to multiple antibiotics which can be life threatening specially for critically ill and hospitalized patients. This article provides up-to-date treatment strategies employed against some major superbugs, like methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Escherichia coli. The pathogen-directed therapeutics decrease the toxicity of bacteria by altering their virulence factors by specific processes. On the other hand, the host-directed therapeutics limits these superbugs by modulating immune cells, enhancing host cell functions, and modifying disease pathology. Several new antibiotics against the global priority superbugs are coming to the market or are in the clinical development phase. Medicinal plants possessing potent secondary metabolites can play a key role in the treatment against these superbugs. Nanotechnology has also emerged as a promising option for combatting them. There is urgent need to continuously figure out the best possible treatment strategy against these superbugs as resistance can also be developed against the new and upcoming antibiotics in future. Rational use of antibiotics and maintenance of proper hygiene must be practiced among patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The COVID-19 outbreak caused by the SARS Corona virus 2 (SARS-CoV-2), that appeared in Wuhan, China in December 2019 evolved into a pandemic and caused a devastating effect in all aspect of life. The aim of this study is to determine the impact of Covid-19 on the management of spine patients requiring surgery and to observe the functioning of a trauma center in a pandemic situation., Methods: A retrospective study was performed at National Trauma Center, Kathmandu, Nepal from January 1 2019 to February 28 2020(Pre-Covid period) and March 1 2020 to April 30 2021(Covid Period) . All patients undergoing spine surgery were included and details regarding demographics, diagnosis, surgical procedures were obtained and compared between pre- covid and covid period and also between complete lockdown period and partial lockdown period of the covid duration., Results: The mean age of the patients undergoing surgery in the Pre covid period was (40.4 ± 14.51) years and covid period was (38.9 ± 14.00) years. The number of spine surgeries performed during the pre covid period was 295 whereas the number decreased to 197 in the covid period. The total number of non traumatic spine surgery in the pre covid period was 22.03% of the total spine surgery cases where as it decreased to 11.68% in the covid period. Similarly out of the total cases instrumented surgery was 91.86% in the pre covid period whereas it was 97.97% in the covid period. While analyzing the spine surgery done in the COVID period we found that most of the cases of surgery done in the complete restriction period was of traumatic spine only (97.77%) where as in the limited restriction period non traumatic spine surgery was also increased with traumatic spine surgery accounting for 85.52% of the total spine surgery cases., Conclusions: The COVID pandemic has had a direct impact on traumatic and non-traumatic spine surgeries performed in this center.

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India., Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7., Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men., Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zaman, Shete, Mishra, Kumar, Reddy, Sahay, Yadav, Majumdar, Pandey, Dwivedi, Deval, Singh, Behera, Kumar, Patil, Kumar, Dudhmal, Joshi, Shukla, Gawande, Kavathekar, Kumar, Kumar, Kumar, Singh, Kumar, Tiwari, Verma, Yadav and Kant.)

Study Design: Retrospective study., Objectives: Cervical spinal cord injury (SCI) is a devastating event for patient and family. It has a huge impact on society because of intensive resources required to manage the patient in both acute and rehabilitation phases. With the limited resource setting in underdeveloped countries like Nepal, questions are often raised regarding whether the outcome justifies the expenses of their care. The objective was to assess the outcomes of cervical SCI patients admitted to intensive care unit (ICU)., Methods: All cervical SCI admitted in ICU during May 2017 to August 2018 were included in this study. Demographic details, mode, morphology, and neurological level of injury, intervention performed and outcomes of ICU stay were analyzed., Results: Out of 48 patients, 36 (75%) were male and 12 female with mean age 43.9 ± 15.9 years. Fall injury was the commonest mode of injury (83.3%). Most patients presented within 1 to 3 days of injury and C5-C6 (33.3%) was the most common involved level and 75% presented with ASIA A neurology. Mechanical ventilation was required in 95.8% of the patients and 22 patients were operated upon. The average stay in ICU was 15 days and 13 patients died in the ICU., Conclusions: Majority of cervical SCI with complete motor paraplegia required ICU care. Inspite of the intensive care, a subset of these patients succumbed to the complications of the injury. Therefore, it is essential to establish trauma ICU care with specific protocols on managing cervical spine injuries.

