Exposure to potentially toxic elements (PTEs) and the risk of male infertility- A Systematic review and meta-analysis.

BACKGROUND: Infertility has been defined as a failure to conceive for at least 12 months of regular unprotected sexual intercourse. The male factors are responsible for about 50 % of cases. Various factors such as endocrine, immunological, genetic, exposure to toxicants, and idiopathic factors are involved in male infertility. Recently, the role of PTEs in reproductive performance has been explored by various studies. OBJECTIVES: Current systematic review and meta-analysis have been carried out to compile and statistically analyze the findings of relevant studies and reach some conclusion. METHODOLOGY: A literature search was done according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines in three scientific literature databases; PubMed, Google Scholar, and Science Direct. Meta-analysis was performed using Review Manager 5.4 software. The study's protocol was registered in PROSPERO (CRD42023465776). RESULTS: Meta-analysis of lead in the blood of infertile cases and healthy controls indicated a significant association with male infertility, observed standard mean difference (SMD) was 0.67 at 95 % confidence interval (CI) (0.07, 1.28), and p = 0.03. In the case of lead analysis in semen, the values are as follows: SMD = 1.19 at 95 % CI (0.42, 1.96) with p = 0.002. Significant association appears for cadmium in semen with SMD 0.92 at 95 % CI (0.54, 1.29) and p < 0.00001. No significant association was observed for arsenic, barium, and mercury in blood. CONCLUSION: Most of the studies focus on the detection of PTE in semen samples followed by blood as sample type. Lead and cadmium exposure is significantly associated with male infertility. However, non-significant results for arsenic, barium, and mercury are observed.

Association of COVID with Mycosis in General.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 is a respiratory disease which created havoc worldwide, was accompanied by another peculiar, otherwise rare, secondary fungal infection Mucormycosis which was observed at exceptionally high incidence in India during the second wave of COVID-19. The article explores possible links between the two infectious diseases to understand a higher-than-normal occurrence of Mucormycosis in COVID-19 patients. Coronavirus enters the patients through ACE-2 and many other receptors like- NRP-1, TfR, CD-126, and CD-26. Virus bind to cells possessing these receptors and affect their proper functioning, disturbing homeostatic metabolism and resulting in conditions like hyperglycemia, Diabetic Ketoacidosis (DKA), low serum pH, iron overload, anemia, hypoxia, and immunosuppression as explained in the article. All these outcomes provide a very supportive environment for the attack and spread of Mucormycosis fungi. The major receptor for Mucormycosis in humans is the GRP-78. Its expression is upregulated by coronavirus entry and by hyperferritinemia, hyperglycemia, and acidic conditions prevalent in COVID patients, thus providing an easy entry for the fungal species. Upregulation of GRP-78 furthermore damages pancreatic ß-cells and intensifies hyperglycemia, showing quite a synergic relationship. Inordinate rise of Mucormycosis cases in India might be explained by facts like- India possessing a large proportion of diabetic patients, emergence of a very deadly strain of coronavirus- Delta strain, higher doses of steroids and antibodies used to treat patients against this strain, overburdened health care services, sudden much higher need of oxygen supply and use of industrial oxygen could explain the Mucormycosis outbreak observed in India during the second wave of COVID-19. OBJECTIVE: The present review discusses the functional interdependence between COVID-19 and Mucormycosis and summarizes the possible synergic links between COVID and Mucormycosis. CONCLUSION: The receptors and metabolic pathways affected by COVID-19 result in severe physiological conditions- hyperglycemia, DKA, anemia, iron overload, immunosuppression, and hypoxia. All these conditions not only increase the expression of GRP-78, the major receptor for entry of fungi but also play a crucial role in providing quality media for Mucormycosis fungus to establish and grow. Hence explains the fungal epidemic observed in India during the second wave of COVID-19 in India.

The development of thymol-isatin hybrids as broad-spectrum antibacterial agents with potent anti-MRSA activity.

