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Air quality has deteriorated in most big cities and becoming the fifth major cause of mortality in India. Among others, vehicle gaseous emission is a major contributor. Plants have different tolerance levels, which can be identified based on Air Pollution Tolerance Index (APTI). The objectives were to study the morphological and biochemical parameters for Air Pollution Tolerance Index (APTI) of selected roadside tree species (Acacia auriculiformis, Alstonia scholaris, Chukrasia tabularis, Cassia fistula, Cassia siamea, Dalbergia sissoo, Heterophragma adenophyllum, and Putranjiva roxburghii) at control (PAU campus) and polluted sites (roadside) during summer and winter seasons. The total chlorophyll content, ascorbic acid, leaf extract pH, leaf relative water content, total soluble sugar, phenols, and carotenoids ranged from 0.59 to 4.16 mg g -1 , 1.03 to 3.75 mg g -1 , 3.16 to 7.04, 46.01 to 71.65%, 10.78 to 23.83 mg g -1 , 0.51 to 1.35 mg  -1 , and 0.19 to 1.96 mg g -1 , respectively. The Air Pollution Tolerance Index of the selected trees ranged between7.65 and 11.19 and followed an order of Cassia fistula > Acacia auriculiformis > Dalbergia sissoo > Alstonia scholaris > Putranjiva roxburghii > Heterophragma adenophyllum > Cassia siamea > Chukrasia tabularis. The evaluation of Anticipated Performance Index (API) categorized the trees into poor (Dalbergia sissoo and Cassia siamea), moderate (Cassia fistula), and good (Acacia auriculiformis, Alstonia scholaris, Chukrasia tabularis, Heterophragma adenophyllum, and Putranjiva roxburghii) categories., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A 44-year-old female presented with dull upper abdominal pain. Contrast-enhanced computed tomography (CECT) of the abdomen revealed a well-distended gallbladder with multiple foci of minimally enhancing, intraluminal, soft tissue lesion, and hyperdensity on non-contrast scan measuring 4.3 × 3.5 cm in the fundus with few calculi embedded in it. There was no evidence of extraluminal extension. The patient underwent extended cholecystectomy with liver wedge resection. Histologically, the tumor showed both carcinomatous and sarcomatous components, with prominent osteosarcomatous differentiation. We report this unusual case and present a review of all cases of carcinosarcoma of the gallbladder with sarcomatous differentiation. Despite curative resection, CSGB prognosis remains poor, and thus, the authors recommend to focus their efforts to improve the surgical outcomes., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2022.)

Objective: To analyze the long-term symptomatic results of laser-assisted sialolithotripsy (LAS) in cases of obstructive sialolithiasis and correlate with objective criteria using diagnostic sialendoscopy (DS) as a method of examination., Methods: This is a retrospective study comprising 50 consecutive patients who underwent holmium-YAG LAS and completed follow-up of at least 6 months. Symptom scoring and endoscopic scoring were done at 6 weeks and 6 months intervals for further study purposes., Results: At the end of 6 weeks post-LAS, 70% patients were asymptomatic (A-sym) and only 30% had residual symptoms (Sym). However, obstructed duct (OB-duct) was observed on endoscopic scoring in 88% due to stenosis, residual stones, or both stenosis and residual stones. The obstructed ducts were treated in outpatient clinic and followed up over time, leading to 98% of patients being in A-sym group at the end of study period of 6 months. At the end of study, 82% of patients had clear duct (CL-duct)., Conclusion: Holmium LAS is a viable option for the management of intermediate-sized stones. LAS if used judiciously, and in properly selected cases, has high rate of stone fragmentation and symptom resolution. A vigilant postoperative protocol taking into account residual mealtime symptoms and altered salivary characteristics combined with early DS can help identify and treat patients with residual stone fragments and ductal stenosis., Level of Evidence: 3 Laryngoscope, 132:2344-2349, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Biohydrogen (bio-H 2 ) is regarded as a clean, non-toxic, energy carrier and has enormous potential for transforming fossil fuel-based economy. The development of a continuous high-rate H 2 production with low-cost economics following an environmentally friendly approach should be admired for technology demonstration. Thus, the current review discusses the biotechnological and thermochemical pathways for H 2 production. Thermochemical conversion involves pyrolysis and gasification routes, while biotechnological involves light-dependent processes (e.g., direct and indirect photolysis, photo/ dark fermentation strategies). Moreover, environmentally friendly technologies can be created while utilizing renewable energy sources including lignocellulosic, wastewater, sludge, microalgae, and others, which are still being developed. Lifecycle assessment (LCA) evaluates and integrates the economic, environmental, and social performance of H 2 production from biomass, microalgae, and biochar. Moreover, system boundaries evaluation, i.e., global warming potential, acidification, eutrophication, and sensitivity analysis could lead in development of sustainable bioenergy transition with high economic and environmental benefits., 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 Ltd. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Introduction The purpose of this study was to compare and evaluate the association of gingival melanin pigmentation with age, sex, and skin tone in pre-school children of Hazaribag, Jharkhand, India. Materials and methods The study included 310 children aged 3 to 6 years, who were divided according to skin color into the following: group I: Fair, group II: wheatish, group III: brown; and group IV: dark. The children were selected using a census method where all participants fulfilling inclusion criteria were selected from the outpatient department of the Department of Pediatric and Preventive Dentistry, Hazaribag College of Dental Sciences and Hospital, Hazaribag. The subjects were further grouped into different age groups of 3-4 years, 4-5 years, 5-6 years, and 6 years. Subjects were examined in natural daylight, and gingival melanin pigmentation was assessed using the Dummett-Gupta Pigmentation Index. The scoring was done for each arch segment. These categorical data were analyzed using the chi-square test. Results Gingival pigmentation was found to increase with increasing age, whereas female subjects showed less pigmentation than males. Majority of the children had wheatish complexion, and a significant positive correlation was found between skin tone and gingival pigmentation; the darker the skin tone, the darker was the gingival pigmentation. Anatomically, greater pigmentation was found in the anterior than posterior region of arches. Greater pigmentation was found in the labial than lingual region; greater pigmentation was also reported in the mandible than maxilla. Conclusion There was a positive correlation of gingival melanin pigmentation with age, sex, and skin tone in pre-school children. Clinical significance The association of gingival pigmentation with skin color had been documented, but very few studies have been published on adults and children on this subject. However, there is no study that evaluates the association of gingival melanin pigmentation with age, sex, and skin tone of children of pre-school age., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Verma et al.)

Mutation in ATP7B gene causes Wilson disease (WD) that is characterized by severe hepatic and neurological symptoms. ATP7B localizes at the trans-Golgi Network (TGN) transporting copper to copper-dependent enzymes and traffics in apically targeted vesicles upon intracellular copper elevation. To decode the cellular underpinnings of WD manifestation we investigated copper-responsive polarized trafficking and copper transport activity of 15 WD causing point mutations in ATP7B. Amino-terminal mutations Gly85Val, Leu168Pro, and Gly591Asp displayed TGN and subapical localization whereas, Leu492Ser mislocalized at the basolateral region. The actuator domain mutation Gly875Arg shows retention in the endoplasmic reticulum (ER), Ala874Val and Leu795Phe show partial targeting to TGN and post-Golgi vesicles. The nucleotide-binding domain mutations His1069Gln and Leu1083Phe also display impaired targeting. The C-terminal mutations Leu1373Pro/Arg is arrested at ER but Ser1423Asn shows TGN localization. Transmembrane mutant Arg778Leu resides in ER and TGN while Arg969Gln is exclusively ER localized. Cellular Cu level does not alter the targeting of any of the studied mutations. Mutants that traffic to TGN exhibits biosynthetic function. Finally, we correlated cellular phenotypes with the clinical manifestation of the two most prevalent mutations; the early onset and more aggressive WD caused by Arg778Leu and the milder form of WD caused by mutation His1069Gln., (© 2022 Wiley Periodicals LLC.)