Background & Objectives: The tribal population in India is considered as one of the vulnerable groups with respect to their achievements in health and other developmental issues. In this context, this mapping review attempted to understand the health profile of the Tharu tribal community residing in the northern State of Uttar Pradesh, India through literature mining. Tharu tribe is one of the indigenous groups living in the Terai plain on the Indo-Nepal border. In 1967, this tribe was documented as a Scheduled Tribe by the Government of India. The present review aimed to map the health-seeking behaviour of the Tharu population and review other factors pertaining to their health such as socioeconomic, developmental, employment, education, etc., Methods: Online data search was carried out on PubMed and Google Scholar using search terms 'Tharu' AND 'India'. In addition, official reports avaibale in public domain and grey literature was also searched., Results: Twenty seven studies including reviews, articles, books/book chapters were evaluated along with 13 reports (including reports from government organizations and grey literature) were retrieved and analyzed. Of the 27 published reports, 16 were found relevant to Tharu tribe in India. A total of 29 (16 articles + 13 reports ) were included in this review., Interpretation & Conclusions: This mapping review highights the health seeking behaviour of the Tharu tribe in India that can help inform future interventions to improve the health status of the Tharu tribe as well as other aspects of their development.

Background: The clinical presentation, biochemical characteristics, and outcomes of patients infected with SARS-CoV-2 can vary in different populations. The purpose of the study is to assess the clinical presentation and identify predictors of mortality among patients with severe acute respiratory distress syndrome admitted to different critical care units in Nepal., Methods: An observational study was conducted among the confirmed SARS-CoV-2 patients admitted to different critical care units in seven provinces of Nepal. Retrospective data was collected for the period of three months (April 14, 2021 to July 15, 2021) in relation to the peak of the second wave of COVID-19 pandemic in Nepal. Clinical, biochemical and mortality data were collected from the admitted patients of different critical care units. Univariate logistic regression analysis was done among the selected variables at 5% significance. Final predictor variables were identified after multiple regression analysis., Results: Out of total of 646 patients admitted to critical care units of different provinces of Nepal, there was a male predominance 420 (65%). A total of 232(35.91 %) patients were non-survivors with the majority of mortality occurring in patients > 50 years of age. Cough (72.3 %), shortness of breath (70.9%) and fever (56 %) were the most common presenting clinical features. Increasing age, presence of comorbidity, critical COVID-19 cases, respiratory rate, temperature, serum urea and alanine aminotransferase were identified as predictors of mortality after multiple regression analysis., Conclusions: Approximately 36 % of the confirmed SARS-CoV-2 patient admitted to critical care units did not survive. There was a male preponderance with most casualties occurring in patients more than 50 years of age. Cough, shortness of breath and fever were the most common presenting features. After multiple regression analysis of the identified clinical and biochemical factors, age, presence of comorbidity, respiratory rate, temperature, severity grade as per the World Health Organization classification, serum urea and alanine aminotransferase were identified as the predictors of mortality.

Background: With limited studies on spinal injuries occurring at the cervicothoracic junction, there is currently a knowledge gap regarding the correlation between morphology of injury and neurology and whether surgery provides a favorable neurological outcome. The primary objective was to determine whether the neurological deficit correlated with the severity of injury at this region of the spine., Methods: All patients with injuries at the cervicothoracic junction from December 2015 to December 2020 in a government trauma hospital were included. Patient demographics, characteristics of the injury, neurological score, imaging findings, surgery details and neurological outcomes were analyzed. All patients had a minimum follow up of 2 years., Results: Of the total 30 patients, 23 were male and 7 female with mean age 42.4 years. 90% had fall injuries with 76.7% sustaining AO type C injury and 10% with AO B2 injury.73.4% had injury at C6-C7 level followed by 13.3% , C7-T1. Only 16.7% patients presented with intact neurology. Plain x-rays failed to detect cervicothoracic junction, injuries in 63.3% patients. Posterior stabilization was performed in 56.7%. Neurological improvement was observed in 9 patients., Conclusions: Though cervicothoracic junction injuries are uncommon, they are highly unstable injuries and difficult to diagnose by plain x-rays. These injuries also result in profound neurological deficit. Surgical stabilization of these injuries should be considered for a favorable neurological and functional outcome.

