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Short nucleotide sequences like miRNA and siRNA have attracted a lot of interest in Oral-biome investigations. miRNA is a small class of non-coding RNA that regulates gene expression to provide effective regulation of post-transcription. On contrary, siRNA is 21-25 nucleotide dsRNA impairing gene function post-transcriptionally through inhibition of mRNA for homologous dependent gene silencing. This review highlights the application of miRNA in oral biome including oral cancer, dental implants, periodontal diseases, gingival fibroblasts, oral submucous fibrosis, radiation-induced oral mucositis, dental Pulp, and oral lichenoid disease. Moreover, we have also discussed the application of siRNA against the aforementioned disease along with the impact of miRNA and siRNA to the various pathways and molecular effectors pertaining to the dental diseases. The influence of upregulation and downregulation of molecular effector post-treatment with miRNA and siRNA and their impact on the clinical setting has been elucidated. Thus, the mentioned details on application of miRNA and siRNA will provide a novel gateway to the scholars to not only mitigate the long-lasting issue in dentistry but also develop new theragnostic approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Tissue engineering (TE) employs scaffolds as a structural support for initially seeding of cells followed by development of new tissues. Electrospun scaffolds generally function as a template of native extracellular matrix (ECM). The chemical composition of the scaffold and its surface morphology strongly influence the interaction between various cell types and materials. In this work, PCL and PCL/HPMC-based composite membranes with varying concentrations of HPMC (20-30% by weight) were fabricated using electrospinning technique. The membranes were evaluated for their surface, physio-chemical and biological properties. It was observed probably for the first time that blending of HPMC with PCL produced super-hydrophilic scaffolds. DSC studies confirmed the semi- crystalline nature of HPMC. PCL/HPMC composite scaffolds are found biocompatible from cytotoxicity assay. From the cell culture studies (apoptosis), PCL/HPMC composite scaffolds did not inhibit the adhesion of L929 cells due to their super-hydrophilic nature. The cell adhesion and spreading varied with HPMC concentration. PCL/HPMC (70/30) membranes showed highest cell adhesion among others due to its porous structure., (© 2022. The Author(s), under exclusive licence to Islamic Azad University.)

Background: SARS-CoV-2 infection that led to the COVID-19 pandemic has changed human health and the economy globally. SARS CoV-2 is a type of Coronaviruses that has caused pneumonia and its complications with many deaths over the past two years. The use of hydroxychloroquine and chloroquine, accepted as generally safe for patients with autoimmune diseases or malaria, was attempted in many trials for COVID-19 treatment. Nigella sativa (NS) (black caraway, also known as black cumin, nigella or Kalonji) is an annual flowering plant of the Ranunculaceae family, chemically composed of the main constituent natural Thymoquinone (TQ) (30%- 48%) in forms of thymohydroquinone, dithymoquinone (Nigellone) is a native to wider regions, including parts of eastern Europe, west Asia, North of Africa and east of Myanmar. In this review, we explored the Randomized Controlled Trial, Controlled Trial, and Systematic review studies that support Nigella sativa Thymoquinone-targeted SARS-CoV-2 targeting. Therefore, A literature search was performed for publications published on the electronic databases (PubMed, Embase, Scopus, CNKI, and Google Scholar) for Nigella sativa, black seeds, Kalonji, coronavirus, SARS-CoV -2 and COVID-19. This review aimed to find relevant evidence of Nigella sativa preferences as a natural feasible remedy with no side effects in COVID-19. Studies reported the benefits of NS as beneficial, another appropriate remedy for patients with COVID-19. However, all studies have shown limitations, such as limiting clinical symptom outcomes due to regulations imposed by isolation policies and lack of adequate funding. Therefore, the evidence suggests that the chemical contents of NS are a safe and possible treatment for COVID-19 patients that helps to improve COVID-19 infection in patients with no side effects., Conclusion: Nigella sativa seeds were one of the well-documented herbal products. Three reviewed randomized controlled trials reported that NS reduced covid-19 risk and could improve immune function. It was also helpful in upper respiratory infections such as asthma and bronchitis, with one RCT showing that honey and NS significantly improved symptoms, viral clearance, and mortality of COVID-19 patients. This review concludes that NS has a positive barrier effect on people at risk of acquiring a COVID-19 infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Coronavirus disease 2019 (COVID-19) pandemic unmasked the huge deficit in healthcare resources worldwide. It highlighted the need for efficient risk stratification in management of cardiovascular emergencies., Aim: To study the applicability of the old, available and affordable nonconventional biomarkers: albumin and fibrinogen in their ability to predict angiographic severity and clinical outcomes in patients with acute coronary syndrome (ACS)., Methods: In this prospective, observational study, 166 consecutive patients with ACS were enrolled. Fibrinogen, albumin and their ratio were determined from serum. Patients with underlying chronic liver disease, active malignancy, autoimmune disease, active COVID-19 infection and undergoing thrombolysis were excluded., Results: Mean age of the population was 60.5 ± 1.5 years, 74.1% being males. ST elevation myocardial infarction (STEMI) was most common presentation of ACS seen in 57% patients. Fibrinogen albumin ratio (FAR) ≥ 19.2, had a sensitivity of 76.9% and specificity of 78.9 % [area under the receiver operating characteristic curves (AUROC) = 0.8, P = 0.001] to predict ≤ thrombolysis in myocardial infarction (TIMI) 1 flow in culprit artery in STEMI patients. Even in non-STEMI patients, FAR ≥ 18.85 predicted the same with 80% sensitivity and 63% specificity (AUROC = 0.715, P = 0.006)., Conclusion: Novel biomarkers, with their high cost, lack of availability and long turn over time are impractical for real-world use. Identifying ≤ TIMI 1 flow in the culprit artery has significant impact of management and outcome. Our study has shown that readily available biomarkers like fibrinogen and albumin can help identify these high-risk patients with good accuracy. This allows risk-stratification and individualization of treatment in ACS., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Nanoscience has emerged as a fascinating field of science, with its implementation in multiple applications in the form of nanotechnology. Nanotechnology has recently been more impactful in diverse sectors such as the pharmaceutical industry, agriculture sector, and food market. The peculiar properties which make nanoparticles as an asset are their large surface area and their size, which ranges between 1 and 100 nanometers (nm). Various technologies, such as chemical and biological processes, are being used to synthesize nanoparticles. The green chemistry route has become extremely popular due to its use in the synthesis of nanoparticles. Nanomaterials are versatile and impactful in different day to day applications, resulting in their increased utilization and distribution in human cells, tissues, and organs. Owing to the deployment of nanoparticles at a high demand, the need to produce nanoparticles has raised concerns regarding environmentally friendly processes. These processes are meant to produce nanomaterials with improved physiochemical properties that can have significant uses in the fields of medicine, physics, and biochemistry. Among a plethora of nanomaterials, silver nanoparticles have emerged as the most investigated and used nanoparticle. Silver nanoparticles (AgNPs) have become vital entities of study due to their distinctive properties which the scientific society aims to investigate the uses of. The current review addresses the modern expansion of AgNP synthesis, characterization, and mechanism, as well as global applications of AgNPs and their limitations.