Background: Postoperative endodontic pain is an enigma for the dentist. This study aimed to evaluate the analgesic effect of 300 mg gabapentin or 75 mg pregabalin in reducing postoperative endodontic pain compared with a placebo., Methods: Ninety patients who needed root canal treatment with an initial numerical rating scale (NRS) pain score of > 4 (T0) were randomly divided into three groups (n=30). Patients were then administered either 300 mg gabapentin (group A), 75 mg pregabalin (group B), or a placebo (group C) 30 min prior to the start of endodontic treatment. A single operator performed single-visit endodontics, and pain was evaluated immediately after endodontic treatment (T1) and at 4 h (T2), 8 h (T3), 12 h (T4), 24 h (T5), 48 h (T6), and 72 h (T7) using the NRS. Ibuprofen/paracetamol (400 mg/325 mg) was administered as a rescue dose if needed., Results: Pregabalin performed significantly better when compared with gabapentin at all time points except at 72 h after treatment (P=0.170). The placebo group showed significantly higher pain scores than the other two groups. The percentage of pain relief was maximum for pregabalin (92.1%), followed by gabapentin (87.6%) and placebo (69.1%) at 72 h after treatment completion., Conclusion: This study showed that pretreatment with a single dose of pregabalin and gabapentin both had greater analgesic effects than a placebo. They can be effectively used to reduce postoperative endodontic pain., Competing Interests: CONFLICTS OF INTEREST: The authors have no conflicts of interest to declare., (Copyright © 2022 Journal of Dental Anesthesia and Pain Medicine.)

Thermal hot springs are present throughout the world and constitute a unique habitat for microbial diversity. The current investigation is conducted to study the bacterial diversity of thermophilic microorganisms in thermal hot springs of the Indian Himalayan Region (IHR). As of today, 110 geothermal hot springs have been explored for microbial diversity. In this study, we observed that the growth of thermophilic bacteria isolated from thermal hot springs of IHR ranges between 40 and 100 °C, and pH of 3.5-8 have been reported in the literature. The major bacterial species reported from the thermal hot springs of IHR are Bacillus spp., Geobacillus spp., Paenibacillus spp., Pseudomonas spp., Anoxybacillus, Paenibacillus , Brevibacillus, Aneurinibacillus, Thermus aquaticus, Aquimonas, Flavobacterium , etc. Furthermore, bacterial isolates from thermal hot springs of IHR have been reported to produce various enzymes and metabolites such as amylase, β -galactosidase, cellulase, nitrate reductase, acetoin, caffeine degradation enzymes, lipase, urease, and laccase. Metagenomic study and the entire genomic shotgun project have established the impact of physicochemical parameters (temperature and pH) on developing the microbiome. We have discussed the discoveries of microbiological data on the hot springs of IHR until the end of year 2021. As a whole, the microbiome adapts themselves as successful inhabitants to extreme environmental conditions and also serves as a diverse resource for potential applications in health, food, and environment., Competing Interests: Conflict of interestThe authors of the manuscript “Bacterial Diversity in 110 Thermal Hot Springs of Indian Himalayan Region (IHR)” have no conflict of interest., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

A bacterial isolate PM1 obtained from the rhizosphere of healthy plants was identified as Pseudomonas aeruginosa by biochemical characteristics and 16S rRNA gene sequence (GenBank ID OL321133.1). It induced resistance in Nicotiana tabacum cv. Xanthi-nc and Cyamopsis tetragonoloba, against Tobacco mosaic virus (TMV) and Sunn-hemp rosette virus (SRV), respectively. Foliar treatment with isolate PM1 curbed TMV accumulation in susceptible N. tabacum cv. White Burley. PM1 was more effective as a foliar than a root/soil drench treatment, evident through a comparative decrease in ELISA values, and reduced viral RNA accumulation. Foliar and soil drench treatment with PM1 resulted in a disease index of 48 and 86 per cent, and a control rate of 48.9 and 8.5 per cent, respectively. PM1 exhibited phosphate solubilization, produced siderophores, auxins, HCN, and ammonia, all important plant growth-promoting traits. Foliar treatment with PM1 enhanced growth in tobacco, while its volatiles significantly promoted seedling growth in C. tetragonoloba. Of the several metabolites produced by the isolate, many are known contributors to induction of systemic resistance, antibiosis, and growth promotion in plants. Soluble metabolites of PM1 were less effective in inducing antiviral resistance in N. tabacum cv. Xanthi-nc in comparison with its broth culture. PM1 and its metabolites were antagonistic to Gram-positive Bacillus spizizenii and Staphylococcus aureus, and fungi Fusarium oxysporum, Aspergillus niger, and Rhizopus stolonifer. Its volatiles were inhibitory to F. oxysporum and R. stolonifer. Thus, PM1 exhibited considerable potential for further evaluation in plant virus control and production of diverse metabolites of use in agriculture and medicine., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Antimicrobial resistance in clinically important microbes has emerged as an unmet challenge in global health. Extensively drug-resistant bacterial pathogens have cropped up lately defying the action of even the last resort of antibiotics. This has led to a huge burden in the health sectors and increased morbidity and mortality rate across the world. The dwindling antibiotic discovery pipeline and rampant usage of antibiotics has set the alarming bells necessitating immediate actions to combat this looming threat. Various alternatives to discovery of new antibiotics are gaining attention such as reversing the antibiotic resistance and hence reviving the arsenal of antibiotics in hand. Antibiotic resistance reversal is mainly targeted against the antibiotic resistance mechanisms, which potentiates the effective action of the antibiotic. Such compounds are referred to as resistance breakers or antibiotic adjuvants/potentiators that work in conjunction with antibiotics. Many studies have been conducted for the identification of compounds, which decrease the permeability barrier, expression of efflux pumps and the resistance encoding enzymes. Compounds targeting the stability, inheritance and dissemination of the mobile genetic elements linked with the resistance genes are also potential candidates to curb antibiotic resistance. In pursuit of such compounds various natural sources and synthetic compounds have been harnessed. The activities of a considerable number of compounds seem promising and are currently at various phases of clinical trials. This review recapitulates all the studies pertaining to the use of antibiotic potentiators for the reversal of antibiotic resistance and what the future beholds for their usage in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chawla, Verma, Gupta and Das.)