The early management, diagnosis, and treatment of emerging and re-emerging infections and the rising burden of non-communicable diseases (NCDs) are necessary. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system has recently acquired popularity as a diagnostic tool due to its ability to target specific genes. It uses Cas enzymes and a guide RNA (gRNA) to cleave target DNA or RNA. The discovery of collateral cleavage in CRISPR-Cas effectors such as Cas12a and Cas13a was intensively repurposed for the development of instrument-free, sensitive, precise and rapid point-of-care diagnostics. CRISPR/Cas demonstrated proficiency in detecting non-nucleic acid targets including protein, analyte, and hormones other than nucleic acid. CRISPR/Cas effectors can provide multiple detections simultaneously. The present review highlights the technical challenges of integrating CRISPR/Cas technology into the onsite assessment of clinical and other specimens, along with current improvements in CRISPR bio-sensing for nucleic acid and non-nucleic acid targets. It also highlights the current applications of CRISPR/Cas technologies.

Primary pancreatic lymphoma is a rare disease. It comprises less than 0.5 % of pancreatic neoplasm and 0.1% of malignant lymphoma. It should be differentiated from pancreatic adenocarcinoma because management differs. At computed tomography, 2 types of morphology of primary pancreatic lymphoma have been described- a localized well-circumscribed tumoral form and another diffuse enlargement infiltrating or replacing most of the pancreatic gland. Here, we are presenting computed tomography (CT) imaging features of a case of primary pancreatic lymphoma in a 27 year old female who presented with a complaint of abdominal pain radiating to the back for 3 months and yellowish discoloration of sclera and skin for the last 15 days. In contrast-enhanced computed tomography an exophytic homogenously hypoenhancing mass arising from head and neck region of pancreas was seen. Involvement of common bile duct (CBD) and duodenum was there. The main pancreatic duct was not dilated. Common hepatic artery was encased by mass without arterial luminal narrowing or distortion. Diagnosis of primary pancreatic lymphoma was suggested on basis of imaging findings and further confirmed with fine-needle aspiration cytology., (© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

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Background: The AO Spine Patient Reported Outcome Spine Trauma has been validated in English and Dutch language, however, there is an absence of a translated and validated version in Nepali language. The purpose of this study was to translate the AO Spine Patient Reported Outcome Spine Trauma into Nepali and adapt cross-culturally as outlined by established guidelines, as well as test its psychometric properties among Nepali speaking spine trauma patients., Methods: Patients were recruited from two Nepali centers as a cross-sectional multicenter validation study. The English version of AO Spine Patient Reported Outcome Spine Trauma was translated and cross-culturally adapted into Nepali language following international guidelines. Next to AO Spine Patient Reported Outcome Spine Trauma also the EQ-5D-3L was filled out by the patients for concurrent validity. Descriptive statistics were used to analyze the patient characteristics. Assessment of measurement properties included content validity (floor and ceiling effects), internal consistency (Cronbach's ? and item total-correlation coefficients) and test-retest reliability by the Bland-Altman plot and Intraclass Correlation Coefficients. Spearman correlation tests were performed within the items and in correlation to EQ-5D-3L., Results: Sixty two spine trauma patients completed the instrument with a mean time of 6.8 minutes. The translated version showed good content validity with no floor and ceiling effects. The internal consistency was excellent with a Cronbach's ? of 0.95. The Spearman correlations within the AO Spine Patient Reported Outcome Spine Trauma items were 0.07 - 0.65 and the test-retest analysis showed excellent results with an Intraclass Correlation Coefficients value of 0.95 (CI 0.93 - 0.97). Inverse correlation was observed between Nepali AO Spine PROST with EQ-5D-3L components., Conclusions: The Nepali version of AO Spine Patient Reported Outcome Spine Trauma demonstrated excellent validity and reliability results for measuring patient-reported outcomes of spine trauma patients.

