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Abstract The present study was aimed at showing the importance of HPV DNA status and the clinical history of the patients required by the cytologist for accurate reporting. A total of 1250 symptomatic women who attended the gynaecology outpatient department of the Mahavir Cancer Sansthan and Nalanda Medical College, Patna, for pap smear examinations were screened and recruited for the study. Due to highly clinical symptoms out of the negative with inflammatory smears reported, one hundred and ten patients were randomly advised for biopsy and HPV 16/18 DNA analysis by a gynaecologist to correlate negative smears included in the study. Pap smear reports revealed that 1178 (94.24%) were negative for intraepithelial lesions (NILM) with inflammatory smears, 23 (1.84%) smears showed low-grade squamous intraepithelial lesions (LSIL), 12 (0.96%) smears showed high-grade squamous intraepithelial lesions, and 37 (2.96%) smears showed an atypical squamous cell of undetermined significance (ASC-US). A biopsy of 110 out of 1178 (NILM) patients revealed that 15 (13.63%) women had cervical cancer, 29 women had CIN I, 17 women had CIN II + CIN III, 35 women had benign cervical changes, and 14 women had haemorrhages. On the other hand, HPV 16/18 DNA was detected as positive in 87 out of 110. The high positivity of HPV in biopsied cases where frank cervical cancer and at-risk cancer were also observed in the negative smear-screened patients reveals that the HPV status and clinical history of the patients will be quite helpful to the cytologist for accurate reporting, and suggests that a negative HPV DNA result may be a stronger predictor of cervical cancer risk than a negative Pap test.

Abstract Protein–protein interactions (PPIs) play a critical role in all biological processes. Menin is tumor suppressor protein, mutated in multiple endocrine neoplasia type 1 syndrome and has been shown to interact with multiple transcription factors including (RPA2) subunit of replication protein A (RPA). RPA2, heterotrimeric protein required for DNA repair, recombination and replication. However, it’s still remains unclear the specific amino acid residues that have been involved in Menin-RPA2 interaction. Thus, accurately predicting the specific amino acid involved in interaction and effects of MEN1 mutations on biological systems is of great interests. The experimental approaches for identifying amino acids in menin-RPA2 interactions are expensive, time-consuming, and challenging. This study leverages computational tools, free energy decomposition and configurational entropy scheme to annotate the menin-RPA2 interaction and effect on menin point mutation, thereby proposing a viable model of menin-RPA2 interaction. The menin–RPA2 interaction pattern was calculated on the basis of different 3D structures of menin and RPA2 complexes, constructed using homology modeling and docking strategy, generating three best-fit models: Model 8 (− 74.89 kJ/mol), Model 28 (− 92.04 kJ/mol) and Model 9 (− 100.4 kJ/mol). The molecular dynamic (MD) was performed for 200 ns and binding free energies and energy decomposition analysis were calculated using Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) in GROMACS. From binding free energy change, model 8 of Menin-RPA2 exhibited most negative binding energy of − 205.624 kJ/mol, followed by model 28 of Menin-RPA2 with − 177.382 kJ/mol. After S606F point mutation in Menin, increase of BFE (ΔGbind) by − 34.09 kJ/mol in Model 8 of mutant Menin-RPA2 occurs. Interestingly, we found a significant reduction of BFE (ΔGbind) and configurational entropy by − 97.54 kJ/mol and − 2618 kJ/mol in mutant model 28 as compared the o wild type. Collectively, this is the first study to highlight the configurational entropy of protein–protein interactions thereby strengthening the prediction of two significant important interaction sites in menin for the binding of RPA2. These predicted sites could be vulnerable for structural alternation in terms of binding free energy and configurational entropy after missense mutation in menin.

Background and Aims: Eutectic mixture of local anesthetics (EMLA) (2.5% lidocaine and 2.5% prilocaine) cream is the commonly used topical anesthetic for painful intradermal procedures. Topical 10% lidocaine spray has successfully been used to anesthetize mucosal surfaces. Owing to its skin penetrative properties, this study was conducted to compare dermal analgesia between 10% lidocaine spray and EMLA cream for intravenous (IV) cannulation in children. Methods: In this prospective single-blind randomized study, ninety-nine Paediatric patients were assigned into Group A (number(n) =51) with Lignocaine 10% spray applied 10 minutes and Group B (n = 48) EMLA cream applied 1 hour prior to cannulation. Vital signs were recorded before, during, and after the procedure. The primary objective of the study was assessment of severity of pain during IV cannulation using 10 cm visual analogue scale (VAS). Secondary objectives such as ease of cannulation and adverse effects were also noted. Results: All cannulations were performed in the first attempt with no adverse effects in both lidocaine group and EMLA group. The median (interquartile range) VAS score was 2 cm (1 to 3) in both the groups with a P value of 0.58. Conclusion: Topical 10% lidocaine spray applied ten minutes before venous cannulation is as effective as EMLA cream applied an hour before cannulation in children in providing dermal analgesia for intravenous cannulation with an added advantage of rapid onset of action in the former group.