Bacterial resistance toward available therapeutic agents has become a nightmare for the healthcare system, causing significant mortality as well as prolonged hospitalization, thereby needing the urgent attention of research groups working on antimicrobial drug development worldwide. Molecular hybridization is a well-established tool for developing multifunctional compounds to tackle drug resistance. Inspired by the antibacterial profiles of isatin and thymol, along with the efficiency of a triazole linker in molecular hybridization, herein, we report the design, synthesis and antibacterial activity of a novel series of triazole tethered thymol-isatin hybrids. Most of the hybrids exhibited a broad-spectrum antibacterial efficacy against standard human pathogenic as well as clinically isolated multidrug-resistant bacterial strains listed in the WHO's 'priority pathogen' list and also in the ESKAPE group. Among them, hybrid compound AS8 was the most effective against methicillin-resistant Staphylococcus aureus (MIC = 1.9 µM and MBC = 3.9 µM), exhibiting biofilm inhibitory potential. AS8 exhibited dehydrosqualene synthase (CrtM) inhibitory potential in MRSA and decreased the production of virulence factor staphyloxanthin, which is one of the key mechanisms of its anti-MRSA efficacy, which was further supported by molecular docking and simulation studies. Moreover, AS8 was found to be non-toxic and showed a potent in vivo antibacterial efficacy (90% survival at 10 mg kg-1) as well as a modulated immune response in the larva-based (Galleria mellonella) model of systemic infections. Overall findings confirmed that AS8 can be a promising candidate or take the lead in the treatment and further drug development against drug-resistant infectious diseases, especially against MRSA infections.

Exploring Microbial Contributions to Nutraceutical Production: From Natural to Designed Foods.

For ages, societies throughout the world have used fermentation as a traditional method for food processing and preservation, helping to create a wide range of staple foods and delicacies. Due to its possible health advantages, mostly attributable to the inclusion of bioactive substances known as nutraceuticals, fermented foods have attracted a lot of interest recently. This in-depth analysis examines the wide range of nutraceuticals present in fermented foods, as well as how they are made, what health benefits they may have, and how they may be used in the nutraceutical and functional food businesses. By stressing how important fermented foods are as a source of beneficial bioactive components that support human health and well-being. Numerous bioactive substances found in fermented foods have been the subject of recent scientific studies. These molecules may find use in the pharmaceutical and nutraceutical sectors. Streptococcus thermophilus, Lactobacillus gasseri, Lactobacillus delbrueckii, Lactobacillus bulgaricus, and Lactobacillus johnsonii are just a few examples of the probiotic bacteria that live in fermented foods and formulas. This review elucidates the importance of microorganisms sourced from fermented foods as potent agents for diverse nutraceuticals and their potential role in preventing various diseases whilst serving as functional food supplements.

Development and characterization of rice bran-gum Arabic based encapsulated biofertilizer for enhanced shelf life and controlled bacterial release.

Introduction: Currently, microbe-based approaches are being tested to address nutrient deficiencies and enhance nutrient use efficiency in crops. However, these bioinoculants have been unsuccessful at the commercial level due to differences in field and in-vivo conditions. Thus, to enhance bacterial stability, microbial formulations are considered, which will provide an appropriate microenvironment and protection to the bacteria ensuring better rhizospheric-colonization. Methods: The present study aimed to develop a phosphobacterium-based encapsulated biofertilizer using the ion-chelation method, wherein a bacterial strain, Myroid gitamensis was mixed with a composite solution containing rice bran (RB), gum Arabic (GA), tricalcium phosphate, and alginate to develop low-cost and slow-release microbeads. The developed microbead was studied for encapsulation efficiency, shape, size, external morphology, shelf-life, soil release behavior, and biodegradability and characterized using SEM, FTIR, and XRD. Further, the wheat growth-promoting potential of microbeads was studied. Results: The developed microbeads showed an encapsulation efficiency of 94.11%. The air-dried beads stored at 4°C were favorable for bacterial survival for upto 6 months. Microbeads showed 99.75% degradation within 110 days of incubation showing the bio-sustainable nature of the beads. The application of dried formulations to the pot-grown wheat seedlings resulted in a higher germination rate, shoot length, root length, fresh weight, dry weight of the seedlings, and higher potassium and phosphorus uptake in wheat. Discussion: This study, for the first time, provides evidence that compared to liquid biofertilizers, the RB-GA encapsulated bacteria have better potential of enhancing wheat growth and can be foreseen as a future fertilizer option for wheat.