Metal-Organic Frameworks (MOFs), a class of inorganic-organic hybrid materials, have been at the center of material science for the past three decades. They are synthesized by metal ions and organic linker precursors and have become very potential materials for different applications ranging from sensing, separation, catalytic behaviour to biomedical applications and drug delivery, owing to their structural flexibility, porosity and functionality. They are also very promising in heterogeneous catalysis for various industrial applications. These catalysts can be easily synthesized with extremely high surface areas, tunable pore sizes, and incorporation of catalytic centers via post-synthetic modification (PSM) or exchange of their components as compared to traditional heterogeneous catalysts, which is the preliminary requirement of a better catalyst. Here, in this review, we have presented the history of MOFs, different synthesis procedures, and MOFcatalysed reactions; for instance, coupling reactions, condensation reactions, Friedel-Crafts reaction, oxidation, etc. Special attention has been given to MOFs containing different catalytic centers, including open metal sites, incorporation of catalytic centers through PSM, and bifunctional acidbase sites. The important role of catalytic centers present in MOFs and reaction mechanisms have also been outlined with examples., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Older children and adults with spinal muscular atrophy (SMA) have been shown to have more anxiety, depression, and other behavioral problems in a few studies. But no similar studies have been performed in infants and young children with SMA., Method: Behavioral co-morbidities of young children with SMA were compared with healthy and children with chronic non-neurological illness control group. Infant Behavior Questionnaire-Revised (IBQ-R) and parent-report version of chid behavior checklist (CBCL) were used for infants and preschool-age children respectively., Results: A total of 35 SMA children (age at symptom onset-5.9 ± 2.8 months, at enrolment-21.4 ± 7.1 months, 65% boys, 11, 19 and 5 were SMA 1, 2 and 3 respectively) and 24 siblings (38.6 ± 11.2 months, 71% boys) were enrolled. We also enrolled 15 children with nephrotic syndrome as age and gender matched control to SMA children in age-group 2-5 years (27.7 ± 9.1 months, 67% boys). In infants with SMA, the scale scores of IBQ-R were significantly higher for distress to limitation, fear, sadness, and falling reactivity/rate of recovery from distress (p = 0.005; 0.03; 0.001, and 0.04) and lower for soothability as compared to healthy control group (p = 0.04). Similarly, for the three dimensions of temperament computed from these 13 domains, the mean scale score for surgency/extraversion was lower and negative affectivity was higher (p = 0.04 and 0.03), in infants with SMA as compared to healthy controls. For preschool age group, the internalizing problem scores (p = 0.009 and 0.03) and stress problem scores (p = 0.002 and 0.04) were higher in the SMA group, as compared to both the healthy control group and diseased control group. While assessing the syndrome scale scores, the score was higher for emotionally reactive (p = 0.0002 and 0.01) and anxious domains (p < 0.0001 and p = 0.0002) compared to both healthy and diseased control groups., Conclusion: Infants and young children with SMA suffer from increased internalizing problems like anxiety, depression and probably their healthy siblings are also at increased levels of stress, depicted by increased somatic complaints., Competing Interests: Declaration of competing interest None., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Convalescent plasma has been used to provide passive immunotherapy to patients with COVID-19 with a high level of safety. Very few efficacy studies were available, and due to COVID being a relatively new disease, its exact therapeutic role was unclear. This observational study on the impact of COVID convalescent plasma (CCP) on clinical outcomes attempts to evaluate the effectiveness of convalescent COVID-19 plasma therapy in the treatment of COVID-19 patients at the tertiary care center in the Uttarakhand state of India., Methods: CCP was collected by plasmapheresis/whole blood from willing COVIDrecovered donors who underwent pre-donation testing including ABO and RhD grouping, mandatory blood screening tests for HIV, HBV, HCV, syphilis and Malaria, Haemoglobin estimation and COVID IgG assay. Hospitalized patients with severe COVID-19 pneumonia who received these CCP units were followed up and the outcome (Recovery/death) was observed., Results: A total of 63 patients who received CCP were included in the study. Out of the total, 13 (20.7%) were females and 50 (79.3%) were males and their ages ranged from 24 to 80 years with a median age of 53 years. The period between the start of symptoms and hospitalization ranged from 1 to 14 days with an average duration of 4.7 days. Symptoms on presentation included Fever 53/63 (84.1%), Tachypnoea 60/63 (95.2%) and Cough 42/63 (66.7%). Among these patients, 22/63 (34.9%) were on non-invasive ventilation (NIV), 6/63 (9.5%) on non-rebreather mask (NRBM) and 32/63 (50.8%) were on Ventilator support. The infused convalescent plasma had a Mean IgG value of 57.3 AU with a range of (10-142 AU). A total of 37 (58.7%) patients were lost to COVID-19 infection and 26 (41.3%) were discharged from the hospital in a healthy state., Conclusion: The use of convalescent plasma in addition to standard treatment in our study on patients with severe pneumonia due to COVID-19 did not demonstrate reduced mortality of COVID-19 patients amidst numerous variables. The results showed that the use of convalescent plasma as a treatment option in the present conditions needs a serious re-evaluation. Studies on a strictly defined recipient group and transfusion of CCP units, with adequate antibody titer and/or neutralization activity, must be analyzed for future works., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: This study aims to compare the cost-effectiveness of oral prednisolone and adrenocorticotropic hormone injection in West syndrome patients, the two most common hormonal therapies used for this condition., Materials and Methods: In this prospective and observational study, we documented sociodemographic, epilepsy, and development-related variables at baseline and up to 6 months after starting hormonal therapy, in all consecutive eligible patients of WS between August 2019 and June 2021, apart from the direct medical and non-medical costs and indirect health-care costs. We selected cost per quality-adjusted life-year (QALY) gained, per one patient with spasm freedom, one positive responder (>50% reduction in spasms), one relapse-free patient, and one patient with development gain. We determined whether incremental cost-effectiveness ratio for these parameters crossed the threshold value in base-case analysis and alternate scenario analysis., Results: Out of 52 patients screened, 38 and 13 patients enrolled in ACTH and prednisolone group. On D28, 76% and 71% achieved spasm cessation ( P = 0.78) and the total cost of treatment was INR 19783 and 8956 ( P = 0.01), in ACTH and prednisolone group respectively. For all pre-specified parameters, the cost/effectiveness ratios including cost/QALY gain were higher in ACTH group and the corresponding ICER values for all these parameters crossed the threshold cost value of INR 148,777 in base-case analysis and also in alternative scenario analysis., Conclusion: Treatment with oral prednisolone is more cost-effective as compared to ACTH injection for children with WS., Competing Interests: There are no conflicts of interest., (© 2023 Published by Scientific Scholar on behalf of Journal of Neurosciences in Rural Practice.)

