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The spinel ferrites are versatile group of metal oxides with good photoelectrochemical and unique magnetic properties, as well as low cost, biocompatible and huge abundance. The magnetic as well as photoelectrochemical properties have been extensively examined. Herein, we have synthesized zinc ferrite (ZnFe2O4) thin films on nickel foam via spray pyrolysis method at substrate temperatures of 300, 400, and 500 °C. The physicochemical properties of ZnFe2O4 films were investigated using X-ray diffraction, scanning electron microscopy, energy dispersive X-ray analysis and fourier transform infrared spectroscopy (FT-IR) spectroscopy. Electrochemical properties oxygen evolution reaction and supercapacitive performance of ZnFe2O4 thin films were investigated through linear sweep voltammetry, cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy. The ZnFe2O4 thin film synthesized at 400 °C exhibited an overpotential of 319 mV at a current density of 50 mA/cm2 with a Tafel slope of 115 mV/dec. Furthermore, it also showed a specific capacitance of 335 F/g at 1 mA/cm2 current density in 1 M KOH electrolyte. [ABSTRACT FROM AUTHOR]

The proteolytic enzymesinvolved in the processing and replication of coronavirus serve a promising drug targetsfor coronavirus. Although a few numbers of vaccines have been made available, there is a great need for effective treatment to manageit. The current study involved the exploration of baicalin analogues as potential inhibitor of viral proteolytic enzyme. Utilizing various computational tools (scaffold morphing, molecular docking and pharmacokinetic studies), the B74 and B86 analogueswere screened as potential inhibitors of main protease. Accordingly, these analogues can be explored further in the search of promising therapy against the coronavirus infection.

Titanium doped WO (Ti doped WO) nanostructures were synthesized by hydrothermal synthesis by the controlled hydrolysis of NaWO using oxalic acid and Titanium tetrachloride. Prepared samples were characterized by X-ray powder diffraction (XRD), scanning electronic microscopy (SEM), and transmission electron microscopy (TEM). As-synthesized pristine WO showed nanorods with diameters of about 10-15 nm and length about 1.2 µm and Ti doped WO composed of numerous small nanocrystals. Introduction of Ti doping by chemical synthesis process suppressed the growth of one-dimensional nanorods along their axis direction and shows agglomeration of particulate like morphology and no elongated structures. Ti doping not only lowered the optimal operating temperature of WO nanostructures sensors from 250 to 200 °C but also increased the maximum value of sensor response. Also the Ti-doped WO nanostructures exhibited rapid response characteristic to NO gas compared to pristine WO. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a viral infection produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus epidemic, which was declared a global pandemic in March 2020. The World Health Organization has recorded around 43.3 billion cases and 59.4 million casualties to date, posing a severe threat to global health. Severe COVID-19 indicates viral pneumonia caused by the SARS-CoV-2 infections, which can induce fatal consequences, including acute respiratory distress syndrome (ARDS). The purpose of this research is to better understand the COVID-19 and ARDS pathways, as well as to find targeted single nucleotide polymorphism. To accomplish this, we retrieved over 100 patients' samples from the Sequence Read Archive, National Center for Biotechnology Information. These sequences were processed through the Galaxy server next generation sequencing pipeline for variant analysis and then visualized in the Integrative Genomics Viewer, and performed statistical analysis using t-tests and Bonferroni correction, where six major genes were identified as DNAH7, CLUAP1, PPA2, PAPSS1, TLR4, and IFITM3. Furthermore, a complete understanding of the genomes of COVID-19-related ARDS will aid in the early identification and treatment of target proteins. Finally, the discovery of novel therapeutics based on discovered proteins can assist to slow the progression of ARDS and lower fatality rates.