The Chikungunya virus (CHIKV) has become endemic in the Africa, Asia and Indian subcontinent, with its continuous re-emergence causing a significant public health crisis. The unavailability of specific antivirals and vaccines against the virus has highlighted an urgent need for novel therapeutics. In the present study, we have identified small molecule inhibitors targeting the envelope proteins of the CHIKV to interfere with the fusion process, eventually inhibiting the cell entry of the virus particles. We employed high throughput computational screening of large datasets against two different binding sites in the E1-E2 dimer to identify potential candidate inhibitors. Among them, four high affinity inhibitors were selected to confirm their anti-CHIKV activity in the in vitro assay. Quercetin derivatives, Taxifolin and Rutin, binds to the E1-E2 dimer at different sites and display inhibition of CHIKV infection with EC 50 values 3.6 μM and 87.67 μM, respectively. Another potential inhibitor with ID ChemDiv 8015-3006 binds at both the target sites and shows anti-CHIKV activity at EC 50  = 41 μM. The results show dose-dependent inhibitory effects of Taxifolin, Rutin and ChemDiv 8015-3006 against the CHIKV with minimal cytotoxicity. In addition, molecular dynamics studies revealed the structural stability of these inhibitors at their respective binding sites in the E1-E2 protein. In conclusion, our study reports Taxifolin, Rutin and ChemDiv 8015-3006 as potential inhibitors of the CHIKV entry. Also, this study suggests a few potential candidate inhibitors which could serve as a template to design envelope protein specific CHIKV entry inhibitors., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Nanoparticles-based multivalent antigen display has the capability of mimicking natural virus infection characteristics, making it useful for eliciting potent long-lasting immune response. Several vaccines are developed against global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However these subunit vaccines use mammalian expression system, hence mass production with rapid pace is a bigger challenge. In contrast E. coli based subunit vaccine production circumvents these limitations. The objective of the present investigation was to develop nanoparticle vaccine with multivalent display of receptor binding domain (RBD) of SARS-CoV-2 expressed in E. coli. Results showed that RBD entrapped PLA (Poly lactic acid) nanoparticle in combination with aluminum hydroxide elicited 9-fold higher immune responses as compared to RBD adsorbed aluminum hydroxide, a common adjuvant used for human immunization. It was interesting to note that RBD entrapped PLA nanoparticle with aluminum hydroxide not only generated robust and long-lasting antibody response but also provided Th1 and Th2 balanced immune response. Moreover, challenge with 1 µg of RBD alone was able to generate secondary antibody response, suggesting that immunization with RBD-PLA nanoparticles has the ability to elicit memory antibody against RBD. Plaque assay revealed that the antibody generated using the polymeric formulation was able to neutralize SARS-CoV-2. The RBD entrapped PLA nanoparticles blended with aluminum hydroxide thus has potential to develop asa subunit vaccine against COVID-19., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To define the spectrum of genetic disorders in patients with short stature visiting the genetic out-patient department in a tertiary care hospital., Methods: A chart review was done for 455 individuals (10 months-16 yrs) with short stature, who were evaluated at the genetic clinic from 1 January, 2017 upto 31 October, 2018. 226 patients who needed detailed evaluation, the spectrum of genetic diagnosis is presented., Results: Proportionate short stature was identified in 63% individuals (n=142) of which 93 (65%) were recognizable syndromes such as Turner syndrome, and William syndrome, and RASopathies. In clinically undefined syndromes (39, 27%), a diagnosis could be made by karyotype (n=3/10), chromosomal microarray (6/12) and exome sequencing (1/6). In the 84 children in the disproportionate short stature group (37%), lysosomal storage disorders (LSDs) (45%, n=38) were identified by enzyme analysis in 86.8% and skeletal dysplasias (44%, n=37) identified by skeletal survey in 89% cases., Conclusions: In undefined syndromic short stature, chromosomal microarray may be the first investigation of choice if phenotyping is not suggestive of a specific genetic syndrome. Exome sequencing can be useful in identifying newer genes among idiopathic and familial short stature cohorts.

The existence of OXA-58 carbapenemase alone or in combination with other beta-lactam resistance factors poses significant beta-lactam resistance. The exact mechanism of action of OXA type beta-lactamases is debatable due to the involvement of multiple residues within or outside the active site. In the present work, we have elucidated the relative role of residues present in the putative omega (W169, L170, K171) and β6-β7 (A226 and D228) loops on the activity of OXA-58 by substituting into alanine (and aspartate for A226) through site-directed mutagenesis. E. coli cells harbouring OXA-58, substituted at the putative omega loop, manifest a significant decrease in the beta-lactam resistance profile than that of the cells expressing OXA-58. Further, a reduction in the catalytic efficiency is observed for the purified variants of OXA-58 carrying individual substitutions in the putative omega loop than that of OXA-58. However, the addition of NaHCO 3 (for carbamylation of K86) increases catalytic efficiency of the individual protein as revealed by nitrocefin hydrolysis assay and steady state kinetics. Moreover, W169A and K171A substitutions show significant effects on the thermal stability of OXA-58. Therefore, we conclude that the putative omega loop residues W169, L170 and K171, individually, have significant role in the activity and stability of OXA-58, mostly by stabilising carbamylated lysine of active site.

Abstract: Neuroendocrine tumors (NETs) are rare, but the incidence and prevalence of NETs are increasing in the United States. While surgery is the preferred treatment for NETs, it is not a viable option for metastatic disease. Lutathera (177Lu-DOTATATE) is approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of gastroenteropancreatic (GEP)-NETs in adults. There is limited information on GEP-NET treatment responses to Lutathera.Our institution launched a peptide receptor radionuclide therapy (PRRT) service line using Lutathera with involvement from a multidisciplinary team and complete collaboration between hospital administration and clinical providers. A prospective registry study was also established in order to collect patient demographics and clinical data regarding the treatment of GEP primary NETs with Lutathera.Between August 2018 and July 2020, 35 GEP-NET patients were treated with Lutathera, of which 65.71% received 4 complete cycles and 25.71% received 3 cycles; 5.71% and 2.86% received 2 and 1 cycles of PRRT, respectively. Most adverse events during the course of our study were low grade using the common terminology criteria for adverse events system. Of the patients who completed all 4 cycles: 22% showed partial response to Lutathera, 44% showed stable disease, and 13% showed disease progression based on a qualitative assessment of positron emission tomography/computed tomography imaging.From our experience, Lutathera was well tolerated in patients with GEP-NET. Additional studies are needed to examine long-term clinical and patient-reported outcomes associated with GEP-NET treatment as well as financial considerations for hospitals embarking on a PRRT program., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Increasing occurrence of infections caused by multidrug-resistant Gram-negative bacteria resulted in colistin being the last agent for treatment. Apart from plasmid-mediated mcr genes, mutations involving several genes like mgrB, phoP/phoQ, pmrA, pmrB, pmrC , and crrABC genes, are leading causes of colistin resistance. Four colistin susceptibility testing methods were compared against broth microdilution (BMD) and determined the presence of the mcr1-5 gene., Methodology: A total of 100 carbapenem-resistant Enterobacterales isolates were tested for colistin susceptibility by commercial broth microdilution (cBMD), E-test, VITEK-2, and rapid polymyxin NP assay (RPNP) and compared with BMD. The presence of the mcr1-5 gene was determined by modified RPNP and PCR. Two non- mcr colistin-resistant XDR isolates were subjected to whole-genome sequencing using Illumina MiSeq sequencing platform., Results: Among 100 carbapenem-resistant Enterobacterales isolates, 15% were resistant to colistin. Essential agreement, categorical agreement, major error, and very major error for cBMD/E-test/VITEK-2/RPNP were 96%/73%/82%/NA; 99%/86%/88%/91%, 1.2%/9.4%/11.8%/8.2% and 0%/40%/13.3%/13.3%, respectively. Only one Klebsiella pneumoniae isolate harbored the mcr-1 gene, observed by both methods. Whole-genome sequencing of two non- mcr XDR Klebsiella pneumoniae showed multiple mutations in 10 genes responsible for lipopolysaccharide biosynthesis., Conclusions: The performance of cBMD was excellent, whereas the E-test was unacceptable. VITEK-2 and RPNP performed better but remained unreliable due to high error rates. Multiple mutations in the target proteins involving lipopolysaccharide formation, modification, and regulation were seen, resulting in colistin resistance., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