In silico molecular modelling studies and antibiofilm efficacy of shikonin against Candida albicans: mechanistic insight.

In the recent past, the occurrence of fungal infections has increased drastically and candidiasis, caused prominently by Candida albicans, is foremost among them which has caused significant mortality and morbidity majorly in immune-compromised patients. Shikonin is a well-known natural naphthazarin derivative with promising antifungal efficacy, but it's mechanism of action is still unclear. Keeping this in view, present work was designed to get a mechanistic insight of anti-candida efficacy of shikonin via in vitro experiments and in situ molecular modelling studies. The current exploratory study is based on research that uses both qualitative and quantitative techniques, including minimum inhibitory concentration, minimum biofilm inhibitory concentration, time kill assay, cell cycle analysis and apoptotic assays, static biofilm formation assays, microscopic biofilm assessment assays, ergosterol content estimation and molecular docking/simulation studies. The study revealed a notable effect of shikonin against Candida albicans, including retardation of biofilms. Shikonin, with its increasing concentration leads to candidal cell apoptosis and necrosis establishing its dose-dependent effect. Additionally, it exhibited fungicidal activity via a mechanism of action likely related to ergosterol complexation which was further corroborated by molecular docking and simulation studies.

Morpho-biochemical Responses and Disturbed Redox Homeostasis in Barley Under Benzyl-butyl Phthalate Stress.

The present study is aimed to address the morphometric consequences, yield attributes, and biochemical responses of barley plants under the stress of an endocrine disruptor i.e., benzyl-butyl phthalate (BBP). The morphometric analyses (plant length, dry weight, and net primary productivity) revealed that the inhibition induced by BBP was concentration- and time-dependent. The seed weight and the number of seeds per spike have also significantly declined with an increase in BBP doses. Similarly, BBP exhibited significant alterations over the control in the biochemical indices viz., pigments, sugars, proteins, proline, malonaldehyde, and hydrogen peroxide contents of barley plants. Furthermore, BBP stress negatively influenced the activities of antioxidative enzymes viz., SOD, POD, CAT, APX, and GR of barley with an increase in doses and exposure durations due to the over-produced reactive oxygen species. The uptake and transport of BBP were determined and observed as a responsible cue for these toxicological implications in barley plants under BBP exposure. The correlation of barley plants' morpho-biochemical responses with BBP uptake and transport was also established using Pearson's correlation. Thus, this study indicated the toxicological behavior of meagerly explored phthalate (i.e., BBP) in the crop plant and these observations can be utilized for the generation of tolerant cultivars.

Long term culturing of CHO cells: phenotypic drift and quality attributes of the expressed monoclonal antibody.