Defining the ecological quality of estuaries is challenging because of the inadequacy of available methods and indices to characterise the ecosystem. In Indian estuaries, there are no scientific attempts to establish multi-metric fish index to determine the ecological status. A multi-metric fish index (EMFI) was customised for twelve predominantly open estuaries on India's western coast. The index was established at the individual estuary level to ensure uniformity and contrast from sixteen metrics that designate the fish community and diversity, composition and abundance, estuarine use and trophic integrity from 2016 to 2019. A sensitivity study was followed to measure the responses of the EMFI under different metric varying scenarios. There were seven metrics identified as the most prominent for the EMFI in metric alteration scenarios. We also deduced a composite pressure index (CPI) based on the anthropogenic pressures described for the estuaries. The ecological quality ratios (EQR) defined based on EMFI (EQR E ) and the CPI (EQR P ) for all the estuaries were positively correlated. The EQR E values calculated based on the regression relationship (EQR E on EQR P ) showed the divisions from 0.43 (bad) to 0.71 (high) for the Indian west coast estuaries. Similarly, the standardised CPI (EQR P ) values for different estuaries indicated that the values range from 0.37 to 0.61. Our results based on the EMFI suggest four estuarine systems (33%) as 'good', seven (58%) as 'moderate' and one (9%) as 'poor'. Generalised Linear Mixed Model for EQR E showed that EQR P and estuary influenced EQR E ; however, the effect of year was not significant. This comprehensive study based on the EMFI is the first record for predominantly open estuaries along the Indian coast. Therefore, the EMFI established in this study could be reliably advocated as a sound, effective and composite tool of ecological quality for tropical open transitional waters., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Fluoride (F) is an effective anticaries agent and can be delivered through various mediums at different concentrations. The ability to increase the enamel resistance to acid by decreasing solubility through the incorporation of F into the enamel apatite structure is the primary function of these agents. The efficacy of topical F can be determined by measuring the amount of F incorporated in and on human enamel., Aim: To compare the F uptake into and onto the enamel surface of two different F varnishes at different temperatures., Materials and Methods: In this study, 96 teeth were divided equally and randomly ( n = 48) into two experimental groups (group I and group II). Each group was further divided into four equal subgroups ( n = 12); depending on the temperature (25°, 37°, 50°, and 60°C) they were subjected to Fluor-Protector® 0.7% and Embrace® 5% F varnishes were allocated to experimental groups I and II, respectively, and every sample was individually treated with the assigned F varnish. After the varnish application, two specimens from each subgroup, the group I and group II ( n = 16), were mounted for hard tissue microtome sectioning for scanning electron microscope (SEM) analysis. The remaining 80 teeth underwent potassium hydroxide (KOH) soluble and KOH-insoluble F estimation., Results: Group I and group II, both, showed maximum F uptake of 2817.07 ppm and 1626.8 ppm at 37°C temperature and the lowest of 1168.9 ppm and 1068.93 ppm at 50°C, respectively. The intergroup comparison was carried out using an unpaired t -test and the intragroup comparison was done using one-way analysis of variance (ANOVA) univariate analysis. Post hoc Tukey test was performed for pairwise comparison between different temperature groups. In group I (Fluor-Protector®), the difference in F uptake was statistically significant when the temperature was increased from 25° to 37° C (mean difference = -9.90, p = 0.016). In group II (Embrace®), a statistically significant difference in F uptake was observed when the temperature was increased from 25° to 50°C (mean difference = 10.00, p = 0.003) and 25° to 60°C (mean difference = 13.38, p = 0.001), respectively., Conclusion: Fluor-Protector® varnish proved to have better F uptake in comparison to Embrace® varnish on human enamel. Topical F varnishes were most effective at 37°C, which is close to the standard human body temperature. Thus, the application of warm F varnish ensures more uptake of F in and onto the enamel surface for greater protection against dental caries., How to Cite This Article: Vishwakarma AP, Bondarde P, Vishwakarma P, et al. Evaluation of Fluoride Uptake of Two Fluoride Varnishes Into and onto the Enamel Surface at Different Temperatures: An In Vitro Study. Int J Clin Pediatr Dent 2022;15(6):672-679., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; The Author(s).)