Abstract Background Malaria is a complex issue due to the availability of few therapies and chemical families against Plasmodium and mosquitoes. There is increasing resistance to various drugs and insecticides in Plasmodium and in the vector. Additionally, human behaviors are responsible for promoting resistance as well as increasing the risk of exposure to infections. Chalcones and their derivatives have been widely explored for their antimalarial effects. In this context, new derivatives of chalcones have been evaluated for their antimalarial efficacy. Methods BALB/c mice were infected with P. berghei NK-65. The efficacy of the three most potent chalcone derivations (1, 2, and 3) identified after an in vitro compound screening test was tested. The selected doses of 10 mg/kg, 20 mg/kg, and 10 mg/kg were studied by evaluating parasitemia, changes in temperature, body weights, organ weights, histopathological features, nitric oxide, cytokines, and ICAM-1 expression. Also, localization of parasites inside the two vital tissues involved during malaria infections was done through a transmission electron microscope. Results All three chalcone derivative treated groups showed significant (p

Aims and Objectives: The purpose of this study was the comparison of hemodynamic variables such as heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure during the extubation period following administration of two doses of intravenous (IV) esmolol. Materials and Methods: This prospective double-blind randomized controlled trial was conducted on patients (American Society of Anesthesiologists Physical Status), aged between 18 and 65 years, scheduled for elective laparoscopic procedure done under general anesthesia with endotracheal intubation. Sixty participants were randomized into three groups of 20 each, the first two groups received IV esmolol injection of 0.5 mg/kg and 1 mg/kg doses, respectively, and the third group received placebo injection of 10 ml of saline intravenously after the completion of surgery before extubation. Statistical Analysis: Statistical analysis of data was done using SPSS 20 software. Repeated measures analysis of variance (ANOVA) test was used for the analysis of trends of different parameters within the group. For comparison between the groups and to find if any significant difference exists, one-way ANOVA was used. Post hoc Tukey's test was used to find where the difference originated from, once significant difference was found. Results: Demographic data were statistically similar between groups. IV administration of esmolol at both 0.5 mg/kg and 1 mg/kg is effective in attenuating heart rate response but IV esmolol bolus of 1 mg/kg is more effective than bolus of 0.5 mg/kg in attenuating blood pressure response to extubation as it provided a more consistent hemodynamic control during the extubation as well as in the postextubation period. Conclusion: Extubation and emergence from general anesthesia cause significant increases in heart rate and blood pressure and emphasis must be given on attenuation of this sympathetic response, especially in vulnerable patients. IV administration of esmolol is effective in attenuation of heart rate response and blood pressure response with consistently good hemodynamic control during extubation postoperatively.

Abstract Objective Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy. Results In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL (intraperitoneal route), 69.89 ± 5.49 µg/mL (oral route), and 3.74 ± 1.64 µg/mL (oral route). The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.

Abstract Objective Chloroquine is used as a conventional drug therapy for the treatment of malaria. The existence of resistance to chloroquine shown among various species of Plasmodium leads to the search for more efficacious therapy to treat malaria. Probiotic (Lactobacillus casei) has been tried as an add-on therapy with chloroquine. Probiotics are ingested microorganisms associated with a beneficial effect on humans and other species. The study was done to check the efficacy of L. casei as an add-on therapy along with conventional drug therapy (chloroquine) to treat malaria. Results Probiotic in combination with chloroquine showed complete suppression in parasitemia rate. Representation of parasitemia rate was done using mean ± SD. p

Abstract Objective Chalcones (1, 3-diaryl-2-propen-1-ones) and their derivatives are widely explored from the past decade for its antimalarial activity. To elucidate their mechanism of action on the malaria parasite, the ultrastructural changes with the action of these derivatives in different organelles of the parasite were studied in vitro. Infected RBCs [CQ sensitive (MRC-2) and CQ resistant (RKL-9) Plasmodium strain] were treated with three chalcone derivatives 1, 2 and 3 and standard drugs, i.e., CQ and artemisinin at twice their respective IC50 values for 24 h and then harvested, washed, fixed, embedded and stained to visualize ultra-structure changes before and after intervention of treatment under in vitro condition through transmission electron microscope. Results The ultrastructural changes demonstrate the significant disturbance of all parasite membranes, including those of the nucleus, mitochondria and food vacuole, in association with a marked reduction of ribosomes in the trophozoites and cessation of developing schizonts which suggest multiple mechanisms of action by which chalcone derivatives act on the malaria parasite. The present study opens up perspectives for further exploration of these derivatives in vivo malaria model to discover more about its effect and mechanism of action.