CTX-M-15 is a major extended-spectrum beta-lactamase disseminated throughout the globe. The roles of amino acids present in the active-site are widely studied though little is known about the role of the amino acids lying at the close proximity of the CTX-M-15 active-site. Here, by using site-directed mutagenesis we attempted to decipher the role of individual amino acids lying outside the active-site in imparting the beta-lactamase activity of CTX-M-15. Based on the earlier evidence, three amino acid residues namely, Glu169, Asp173 and Arg277 were substituted with alanine. The antibiotic susceptibility of E. coli cells harboring E169A and N173A substituted CTX-M-15 were enhanced by ∼ >32 fold for penicillins and ∼ 4-32 fold for cephalosporins, in comparison to CTX-M-15. However, cells carrying CTX-M-15_R277A did not show a significant difference in antibiotic susceptibility as compared to the wild-type. Further, the catalytic efficiency of the purified CTX-M-15_E169A and CTX-M-15_N173A were compromised when compared with the efficient beta-lactam hydrolysis of purified CTX-M-15. Moreover, the thermal stability of the mutated proteins CTX-M-15_E169A and CTX-M-15_N173A were reduced as compared to the wild type CTX-M-15. Therefore, we conclude that E169 and N173 are crucial non-active-site amino acids that are able to govern the CTX-M-15 activity., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Background: Late onset Pompe disease (LOPD) is rare and generally manifests predominantly as progressive limb girdle muscle weakness. It is linked to the pathogenic mutations in GAA gene, which leads to glycogen accumulation in various tissues., Materials and Methods: We describe the unusual clinical, biochemical, histopathological and genetic characteristics of 5 cases of LOPD., Results: The first case had progressive anterior horn cell like disease (AHCD) that evolved later to classical limb girdle syndrome and respiratory failure, the second patient had rigid spine syndrome with gastrointestinal manifestations, the third had limb girdle weakness superimposed with episodic prolonged worsening and respiratory failure, the fourth had large fibre sensory neuropathy without primary muscle involvement and the fifth presented with classical limb girdle muscle weakness. Two homozygous missense mutations c.1461C > A (p.Phe487Leu) and c.1082C > T (p.Pro361Leu) in the GAA gene were identified in case 1 and 2 respectively. Case 3 was compound heterozygous with inframe c.1935_1940del (p.Val646_Cys647del) and an intronic splice effecting variant c.-32-13T > G. Compound heterozygous missense variants c.971C > T (p.Pro324Leu) and c.794G > A (p.Ser265Asn) were identified in case 4. Case 5 had a frameshift insertion c.1396dupG (p.Val466GlyfsTer40) and a synonymous splice affecting variant c.546G > T(p.Thr182=)., Conclusion: We are describing for the first time from India on LOPD with unusual phenotypes identified. A high degree of clinical suspicion and diagnosing rare phenotypes of Pompe disease is imperative to consider early initiation of Enzyme Replacement Therapy (ERT).

Sepsis is a highly heterogeneous, life-threatening organ dysfunction primarily caused by a dysregulated immune response to counter bacterial, viral, or fungal infections, resulting in haemodynamic changes and significant morbidity and mortality across all ages. In recent times, it has become one of the foremost causes of morbidity and mortality among newborns globally. The neonates, particularly the preterm neonates, due to their immature immune systems and non-canonical microbial community acquisition in the gastrointestinal tract and other body habitats, are adversely affected compared to the elderly with immunocompromised conditions. The neonates could acquire microbiota in utero or during delivery from the mother's genital tract or postnatally from contact with hospital personnel and the immediate hospital environment after the birth. Other factors that may enhance the risk include early colonization of microbiota by pathogens that trigger dysbiosis of the gut microbiome accompanied by a dysregulated immune response, organ dysfunction, and potential death. The sepsis-linked mortality could be prevented by timely diagnosis, selective antibiotic therapy, and supportive postnatal care. Infections due to antibiotic-resistant bacteria severely restrict possible therapeutic options, thus extending hospital stays. A comprehensive analysis of the infecting pathogens, cognate host responses, and the microbiota present would certainly help formulate appropriate interventions., Competing Interests: Conflict of interests The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

CAP-34 is a previously reported phytoprotein isolated from Clerodendrum aculeatum (syn. Volkameria aculeata ), inducing systemic antiviral resistance against plant virus infection in susceptible plants. This paper compares the resistance inducing efficacy of CAP-34 and a rhizobacterial isolate P1f on tomato (systemic) and tobacco Xanthi-nc (hypersensitive), against tobacco mosaic virus (TMV). The PGPR isolate was identified as an isolate of Pseudomonas putida through molecular and biochemical characterization, and it exhibited PGPR traits such as production of auxin and siderophore. GC-MS examination of the volatiles produced by P1f included several that are implicated in antimicrobial activity, growth promotion and induced systemic resistance. Foliar treatment of tobacco plants with P1f and CAP-34 led to an induced antiviral state in hypersensitive tobacco that persisted for 5 and 3 days, post-treatment, respectively, with a percent reduction in lesion number greater than 90. A higher accumulation of hydrogen peroxide and production of peroxidase enzyme was recorded in P1f-treated leaves, in comparison to those with CAP-34 treatment. The disease incidence in tomato plants treated with CAP-34 and P1f was 30 and 60 percent, respectively, 28dpi. A significant increase was noted in growth parameters such as number of branches and flowers in CAP-34 treated plants, while a significant enhancement in plant height and dry shoot and root weight was observed in P1f-treated set, compared to the control set. ELISA values for the presence of TMV were significantly lower in the infected tomato plants in the treated sets, as compared to the control set, with CAP-34 treatment exhibiting better results as against the P1f-treated set. In the resistant plants from either set, no viral RNA or viral coat protein was detected through RT-PCR and serology. These results suggest that CAP-34 affords more pronounced protection against virus infection compared to the rhizobacterial isolate P1f., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2021.)

Microbes evolve rapidly by modifying their genome through mutations or acquisition of genetic elements. Antimicrobial resistance in Helicobacter pylori is increasingly prevalent in India. However, limited information is available about the genome of resistant H. pylori isolated from India. Our pan- and core-genome based analyses of 54 Indian H. pylori strains revealed plasticity of its genome. H. pylori is highly heterogenous both in terms of the genomic content and DNA sequence homology of ARGs and virulence factors. We observed that the H. pylori strains are clustered according to their geographical locations. The presence of point mutations in the ARGs and absence of acquired genetic elements linked with ARGs suggest target modifications are the primary mechanism of its antibiotic resistance. The findings of the present study would help in better understanding the emergence of drug-resistant H. pylori and controlling gastric disorders by advancing clinical guidance on selected treatment regimens., (Copyright © 2021. Published by Elsevier Inc.)