OBJECTIVE: Establishing cell lines with enhanced protein production requires a deep understanding of the cellular dynamics and cell line stability. The aim of the study is to investigate the impact of long term culturing (LTC) on cell morphology and altered cellular functions possibly leading to phenotypic drift, impacting product yield and quality. Study highlights the orthogonal cellular and analytical assay toolbox to define cell line stability for optimal culture performance and product quality. METHODS: We investigated recombinant monoclonal antibody (mAb) expressing CHO cells for 60 passages or 180 generations and assessed the cell growth characteristics and morphology by confocal and scanning electron microscopy. Quality attributes of expressed mAb is accessed by performing charge variants, glycan, and host cell protein analysis. RESULTS: We observed a 1.65-fold increase in viable cell population and 1.3-fold increase in cell specific growth rate. A 2.5-fold decrease in antibody titer and abatement of actin filament indicate cellular phenotypic drift. Mitochondrial membrane potential (∆ΨM) signified cell health and metabolic activity during LTC. Host cell protein production is reduced by 1.8-fold. Charge heterogeneity was perturbed with 12.5% and 43% reduction in abundance of acidic and basic charge variants respectively. Glycan profile indicated a decline in fucosylation with 17% increase in galactosylated species as compared with early passaged cells. CONCLUSION: LTC impinges on cellular phenotype as well as the quality of the expressed antibody, suggesting a defined subculturing limit to retain stable protein expression and cell morphology to achieve consistent product quality. Study signifies the changes in cellular and metabolic markers, suggesting cellular and analytical toolbox which could play a significant role in defining cell characteristics and ensured product quality.

Maternal candidate gene variants, epigenetic factors, and susceptibility to idiopathic recurrent pregnancy loss: A systematic review.

BACKGROUND: Recurrent pregnancy loss is defined as the loss of two or more pregnancies and is a distressing condition for couples. OBJECTIVE: To investigate the relationship between variants in the candidate susceptibility genes and epigenetic factors to identify risk factors for idiopathic recurrent pregnancy loss (iRPL). SEARCH STRATEGY: A systematic literature search was performed using PubMed, Google Scholar, ScienceDirect, and Scopus databases. Insilico analysis was carried out using ShinyGO and STRING software. SELECTION CRITERIA: Research papers examining the association between variations in genetic and epigenetic factors and iRPL. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors. MAIN RESULTS: In total, 83 research papers were finally selected for the present study. Among all the genes involved in the pathogenesis of recurrent pregnancy loss, polymorphisms in IL superfamily genes, VEGF, ESR, and MTHFR were the most investigated. CONCLUSION: Polymorphisms in angiogenesis, immune tolerance, and thrombophilia pathway genes, which occur independently or synergistically, may lead to various complications during fetal development. Identification of multi-allele risk variants and epigenetic factors in women will be helpful in the identification of high-risk pregnancies. PROSPERO REGISTRATION NUMBER: Prospero CRD42021287315.

Factors affecting stress levels in parents of surgical neonates: A prospective observational study.

BACKGROUND: There is a paucity of research focusing on the stress levels in parents of newborns undergoing surgery. Resource challenged systems have to deal with overcrowding, a shortage of workforce along with demographic and socioeconomic issues like delayed presentations and out of pocket expenses. The primary objective of this study was to understand the factors associated with stress in the parents of these congenitally malformed neonates. METHODOLOGY: This was a prospective cohort study, which was conducted in a neonatal surgical ICU of a tertiary care teaching hospital. Factors affecting stress levels in parents of surgical neonates were studied in 100 participants. A multi-dimensional questionnaire - The PSS: NICU score was utilized in the study. The parents were interviewed on Day 3-5 after surgery. RESULT: 59% of the respondents were fathers. The majority of the parents were in the age bracket of 24 to 35 years. The mean scores for the subscales sights and sounds, looks and behavior and alteration in the parental role were 3.24±0.8, 3.52±0.63, 3.55±0.8 and 2.8 ± 0.9 respectively. The highest level of stress was found in the domains of alteration of parental role and infant appearance and behavior. Comparisons showed significantly higher maternal scores in all the domains. Overall stress scores were highest for abdominal wall defects. CONCLUSION: Parents of neonates undergoing surgery suffer from significant stress levels and appropriate counseling targeted towards specific stressors is required to allay this important parental issue.

Development of a cost-effective ex vivo lung perfusion system for lung transplantation in India.