Abstract Background Malaria extensively leads to mortality and morbidity in endemic regions, and the emergence of drug resistant parasites is alarming. Plant derived synthetic pharmaceutical compounds are found to be a foremost research to obtain diverse range of potent leads. Amongst them, the chalcone scaffold is a functional template for drug discovery. The present study involves synthesis of ten chalcones with various substitution pattern in rings A and B and assessment of their anti-malarial efficacy against chloroquine sensitive and chloroquine resistant strains as well as of their cytotoxicity and effect on haemozoin production. Methods The chalcones were synthesized by Claisen-Schmidt condensation between equimolar quantities of substituted acetophenones and aryl benzaldehydes (or indole-3-carboxaldehyde) and were screened for anti-malarial activity by WHO Mark III schizont maturation inhibition assay. The cytotoxicity profile of a HeLa cell line was evaluated through MTT viability assay and the selectivity index (SI) was calculated. Haemozoin inhibition assay was performed to illustrate mode of action on a Plasmodium falciparum strain. Results The IC50 values of all compounds were in the range 0.10–0.40 μg/mL for MRC-2 (a chloroquine sensitive strain) and 0.14–0.55 μg/mL for RKL-9 (a chloroquine resistant strain) of P. falciparum. All the chalcones showed low cellular toxicity with minimal haemolysis. The statistically significant reduction (p

The article presents the replicable model of Curriculum and Community Based Academic Learning with Research, Action and Service (CCBALwRAS) through a framework of '2 Cs', the 'curriculum' and the 'community'. It puts forth a support strategy for participatory community-based interventions by formally inducting higher education institutions (HEIs) to achieve long-term sustainable, workable solutions for local communities. The study is based on a multi-stakeholder partnership, facilitated through partnerships between the HEI, committed faculty-student participation and civil society, executed between 2015 and 2020. The article draws from the execution and actual field experience of the partnership, along with qualitative data from the evaluation and assessment of the programme delivered. Given that the model developed is based on the experiences of a private fee-dependent HEI in a metro city, the study does not take into consideration infrastructural and resource constraints of other HEIs. The article focuses on the role of HEIs as fulfilling dual responsibilities of knowledge creation and dissemination while addressing socioeconomic, developmental and environmental needs within their immediate communities. The resultant pedagogical shift and the model proposed is an effective solution for equity, capacity building and civic-mindedness, which will nurture socially aware and critically conscious global citizens.

The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000–2,000,000 compounds per screening campaign), before pre-clinical trials to select optimum lead. Carrying out in vitro screening of antimalarials is very difficult as different assay methods are subject to numerous sources of variability across different laboratories around the globe. Despite this, in vitro screening is an essential part of antimalarial drug development as it enables to resource various confounding factors such as host immune response and drug–drug interaction. Therefore, in this article, we try to illustrate the basic necessity behind in vitro study and how new methods are developed and subsequently adopted for high-throughput antimalarial drug screening and its application in achieving the next level of in vitro screening based on the current approaches (such as stem cells).

Background Interleukin 7R (IL-7R), a cytokine receptor gene, plays an important role in the development of innate and adaptive inflammatory response in asthma etiology. Objective IL-7R is a heterodimeric protein composed of α chain and γ chain. The α chain of IL-7R has a range of single nucleotide polymorphisms, which give rise to nonsynonymous amino-acid substitutions that might result in an increased production of inflammatory cytokines and cause asthma. Methods A case-control study was conducted with a total of 964 subjects, including 483 healthy controls and 481 patients with asthma. DNA samples were extracted from blood, and genotyping was done by using sequence-specific-primer–polymerase chain reaction. Results Statistical analysis revealed that IL-7R + 1237A/G (rs1494555) gene polymorphism shows a highly protective association toward asthma (odds ratio [OR] 0.56, p < 0.001) in AG genotype as well as in mutant GG genotype (OR 0.64, p = 0.029). However, IL-7R + 2087T/C (rs6897932) polymorphism showed an increased risk toward asthma in TC genotype (OR 1.70, p = 0.002) as well as in the CC genotype (OR 1.68, p = 0.002). Furthermore, the GT and AC haplotypes in the IL-7R polymorphisms were also found to be significantly associated with asthma (p = 0.001 and p = 0.037, respectively). Conclusions The study conducted in a north Indian population indicated that the protective association was observed for the + 1237A/G position, and a significant risk was observed for the + 2087T/C position in asthma.