Memory is the process of retaining of knowledge over a period for the function of affecting future actions. It can be divided into declarative and procedural types. The process of memory consolidation is done in the hippocampus. The long-term memories are spread among various areas of the cerebrum depending on the different perceptual properties. The process of long-term potentiation and molecular changes occurring during memory formation are discussed in detail below. The steps involved in memory formation include encoding, storage, and recall (retrieval) in that order. Amnesia is a phenomenon in which there is the problem in memory formation which can be due to trauma to the brain, certain diseases, or stressors. While the assessment of memory has greatly improved, we are only beginning to understand the underlying mechanisms., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

Background: By 2040, dementia is projected to rise exponentially by 300% in India. Studies addressing the need for psychiatric care in the community being few and those focusing in old age homes even fewer, a study was undertaken to study the prevalence of dementia and the association with sociodemographic factors and psychiatric morbidity., Materials and Methods: A total of 558 elderly aged 60 years and above, residing in old age homes in Pune were studied. 179 inmates were included based on the inclusion and exclusion criteria. Those who scored a predetermined cut-off score on the screening tool were included to undergo a detailed physical and neurological examination, cognitive profile using subtests from the cognitive test (community screening instrument for Dementia of 10/66 group)., Results: Mean age of the sample was 75.02 years majority (39.7%) was in the 60-70 years group. Males 25.7% versus females 74.3%. The sample consisted of the following socioeconomic groups: 40.2% middle, 26.3% low middle, 24% high middle, 8.4% high income, and 1.1% in low income. 60.3% widow/widower category, 36.3% never married, 4.5% had family history of dementia. Mean scores of mini mental state examination in the overall sample was 26.02 compared to 18.02 in those cut-off point of 23. The prevalence of dementia in the sample was 22.9%. There was the high prevalence of psychiatric symptoms and psychiatric morbidity in the dementia group than the rest. Frontal lobe dysfunction and impairment of orientation with increasing severity of dementia were observed., Conclusions: Sociodemographic factors, which were considered protective against the prevalence of dementia, identified were less restriction in physical activity and having fish in the diet regularly., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

Obsessive-compulsive disorders (OCDs) are one of the top 10 contributors of debilitating medical illnesses and are the fourth most common psychiatric disorder. Blasphemous thoughts, also known as scrupulosity, as an obsessional theme has piqued curiosities long before it was considered a neurosis. Such obsessions may or may not have an accompanying compulsion and comprise 5% of the patients of OCD. The case series is of three patients suffering from repetitive, intrusive, ego-dystonic, and distressing blasphemous thoughts, which are extremely distressing to them, rendering them unable to perform any other activity. The symptoms also indicate the presence of comorbid depressive and anxiety disorders, developing secondary to the blasphemous thoughts. Inadequate knowledge in this subtype of OCD mandates the need for more studying and research, especially with new texts suggesting the implementation of faith-assisted psychotherapy in addition to the conventional psychotherapy and pharmacotherapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

" Necessity is the mother of invention: " An adage was brought to life with the emergence of the mRNA vaccine against the backdrop of the foreboding and mercurial COVID-19 pandemic. Considering a negligible adverse-effect profile and a break-neck manufacturing speed, it shone bright as the ideal vaccine candidate. However, " all that glitters is not gold ," as was evidenced by the significant reactogenicity, a host of multi-systemic side-effects, that are being reported by the vaccine recipients; which is palpably resulting in a shift of emotions for the vaccine, accounting for vaccine hesitancy. Anaphylaxis, antibody-dependent enhancements, and deaths, comprise the most serious side-effects, albeit occurring in sparing numbers. Storage and transportation require fastidious temperatures, rendering it substantially inaccessible to a country like India. The biggest jolt, however, was the unfolding of the biases in reporting vaccine efficacy, as only the attractively high numbers of the relatively equivocal relative risk reduction were reported while keeping at bay the meager numbers of the more forthright absolute risk reduction. Notwithstanding the fallacies, the mRNA vaccine still promises hope; and with the right precautions and finesse, can be potentiated, as " a watched pot never boils .", Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

Child sexual abuse (CSA) occurs when a person involves the child in sexual activities for his/her sexual gratification, commercial gain, or both. We report a series of 12 cases of CSA, who presented to the psychiatry department with diverse psychiatric presentations associated with CSA. In most of these cases, the perpetrator was unmarried and known to the child. The presentation was varied with patients being diagnosed with obsessive-compulsive disorder, schizophrenia, acute and transient psychotic disorder, dysthymic disorder, recurrent depressive disorder, acute stress reaction, conversion disorder, borderline personality disorder, and moderate depressive episode with somatic symptoms. Individual and family counseling was an important part of management of these cases along with pharmacotherapy. More vigilance about CSA and mental health in all categories of health-care personnel would help in early detection and timely management of these cases., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

Competing Interests: There are no conflicts of interest.