Uttar Pradesh is the densely populated state of India and is the sixth highest COVID-19 affected state with 22,904 deaths recorded on November 12, 2021. Whole-genome sequencing (WGS) is being used as a potential approach to investigate genomic evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, a total of 87 SARS-CoV-2 genomes-49 genomes from the first wave (March 2020 to February 2021) and 38 genomes from the second wave (March 2021 to July 2021) from Eastern Uttar Pradesh (E-UP) were sequenced and analyzed to understand its evolutionary pattern and variants against publicaly available sequences. The complete genome analysis of SARS-CoV-2 during the first wave in E-UP largely reported transmission of G, GR, and GH clades with specific mutations. In contrast, variants of concerns (VOCs) such as Delta (71.0%) followed by Delta AY.1 (21.05%) and Kappa (7.9%) lineages belong to G clade with prominent signature amino acids were introduced in the second wave. Signature substitution at positions S:L452R, S:P681R, and S:D614G were commonly detected in the Delta, Delta AY.1, and Kappa variants whereas S:T19R and S:T478K were confined to Delta and Delta AY.1 variants only. Vaccine breakthrough infections showed unique mutational changes at position S:D574Y in the case of the Delta variant, whereas position S:T95 was conserved among Kappa variants compared to the Wuhan isolate. During the transition from the first to second waves, a shift in the predominant clade from GH to G clade was observed. The identified spike protein mutations in the SARS-CoV-2 genome could be used as the potential target for vaccine and drug development to combat the effects of the COVID-19 disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deval, Nyayanit, Mishra, Yadav, Zaman, Shankar, Misra, Behera, Kumar, Kumar, Bhardwaj, Dwivedi, Singh, Shete, Pandit, Pandey, Yadav, Gupta, Kumar, Kavathekar, Singh, Prajapati and Kant.)

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide-zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO-CS), a zinc oxide decorated graphene oxide-chitosan nanocomposite (GO-CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa . These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis.

Background: India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs)., Methods and Findings: We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey., Conclusions: Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions., Competing Interests: The authors have declared that no competing interests exist.

We explored the antibacterial potential (alone and combination) against multidrug resistant (MDR) Pseudomonas aeruginosa isolates KG-P2 using synthesized thieno[3,2-c]pyran-2-ones in combination with different antibiotics. Out of 14 compounds, two compounds (3g and 3l) abridged the MIC of tetracycline (TET) by 16 folds. Compounds was killing the KG-P2 cells, in time dependent manner, lengthened post-antibiotic effect (PAE) of TET and found decreased the mutant prevention concentration (MPC) of TET. In ethidium bromide efflux experiment, two compounds repressed the drug transporter (efflux pumps) which is further supported by molecular docking of these compounds with efflux complex MexAB-OprM. In another study, these compounds inhibited the synthesis of biofilm., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May-June 2020 and 7.1% in August-September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India., Methods: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated., Results: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0-25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5-27.8%)., Conclusions: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Emergency Department of National Trauma Center Nepal Center is the only specialized trauma care hospital in Nepal, in operation since 2012. Traumatic injury is one of the major causes for mortality worldwide. This study aims to see the epidemiology, pattern of injuries and outcome of the patients presenting to the emergency room., Methods: After getting ethical approval, we included all patients presenting to the Emergency Department with at least one injury, between Jan 2018 to Dec 2020. Informations on age, gender, mechanism of injury and outcome was abstracted for all patients presenting to the emergency department. Data were extracted from hospital database with the permission of hospital authority., Results: Total of 49991 patients presented to emergency department with different types of injuries.  Among them 7792 (14.0%) needed hospital admission. Fall and road crashes comprised almost 80% of admitted cases. Mortality was 2.1% of admitted patients, mostly with head injuries followed by multiple injuries., Conclusions: Among the patient visiting the trauma center during the study period most common mechanism of the injury were fall and road crash with head and neck injury. Majority of the patients were only managed in the ward without surgery.

Background: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India., Methods: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys., Findings: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case., Interpretation: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country., Funding: Indian Council of Medical Research., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background & Objectives: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India., Methods: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity., Results: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths., Interpretation & Conclusions: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country., Competing Interests: None