Background Interleukin 13 (IL13) is directly involved in the secretion of total serum immunoglobulin E (IgE), which plays a major role in the asthma pathogenesis. Objective One of the polymorphic receptor of IL13 is IL13Rα1, which after binding to IL13, initiates signal transduction that results in mucin secretion, airway hyperreactivity, fibrosis, and chitinase up-regulation, which increases asthma risk. Methods In the present study, the role of IL13Rα1 + 1398A/G gene polymorphisms in asthma was detected with a total of 964 individuals, including 483 healthy controls and 481 asthma patients from a North Indian population using polymerase chain reaction-restriction fragment length polymorphism method. Results Statistical analysis revealed that the mutant allele (G) is predominant in asthma patients (42.7%) than the controls (38.2%), which shows an increased risk toward asthma with odds ratio = 1.21, 95% confidence interval (1.00 −1.45), χ 2 = 4.10 and p = 0.043. Furthermore, the phenotypic characteristics also reveal a significant association with the disease (p < 0.05). Conclusions This is the first study conducted in India and + 1398A/G polymorphism in noncoding region of IL13Rα1 confer risk toward asthma in the studied population.

The Indian Subcontinent witnessed its first urbanization in the middle of the third millennium BC as a result of continued cultural development that started around the beginning of seventh millennium BC at Mehragrh on the Kachi Plains. Extensive research in other parts of India, revealed the presence of contemporary early farming cultures, with characteristic rural features. The recent archaeological evidence from Bagor, Balathal and Gilund (Mewar, Rajasthan) suggests independent origin of a settled life style around the middle of 4th millennium BC contemporary with the Pre/Early Harappan cultures of western Indian subcontinent. These sites have brought to light traces of infant urbanization or pro-urbanisation associated with the Ahar culture of Mewar. Available evidence demonstrates the influence of Harappan urbanization on Chalcolithic sites, though on a much smaller scale as a result of interactions and trade contacts between the two by the middle of the 3rd millennium BC.

The identification of the Harappan Civilization in the early twentieth century was considered to be the most significant archaeological discovery in the Indian Subcontinent as it pushed the beginning of settled life by 2000 years. Contemporary to the Mesopotamian and Egyptian Civilizations it was unique in its town planning. Spread over major parts of the western and north-western subcontinent, its influence is seen to the Tajikistan border in the north and the Gulf region in the west with over two thousand sites found till date. The past eight decades of research have brought to light many important details of the culture including the cultural process involving its origin, maturity and decline but certain aspects such as the terminology, climatic influence, regional variations, script etc are still very flimsy. To gain more information the focus of research will have to shift from Mega Site Archaeology to Small Site Archaeology with large multidisciplinary research projects to acquire a more holistic picture of the Harappan culture.

Genetic diversity of Ralstonia solanacearum, causal agent of bacterial wilt of tomato was assessed by using three different molecular methods such as random amplified polymorphism DNA (RAPD), BOX-PCR and hrp (hypersensitive response and pathogenicity) gene sequence analysis technique. Twelve isolates of Ralstonia solanacearum belonging to biovar 3 (9 isolates) and 4 (3 isolates) were collected from Northern parts of India including Himachal Pradesh and Uttarakhand states from infected tomato plants. Out of 16 primers used in RAPD fingerprinting, four primers (OPA-2, OPA-11, OPC-5, OPE-7) showed monomorphic bands and remaining 12 primers exhibited polymorphic amplified products of both the biovars of R. solanacearum. The primer OPE-10 showed the highest level of genetic diversity among the isolates. Ten isolates of R. solanacearum were classified into two clusters at 20 per cent similarity coefficient and cluster 1 represented all isolates of biovar 3 (UTT-23, UTT-10, UTT-26, HPT11, UTT-9, UTT-32, HPC-3) and cluster 2 comprised the biovar 4 (UTT-22, HPT-3, UTT-24). BOX-PCR fingerprint of R. solanacearum clearly distinguished biovar 3 and 4 grouped into two distinct clusters at 40% similarity coefficient. Cluster 1 represented all isolates of R. solanacearum biovar 3 and cluster 2 comprised the biovar 4 isolates. The isolates of R. solanacearum have genetic diversity in hrpB gene, but it could not differentiate the isolates of biovar 3 and 4. However, the biovars 3 and 4 of R. solanacearum can be genetically distinguished by using BOX- PCR and specific primer of RAPD.