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled. This system was used on five pairs of lungs retrieved from brain-dead organ donors. The lungs were ventilated and pulmonary circulation was continuously perfused with a solution containing oxygen and nutrients for four hours. The system was tested without red blood cells (RBCs) added to the solution (acellular group; n=3; A1, A2 and A3) and also with RBCs added to the solution (cellular group; n=2; C1 and C2). Results: The EVLP system was successfully used in four (A1, A2, A3 and C2) of the five lung pairs. Mechanical and gas exchange functions of the lungs were preserved in these lung pairs. One lung pair (C1) worsened and developed pulmonary oedema. Histopathological examination of all five lung pairs was satisfactory at the end of the procedure. Major challenges faced were leakage of solution from the system and obstruction to drainage of RBCs containing solution from the lungs. Interpretation & conclusions: The results of the present study suggest that, it is possible to maintain the lungs retrieved for transplantation in a physiological condition using a locally prepared EVLP system and a solution without RBCs.

Microbial endophytes: application towards sustainable agriculture and food security.

Microbial endophytes are ubiquitous and exist in each recognised plant species reported till date. Within the host plant, the entire community of microbes lives non-invasively within the active internal tissues without causing any harm to the plant. Endophytes interact with their host plant via metabolic communication enables them to generate signal molecules. In addition, the host plant's genetic recombination with endophytes helps them to imitate the host's physicochemical functions and develop identical active molecules. Therefore, when cultured separately, they begin producing the host plant phytochemicals. The fungal species Penicillium chrysogenum has portrayed the glory days of antibiotics with the invention of the antibiotic penicillin. Therefore, fungi have substantially supported social health by developing many bioactive molecules utilised as antioxidant, antibacterial, antiviral, immunomodulatory and anticancerous agents. But plant-related microbes have emanated as fountainheads of biologically functional compounds with higher levels of medicinal perspective in recent years. Researchers have been motivated by the endless need for potent drugs to investigate alternate ways to find new endophytes and bioactive molecules, which tend to be a probable aim for drug discovery. The current research trends with these promising endophytic organisms are reviewed in this review paper. KEY POINTS: • Identified 54 important bioactive compounds as agricultural relevance • Role of genome mining of endophytes and "Multi-Omics" tools in sustainable agriculture • A thorough description and graphical presentation of agricultural significance of plant endophytes.

Music as an aid to Allay Anxiety in Patients Undergoing Orthopedic Surgeries under Spinal Anesthesia.

Introduction: Patients undergoing surgery are anxious owing to the surgery, anesthesia, and unfamiliar environment of the operation theater. This anxiety can hamper the health and recovery of the patients. Among various nonpharmacologic modalities available, music can be used as a coping strategy to change uncomfortable conditions to the pleasant ones. Aims: To evaluate the role of music on perioperative anxiety, hemodynamic parameters, and patient satisfaction in patients undergoing orthopedic surgeries under spinal anesthesia. Settings and design: Tertiary care hospital, randomized control trial. Materials and methods: : The study was conducted after approval by Hospital Ethical Committee on 70 adult patients of either gender scheduled to undergo lower limb surgeries under spinal anesthesia. In group M (n = 35), patients listened to standard relaxation music, and in group C (n = 35), patients listened to standard operation theater noise tape through noise canceling headphones. The intraoperative hemodynamic parameters were recorded. Perioperative anxiety was assessed using visual analog scale for anxiety. Sedation score was observed using observer's assessment of alertness/sedation scale. Patient's satisfaction was also assessed in both the groups. Statistical analysis: Student t test, Chi-squared test, and paired sample t test. Results: : In group M, heart rate was lower when compared with group C. The difference was statistically significant at 10 minutes of assessment (P = 0.003) and statistically highly significant (P < 0.001) for rest of the time period. Statistically significant lower respiratory rate was there in group M when compared with group C (P = 0.05). Patients were more satisfied in the music group when compared with control group. Conclusion: The potential of music therapy can be used to allay patient anxiety, stabilize hemodynamics, and improve patient satisfaction.