Study Design: Epidemiological retrospective study., Objective: To describe the demographics, timing to surgery, delay, short-term neurological recovery, and complications in surgically treated subaxial cervical trauma in a resource-constrained country., Methods: Thirty consecutive subaxial cervical trauma patients presenting to a trauma hospital in Nepal between December 2015 and August 2017 were analyzed as a retrospective cohort. Patients were segregated into 4 groups based on the timing to surgery: within 2 days, 3 to 7 days, 8 to 30 days, and >31 days., Results: There were 27 male and 3 female patients with mean age 40 years. Twenty-four sustained fall injury, and 27 patients were from outside Kathmandu. No patients were treated within the first 48 hours; only 9 were treated between 3 and 7 days, 16 between 8 and 30 days, and 5 a month later. Major delay was finance and operating room availability. Thirteen patients had a C6C7 involvement followed by C5C6 in 6 patients. Seven patients had complete neurological deficit while 18 patients had incomplete deficit. A total of 46.7% improved their neurology in 6 months. No neurological recovery was observed in complete deficit patients., Conclusion: Seventy percent of our patients were treated longer than 1 week after injury, which would likely be considered unacceptable in most first world countries. As expected, the outcomes for many of these patients were far worse than reported in North American centers with early access to medical care and insurance. Despite this, nearly half of our patients improved neurologically following treatment; hence, surgery holds hope of some restoration of neurologic deficits., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: K. Daniel Riew: Biomet, Medtronic—Royalties. Osprey, Expanding Orthopedics, Spineology, Spinal Kinetics, Nexgen Spine, Amedica, Vertiflex, Benvenue, Paradigm Spine, PSD—Stock. Spine, GSJ, ESJ, Neurosurgery, Clinics in Orthopedics, Spine Surgery Today—Editorial/Board. AO Spine—Board. The remaining authors have no conflicts of interest to disclose.

Background: Selective Nerve Root Block using steroid is a proven technique for management of lumbar radiculopathy. The aim of the study was to determine the effectiveness of selective nerve root block in lumbar radiculopathy., Methods: A prospective observational study was conducted for duration of one year in patients diagnosed with lumbar radiculopathy. Patients with leg pain, positive straight leg raising test and single level disc prolapse were included in the study. The procedure was performed under fluoroscopic guidance and Visual Analogue Pain rating scale and Oswestry Disability Index score was used for assessment pre-injection, 1 week, 1 month, 6 months and 1-year post injection., Results: Total 35 patient with mean age of 37.7± 9.31 years were included in the study. The pre-injection Visual Analogue Pain Score(Mean ± S.D:7.8±0.7) was significantly reduced at one week (4.2±1.47, p <0.00001), one month (2.74±1.06, p <0.00001), six months (2.31±0.75, p <0.00001) and one year (2.62±0.84, p <0.00001). Similarly, pre-injection Oswestry Disability Index score (Mean ± S.D: 32.09±5.95) was significantly reduced at one week (19.51±7.26, p <0.00001), one month (12.71±4.56, p <0.00001), six months (9.8±2.87, p <0.00001) and one year (10.09±2.97, p <0.00001) but not significantly improved when compared at 6 months and 1 year (p < 0.44)., Conclusions: Selective Nerve Root Block in lumbar radiculopathy significantly reduces Visual Analogue Pain Score up to a year, however, the reduction in pain plateaus around six months.Disability index score only reduces for first 6 months but doesn't significantly reduce from six months to one year.

The emergence of multi drug resistance (MDR) in Gram-negative bacteria (GNB) and lack of novel classes of antibacterial agents have raised an immediate need to identify antibacterial agents, which can reverse the phenomenon of MDR. The purpose of present study was to evaluate synergy potential and understanding the drug resistance reversal mechanism of chanoclavine isolated from Ipomoea muricata against the multi-drug-resistant clinical isolate of Escherichia coli (MDREC). Although chanoclavine did not show antibacterial activity of its own, but in combination, it could reduce the minimum inhibitory concentration (MIC) of tetracycline (TET) up to 16-folds. Chanoclavine was found to inhibit the efflux pumps which seem to be ATPase-dependent. In real-time expression analysis, chanoclavine showed down-regulation of different efflux pump genes and decreased the mutation prevention concentration of tetracycline. Further, in silico docking studies revealed significant binding affinity of chanoclavine with different proteins known to be involved in drug resistance. In in silico ADME/toxicity studies, chanoclavine was found safe with good intestinal absorption, aqueous solubility, medium blood-brain barrier (BBB), no CYP 2D6 inhibition, no hepatotoxicity, no skin irritancy, and non-mutagenic indicating towards drug likeliness of this molecule. Based on these observations, it is hypothesized that chanoclavine might be inhibiting the efflux of tetracycline from MDREC and thus enabling the more availability of tetracycline inside the cell for its action.