Background & Aims: Lysosomal storage disorders (LSDs) remain a significant cause of morbidity in the Indian population and treatment is largely out of reach for most patients. Although data on enzymatic and molecular diagnosis of Gaucher disease (GD) and Fabry disease (FD) in Indian patients are available, the present study intended to establish the pathogenic levels of Lyso GL-1 and Lyso GL-3 in patients of GD and FD respectively as diagnostic aids., Materials and Methods: From 2017 to 2019, ninety confirmed Gaucher cases (by enzymatic and molecular analysis) were tested for chitotriosidase (fluorometrically) and Lyso GL-1 (LC-MS/MS) and ten confirmed Fabry cases were analyzed for Lyso GL-3 (LC-MS/MS)., Results: Lyso GL-1 (median: 685.5 ng/mL, cut-off: 14) and Lyso GL-3 (median: 75.6 ng/mL, cut-off: 3.5) were found to be elevated in all enzymatically deficient patients of GD and FD respectively, however, no specific trend was observed between the levels of these biomarkers and the pathogenic variant(s) present in the patients of these disorders., Conclusions: This is the first report on Lyso GL-1 and Lyso GL-3 levels in Indian patients of GD and FD respectively. These results will be useful for early diagnosis to improve management of these LSDs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: In today's world, everyone is mindful of one's appearance and appreciates aesthetics. Of the various restorative materials available, composites are considered as the most aesthetic with good color stability. This study aims at finding the effect of brushing on the color stability of nanohybrid composite after being immersed in various beverages., Methods: Thirty disk specimens were prepared for each staining solution (N=30), with a total of 90 specimens. The disk specimens for each staining solution were then sub divided into 2 groups (N=15): brushing and non-brushing. After preparation, the specimens were soaked in distilled water for 24 hours in separate containers. Baseline color of the samples was evaluated using spectrophotometer. The samples were then immersed in tea, coffee or water. The groups of samples to be brushed were held in the mold and 20 strokes of brushing using an electronically powered toothbrush were done on each side of the disk sample. The color was re-evaluated after a period of 14 days., Results: When comparing among the three beverages, tea showed the highest ΔE*ab indicating greatest discoloration when compared to coffee and water. This can be graded as tea > coffee > water. However, statistically there was no significant difference between tea and coffee. When compared within tea, coffee, or water specimens the non-brushed specimens showed greater discoloration compared to the brushed specimens both clinically and statistically., Conclusion: When immersing the specimens in the solutions, tea showed more color change compared to coffee, making the specimens clinically unacceptable. However, brushing the specimens reduced the discoloration when compared to non-brushing, making the coffee specimens clinically acceptable.

Mycobacterium tuberculosis can sustain inside the host in dormant (non-replicating) state for years. It suppresses the host immune system by residing in the host alveolar macrophage, resulting in the development of latent tuberculosis. Despite many antibiotics available for the treatment of tuberculosis, the major hurdle in complete elimination is the ability of the bacilli to undergo dormancy and develop resistance against the existing drugs. Cyclopropanation of mycolic acids present in the cell wall of mycobacteria is required for its persistence and virulence. Cyclopropane synthases such as PcaA, CmaA1 and CmaA2, introduce site-specific modifications in mycolic acids. PcaA expression levels are high during dormancy and the gene mutants fails to persist, showing reduced survival in host macrophage. Hence, PcaA appears as a potential target to develop inhibitors against the dormant bacilli. In this study, we have identified compounds with maximum binding affinity against PcaA by in-silico virtual screening of anti-tuberculosis compounds and their structural analogues. In-silico docking followed molecular dynamic simulations and free energy calculations of the compounds with highest docking score in their respective libraries. This study reports novel inhibitors that can act as better anti-tuberculosis compounds targeting PcaA.Communicated by Ramaswamy H. Sarma.

The fall of 2020 brought several new variants of SARS-CoV-2 circulating across the globe, and the steadily increasing COVID-19 cases are responsible for the emergence of these variants. All the SARS-CoV-2 variants reported to date have multiple mutations in the spike (S) protein, specifically in the receptor-binding domain (RBD). Here, we employed an integrated computational approach involving structure and sequence based predictions to study the effect of naturally occurring variations in the S-RBD on its stability and ACE2 binding affinity. The hotspot stabilizing residue mutations N501I, N501Y, Q493L, Q493H and K417R, strengthen the RBD-ACE2 complex by modulating the interaction statistics at the interface. Thus, we report here some critical mutations that could increase the binding affinity of the SARS-CoV-2 RBD with ACE2, increasing the viral infectivity and pathogenicity. Understanding the effect of these mutations will help in developing potential vaccines and therapeutics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The present study was conducted to evaluate the clinical efficacy of resin infiltration technique alone or in combination with microabrasion and in-office bleaching in adults with mild-to-moderate fluorosis stains on permanent maxillary anterior teeth at the end of 1 month., Materials and Methods: A total of 30 patients with nonpitted fluorosis stains on maxillary anterior were classified as mild ( n = 15) and moderate ( n = 15). Each grade is subdivided into three groups as Group A, Group B, and Group C. Group 1: Mild (score 2), Subgroup A: Resin infiltration ( n = 5 patients), Subgroup B: Microabrasion followed by resin infiltration ( n = 5 patients), Subgroup C: Microabrasion and bleaching followed by resin infiltration after 2 weeks ( n = 5 patients). Group 2: Moderate (score 3), Subgroup A: Resin infiltration ( n = 5 patients), Subgroup B: Microabrasion followed by resin infiltration ( n = 5 patients), and Subgroup C: Microabrasion and bleaching followed by resin infiltration after 2 weeks ( n = 5 patients). Microabrasion was performed with the opalustre kit from Ultradent according to the manufacturer's instructions. Pola office bleaching from SDI and Icon infiltrant was performed. Stain score, improvement in appearance score, need for further treatment, patient satisfaction score, tooth sensitivity immediately after treatment, 24 h and 72 h were recorded., Results: The mean appearance score in Group 1A was 73.60, in Group 1B was 72.87, in Group 1C was 65.27, in Group 2A was 68.00, in Group 2Bwas 72.93 and in Group 2C was 84.73. The mean need for further treatment score in Group 1A was 72.80, in Group 1B was 78.40, in Group 1C was 68.73, in Group 2A was 71.20, in Group 2B was 79.53 and in Group 2C was 88.73. The mean patient satisfaction score in Group 1A was 91.40, in Group 1B was 95.20, in Group 1C was 98.00, in Group 2A was 90.20, in Group 2B was 99.40 and in Group 2C was 100.00. There was a significant difference in mean tooth sensitivity immediately after treatment between Groups 1A, 1B, 1C, 2A, 2B, and 2C. There was a significant difference in mean tooth sensitivity after 24 h between Groups 1A, 1B, 1C, 2A, 2B, and 2C., Conclusion: Resin infiltration technique in combination with bleaching and microabrasion technique found to be effective in the management of dental fluorosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Pharmacy and Bioallied Sciences.)