Background: Depression is a significant public health issue that needs to be taken care of, as it poses a great economic burden on the society at large. Early identification and treatment of the patients will reduce mental morbidity and disability., Aim: The aim is to study the prevalence and functional status of subjects with major depressive disorder in the community., Materials and Methods: After identification of the sample population, the sociodemographic details were recorded. Subsequently, assessment was carried out by General Health Questionnaire (GHQ), Patient Health Questionnaire-9 (PHQ-9), Functional Status Questionnaire (FSQ), and Mini Mental State examination (MMSE)., Results: A total of 2000 subjects were screened using the GHQ and PHQ and 544 subjects were selected. These 544 subjects were further assessed with FSQ and MMSE. Out of the 544 subjects, 65.1% had a GHQ score of <14, 22.1% had a score between 15 and 19, and 12.9% had a score of >20. The PHQ-9 score was found to be <5 in 28.9% subjects, 5-14 in 64.3% subjects, and >14 in 6.8% subjects. Majority of the sample population was in the warning zone according to the FSQ. The MMSE scores were ≥23 in 86% and ≤22 in 14% of the patients. Over 65% of the subjects were relatively mentally healthy. Out of the remaining 35%, 22% of the subjects required screening for psychiatric disorders and 13% of them did require active psychiatric intervention., Conclusions: It would be beneficial to the community if a database is created regarding the psychiatric disorders such as depression prevalent in the community and their functional status so that the effective measures can be implemented to minimize the suffering by providing effective psychiatric care at the earliest and follow them up in the long run., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

Background: With the availability of potent antipsychotics, the prognosis of schizophrenia has improved. As a result, there is increasing interest in assessing the quality of life (QOL) and marital adjustment of patients with schizophrenia. However, there is a paucity of Indian data in this area., Aim: To evaluate and compare the QOL and marital adjustment in spouses of patients with schizophrenia and controls., Materials and Methods: This cross-sectional, hospital-based study comprised of consenting female individuals of the age group of 20-40 years. The study group included 30 spouses of male patients with schizophrenia (according to ICD 10-DCR) and control group included 30 age-matched spouses of male participants without psychiatric disorders. The participants were selected from the psychiatry ward and outpatient department and neighboring areas of the Dr. D. Y. Patil Medical College, Pune, India. Only couples married for at least 5 years were included in the study. Wives with a history of any major psychiatric or major medical disorders were excluded. All the participants were evaluated with a sociodemographic data sheet, the World Health Organization QOL (WHOQOL)-BREF, and the Marital Adjustment Questionnaire. The statistical analysis was done using descriptive frequency, Chi-square, and Mann-Whitney U-test., Results: Wives of patients with schizophrenia had significantly lower scores on psychological, social, and environmental domains of WHOQOL BREF and on sexual adjustment, social adjustment, emotional adjustment, and total score on the marital adjustment questionnaire as compared to the control group., Conclusion: Wives of patients with schizophrenia have lower QOL and marital adjustment compared to controls., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

Self-injurious behavior (SIB) can be described as an act involving self-inflicted destruction of tissue, right away or over a period of time. Patients with epilepsy have to deal with an often chronic and unpredictable disorder leading to adversity in many psychosocial variables such as employment, stigma, and overall quality of life. The above factors contribute toward SIB in these patients. Behavioral problems occurring in people with epilepsy can range from aggressiveness, mood fluctuations to SIB. We report a 23-year-old male, married, educated up to 10 th standard, referred from neurology department for psychiatric evaluation. The patient had gone to neurologist with the chief complaints of generalized tonic-clonic convulsions and was hospitalized for breakthrough seizure. There was a history of indulging in episodes of self-SIB since the past 8 months. He responded satisfactorily to adjustment of antiepileptic medication along with fluoxetine and low-dose risperidone. Early identification of such behavior in epilepsy patients should be done so that a holistic management is undertaken leading to better functioning and improved quality of life., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Industrial Psychiatry Journal.)