Introduction: The clinical assessment scale for autoimmune encephalitis (CASE) is a recently developed and validated scale to rate the severity of autoimmune encephalitis (AE) in adults. But it is yet to be validated in pediatric AE cases., Methods: In a prospective observational study, we determined the validity and prognostic utility of CASE in the pediatric population with a diagnosis of probable or definite AE. We also determined clinical, neuroimaging, or laboratory-based prognostic factors for favorable clinical outcomes at 3 months after presentation. We used weighted kappa statistics and the intra-class correlation coefficient of individual item scores and total scores for determining inter-observer and intra-observer reliability respectively., Results: We enrolled a total of 54 patients (28 girls, probable [45%] or definite [55%] AE). Functional status score (FSS), CASE score, and other scores showed significant improvement at the time of discharge and 3-months, as compared to baseline (p < 0.0001). The intra-observer and interobserver reliability of the total scores was excellent (k = 0.94 and 0.95 respectively). CASE was also found to have good internal consistency (Cronbach-α = 0.83). The corrected item-total correlations of all items were >0.40. The correlation between the total CASE score and FSS score at admission, at discharge, and at 3 months was strong (r = 0.90, 0.92, and 0.94, p < 0.001). In multivariate analysis, only seropositivity or definite AE and CASE score at baseline was found to be significant predictive factors for functional status at 3 months (p = 0.03, 0.01)., Conclusion: CASE score can be used for monitoring the severity of pediatric AE patients. It also has prognostic usefulness for predicting functional independence on follow-up., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Covid 19 pandemic has severe implications on health and life of people. Asia being the most populous region has higher fatalities burden. Health infrastructure, stringent preventive measures by the government and public participation through adhering to social distancing have influence to check on fatalities' burden. The level of Social capital as well as voters' participation in a particular country can have influence on containment of COVID cases and fatalities. In this context, the main objectives of this study are to analyse pattern and trend of death burden for 45 Asian countries and impact of stringency measures by government, and voters' turnout ratio on death burden. However, for regression analysis only 32 countries are taken into account considering the availability of data for all variables. Multiple linear regression analysis is employed in a cross-sectional framework and Ordinary least square estimation technique with heteroscedastic adjusted standard errors have been used for estimation of coefficients. The results show that southern Asia contributes the highest share of fatality cases in total fatality cases of Asia with 71.43% share. It also has the highest share of confirmed cases in total confirmed cases of Asia with 71.72%. However, when we take the population into account, Western Asia leads in the share of confirmed COVID-19 cases and its associated fatality cases per million populations in Asia as compared to other Asian regions. The factors like health infrastructure and voters' turnover ratio are found to be significant and potential in reducing the new deaths per million populations. Though the coefficient of Stringency index has been negative and it did not emerge to be significant in Asian countries. The COVID related fatalities in Asian region are urban centric and urbanization proxy is found to be positive and significant. Diabetes prevalence rate has some heterogeneous result and in the present study its coefficient is not in the hypothesized direction. . The Countries should ramp up health infrastructure and necessary preparedness to deal with the subsequent waves and COVID related fatalities. Importance need to be given people's participation and their shared responsibilities in dealing with COVID cases and checking on fatalities. The realisation of social responsibility among the masses can lead to community participation and adhering to the protocols imposed by the government and helps in checking on spread of virus and associated death., (© 2022 The Author(s).)

Owing to its biodegradability, non-toxicity, and biocompatibility, chitosan (Cs) is a ubiquitous biopolymer. However, applications of Cs are limited owing to the existence of strong inter- and intra-molecular hydrogen bonds within its network. To address this issue, we regenerated medium-molecular-weight Cs to enhance the physico-chemical and functional properties using a cationic approach. Accordingly, alkaline modification was employed to introduce an additional positive charge to the amine functional groups of Cs and moderately disintegrate the inter- and intra-hydrogen bonds. The chemical structure of Cs and regenerated chitosan (RCs) was confirmed through Fourier transform infrared and 1 H-NMR spectroscopy. RCs showed higher zeta potential value compared to Cs. Additionally, using X-ray diffraction, RCs exhibited low crystallinity, which can be attributed to the repulsive force caused by the positive surface charge and the destruction of hydrogen bonds. The RCs exhibited stronger antioxidant activity than Cs. Furthermore, the minimum inhibition concentrations (MICs) of RCs against Escherichia coli and Staphylococcus aureus were reduced by almost four times compared with those of Cs. The superior functional properties of RCs can be attributed to the formation of a polycationic structure after alkaline modification. Thus, RCs can be introduced as potent agents for various biomedical purposes.

Two novel classes of reduced triphyrin(2.1.1), namely, triphachlorin and triphabacteriochlorin, are realized via selective reduction of the newly synthesized 7,12-bis(trifluoromethyl)triphyrin(2.1.1) 1 using p -tosylhydrazide. Triphachlorin 2 displayed red-shifted absorption (580 nm). Harsher conditions, however, led to a unique direct detrifluoromethylation of one CF 3 moiety to form two isomeric triphabacteriochlorins 3 and 4 , which exhibit blue-shifted intense lowest-energy absorption bands and intense emission (ϕ f = 0.52 and 0.36, respectively) while generating singlet oxygen very efficiently (ϕ Δ = 0.88 and 0.86, respectively). These reduced porphyrinoids show very high oxidative stability as they remain unchanged upon refluxing with 2,3-dichloro-5,6-dicyanobenzoquinone in toluene.

Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: In adult patients with epilepsy, predictive models have been developed and validated for anticipating a favorable response to immunotherapy. However, no such model has been evaluated in children., Methods: This retrospective cohort study intended to assess the performance of a pediatric adaptation of the Response to Immunotherapy in Epilepsy (RITE 2 ) score: P-RITE 2 score and Antibody Prevalence in Epilepsy (APE 2 ) score: P-APE 2 score in patients aged 1-18 years. We included data of those patients who had epilepsy duration of not more than 12 months, no other known etiology (e.g., genetic, metabolic, neoplastic, or structural causes), and tested for neural-specific antibody in cerebrospinal fluid or serum for P-APE 2 score and only those who received immunotherapy for P-RITE 2 score. We added cognitive dysfunction, speech dysfunction, sleep disturbance, and movement disorder to the original scores to increase specificity for pediatric autoimmune epilepsy. We assumed at least a 50% reduction in seizure frequency at 6 months as a favorable response to immunotherapy. Cut-offs were chosen for both scores to maximize true positives and minimize false negatives using ROC curves., Results: We included data from a total of 237 patients with epilepsy (10.4 ± 2.5 years, 129 boys, 54%), out of which, 25 (10.5%, 13 girls, 52%) tested positive for autoantibodies. The median P-APE 2 score in the subgroup with and without antibody positivity were 7 (IQR: 5-11) and 2 (IQR: 1-5), respectively (p<0.0001). ROC analysis of the P-APE 2 score determined an AUC of 0.96. The sensitivity and specificity values of the P-APE 2 score ≥6 were 94% and 92%, respectively. A total of 162 patients (10.3 ± 2.5 years, 88 boys, 54%) received immunotherapy, out of which, 101 had a favorable response at 6 months. The median P-RITE 2 score in the subgroup with and without favorable response following a trial of immunotherapy were 10 (IQR: 6-17) and 3 (IQR: 1-6), respectively (p<0.0001). ROC analysis of the P-RITE 2 score determined an AUC of 0.96. The sensitivity and specificity values of P-RITE 2 score ≥8 were 95% and 93%, respectively. The AUC of both these ROCs was significantly higher than the AUC of ROCs for original scores in our cohort., Conclusion: The P-RITE 2 and P-APE 2 scores can be used to predict the response to immunotherapy and predict autoantibody positivity in children with epilepsy with/without encephalopathy or cognitive dysfunction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Selumetinib is a MEK inhibitor, which is effective with an acceptable safety profile in reducing the volume of symptomatic inoperable plexiform neurofibromas in some clinical trials and also has been recently approved by FDA for use in children aged 2 years or older. However, no systematic review has yet been performed to provide a collective estimate of the results of all these trials., Evidence Acquisition: Articles describing the use of selumetinib in patients with neurofibromatosis type-1 (NF1) with inoperable plexiform neurofibromas were searched from different electronic databases. The objectives were to provide a pooled estimate of efficacy evaluated by direct measurement and also by various functional measures, as well as the proportion of patients with adverse events. For determining pooled estimates, we included only studies with a minimum sample size of 15 with a prospective study design., Evidence Synthesis: A total of eight articles with 137 patients were found and 134 patients in six uncontrolled trials were included in the quantitative review. Out of these 26 were adults (69% male; 33.2±18.4 years, range 18-60 years) and 108 were in the pediatric age group (74% boys, 10.9±2.3 years, range-2-18 years,). Total 77.86% (95% CI: 55.91-99.81%) patients had a partial response, 71.24% (95% CI: 53.62-89.93%) had a confirmed partial response, and 56.25% (95% CI: 37.53-72.49%) had a durable partial response. The average time to initial response was 7.3±2.9 cycles (range, 4 to 20), and the median time to best response was 15.4±5.8 cycles (range, 4 to 36). The average change in neurofibroma volume at best response was -28.15% (95% CI: -17.95%, -38.34%, range, -55.1% to 2.2%). Progression-free survival was observed in 93.12% of patients at the time of data cut-off. Overall, 73.26% (95% CI: 54.07%, 92.45%) patients had improvement in at least one of the functional or patient-reported outcome assessments. The most common adverse effects were grade 1 and 2 gastrointestinal symptoms (65%), an asymptomatic increase in the creatine phosphokinase level (31%), paronychia (6%), and acneiform rash (17%). A total of 17% patients required dose reduction due to these toxic effects and 10.5% (95% CI: 4.0%, 17.0%) of patients discontinued due to toxic effects., Conclusions: Selumetinib can produce sustained shrinkage in the majority of patients with NF1 and symptomatic plexiform neurofibroma to provide clinically meaningful benefit in functional ability, with more robust evidence in children. The acceptable safety profile and absence of cumulative toxic effects permit long-term treatment with selumetinib.

Phage Tail Like bacteriocins (PTLBs) has been an area of interest in the last couple of years owing to their varied application against multi-drug resistant (MDR), anti-microbial resistant (AMR) pathogens and their evolutionary link with the dsDNA virus and bacteriophages. PTLBs are defective phages derived from Myoviridae and Siphoviridae phages, PTLBs are distinguished into R-type (Rigid type) characterized by a non-flexible contractile nanotube resembling Myoviridae phage contractile tails, and F-type (Flexible type) with a flexible non-contractile rod-like structure similar to Siphoviridae phages. In this review, we have discussed the structural association, mechanism, and characterization of PTLBs. Moreover, we have elucidated the symbiotic biological function and application of PTLBs against MDR and XDR pathogens and highlighted the evolutionary role of PTLBs. The difficulties that must be overcome to implement PTLBs clinically are also discussed. It is imperative that these issues be addressed by academics in future studies before being implemented in clinical settings. This article is novel in its way as it will not only provide us with a gateway that acts as a novel strategy for scholars to mitigate and control the uprising issue of AMR pathogens but also promote the development of clinical studies for PTLBs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest There is no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The lncRNA GAS5 acts as a tumor suppressor and is downregulated in gastric cancer (GC). In contrast, E2F1, an important transcription factor and tumor promoter, directly inhibits miR-34c expression in GC cell lines. Furthermore, in the corresponding GC cell lines, lncRNA GAS5 directly targets E2F1. However, lncRNA GAS5 and miR-34c remain to be studied in conjunction with GC. Here, we present a dynamic Boolean network to classify gene regulation between these two non-coding RNAs (ncRNAs) in GC. This is the first study to show that lncRNA GAS5 can positively regulate miR-34c in GC through a previously unknown molecular pathway coupling lncRNA/miRNA. We compared our network to several in-vivo/in-vitro experiments and obtained an excellent agreement. We revealed that lncRNA GAS5 regulates miR-34c by targeting E2F1. Additionally, we found that lncRNA GAS5, independently of p53, inhibits GC proliferation through the ATM/p38 MAPK signaling pathway. Accordingly, our results support that E2F1 is an engaging target of drug development in tumor growth and aggressive proliferation of GC, and favorable results can be achieved through tumor suppressor lncRNA GAS5/miR-34c axis in GC. Thus, our findings unlock a new avenue for GC treatment in response to DNA damage by these ncRNAs., (© 2022. The Author(s).)

COVID-19 has caused devastating effects worldwide ever since its origin in December 2019. IL-6 is one of the chief markers used in the management of COVID-19. We conducted a longitudinal study to investigate the role of IL-6 in diagnosis, treatment, and prognosis of COVID-19-related cytokine storm. Patients with COVID-19 who were admitted at AIIMS Rishikesh from March to December 2020 were included in the study. Patients with no baseline IL-6 value at admission and for whom clinical data were not available were excluded. Clinical and laboratory data of these patients were collected from the e-hospital portal and entered in an excel sheet. Correlation was seen with other inflammatory markers and outcomes were assessed using MS Excel 2010 and SPSS software. A total of 131 patients were included in the study. Of these, 74.8% were males, with mean age 55.03 ± 13.57 years, and mean duration from symptom onset being 6.69 ± 6.3 days. A total of 82.4% had WHO severe category COVID-19, with 46.56% having severe hypoxia at presentation and 61.8% of them having some comorbidity. Spearman rank correlation coefficient of IL-6 with D-dimer was 0.203, with LDH was -0.005, with ferritin was 0.3, and with uric acid was 0.123. A total of 11 patients received Tocilizumab at a mean duration from symptom onset of 18.09 days, and 100% mortality was observed. Deaths were reported more in the group with IL-6 ≥ 40 pg/mL (57.1% vs. 40.2%, p = 0.06). ICU admissions and ventilator requirement were higher in the IL-6 ≥ 40 pg/mL group (95.9% vs. 91.4%, p = 0.32 and 55.1% vs. 37.8%, p = 0.05). The study showed that IL-6 can be used as a possible "thrombotic cytokine marker". Higher values of IL-6 (≥40 pg/mL) are associated with more deaths, ICU admissions, and ventilator requirement.