From the discovery to the golden age of antibiotics (miracle), millions of lives have been saved. The era of negligence towards chemotherapeutic agents gave birth to drug resistance. Among all the regulators of drug resistance, drug transporters are considered to be the key regulators for multidrug resistance. These transporters are prevalent from prokaryotes to eukaryotes. Endophytes are one of the unexplored wealths of nature. Endophytes are a model mutualistic partner of plants. They are the reservoir of novel therapeutics. The present review deals with endophytes as novel drug resistance reversal agents by inhibiting the drug transporters across the genera. This review also focuses on drug transporters, and mutualistic chemical diversity, exploring drug transporter modulating potential of endophytes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multidrug resistance (MDR) put an alarming situation like preantibiotic era which compels us to invigorate the basic science of anti-infective chemotherapy. Hence, the drug resistant genes/proteins were explored as promising drug targets. Keeping this thing in mind, proteome of Pseudomonas aeruginosa PA01 was explored, which resulted in the identification of tripartite protein complexes (MexA, MexB, and OprM) as promising drug target for the screening of natural and synthetic inhibitors. The purpose of present investigation was to explore the drug resistance reversal potential mechanism of catharanthine isolated from the leaves of Catharanthus roseous. Hence, the test compound catharanthine was in silico screened using docking studies against the above receptors, which showed significant binding affinity with these receptors. In order to validate the in silico findings, in vitro evaluation of the test compound was also carried out. In combination, catharanthine reduced the minimum inhibitory concentration MIC of tetracycline (TET) and streptomycin up to 16 and 8 folds, respectively. Further, in time kill assay, catharanthine in combination with TET reduced the cell viability in concentration dependent manner and was also able to reduce the mutation prevention concentration of TET. It was also deduced that drug resistance reversal potential of catharanthine was due to inhibition of the efflux pumps.

Introduction: γH2AX assay has been used for DNA damage assessment at higher doses of radiation exposure. Its expression has not been studied in cases with diagnostic low dose radiation exposure. Concerns have been raised about the after-effects of radiation in diagnostic procedures like Computed Tomography (CT) scan, Angiography etc especially when such scans are repeated within short span of time. The purpose of the present study was to assess immediate DNA damage after exposure to low level of ionizing radiation by the flow cytometric method of gamma-H2AX., Material and Methods: Study sample includes total 60, cases and controls with two groups Group I-Normal controls (n = 15); Group II-Low dose, further divided in three groups: Group IIA-single CT scan (n = 15); Group IIB-Multiple CT scans (n = 15); and Group IIC-angiography single exposure (n = 15). For Low dose group blood was collected within 1 h after exposure in EDTA vaccutainers and immediately kept on ice. Lymphocytes were isolated and were fixed in 80% chilled ethanol and stored at -20 °C till further analysis. The H2AX assay was done and 10,000 cells were analysed for gamma H2AX positivity in flowcytometer., Results: Significant gamma-H2AX positivity was found in cases versus control, the most significant DNA damage amongst cases was observed in cases with multiple CT scans., Conclusion: The exposure to multiple CT scans causes more double strand breaks as compared to single scan. DNA damage can be studied by flow cytometric analysis of gamma-H2AX in human peripheral lymphocytes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The factors responsible for seizure recurrence in patients with Solitary calcified neurocysticercosis (NCC) are not well understood. Blood brain barrier (BBB) breach may be associated with seizure recurrence. Dynamic contrast enhanced (DCE) MRI derived indices k ep, k trans and v e are useful in quantifying BBB permeability. In this study, we assessed the possible role of DCE-MRI and matrix metalloproteinases (MMP)-9 levels in predicting seizure recurrence., Methods: In this prospective-observational study, patients with new-onset seizures and a solitary calcified NCC were included. DCE-MRI was done to quantify BBB integrity. DCE-MRI parameters were measured as k ep , k trans and v e . MMP-9 levels were estimated. Patients were followed for 1 year, when DCE-MRI and MMP-9 levels were repeated. Patients were classified into two groups on the basis of seizure recurrence, which was defined as the recurrence of an episode of seizure at least 1 week after the initiation of the anti-epileptic drugs. Logistic regression analysis was done., Results: At 1-year of follow up, 8 out of 32 patients had seizure recurrence. Baseline DCE-MRI derived k ep (p = 0.015) and MMP-9 levels (p = 0.019) were significantly higher in the seizure "recurrence" group compared with the "no recurrence" group. On within-group analysis, a significant increase in k ep (p = 0.012), v e (p = 0.012), and MMP-9 levels (p = 0.017) was observed in the seizure "recurrence" group while a decrease was seen in v e and MMP-9 levels in the "no recurrence" group., Conclusion: Higher values of DCE-MRI indices and MMP-9 levels, with a corresponding trend in the follow-up, can be useful in predicting lesions with a higher propensity for seizure recurrence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Radiation causes oxidative lesions and strand breaks in DNA of exposed cells. Extended length PCR is a reliable method for assessing DNA damage. Longer DNA strands with DNA damage are difficult to amplify compared to smaller DNA strands by PCR. The present study was aimed to evaluate DNA damage caused by ionising radiation exposure in therapeutic and diagnostic medicine. Materials and Methods: The study group comprised 50 cases with low dose single exposure (LDS), low dose multiple exposure (LDM) and low dose angiography (LDA) which were compared with 25 high dose controls (HDC) and 25 controls with no exposure (NEC). Blood samples were collected within 1 hour of radiation exposure. DNA was isolated using a kit based protocol, 50 ng aliquots of DNA were used to amplify a long 13kbp DNA fragment of the β-actin gene by conventional PCR and band intensity was then quantified. Relative amplification was calculated and damage was expressed in terms of lesions per kilobase (kbp) by assuming a Poisson distribution. Result: Relative amplification was found to be 1.0, 0.87, 0.86, 0.72 and 0.69 with NEC, LDS, LDM, LDA and HDC groups, respectively. Cases undergoing angiography as well as high dose controls had high values, compared to NEC. The lesions/kbp calculated for LDS was 0.13, for LDM 0.15, for LDA 0.32 and for HDC 0.37 suggesting a linear increase in quantity with increasing radiation dose. Conclusion: DNA damage, even at low doses of radiation can be assessed by quantitative extra long PCR., (Creative Commons Attribution License)