The influence of the substrate temperature on pulsed laser deposited (PLD) CoFe 2 O 4 thin films for supercapacitor electrodes was thoroughly investigated. X-ray diffractometry and Raman spectroscopic analyses confirmed the formation of CoFe 2 O 4 phase for films deposited at a substrate temperature of 450 °C. Topography and surface smoothness was measured using atomic force microscopy. We observed that the films deposited at room temperature showed improved electrochemical performance and supercapacitive properties compared to those of films deposited at 450 °C. Specific capacitances of about 777.4 F g -1 and 258.5 F g -1 were obtained for electrodes deposited at RT and 450 °C, respectively, at 0.5 mA cm -2 current density. The CoFe 2 O 4 films deposited at room temperature exhibited an excellent power density (3277 W kg -1 ) and energy density (17 W h kg -1 ). Using electrochemical impedance spectroscopy, the series resistance and charge transfer resistance were found to be 1.1 Ω and 1.5 Ω, respectively. The cyclic stability was increased up to 125% after 1500 cycles due to the increasing electroactive surface of CoFe 2 O 4 along with the fast electron and ion transport at the surface., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Low back pain due to degeneration of intervertebral disc (IVD) is a major health problem resulting in significant disability as well as adding to the economic burden. Discectomy is a very common procedure done worldwide to relieve this pain. At present all the surgically removed disc tissue is mostly discarded. However, there are reports that state that progenitor cells in the IVD can be grown ex vivo and have the potential to be used for IVD repair and regeneration. We report here that viable cells can be harvested from surgically removed, herniated disc tissue and can be potentially used in cell based therapy. Further, we have successfully replaced xenogenic supplements such as foetal bovine serum with either autologous serum or human platelet lysate for culturing IVD cells from patient's surgically removed disc tissue, without loss of any cell characteristics, including cell surface markers, growth factor secretion in the conditioned medium and osteogenic and chondrogenic differentiation potential in vitro . The present work will not only contribute to overcoming some of the major barriers in carrying out human clinical trials, but also provide a cheap, alternate source of proteins and growth factors for growing IVD cells ex vivo for therapy.

Nosocomial infections have become alarming with the increase of multidrug-resistant bacterial strains of Acinetobacter baumannii . Being the causative agent in ~80% of the cases, these pathogenic gram-negative species could be deadly for hospitalized patients, especially in intensive care units utilizing ventilators, urinary catheters, and nasogastric tubes. Primarily infecting an immuno-compromised system, they are resistant to most antibiotics and are the root cause of various types of opportunistic infections including but not limited to septicemia, endocarditis, meningitis, pneumonia, skin, and wound sepsis and even urinary tract infections. Conventional experimental methods including typing, computational methods encompassing comparative genomics, and combined methods of reverse vaccinology and proteomics had been proposed to differentiate and develop vaccines and/or drugs for several outbreak strains. However, identifying proteins suitable enough to be posed as drug targets and/or molecular vaccines against the multidrug-resistant pathogenic bacterial strains has probably remained an open issue to address. In these cases of novel protein identification, the targets either are uncharacterized or have been unable to confer the most coveted protection either in the form of molecular vaccine candidates or as drug targets. Here, we report a strategic approach with the 3,766 proteins from the whole genome of A. baumannii ATCC19606 (AB) to rationally identify plausible candidates and propose them as future molecular vaccine candidates and/or drug targets. Essentially, we started with mapping the vaccine candidates (VaC) and virulence factors (ViF) of A. baumannii strain AYE onto strain ATCC19606 to identify them in the latter. We move on to build small networks of VaC and ViF to conceptualize their position in the network space of the whole genomic protein interactome (GPIN) and rationalize their candidature for drugs and/or molecular vaccines. To this end, we propose new sets of known proteins unearthed from interactome built using key factors, KeF, potent enough to compete with VaC and ViF. Our method is the first of its kind to propose, albeit theoretically, a rational approach to identify crucial proteins and pose them for candidates of vaccines and/or drugs effective enough to combat the deadly pathogenic threats of A. baumannii .