Recently nanotechnology has evolved as one of the most revolutionary technologies in the world. It has now become a multi-trillion-dollar business that covers the production of physical, chemical, and biological systems at scales ranging from atomic and molecular levels to a wide range of industrial applications, such as electronics, medicine, and cosmetics. Nanobiomaterials synthesis are promising approaches produced from various biological elements be it plants, bacteria, peptides, nucleic acids, etc. Owing to the better biocompatibility and biological approach of synthesis, they have gained immense attention in the biomedical field. Moreover, due to their scaled-down sized property, nanobiomaterials exhibit remarkable features which make them the potential candidate for different domains of tissue engineering, materials science, pharmacology, biosensors, etc. Miscellaneous characterization techniques have been utilized for the characterization of nanobiomaterials. Currently, the commercial transition of nanotechnology from the research level to the industrial level in the form of nano-scaffolds, implants, and biosensors is stimulating the whole biomedical field starting from bio-mimetic nacres to 3D printing, multiple nanofibers like silk fibers functionalizing as drug delivery systems and in cancer therapy. The contribution of single quantum dot nanoparticles in biological tagging typically in the discipline of genomics and proteomics is noteworthy. This review focuses on the diverse emerging applications of Nanobiomaterials and their mechanistic advancements owing to their physiochemical properties leading to the growth of industries on different biomedical measures. Alongside the implementation of such nanobiomaterials in several drug and gene delivery approaches, optical coding, photodynamic cancer therapy, and vapor sensing have been elaborately discussed in this review. Different parameters based on current challenges and future perspectives are also discussed here., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Only a few studies have explored prognostic factors for tuberculous meningitis (TBM) in children, and an easily applicable bedside prognostic score for TBM has not been developed yet. We compared the sociodemographic, clinical, radiological, and cerebrospinal fluid parameters in the cohort of 94 TBM cases aged 1 to 18 years, with at least 6 months of completed follow-up and determined the prognostic factors associated with poor functional outcome. We assessed our proposed prognostic model using both discrimination and calibration and subsequently used the bootstrap method to validate the model internally. We finally derived an easily applicable bedside prognostic score by rounding off the regression coefficients to the nearest integers. A total of 39 (41%) and 55 (59%) patients had poor and good functional outcomes, respectively, at the end of 6 months (12 died, 13%). In multivariate analysis, a high baseline Pediatric Cerebral Performance Category (PCPC) score, brain infarction in neuroimaging, tonic motor posturing, younger age, and stage III TBM were independent predictors of poor functional outcomes. The final model showed good discrimination (area under the curve = 88.2%, P < 0.001) and good calibration (Hosmer-Lemeshow test, P = 0.53). Bootstrapping also confirmed the internal validity of this model. The PITAS (PCPC score [P], brain infarction in neuroimaging [I], tonic motor posturing [T], age [A], and stage of TBM [S]) score developed from this model has a score ranging from 0 to 12, with a higher score predicting a higher risk of poor functional outcome. The PITAS score performed better than medical research council staging alone in predicting poor functional outcomes (area under the curve = 87.1% versus 82.3%). Our study's PITAS score, developed and internally validated, has good sensitivity and specificity in predicting poor functional outcomes in pediatric TBM cases at 6 months.

Background: The old definitions of fever are based on cross-sectional surveys of the population without analyzing the associated symptomatology as fever is a sign, not symptom. Therefore, a longitudinal follow-up study is the need of hour to analyze associated symptoms with fever., Methods: In a longitudinal study over one year, 196 participants recorded three temperature readings daily, one after waking up, one between 12 and 3 PM, one before sleeping, and filled the symptomatology questionnaire in a thermometry diary., Results: Per protocol analysis was done for febrile participants (n = 144). Fatigue (50.3%), warmth (47.3%), headache/head heaviness (47.0%), feeling malaise/general weakness (46.7%), loss of appetite (46.5%), muscle cramps/muscle aches (45.6%), chills/shivering (44.6%), increased sweating (43.0%), nausea (42.5%), irritability (38.9%), increased breathing rate (37.1%), and restlessness/anxiety/palpitations (36.5%) were the symptoms maximally seen during the febrile phase. A higher number of associated symptoms are associated with higher temperature readings. Dehydration suggested the numerically highest temperature values (100.86 ± 1.70°F) but seen in few febrile patients., Conclusions: Incorporation of symptom analysis in febrile patients is the need of the hour. Fatigue and warmth are found to be the most prevalent symptoms during febrile phase. Associated symptoms can help in predicting the intensity of fever also., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Objectives: The primary objective of the study was to compare the number of patients with febrile seizure recurrence within 1 year of presenting to our institute, among patients who received and didn't receive oral iron supplementation., Materials and Methods: This prospective intervention study with historical controls was conducted to compare the number of patients with febrile seizure recurrence within 1 year, among patients who received and did not receive oral iron supplementation. The intervention group additionally received prophylactic iron supplementation of 20 mg biweekly for 1 year., Results: A total of 53 patients each were enrolled in both the groups, with comparable baseline characteristics. Although there was a trend toward a lower rate of recurrence of febrile seizures in the interventional group, as compared to the control group, it did not reach the point of statistical significance ( P = 0.35). Both in the worst-case scenario and best-case scenario, there was a trend toward less risk of recurrence of febrile seizure in the intervention group, but it did not reach the point of statistical significance ( P = 0.43 and 0.52). For the original scenario, worst-case scenario, and best-case scenario, the absolute risk reduction was 6.5%, 7%, and 6%, respectively, with corresponding number needed to treat (NNT) being 15, 14, and 16, respectively. The trend for absolute risk reduction was more pronounced in those with complex febrile seizures with an NNT of 6.5, but it still did not reach the point of statistical significance ( P = 0.16). Moderate/severe IDA was also found to be an independent risk factor for recurrence of febrile seizure in the intervention group ( P = 0.03)., Conclusion: Oral serum iron supplementation does not significantly reduce the recurrence rate of febrile seizures in children aged 6-60 months. However, there is a trend toward reduction in the frequency of recurrence of febrile seizures, which is more pronounced in the subset with complex febrile seizures., Competing Interests: There are no conflicts of interest., (© 2022 Published by Scientific Scholar on behalf of Journal of Neurosciences in Rural Practice.)