Uptake of a plasticizer (di-n-butyl phthalate) impacts the biochemical and physiological responses of barley.

BACKGROUND: DBP is one of the most commonly used plasticizers for imparting desirable properties to polymers. The introduction of phthalates is reported to have occurred in the late 1920s, and there has been a significant rise in their release into the environment in past decades due to a lack of covalent bonding with the parent matrix. Because of their numerous applications in day-to-day life, phthalates have become ubiquitous and also classified as endocrine disruptors. Hence, several studies have been conducted to investigate the phthalate-mediated toxicities in animals; however, plants have not been explored to the same amount. METHODS: Therefore, in the present study, the accumulation and translocation along with morpho-physiological perturbations in barley plants after 15, 30, 60, and 120 days of exposure to di-n-butyl phthalate (DBP) are investigated using standard protocols. RESULTS: The maximal accumulation and translocation of DBP in the roots and shoots of barley plants was observed after 60 days of exposure. The exposure of DBP from 15 to 120 days was recorded to decline all the morphological indices (i.e., dry weight, net primary productivity, seed number per spike, and seed weight) of barley plants. The pigments content declined under DBP treatment for all exposure durations except 120 days exposure. Carbohydrate content increased after 15-30 days of exposure afterward it was observed to be decreased under 60 and 120 days of exposure. The protein content was declined in DBP stressed plants for 15-120 days. Proline content was increased in all exposure durations and maximal percent increase was recorded in 120 days of exposure. MDA content showed an increase at earlier exposure durations then followed by a decline in long-term exposure. Hydrogen peroxide content increased at all exposure durations. There were significant alterations observed in the activities of all antioxidative enzymes in comparison to the control. Furthermore, DBP stressed plants after 60 days were analyzed for the macromolecular variations using Fourier transform infrared spectroscopy (FTIR). CONCLUSION: Thus, the outcomes of the current work provide an appraisal of phthalates' uptake and translocation mediated phytotoxic responses in barley plants. These observations can help in developing genetically modified edible plants that are resistant to phthalates uptake, thereby ensuring food security.

Exploration of phytate-mineralizing bacteria with multifarious plant growth-promoting traits.

Phytate-mineralizing bacteria (PMB) with plant growth-promoting activity can be considered as a potential biofertilizer for plant nutrition. PMB catalyzes the conversion of insoluble sugar phosphates, inositols, nucleic acids, phospholipids, nucleotides, phytate, and phytin into soluble forms that can be assimilated by plants. The present study aimed to isolate potential PMB from rhizospheric soils and to study their plant growth-promoting potential for the possible development of a potential phosphobacterium biofertilizer. For this purpose, 34 PMB isolates were isolated that showed potent phytate-mineralizing potential. These isolates were tested for their potential to solubilize tricalcium phosphate (TCP) and for various other plant growth-promoting activities. Significant differences were found among the isolates with regard to phytate mineralization and other plant growth-promoting characteristics. The bacterial isolates biochemically identified as Bacillus, Paenibacillus, Arthrobacter, and Burkholderia exhibited high/medium P solubilization, medium/high phytohormone production, and medium/low siderophore and ammonia production. Among all these isolates, isolate A14 (Burkholderia cenocepacia strain FDAARGOS_7) was the promising isolate with high TCP solubilization, medium phytate mineralization, high enzyme production, medium/high phytohormone production, and medium ammonia production. This strain also showed nitrogen fixation activity, zinc solubilizing potential, potassium solubilization, ACC deaminase production, and catalase production. Hence, it can be concluded that B. cenocepacia can be the potential candidate for biofertilizer development. Future studies are planned for exploring the role of PMB in biofertilizer formulations.

Increased incidence of spontaneous abortions on exposure to cadmium and lead: a systematic review and meta-analysis.