Rationale & Objective: The concept of Prakriti is unique to Ayurveda, which is used for deciding the preventive and curative strategy to be adopted in the treatment of patients. It is the total of anatomical, physiological, and psychological domains of an individual. The diseases often manifest by susceptibility that depends upon Prakriti of individuals. COVID 19 is a new disease, where the status of the susceptibility of its victim in terms of Prakriti is not known. This study has been undertaken to determine the Prakriti of COVID 19 positive patients., Method: The validated instrument CCRAS Prakriti assessment scale has been applied to the COVID 19 positive patients admitted between 16 May 2020 to 10 June 2020 at COVID hospital., Result: Data of 117 patients aged 10 to 80 years have been analyzed. The ratio of male-female patients was 1.8:1. Most patients belonged to Vata-KaphaPrakriti (27%).Individuals with their Prakriti found in order of frequency were Pitta-Kapha (21%), Kapha (20%), Vata (13%), Vata-Pitta (11%), Sama (4%) and Pitta (3%)., Conclusion: Patients with Vata-Kapha, Pitta-Kapha, and Kapha dominant Prakriti have been found more in COVID19. The treatment strategies can be accordingly decided in respect of each patient.

The batteries based on metals-ions have the potential to meet the future needs of electric vehicle (EV) applications. This article reviews the key technological developments and scientific challenges of a broad range of Li-ion, Mg-ion and Al-ion batteries for electric vehicles. The fundamental configurations and corresponding reaction mechanisms of metal-ion strategies are tangibly discussed in this review article. After a brief revision of the fundamentals, the performance is analysed among Li-ion, Mg-ion and Al-ion battery technologies. The key parameters for the present compilation are the abundance, the volumetric capacity, the gravimetric capacity, the cycling life, cost and safety. Further, it summarizes the recycling methodologies, strengths and limitations of these batteries. Finally, future directions of all these batteries are highlighted and discussed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We evaluated the clinical histories, motor and pulmonary functions, cardiac phenotypes and GAA genotypes of an Indian cohort of twenty patients with late onset Pompe disease (LOPD) in this multi-centre study. A mean age at onset of symptoms and diagnosis of 9.9 ± 9.7 years and 15.8 ± 12.1 years respectively was identified. All patients had lower extremity limb-girdle muscle weakness. Seven required ventilatory support and seven used mobility assists. Of the four who used both assists, two received ventilatory support prior to wheelchair use. Cardiac involvement was seen in eight patients with various combinations of left ventricular hypertrophy, tricuspid regurgitation, cardiomyopathy, dilated ventricles with biventricular dysfunction and aortic regurgitation. Amongst 20 biochemically diagnosed patients (low residual GAA enzyme activity) GAA genotypes of 19 patients identified homozygous variants in eight and compound heterozygous in 11: 27 missense, 3 nonsense, 2 initiator codon, 3 splice site and one deletion. Nine variants in 7 patients were novel. The leaky Caucasian, splice site LOPD variant, c.-32-13T>G mutation was absent. This first study from India provides an insight into a more severe LOPD phenotype with earlier disease onset at 9.9 years compared to 33.3 years in Caucasian patients, and cardiac involvement more than previously reported. The need for improvement in awareness and diagnosis of LOPD in India is highlighted., Competing Interests: Declaration of Competing Interest Access to ERT (alglucosidase alfa) is provided under the Indian Charitable Access Program (INCAP) of Sanofi Genzyme for patients of authors RDP, NG, SN, SJ, MK, MM, MB and ICV. The association is purely academic, and no financial compensation is provided. The authors are also committee members of the INCAP and/or CAP programs. The authors declare no other conflicts of interest. PSK is a member of the IMAB (India Medical Advisory Board) and an advisor within the INCAP. PSK has received research/grant support from Sanofi Genzyme, Valerion Therapeutics, and Amicus Therapeutics. PSK has received consulting fees and honoraria from Sanofi Genzyme, Amicus Therapeutics, Maze Therapeutics and Asklepios Biopharmaceutical, Inc. (AskBio). PSK is a member of the Pompe and Gaucher Disease Registry Advisory Board for Sanofi Genzyme, Amicus Therapeutics, and Baebies. PSK has equity in Asklepios Biopharmaceutical, Inc. (AskBio), which is developing gene therapy for Pompe disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Understanding the structure-function of inclusion bodies (IBs) in the last two decades has led to the development of several mild solubilization buffers for the improved recovery of bioactive proteins. The recently developed freeze-thaw-based inclusion body protein solubilization method has received a great deal of attention due to its simplicity and cost-effectiveness. The present report investigates the reproducibility, efficiency, and plausible mechanism of the freeze-thaw-based IB solubilization. The percentage recovery of functionally active protein species of human growth hormone (hGH) and L-asparaginase from their IBs in Escherichia coli and the quality attributes associated with the freeze-thaw-based solubilization method were analyzed in detail. The overall yield of the purified hGH and L-asparaginase protein was found to be around 14 and 25%, respectively. Both purified proteins had functionally active species lower than that observed with commercial proteins. Biophysical and biochemical analyses revealed that the formation of soluble aggregates was a major limitation in the case of tough IB protein like hGH. On the other hand, the destabilization of soft IB protein like L-asparaginase led to the poor recovery of functionally active protein species. Our study provides insight into the advantages, disadvantages, and molecular-structural information associated with the freeze-thaw-based solubilization method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Singhvi, Verma, Panwar, Wani, Singh, Qudratullah, Chakraborty, Saneja, Sarkar and Panda.)

An emerging experimental framework suggests that plants under biotic stress may actively seek help from soil microbes, but empirical evidence underlying such a 'cry for help' strategy is limited. We used integrated microbial community profiling, pathogen and plant transcriptive gene quantification and culture-based methods to systematically investigate a three-way interaction between the wheat plant, wheat-associated microbiomes and Fusarium pseudograminearum (Fp). A clear enrichment of a dominant bacterium, Stenotrophomonas rhizophila (SR80), was observed in both the rhizosphere and root endosphere of Fp-infected wheat. SR80 reached 3.7 × 10 7 cells g -1 in the rhizosphere and accounted for up to 11.4% of the microbes in the root endosphere. Its abundance had a positive linear correlation with the pathogen load at base stems and expression of multiple defence genes in top leaves. Upon re-introduction in soils, SR80 enhanced plant growth, both the below-ground and above-ground, and induced strong disease resistance by boosting plant defence in the above-ground plant parts, but only when the pathogen was present. Together, the bacterium SR80 seems to have acted as an early warning system for plant defence. This work provides novel evidence for the potential protection of plants against pathogens by an enriched beneficial microbe via modulation of the plant immune system., (© 2020 The Authors New Phytologist © 2020 New Phytologist Foundation.)

Coronaviruses are the paradigm of emerging 21 st century zoonotic viruses, triggering numerous outbreaks and a severe global health crisis. The current COVID-19 pandemic caused by SARS-CoV-2 has affected more than 51 million people across the globe as of 12 November 2020. The crown-like spikes on the surface of the virion are the unique structural feature of viruses in the family Coronaviridae. The spike (S) protein adopts distinct conformations while mediating entry of the virus into the host. This multifunctional protein mediates the entry process by recognizing its receptor on the host cell, followed by the fusion of the viral membrane with the host cell membrane. This review article focuses on the structural and functional comparison of S proteins of the human betacoronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we review the current state of knowledge about receptor recognition, the membrane fusion mechanism, structural epitopes, and glycosylation sites of the S proteins of these viruses. We further discuss various vaccines and other therapeutics such as monoclonal antibodies, peptides, and small molecules based on the S protein of these three viruses.