Introduction: Cluster headache is rare in children and only a few clinical studies have systematically evaluated cluster headache in children. Methods: This study was conducted between August 2019 and December 2021 with the primary aim to evaluate the feasibility and utility of the Cluster Headache Severity Scale in determining the severity of cluster headache in patients aged less than 18 years and monitoring response to prescribed treatment. Secondary objectives were to evaluate the feasibility and utility of Cluster Headache Quality of Life, Cluster Headache Index, and 6-item Headache Impact Test in pediatric cluster headache patients to assess the quality of life, severity, and impact of cluster headache. Results: A total of 32 children (age of onset 11.9 ± 2.3 years, age of diagnosis 13.7 ± 2.4 years, 68% boys) were enrolled. Although 30 cases had their headache episodes occurring during nighttime, only 16 children had a Children's Sleep Habits Questionnaire (CSHQ) score >41 at baseline. All children responded to prednisolone as bridging therapy and 23 of 32 showed adequate pain relief after sumatriptan nasal spray for an acute attack. The average time taken for completion of Cluster Headache Index, Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 scores were 5.2 ± 0.7, 5.1 ± 0.8, 27.4 ± 3.5, and 6.2 ± 0.8 minutes, respectively. The interrater reliability was good for Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 (Cronbach α 0.93, 0.81, and 0.89, respectively). There was a strong positive correlation between the Cluster Headache Severity Scale score with Headache Impact Test-6 score and Cluster Headache Quality of Life score (correlation coefficient r  = 0.90 and 0.98). Conclusion: Majority of pediatric cluster headache patients are likely to respond to prednisolone and sumatriptan. Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 can be used for pediatric cluster headache patients for treatment monitoring.

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs)., Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support., Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30])., Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable., (© 2022. The Author(s).)

Background: This pilot survey aims to provide an insight into the variations of corticosteroid prescription among health care professionals across the Indian subcontinent and serve as a prerequisite for the future development of corticosteroid therapy guidelines in brain tumor patients., Materials and Methods: Participants of this anonymized online questionnaire-based survey included health care professionals involved in treating brain tumor patients. Unique links were electronically mailed to health care professionals from a database populated from professional associations. Descriptive statistical analysis, Chi-square test, and/or exact test were used for data analysis., Results: Seventy-three percent of the respondents were radiation oncologists followed by neurosurgeons (23%), medical oncologists (2%), and other specialties (2%). Raised intracranial pressure (90%) was the commonest indication for prescribing corticosteroids. Fifty percent of neurosurgeons preferred corticosteroids to be given routinely for all patients undergoing surgery for brain tumors while 64% of the radiation oncologists would prescribe based on imaging findings and/or on appearance of neurologic symptoms. Most of the respondents (90%) used a flat dosage pattern for determining the starting dose of corticosteroids. Emerging data about the long-term use of corticosteroids having a negative impact on the survival of brain tumor patients were not known by 52% of the respondents. The majority of the practitioners (94%) agreed regarding the formulation of evidence-based guidelines for prescribing corticosteroids in brain tumor patients., Conclusion: In view of the wide variations of corticosteroid therapy practices among health care professionals across various parts of the world, our pilot survey provides significant information which can act as a suitable benchmark to form uniform practice guidelines., Competing Interests: None

Introduction: Present study was planned to identify various sociodemographic factors influencing nutritional status in elderly and impact of nutritional status on activities of daily living in them., Methods: Total of 177 patients were enrolled in a prospective observational study. Nutritional status was assessed at the time of discharge by using Mini Nutritional Assessment form (MNA). Kartz Activity of Daily Living was assessed at 3 months before admission, at the time of admission, at discharge and 3 months after discharge. After written informed consent and ethics clearance patients were enrolled in the study. Analysis was done using the SPSS version 23 and Chi Square test was used to find the association between different qualitative variables. Statistical significance was set at P < 0.05., Results: Mean age of the study participants was 68.64 ± 7.73 years. 40 patients (22.6%) were found to be malnourished. Higher age, living alone, high CCI score and low ADL at discharge were associated with malnutrition. Mean ADL score was 5.82 at - 3 months time point in well-nourished patients which decreased during admission and then increased to 4.94 at the 3 months after discharge. Mean ADL score was of 5.33 at -3 months time point which kept on decreasing during admission and at 3 months after discharge in malnourished group. All these changes were statistically significant ( P < 0.001)., Conclusion: Nutritional status is a modifiable risk factor in elderly so identifying and optimizing nutritional status of elderly will optimise their functional status and improve quality of life., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with the most contagious variants, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and Omicron (B.1.1.529) has continuously added a higher number of morbidity and mortality, globally. The present integrated bioinformatics-cheminformatics approach was employed to locate potent antiviral marine alkaloids that could be used against SARS-CoV-2. Initially, 57 antiviral marine alkaloids and two repurposing drugs were selected from an extensive literature review. Then, the putative target enzyme SARS-CoV-2 main protease (SARS-CoV-2-Mpro) was retrieved from the protein data bank and carried out a virtual screening-cum-molecular docking study with all candidates using PyRx 0.8 and AutoDock 4.2 software. Further, the molecular dynamics (MD) simulation of the two most potential alkaloids and a drug docking complex at 100 ns (with two ligand topology files from PRODRG and ATB server, separately), the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy, and contributions of entropy were investigated. Then, the physicochemical-toxicity-pharmacokinetics-drug-likeness profiles, the frontier molecular orbitals energies (highest occupied molecular orbital, lowest unoccupied molecular orbital, and ΔE), and structural-activity relationship were assessed and analyzed. Based on binding energy, 8-hydroxymanzamine (-10.5 kcal/mol) and manzamine A (-10.1 kcal/mol) from all alkaloids with darunavir (-7.9 kcal/mol) and lopinavir (-7.4 kcal/mol) against SARS-CoV-2-Mpro were recorded. The MD simulation (RMSD, RMSF, Rg, H-bond, MM/PBSA binding energy) illustrated that the 8-hydroxymanzamine exhibits a static thermodynamic feature than the other two complexes. The predicted physicochemical, toxicity, pharmacokinetics, and drug-likeness profiles also revealed that the 8-hydroxymanzamine could be used as a potential lead candidate individually and/or synergistically with darunavir or lopinavir to combat SARS-CoV-2 infection after some pharmacological validation., (© 2022 Wiley Periodicals LLC.)

Hexachlorocyclohexane (HCH) has been recognized as an effective insecticide to protect crops against grasshoppers, cohort insects, rice insects, wireworms, and other agricultural pests and; for the control of vector-borne diseases such as malaria. It is a cyclic, saturated hydrocarbon, which primarily exists as five different stable isomers in the environment. Though the use of HCH is banned in most countries owing to its adverse effects on the environment, its metabolites still exist in soil and groundwater, because of its indiscriminate applications. In this study, a dose-dependent toxicity assay of the HCH isomers isolated from soil and water samples of different regions of Odisha, India was performed to assess the in vivo developmental effects and oxidative stress in zebrafish embryos. Toxicity analysis revealed a significant reduction in hatching and survivability rate along with morphological deformities (edema, tail malformations, spinal curvature) upon an increase in the concentration of HCH isomers; beta isomer exhibiting maximum toxicity (p < 0.05). Oxidative stress assay showed that ROS and apoptosis were highest in the fish exposed to β-2 and δ-2 isomers of HCH in comparison to the untreated one. Zebrafish proved to be a useful biological model to assess the biological effects of HCH isomers. In addition, the results suggest the implementation of precautionary measures to control the use of organochlorine compounds that can lead to a decrease in the HCH isomers in the field for a healthier environment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

High-quality point-of-care is critical for timely decision of disease diagnosis and healthcare management. In this regard, biosensors have revolutionized the field of rapid testing and screening, however, are confounded by several technical challenges including material cost, half-life, stability, site-specific targeting, analytes specificity, and detection sensitivity that affect the overall diagnostic potential and therapeutic profile. Despite their advances in point-of-care testing, very few classical biosensors have proven effective and commercially viable in situations of healthcare emergency including the recent COVID-19 pandemic. To overcome these challenges functionalized magnetic nanoparticles (MNPs) have emerged as key players in advancing the biomedical and healthcare sector with promising applications during the ongoing healthcare crises. This critical review focus on understanding recent developments in theranostic applications of functionalized magnetic nanoparticles (MNPs). Given the profound global economic and health burden, we discuss the therapeutic impact of functionalized MNPs in acute and chronic diseases like small RNA therapeutics, vascular diseases, neurological disorders, and cancer, as well as for COVID-19 testing. Lastly, we culminate with a futuristic perspective on the scope of this field and provide an insight into the emerging opportunities whose impact is anticipated to disrupt the healthcare industry., (© 2022. The Author(s).)