Enterovirus A71 (EV-A71) is an emerging pathogen in the Enterovirus A species group. EV-A71 causes hand, foot and mouth disease (HFMD), with virulent variants exhibiting polio-like acute flaccid paralysis and other central nervous system manifestations. We analysed all enterovirus A71 complete genomes with collection dates from 2008 to mid-2018. All sub-genotypes exhibit a strong molecular clock with omega (dN/dS) suggesting strong purifying selection. In sub-genotypes B5 and C4, positive selection can be detected at two surface sites on the VP1 protein, also detected in positive selection studies performed prior to 2008. Toggling of a limited repertoire of amino acids at these positively selected residues over the last decade suggests that EV-A71 may be undergoing a sustained frequency-dependent selection process for immune evasion, raising issues for vaccine development. These same sites have also been previously implicated in virus-host binding and strain-associated severity of HFMD, suggesting that immune evasion may be an indirect driver for virulence (154 words).

Background: Rheumatic mitral stenosis (MS) is a significant cause of morbidity and mortality in India. Percutaneous transvenous mitral commissurotomy (PTMC) has become the procedure of choice for severe MS with pliable leaflets. Despite a wealth of literature on the technical aspects of PTMC, there is a dearth of literature addressing the impact of PTMC on the quality of life (QOL)., Aim: The aim of the study is to assess the impact of PTMC on clinical status and QOL of patients with severe MS., Materials and Methods: Twenty-five consecutive patients with severe MS undergoing PTMC were included in the study with their informed consent. All patients were subjected to routine blood tests, electrocardiogram, chest X-ray, two-dimensional and color echocardiography, treadmill test (TMT), and World Health Organization (WHO) QOL scale. The echocardiography, TMT, and WHOQOL scale were repeated after the procedure., Results: The procedural success was 98%. The mean (range) mitral valve area preprocedure was 0.82 (0.59-0.92) cm 2 and postprocedure was 1.61 (1.51-1.76) cm 2 . The difference was statistically significant ( t = 5.02; P < 0.01). The mean (range) of TMT preprocedure was 4.05 (3.0-7.0) METS and postprocedure was 8.52 (6-12) METS. The difference was statistically significant ( T = 3.08; P < 0.01). The mean (range) of QOL assessment pre- and post-procedure on physical domain was 8.83 (8.3-10.1) which increased to 11.11 (10-12.7); on social relationship domain from 9.17 (7.5-12.4) to 11.37 (9.4-12.0); on personal relationship from 11.6 (11-13) to 12.52 (12-13); on environment domain from 10.78 (10.2-11.7) to 11.56 (10.8-12); and on level of independence from 9.02 (8-10) to 12.29 (11.0-13.6). All the differences were statistically significant (Wilcoxon signed-rank test z = -4.376; -4.379; -4.234; -4.200; -4.375; respectively, all P < 0.001 highly significant)., Conclusions: PTMC resulted in a significant improvement in the QOL of patients with severe MS. The significant improvement in QOL post-PTMC may be an indication for offering PTMC at an earlier stage to those patients whose QOL is severely compromised., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Industrial Psychiatry Journal.)