Objectives: Diagnosis of lysosomal storage disorders (LSDs) remains challenging due to wide clinical, biochemical and molecular heterogeneity. The study applies a combined biochemical and genetic approach to diagnose symptomatic Indian patients of Pompe, Fabry, Gaucher and Hurler disease to generate a comprehensive dataset of pathogenic variants for these disorders., Design & Methods: Symptomatic patients were biochemically diagnosed by fluorometric methods and molecular confirmation was carried out by gene sequencing. Genetic variants were analyzed according to the ACMG/AMP 2015 variant interpretation guidelines., Results: Amongst the 2181 suspected patients, 285 (13%) were biochemically diagnosed. Of these, 22.5% (64/285) diagnosed with Pompe disease harboured c.1933G>A, c.1A>G, c.1927G>A and c.2783G>C as common and 10 novel pathogenic variants while 7.4% (21/285) patients diagnosed with Fabry disease carried c.851T>C, c.902G>A, c.905A>C and c.1212_1234del as frequent disease-causing variants along with 7 novel pathogenic variants. As many as 48.4% (138/285) patients were diagnosed with Gaucher disease and had c.1448T>C as the most common pathogenic variant followed by c.1342G>C and c.754T>C with 7 previously unreported disease-causing variants and in the 21.7% (62/285) diagnosed cases of Hurler disease, c.1469T>C, c.754delC c.568_581del and c.1898C>T were identified as the most common causative variants along with 21 novel pathogenic variants., Conclusion: This comprehensive data set of disease-causing frequent and novel pathogenic variants reported for the first time in such a large patient cohort for each of these four LSDs from the Indian sub-continent, along with their biochemical and clinical spectrum will contribute towards providing definitive diagnosis and treatment, identifying carrier status, as well as in counselling prenatal cases to reduce the morbidity and mortality associated with these disorders., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Cancer is a community health hazard which progress at a fatal rate in various countries across the globe. An agent used for chemotherapy should exhibit ideal properties to be an effective anticancer medicine. The chemotherapeutic medicines used for treatment of various cancers are, gemcitabine, paclitaxel, etoposide, methotrexate, cisplatin, doxorubicin and 5-fluorouracil. However, many of these agents present nonspecific systemic toxicity that prevents their treatment efficiency. Of all, gemcitabine has shown to be an active agent against colon, pancreatic, colon, ovarian, breast, head and neck and lung cancers in amalgamation with various anticancer agents. Gemcitabine is considered a gold-standard and the first FDA approved agent used as a monotherapy in management of advanced pancreatic cancers. However due to its poor pharmacokinetics, there is need of newer drug delivery system for efficient action. Nanotechnology has shown to be an emerging trend in field of medicine in providing novel modalities for cancer treatment. Various nanocarriers have the potential to deliver the drug at the desired site to obtain information about diagnosis and treatment of cancer. This review highlights on various nanocarriers like polymeric nanoparticles, solid lipid nanoparticles, mesoporous silica nanoparticles, magnetic nanoparticles, micelles, liposomes, dendrimers, gold nanoparticles and combination approaches for delivery of gemcitabine for cancer therapy. The co-encapsulation and concurrent delivery of Gem with other anticancer agents can enhance drug action at the cancer site with reduced side effects., (Copyright © 2020. Published by Elsevier B.V.)

Angiomatous meningioma is a rare variant tumor classified as WHO grade 1 meningioma and accounts for about 2.1% of all meningioma. Their clinical presentation, surgical management, and prognosis are almost similar to the classical meningioma. Despite of benign nature and being comparatively small in size, they look aggressive on radiology images like massive peritumoral edema and intense contrast enhancement. Being a unique subtype of meningioma, the studies on angiomatous meningioma are very limited. In this cross sectional retrospective study, we described the clinical presentation, radiology, histopathological features and differential diagnosis of 30 cases of angiomatous meningioma from a single centre. The clinical parameters include demographic profile, symptoms and radiological findings including location, extent, pattern, histopathology with World Health Organization (WHO) grade-2016, extent of tumour excision, recurrence and surgical outcome. Incidence of angiomatous meningioma in our study was 2.46% with male predominance. The most common location in our study was convexity. 27 out of 30 had histopathology reports of angiomatous meningioma and 3 had lipoangiomatous meningioma. The high vascularity and disproportionate peri-tumoral edema makes it a surgical challenge for excision. The complications and surgical outcome were analysed. The radiological anticipation of tumour subtype, meticulous pre-operative planning and intraoperative precautions remains a key for success., 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 © 2020 Elsevier Ltd. All rights reserved.)

Attachment of a virus with a specific receptor on the cell surface is the first and foremost step in virus infection. In case of enveloped viruses, their interaction with the host cell receptor is mediated by viral encoded glycoproteins on its envelope, a host derived lipid bilayer. Since, virus entry is a multistep process, after receptor recognition, envelope proteins mediate internalisation of virus particles into the host cell. Envelope glycoproteins are the first proteins that the host immune system encounters upon infection. Thus, envelope proteins are important drug target with multiple strategies to inhibit entry of the virus into the host. Currently, there are very few drugs that function as envelope protein inhibitors which are approved for human use. Here, we reviewed different classes of envelope proteins of various viruses and emphasised the use of small molecules to inhibit fusion of envelope proteins. Based on the available information in the literature, envelope proteins can be important drug targets and small molecules inhibitors can serve as potential antiviral drugs to block viral infection at an initial stage.

Background: A pneumonia outbreak of unknown etiology took place in Wuhan, Hubei province, China and spread quickly worldwide in December 2019. Chinese Center for Disease Control and Prevention identified a novel beta-coronavirus called 2019-nCoV, now officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) that is responsible for the pandemic. The coronavirus COVID-19 affected 215 countries and territories around the world and more than 99 hundred thousand people at present (Nature Nanotechnology, 2020). At present, there are no specific vaccines or treatments available for COVID-19. However, there are many ongoing clinical trials evaluating potential treatments. At this time the experts recommend precautions such as social distancing, hand washing, and wearing face masks to reduce disease transmission. This review article aims to improve the readers' awareness towards the important role of mobile technology for SARS-CoV-2., Methodology: To achieve this objective, we performed a COVID-19 literature review from various sources that include data from the published articles as well as World Health Organization reports on coronavirus disease and how mobile technology is useful to fight against this disease., Results: Mobile technology can be helpful in mapping disease spread and provides an easy way to provide awareness that promotes safety and adoption of necessary precautions to mitigate and stop community transmission., Conclusion: The spread rate of COVID-19 is very high and until now no vaccines are available to control this disease. To this end we should leverage other avenues such as digital technologies to protect ourselves from this disease. Mobile technology such as smartphones are playing an important role in this pandemic, by launching apps to track coronavirus infected people. These apps are very easy to use and provide self-isolation guidelines as well as other safety tips., Competing Interests: Amar Shankar Mishra is employed by CIPL, New Delhi and the authors declare that they have no competing interests., (© 2020 Verma and Mishra.)