Inflammatory granulomas (neurocysticercosis [NCC] and tuberculomas) are important causes of seizures in children and adults in the developing world. Although several studies have explored seizure characteristics individually in patients with either NCC or tuberculoma, none has compared the seizure recurrence rate between them. This study included patients aged 5 to 18 years with viable parenchymal NCC or tuberculomas who had completed regular follow-up of at least 12 months at a tertiary institute in India. Their baseline seizure and electroencephalographic characteristics, antiseizure medications (ASMs), and breakthrough seizure rates at 12, 24, and 52 weeks were noted. A total of 103 and 54 patients with active NCC and tuberculomas respectively were included. The number of patients who had at least one breakthrough seizure at 12, 24, and 52 weeks in both groups was comparable (P = 0.32, 0.27, and 0.13), and the vast majority were controlled on monotherapy (98% cases in each group). The proportion of patients who required an increase in the dose or change of ASMs or polytherapy, the proportion of children who had status epilepticus at or before 12 months, abnormal electroencephalogram at 12 months, and calcified and active granuloma in neuroimaging at 12 months were also comparable between the two groups (P > 0.05 for all). The number of patients who had ASM-related adverse events and discontinued ASM due to serious adverse events was comparable between both groups, except for hepatotoxicity in the tuberculoma group. The predictors for breakthrough seizures that were found to be statistically significant in the NCC group were the presence of perilesional edema in the baseline magnetic resonance imaging (P = 0.02) and more than five active granulomas (P = 0.01); predictors in the tuberculoma group were the presence of severe perilesional edema causing midline shift in the baseline magnetic resonance imaging (P = 0.01) and more than five active granulomas (P = 0.04). The recurrence rates of breakthrough seizures over the next 12 months in newly detected cases of active NCC and tuberculomas were comparable.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2  M&#95;{⊙} and 1.0  M&#95;{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14  yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200]  Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2  M&#95;{⊙}

Background: Vinpocetine as a neuroprotective agent is effective in acute ischemic stroke in some randomized controlled trials (RCTs). Since the last systematic review has been published in 2008, which didn't find conclusive evidence favoring its use, two more RCTs have also been completed., Methods: Relevant electronic databases were searched with a suitable combination of Medical Subject Headings terms to detect publications describing RCTs exploring the safety and efficacy of vinpocetine in patients with acute ischemic stroke. The risk of bias was determined by using the Cochrane Collaboration's tool for assessing the risk of bias in RCTs after full-text review and relevant data extraction. Higgins and Thompson's I 2 method was used to assess heterogeneity in studies. The presence of publication bias was assessed by Egger's test. We used a random effect model when I 2 was more than 50% and a fixed-effect model for other parameters., Results: Four placebo-controlled RCTs enrolling a total of 601 and 236 patients in vinpocetine and placebo groups, respectively, were included. The number of patients with death or significant disability was lower in the vinpocetine group than that in the placebo group at both 1 and 3 months (relative risk 0.80, 95% confidence interval [CI] 0.65-0.99 and relative risk 0.67, CI 0.48-0.92, p = 0.04 and 0.02, respectively). The degree of disability in participants at 1 month and 3 months was also lower in vinpocetine group than that in the placebo group (standardized mean difference (SMD) 0.49, 95% CI 0.03-0.95 and SMD 1.22, CI 0.23-2.24, p = 0.001 and 0.04, respectively). Change in mini-mental state examination score compared with baseline at trial enrolment was also better in the vinpocetine group than in the placebo group (pooled weighted mean difference 0.92, 95% CI 0.02-1.82, p = 0.04)., Conclusions: Vinpocetine has some promising efficacy in patients with ischemic stroke when used in the acute stage in reducing the disability, but presently there is not enough evidence to suggest that it also reduces case fatality. More double-blind, placebo-controlled RCTs of adequate sample size are needed before making recommendations for the routine administration of vinpocetine for all patients with acute ischemic stroke., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Context: The novel coronavirus disease 2019 (COVID-19) that has emerged as a pandemic now has put health care workers (HCWs) at great risk as they are the warriors in frontlines screening and treating the infected patients. When a COVID-19-positive HCW is identified, its contacts need to be traced to check the spread of the infection among patients and other HCWs., Aims: This study was aimed to study epidemiology and risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection among HCWs and to quantify the risk of infection among HCWs in a tertiary level health care setting., Settings and Design: This cross-sectional study enrolled all the HCWs who were exposed to a patient with COVID-19 in a tertiary level health care center, Rishikesh, Uttarakhand from 1 st May to 30 th July, 2020., Methods and Material: All the exposed HCWs were followed up for 14 days after the last exposure to a patient with confirmed COVID-19 infection. Epidemiological data were obtained using structured interviews., Statistical Analysis Used: The data were analyzed using SPSS 23.0. Frequencies and proportions were calculated for descriptive variables, and risk ratios were calculated for risk factors affecting the transmission of disease., Results: We observed that 1,141 HCWs of the tertiary level health care hospital were exposed to COVID-19 patients during the study period. A total of 22 HCWs were tested COVID-19 positive among these exposed HCWs. Univariate analysis revealed a high risk of exposure to be significantly associated with a higher secondary attack rate of SARS CoV-2., Conclusions: The study demonstrates the risk of COVID-19 transmission through asymptomatic carriers. Therefore, periodic testing of all health care workers is necessary to ensure early mitigation of the shortage of health care providers., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Introduction: Quality of life (QOL) in older children, adolescents, and adults with cerebral palsy (CP) is significantly impaired. Level of functioning is one of the probable determinants of impairment in QOL. However, such studies in young children with CP are scarce in the literature., Methods: Parents of all consecutive children aged between 1 and 4 years with a confirmed diagnosis of CP completed the Infant Toddler Quality of Life (ITQOL) questionnaire. Total and individual subdomain scores of ITQOL were examined for association with the level of functioning measured by Gross Motor Function Classification System-Expanded & Revised (GMFCS E&R), Mini-Manual Ability Classification System (Mini-MACS), Communication Function Classification System (CFCS), and Eating and Drinking Ability Classification System (EDACS), with/without adjustment to probable confounding variables., Results: One hundred three children with CP (74 boys, mean age: 2.6 ± 0.9 years, 49% lower and 39% middle socioeconomic status) were enrolled. All four scales (GMFCS, Mini-MACS, CFCS, and EDACS) describing levels of functioning had significant association with ITQOL total score (β= -0.19, -0.15, -0.11, -0.09, respectively), which persisted even after adjusting for confounding variables ( p  = 0.004, 0.01, 0.03, and 0.046, respectively). Among the confounding variables, uncontrolled seizures, significant vision impairment, lower socioeconomic status, type of CP, and institution of comprehensive rehabilitation measures for ≥6 months had a significant association with ITQOL score ( p  = 0.03, 0.04, 0.02, 0.02, and 0.01, respectively)., Conclusion: Level of functioning as measured by GMFCS, Mini-MACS, EDACS, and CFCS is independent predictors of impairment in QOL in young children with CP., Competing Interests: None declared., (Thieme. All rights reserved.)