Introduction: Outcome of spine injury treated in resource constrained regions may not be the same as in developed nations. The aim of the present study was to study the epidemiological characteristics, delay, complications, and outcome of surgically treated dorsal and lumbar trauma., Methods: Retrospective study of dorsal and lumbar spine injury patients treated between December 2015 and August 2017. Patients were segregated into four groups based on the timing of surgery: 0-2 days, 3-7 days, 8-30 days, and more than 31 days. Only one operating room twice a week was allotted to spine surgery, and spine had to compete with orthopedic and surgical trauma for admission and surgery., Results: Ninety-one patients (male 61) with mean age 33 years were operated for dorsal and lumbar spine injuries. 84% of the total patients sustained a fall, and 86.8% were from the periphery. Though 69.2% presented within 2 days, only 4.4% were operated within 2 days. Majority of the delay was due to unavailability of the operating room followed by financial constraints. Twenty-seven patients had complete deficit, 32 incomplete deficit, and 32 normal neurology. Four patients operated within 2 days improved their neurology, 7 incomplete deficit patients in 3-7 days group improved, 6 in 8-30 days group improved, whereas no patient in more than 31 days group improved. Overall 53.1% of neurologically incomplete deficit patients improved if operated within 30 days. No neurological improvement was seen in the 27 complete deficit patients. Wound infection, pulmonary contusion, and deep vein thrombosis were seen in 3 patients., Conclusions: As expected 95.6% of our patients were treated more than 3 days after injury and 60% more than a week later, which may not be acceptable in advanced countries. Despite the delay, 53.1% had an improvement in neurology when operated within 30 days. Hence, surgery still holds the hope of neurological recovery and quicker rehabilitation., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.

Background: Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls)., Methods: The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA)., Results: The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations., Conclusion: On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

Infectious diseases are one of the major causes of morbidity and mortality in children in developing and underdeveloped countries. Limited knowledge of targets (cell wall synthesis, replication, transcription, protein synthesis) for antibiotics and lack of novel antibiotics have lead to an emergence of different level of resistance in bacterial pathogens. Multidrug resistance is the phenomenon by which the bacteria exerts resistance against the two or more structurally unrelated drugs/antibiotics. A common goal in the post-genomic era is to identify novel targets/drugs for various life threatening bacterial pathogens. Nanoparticles are broadly defined as submicron colloidal particles of size less than 1μm. Nanoparticles of size less than 100nm are the most promising warheads to overcome microbial drug resistance because they can act as antibacterial/antibiotic modulating agents at the site of infection and may have more than one mode of action. These nanoparticles will be of immense help in transporting drugs directly at the infected sites. Thus prevent drug resistance development to a great extent. In this review, the key mechanisms of resistance in bacterial superbugs have been discussed as well as how nanoparticles can overcome them. It is hypothesized that the nanoparticles can overcome the drug resistance via a novel mechanism of action. Additionaly, nanopaticles may also work synergistically with antibiotics via increased uptake, decreased efflux and inhibition of biofilm formation. The degradation by metallo beta lactamases and synthesis of porins may also be facilitated through these nanoparticles.