Regulation of gene expression programs is crucial for the survival of microbial pathogens in host environments and for their ability to cause disease. Here we investigated the epigenetic regulator RSC (Remodels the Structure of Chromatin) in the most prevalent human fungal pathogen Candida albicans. Biochemical analysis showed that CaRSC comprises 13 subunits and contains two novel non-essential members, which we named Nri1 and Nri2 (Novel RSC Interactors) that are exclusive to the CTG clade of Saccharomycotina. Genetic analysis showed distinct essentiality of C. albicans RSC subunits compared to model fungal species suggesting functional and structural divergence of RSC functions in this fungal pathogen. Transcriptomic and proteomic profiling of a conditional mutant of the essential catalytic subunit gene STH1 demonstrated global roles of RSC in C. albicans biology, with the majority of growth-related processes affected, as well as mis-regulation of genes involved in morphotype switching, host-pathogen interaction and adaptive fitness. We further assessed the functions of non-essential CaRSC subunits, showing that the novel subunit Nri1 and the bromodomain subunit Rsc4 play roles in filamentation and stress responses; and also interacted at the genetic level to regulate cell viability. Consistent with these roles, Rsc4 is required for full virulence of C. albicans in the murine model of systemic infection. Taken together, our data builds the first comprehensive study of the composition and roles of RSC in C. albicans, showing both conserved and distinct features compared to model fungal systems. The study illuminates how C. albicans uses RSC-dependent transcriptional regulation to respond to environmental signals and drive survival fitness and virulence in mammals., Competing Interests: The authors have declared that no competing interests exist.

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome of Vibrio cholerae harbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome of V. cholerae and examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in the V. cholerae chromosome. We have deleted more than 250 acquired genes from 6 different loci in the V. cholerae chromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, including Escherichia coli In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypass V. cholerae immunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome of V. cholerae to remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes., Competing Interests: The authors declare no competing interest.

The NLRP3 inflammasome has emerged as a central immune regulator that senses virulence factors expressed by microbial pathogens for triggering inflammation. Inflammation can be harmful and therefore this response must be tightly controlled. The mechanisms by which immune cells, such as macrophages, discriminate benign from pathogenic microbes to control the NLRP3 inflammasome remain poorly defined. Here we used live cell imaging coupled with a compendium of diverse clinical isolates to define how macrophages respond and activate NLRP3 when faced with the human yeast commensal and pathogen Candida albicans. We show that metabolic competition by C. albicans, rather than virulence traits such as hyphal formation, activates NLRP3 in macrophages. Inflammasome activation is triggered by glucose starvation in macrophages, which occurs when fungal load increases sufficiently to outcompete macrophages for glucose. Consistently, reducing Candida's ability to compete for glucose and increasing glucose availability for macrophages tames inflammatory responses. We define the mechanistic requirements for glucose starvation-dependent inflammasome activation by Candida and show that it leads to inflammatory cytokine production, but it does not trigger pyroptotic macrophage death. Pyroptosis occurs only with some Candida isolates and only under specific experimental conditions, whereas inflammasome activation by glucose starvation is broadly relevant. In conclusion, macrophages use their metabolic status, specifically glucose metabolism, to sense fungal metabolic activity and activate NLRP3 when microbial load increases. Therefore, a major consequence of Candida-induced glucose starvation in macrophages is activation of inflammatory responses, with implications for understanding how metabolism modulates inflammation in fungal infections., Competing Interests: The authors have declared that no competing interests exist. We note that MCC950 is a compound that is in the public domain. More broadly AABR is inventor on three patents on novel NLRP3 inhibitors:WO2016131098, WO2017140778, WO2018215818.

In the present study, we have developed an anti-bacterial as well as mechanically-strengthened super protective coating material, which can be used as a marine antifouling paint. In this research, silica, titania and silica-titania core-shell nanoparticles were individually prepared via sol-gel and peptization processes. The idea behind the synthesis of core-shell nanoparticles was to utilize the mechanical strength of silica and the antimicrobial property of TiO 2 together. These nanoparticles were characterized via dynamic light scattering, UV-Visible spectroscopy, X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. Coating formulations were developed with two types of model binders, i.e. , solvent-based polyurethane and water-based poly-acrylic, containing all nanoparticles individually at various concentrations for a better comparative study. These coating formulations were applied onto mild steel for anti-bacterial testing that was performed against Escherichia coli and Bacillus . The nanoparticle concentration was varied from 1% (wt) to 6% (wt). The best anti-bacterial result was obtained with 4% (wt) of silica-titania core-shell nanoparticles prepared via the peptization process among all the nanoparticles. The scratch testing was performed successfully using an Erichsen scratch tester; the formulated PU coating passed up-to 20 N load with good adhesion, impact resistance, flexibility and has shown satisfactory anti-corrosion performance., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The HEP II (Heparin-binding site II) region of fibronectin (FN) containing domain III 14 plays a crucial role in cell adhesion and migration through heparin-binding on the cell surface. There are two such fibronectin heparin interacting peptide (FHIP I and FHIP II) sequences present in HEP II. However, the molecular principles by which these sites orchestrate heparin-binding processes are poorly understood. Such knowledge would have great implications in the therapeutic targeting of FN. With this aim, we have explored the binding studies of FHIP I and FHIP II with heparin using various biophysical methods. A fluorescence melting study specifically revealed the preference of heparin for domain III in FN, indicating the key contribution of FHIP I and FHIP II in heparin binding. In isothermal titration calorimetry (ITC), the higher binding affinity observed for FHIP II (∼10 7 mol -1 ) compared to FHIP I (∼10 6 mol -1 ) is expected due to the presence of a superior cluster of Arg and Lys residues in FHIP II, which can facilitate specific H-bonding interactions with heparin. Based on heat capacity changes, the key role of H-bonding, electrostatic and hydrophobic interactions was demonstrated in binding. Finally, the molecular docking and MD simulation results reinforced that the interaction of heparin (dodecasaccharide) is stronger and stable with the FHIP II peptide. The results described here suggest that these peptides provide all the structural and thermodynamic elements necessary for heparin-binding of HEP II of FN. Subsequently, it can be concluded that FHIP II could be a better location for therapeutic intervention in cell adhesion activity by FN., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Identification of multiple histone acylations diversifies transcriptional control by metabolism, but their functions are incompletely defined. Here we report evidence of histone crotonylation in the human fungal pathogen Candida albicans. We define the enzymes that regulate crotonylation and show its dynamic control by environmental signals: carbon sources, the short-chain fatty acids butyrate and crotonate, and cell wall stress. Crotonate regulates stress-responsive transcription and rescues C. albicans from cell wall stress, indicating broad impact on cell biology. The YEATS domain crotonylation readers Taf14 and Yaf9 are required for C. albicans virulence, and Taf14 controls gene expression, stress resistance, and invasive growth via its chromatin reader function. Blocking the Taf14 C terminus with a tag reduced virulence, suggesting that inhibiting Taf14 interactions with chromatin regulators impairs function. Our findings shed light on the regulation of histone crotonylation and the functions of the YEATS proteins in eukaryotic pathogen biology and fungal infections., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)