The ecotoxicological effect of after-usage released TiO 2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO 2 nanoparticles with Paramecium caudatum. TiO 2 nanoparticles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO 2 nanoparticles; TiO 2 (N15); of size 36 ± 12 nm were synthesized with a zeta potential of - 20.2 ± 8.8 mV and bandgap of 4.6 ± 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO 2 , the TiO 2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 µg/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO 2 nanoparticles in daily activity with a concern for ecological and biomedical aspects., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The Host-microbiome interactions that exist inside the gut microbiota operate in a synergistic and abnormal manner. Additionally, the normal homeostasis and functioning of gut microbiota are frequently disrupted by the intervention of Multi-Drug Resistant (MDR) pathogens. CRISPR-Cas (CRISPR-associated protein with clustered regularly interspersed short palindromic repeats) recognized as a prokaryotic immune system has emerged as an effective genome-editing tool to edit and delete specific microbial genes for the expulsion of bacteria through bactericidal action. In this review, we demonstrate many functioning CRISPR-Cas systems against the anti-microbial resistance of multiple pathogens, which infiltrate the gastrointestinal tract. Moreover, we discuss the advancement in the development of a phage-delivered CRISPR-Cas system for killing a gut MDR pathogen. We also discuss a combinatorial approach to use bacteriophage as a delivery system for the CRISPR-Cas gene for targeting a pathogenic community in the gut microbiome to resensitize the drug sensitivity. Finally, we discuss engineered phage as a plausible potential option for the CRISPR-Cas system for pathogenic killing and improvement of the efficacy of the system., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: To report our experience with image guided pencil beam proton beam therapy (PBT) for craniospinal irradiation (CSI)., Materials and Methods: Between January 2019 and December 2021, we carried out a detailed audit of the first forty patients treated with PBT. We had recorded acute toxicities, reporting early outcomes and discuss limitations of current contouring guidelines during CSI PBT planning., Results: Median age of the patient cohort was 8 years, and histologies include 20 medulloblastoma, 7 recurrent ependymoma, 3 pineoblastoma, 3 were germ cell tumors and remaining 7 constituted other diagnoses. Forty percent patients received concurrent chemotherapy. Median CSI dose was 23.4 Gy (Gray; range 21.6-35 Gy). Thirty-five patients (87.5%) completed their CSI without interruption, 5 required hospital admission. No patient had grade 2/ > weight loss during the treatment. Forty-five percent (18) developed grade 1 haematological toxicities and 20% (8) developed grade 2 or 3 toxicities; none had grade 4 toxicities. At median follow up of 12 months, 90% patients are alive of whom 88.9% are having local control. Special consideration with modification in standard contouring used at our institute helped in limiting acute toxicities in paediatric CSI patients., Conclusion: Our preliminary experience with modern contemporary PBT using pencil beam technology and daily image guidance in a range of tumours suitable for CSI is encouraging. Patients tolerated the treatment well with acceptable acute toxicity and expected short-term survival outcome. In paediatric CSI patients, modification in standard contouring guidelines required to achieve better results with PBT., (© 2022. The Author(s).)

Purpose: To compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen., Materials and Methods: Twelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance., Results: Proton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT., Conclusion: Proton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference., Competing Interests: Conflicts of Interest: Srinivas Chilukuri, MD, has received a speaker honorarium from Astra Zeneca, maintains a leadership role in Optimus Oncology, and owns stock in Optimus Oncology. The authors have no other conflicts of interest to disclose., (©Copyright 2022 The Author(s).)

Background Fungal infection in patients with coronavirus disease 2019 (COVID-19) has emerged as a new challenge in healthcare facilities. This study aimed to describe the demographic and clinical characteristics of COVID-19-associated mucormycosis (CAM). Methodology This retrospective, single-center case series included patients who were hospitalized and diagnosed with COVID-19 and mucormycosis at the All India Institute of Medical Sciences, Rishikesh (North India) from April 15, 2021, onwards and last followed up on June 30, 2021. Demographic, clinical, laboratory, radiological, microbiological, pathological, and outcome data were then collected and analyzed. Results Of the 100 consecutive inpatients with CAM, 95 (95%) had diabetes mellitus. At the onset of illness, the most common manifestations were facial swelling (85%), eye swelling (83%), headache (68%), pain around the eyeball (67%), malaise (57%), and fever (50%). The most common organ involved on examination was the nose and paranasal sinus (96%), followed by the orbit (83%), palate (19%), and cranial nerves (7%). Pulmonary involvement was seldom observed (1%). Predominant pathological findings were the presence of aseptate hyphae (75%), necrosis (75%), angioinvasion (36%), and perineural invasion (2.6%). During the last follow-up, 13 patients died, with 11 (84.6%) having severe COVID-19 and two (15.3%) having moderate COVID-19. Conclusions Steroid use and diabetes mellitus are the significant risk factors of CAM. Patients with CAM usually present with face/eye swelling with radiological involvement of the nose and sinus and may die because of severe COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kant et al.)

Foodborne infection is one of the leading sources of infections spreading across the world. Foodborne pathogens are recognized as multidrug-resistant (MDR) pathogens posing a significant problem in the food industry and healthy consumers resulting in enhanced economic burden, and nosocomial infections. The continued search for enhanced microbial detection tools has piqued the interest of the CRISPR-Cas system and Nanoparticles. CRISPR-Cas system is present in the bacterial genome of some prokaryotes and is repurposed as a theragnostic tool against MDR pathogens. Nanoparticles and composites have also emerged as an efficient tool in theragnostic applications against MDR pathogens. The diagnostic limitations of the CRISPR-Cas system are believed to be overcome by a synergistic combination of the nanoparticles system and CRISPR-Cas using nanoparticles as vehicles. In this review, we have discussed the diagnostic application of CRISPR-Cas technologies along with their potential usage in applications like phage resistance, phage vaccination, strain typing, genome editing, and antimicrobial. we have also elucidated the antimicrobial and detection role of nanoparticles against foodborne MDR pathogens. Moreover, the novel combinatorial approach of CRISPR-Cas and nanoparticles for their synergistic effects in pathogen clearance and drug delivery vehicles has also been discussed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)