BACKGROUND: Spontaneous abortions are the most severe complication of early pregnancy and are a major reproductive health problem. Although this could be caused due to various cytogenetic, immunological, or endocrinological reasons, role of environmental toxicants cannot be ruled out. In order to explore the role of cadmium and lead in causing spontaneous abortions, current systematic review and meta-analysis had been carried out. METHODOLOGY: Literature search was performed using appropriate keywords in PubMed, Science Direct, Cochrane Library, and Google Scholar databases up to December 25 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Metananalysis was carried out with the help of RevMan software (version 5.3). RESULTS: Meta-analysis of nine studies on cadmium concentrations in blood of women with at least one spontaneous abortions and controls revealed standardized mean difference (SMD)=3.39, 95% CI (2.17, 4.61), with p < .05. Similarly, meta-analysis of eight studies on lead concentrations revealed standardized mean difference (SMD)=6.24, 95% CI (4.34, 8.14), with p < .05. CONCLUSION: Populations exposed to heavy metals such as cadmium and lead are at higher risk of pregnancy loss. Therefore, couples experiencing repeated pregnancy losses may be screened for heavy metal load.

MSMEG_3955 from Mycobacterium smegmatis is a FMN bounded homotrimeric NAD(P)H:Flavin mononucleotide (FMN) oxidoreductase.

BACKGROUND: Tuberculosis (TB) remains an important public health problem since it is the major cause of elevated morbidity and mortality globally. Previous works have shown that Mycobacterium tuberculosis (Mtb); the prime causative agent of the deadly disease has dormancy survival regulator (DosR) regulon, a two-component regulatory system which controls the transcription of more than 50 genes. However, the structure and detailed functions of these DosR regulated genes are largely undetermined. Out of many DosR regulon genes, Rv3131 gets up regulated in hypoxic conditions and was believed to encode for a nitroreductase flavoprotein. The utilization of mycobacteria-specific model systems has greatly added to our understanding of the molecular mechanisms involved in the life cycle and pathogenesis of Mtb. RESULTS: In this study the non-pathogenic mycobacterial model organism Mycobacterium smegmatis (Msmeg) was used to reveal the structure and function of MSMEG_3955; which is a homologue of Rv3131 from Mtb. Using chromatography and spectroscopy techniques it was revealed that cofactor flavin mononucleotide (FMN) was bound to flavoprotein MSMEG_3955. Consistent with the homology modelling predictions, Circular Dichroism (CD) analysis indicated that the MSMEG_3955 is composed of 39.3% α-helix and 24.9% ß-pleated sheets. In contrast to the current notions, the enzymatic assays performed in the present study revealed that MSMEG_3955 was not capable of reducing nitro substrates but showed NADPH dependent FMN oxidoreductase activity. Also, gel permeation chromatography, dynamic light scattering and native acidic gels showed that MSMEG_3955 exists as a homotrimer. Furthermore, the presence of NADPH dependent FMN oxidoreductase and homotrimeric existence could be an alternative function of the protein to help the bacteria survive in dormant state or may be involved in other biochemical pathways. CONCLUSION: MSMEG_3955 is a FMN bound flavoprotein, which exits as a trimer under in vitro conditions. There is no disulphide linkages in between the three protomers of the homotrimer MSMEG_3955. It has a NADPH dependent FMN oxidoreductase activity.

Multipotential Alkaline Protease From a Novel Pyxidicoccus sp. 252: Ecofriendly Replacement to Various Chemical Processes.