Over recent years, typhoid fever has gained increasing attention with several cases reporting treatment failure due to multidrug resistant (MDR) strains of Salmonella enterica serovar Typhi. While new drug development strategies are being devised to combat the threat posed by these MDR pathogens, drug repurposing or repositioning has become a good alternative. The latter is considered mainly due to its capacity for saving sufficient time and effort for pre-clinical and optimization studies. Owing to the possibility of an unsuccessful repositioning, due to the mismatch in the optimization of the drug ligand for the changed biochemical properties of "old" and "new" targets, we have chosen a "targeted" approach of adopting a combined chemical moiety-based drug repurposing. Using small molecules selected from a combination of earlier approved drugs having phenalenone and furanone moieties, we have computationally delineated a step-wise approach to drug design against MDR Salmonella . We utilized our network analysis-based pre-identified, essential chaperone protein, SicA, which regulates the folding and quality of several secretory proteins including the Hsp70 chaperone, SigE. To this end, another crucial chaperone protein, Hsp70 DnaK, was also considered due to its importance for pathogen survival under the stress conditions typically encountered during antibiotic therapies. These were docked with the 19 marketed anti-typhoid drugs along with two phenalenone-furanone derivatives, 15 non-related drugs which showed 70% similarity to phenalenone and furanone derivatives and other analogous small molecules. Furthermore, molecular dynamics simulation studies were performed to check the stability of the protein-drug complexes. Our results showed the best binding interaction and stability, under the parameters of a virtual human body environment, with XR770, a phenaleno-furanone moiety based derivative. We therefore propose XR770, for repurposing for therapeutic intervention against emerging and significant drug resistance conferred by pathogenic Salmonella strains.

Catheter-associated urinary tract infections (CAUTI) is an alarming hospital based disease with the increase of multidrug resistance (MDR) strains of Proteus mirabilis . Cases of long term hospitalized patients with multiple episodes of antibiotic treatments along with urinary tract obstruction and/or undergoing catheterization have been reported to be associated with CAUTI. The cases are complicated due to the opportunist approach of the pathogen having robust swimming and swarming capability. The latter giving rise to biofilms and probably inducible through autoinducers make the scenario quite complex. High prevalence of long-term hospital based CAUTI for patients along with moderate percentage of morbidity, cropping from ignorance about drug usage and failure to cure due to MDR, necessitates an immediate intervention strategy effective enough to combat the deadly disease. Several reports and reviews focus on revealing the important genes and proteins, essential to tackle CAUTI caused by P. mirabilis . Despite longitudinal countrywide studies and methodical strategies to circumvent the issues, effective means of unearthing the most indispensable proteins to target for therapeutic uses have been meager. Here, we report a strategic approach for identifying the most indispensable proteins from the genome of P. mirabilis strain HI4320, besides comparing the interactomes comprising the autoinducer-2 (AI-2) biosynthetic pathway along with other proteins involved in biofilm formation and responsible for virulence. Essentially, we have adopted a theoretical network model based approach to construct a set of small protein interaction networks (SPINs) along with the whole genome (GPIN) to computationally identify the crucial proteins involved in the phenomenon of quorum sensing (QS) and biofilm formation and thus, could be therapeutically targeted to fight out the MDR threats to antibiotics of P. mirabilis . Our approach utilizes the functional modularity coupled with k-core analysis and centrality scores of eigenvector as a measure to address the pressing issues.

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

Lung cancer being the most common disease worldwide that leads to a number of deaths. A huge amount of effort has been done in screening trials for early diagnose treatment which increases the disease-free survival rate. Based on the expression of protein of mouse double minute 2 and tumor protein 53 complex, we have identified the antagonist for this complex that would facilitate the treatment for specific lung cancer. It is a complex disease that involves vast investigation for the characterization of a lung cancer and thus, computational study is being developed to mimic the in vivo system. In this work, a computational process was employed for the identification of these proteins, with a short and simple method to discover protein-protein interactions. Moreover, these proteins have more similarities in their function with the known cancer proteins as compared to those identified from the protein expression specific profiles. A new method that utilizes experimental information to improve the extent of numerical calculations based on free energy profiles from molecular dynamics simulation. The experimental information guides the simulation along relevant pathways and decreases overall computational time. This method introduces umbrella sampling simulations. A new technique umbrella sampling is described where the high efficacy100 of this technique enables uniform sampling with several degrees of freedom. Here, we review the protein interactions techniques and we focus on main concepts in the molecular of in-silico study in lung cancer. This study recruiting new methods proved the efficiency and showed good results.