Antibacterial and synergy potential of naturally occurring indole alkaloids (IA): 10-methoxy tetrahydroalstonine (1), isoreserpiline (2), 10 and 11 demethoxyreserpiline (3), reserpiline (4), serpentine (5), ajmaline (6), ajmalicine (7), yohimbine (8), and α-yohimbine (9) was evaluated using microbroth dilution assay. Further, α-yohimbine (9) was chemically transformed into six semisynthetic derivatives (9A-9F), and their antibacterial and synergy potential in combination with nalidixic acid (NAL) against E. coli strains CA8000 and DH5α were also evaluated. The IA 1, 2, 4, 5, 9 and the derivative 9F showed eightfold reduction in the MIC of NAL against the DH5α and four- to eightfold reduction against CA8000. These alkaloids also reduced MIC of another antibiotic, tetracycline up to 8folds, against the MDREC-KG4, a multidrug-resistant clinical isolate of E. coli. Mode of action study of these alkaloids showed efflux pumps inhibitory potential, which was supported by their in silico binding affinity and downregulation of efflux pump genes. These results may be of great help in the development of cost-effective antibacterial combinations for treating patients infected with multidrug-resistant Gram-negative infections., (© 2015 John Wiley & Sons A/S.)

As a part of our drug discovery program, ursolic acid was chemically transformed into six semi-synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with conventional antibiotic nalidixic acid against the nalidixic acid-sensitive and nalidixic acid-resistant strains of Escherichia coli. Although ursolic acid and its all semi-synthetic derivatives did not show antibacterial activity of their own, but in combination, they significantly reduced the minimum inhibitory concentration of nalidixic acid up to eightfold. The 3-O-acetyl-urs-12-en-28-isopropyl ester (UA-4) and 3-O-acetyl-urs-12-en-28-n-butyl ester (UA-5) derivatives of ursolic acid reduced the minimum inhibitory concentration of nalidixic acid by eightfold against nalidixic acid-resistant and four and eightfold against nalidixic acid-sensitive, respectively. The UA-4 and UA-5 were further evaluated for their synergy potential with another antibiotic tetracycline against the multidrug-resistant clinical isolate of Escherichia coli-KG4. The results showed that both these derivatives in combination with tetracycline reduced the cell viability in concentration-dependent manner by significantly inhibiting efflux pump. This was further supported by the in silico binding affinity of UA-4 and UA-5 with efflux pump proteins. These ursolic acid derivatives may find their potential use as synergistic agents in the treatment of multidrug-resistant Gram-negative infections., (© 2014 John Wiley & Sons A/S.)

DbMDR is non-redundant reference database of multidrug resistance (MDR) genes and their orthologs acting as potential drug targets. Drug resistance is a common phenomenon of pathogens, creating a serious problem of inactivation of drugs and antibiotics resulting in occurrence of diseases. Apart from other factors, the MDR genes present in pathogens are shown to be responsible for multidrug resistance. Much of the unorganized information on MDR genes is scattered across the literature and other web resources. Thus, consolidation of such knowledge about MDR genes into one database will make the drug discovery research more efficient. Mining of text for MDR genes has resulted into a large number of publications but in scattered and unorganized form. This information was compiled into a database, which enables a user not only to look at a particular MDR gene but also to find out putative homologs based on sequence similarity, conserved domains, and motifs in proteins encoded by MDR genes more efficiently. At present, DbMDR database contains 2843 MDR genes characterized experimentally as well as functionally annotated with cross-referencing search support. The DbMDR database (http://203.190.147.116/dbmdr/) is a comprehensive resource for comparative study focused on MDR genes and metabolic pathway efflux pumps and intended to provide a platform for researchers for further research in drug resistance., (© 2011 John Wiley & Sons A/S.)