A newly isolated alkaline protease-producing myxobacterium was isolated from soil. The strain was identified as Pyxidicoccus sp. S252 on the basis of 16S rRNA sequence analysis. The extracellular alkaline proteases produced by isolate S252 (PyCP) was optimally active in the pH range of 11.0-12.0 and temperature range of 40-50°C The zymogram of PyCP showed six caseinolytic protease bands. The proteases were stable in the pH range of 8.0-10.0 and temperature range of 40-50°C. The activity of PyCP was enhanced in the presence of Na+, Mg2+, Cu2+, Tween-20, and hydrogen peroxide (H2O2) (hydrogen peroxide), whereas in Triton X-100, glycerol, ethylenediaminetetraacetic acid (EDTA), and Co2+, it was stable. PyCP showed a potential in various applications. The addition of PyCP in the commercial detergent enhanced the wash performance of the detergent by efficiently removing the stains of tomato ketchup and coffee. PyCP efficiently hydrolyzed the gelatin layer on X-ray film to release the embedded silver. PyCP also showed potent dehairing of goat skin and also efficiently deproteinized sea shell waste indicating its application in chitin extraction. Thus, the results of the present study indicate that Pyxidicoccus sp. S252 proteases have the potential to be used as an ecofriendly replacement of chemicals in several industrial processes.

Deceased Donor Renal Transplantation: A Single Center Experience.

INTRODUCTION: Deceased donor kidney transplant are still not common across India. This study was done to assess various measures taken at a single center level to increase organ donation rate and to analyse the outcomes of transplants performed from these donors. METHODS: All deceased donor renal transplants performed from November 2011 to February 2017 were analysed for patient and death censored graft survival, rate of delayed graft function, rate of rejection and mortality. Kaplan Meir analysis for Survival Curves was used. RESULTS: Organ donation rate at our center improved from one donation every alternate year in 2004 to a peak of 44 donations in 2017. Patient survival was 93.42%, 89.44%, 85.53%, and death censored graft survival was 94.07%, 88.21%, and 82.86% at 1, 2 and 3 years respectively. Mean duration of hemodialysis pre transplantation was 34.6 ± 27.43 months. CONCLUSIONS: This study has shown that steps taken at a single center level alone can also significantly improve organ donation rates. Employment of dedicated professionals including transplant surgeons and coordinators, developing a protocol-based approach for referral, and early counseling in triage along with regular audits can help to establish deceased donor program with acceptable outcomes elsewhere in the country.

Neurological manifestations and neuroimaging findings in patients with SARS-CoV2-a systematic review.

BACKGROUND: The COVID-19 pandemic has drastically affected everyone in a hit or miss manner. Since it began, evidence of the neuro-invasive potential of the virus has been intensifying significantly. Several pathways have been hypothesized to elucidate the neurotropic nature of SARS-CoV2. It is the need of the hour to collect vital information. OBJECTIVE: To evaluate and correlate the neuro-radiological and neurological manifestations in patients diagnosed with SARS-CoV2.To identify neuro-invasive pathways of COVID infection. METHODS: Relevant studies were identified through four databases-the Cochrane Library, PubMed, Science Direct, and Web of Science. These were searched using relevant keywords-"COVID-19," "SARS-CoV2," "neurological manifestations," "neuroimaging," "CT," and "MRI." Relevant articles were screened according to a pre-defined inclusion and exclusion criteria from December 2019 to August 2020. RESULTS: Our review included a total of 63 full text publications with 584 patients, composed mainly of observational studies, case reports, and case series. The most common neurological manifestations associated with COVID-19 were altered mental status, stroke, and paralysis. About 17.85% patients who underwent neuroimaging were found to be having ischemic changes suggestive of a stroke. This was followed by hemorrhagic changes as the second most common finding. The most commonly involved vessel was the Middle Cerebral Artery. Besides stroke, we found that SARS-CoV2 could be the cause for new-onset seizures, Guillain-Barre Syndrome, encephalitis, and many other severe neurological diseases. CONCLUSION: The information that we have obtained so far will prove dynamic to healthcare providers working against the COVID-19 pandemic. It is necessary to be aware of these atypical neurological findings for the early diagnosis and treatment of COVID-19 infected patients. However, to completely understand the connection between SARS-CoV2 and the nervous system, further research is necessary.