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Gabapentin is a new gamma aminobutyric acid (GABA) analogue that has anticonvulsant activity. Preliminary results are promising with gabapentin for the treatment of refractory anxiety disorders. In a supplementary role in several behavioral disorders, especially in acute mania, it has produced significant beneficial results. In this study, the anxiolytic activity of gabapentin was examined in mice. There was a significant decrease in time spent in the central square, an increase in the crossings, and an increase in rearing in the open field with the low-dose gabapentin (10 and 30 mg/kg), implying anxiolysis. Furthermore, potentiation of diazepam with gabapentin was also reported. On screening the gabapentin for learning and memory with passive avoidance response, there was significant prolongation of step-down latency, decrease in step-down error, and decrease in the total time spent by the mice in the shock zone at 10 and 100 mg/kg of gabapentin. Gabapentin was not associated with any adverse effect on the memory of mice.The lack of effect of gabapentin on memory, exhibiting anxiolytic activity at a low dose, the lack of cognition deficits, lack of drug interaction, alleviating the requirement for plasma monitoring, and its freedom from dependence or abuse liability suggest the potential advantage of gabapentin over the exiting anxiolytics. [ABSTRACT FROM AUTHOR]

Current study is the first report of the combined application of chemical (deep eutectic solvent), physical (microwave irradiation) and biological (laccase) pretreatment strategies for enhancing the enzymatic digestibility of rice straw biomass. Pretreated rice straw biomass was saccharified by cellulase/xylanase from Aspergillus japonicus DSB2 to get a sugar yield of 252.36 mg/g biomass. Design of Experiment based optimization of pretreatment and saccharification variables increased the total sugar yield by 1.67 times (421.5 mg/g biomass, saccharification efficiency 72.6%). Sugary hydrolysate was ethanol-fermented by Saccharomyces cerevisiae and Pichia stipitis to achieve an ethanol yield of 214 mg/g biomass (bioconversion efficiency 72.5%). Structural/chemical aberrations induced in the biomass due to pretreatment were elucidated by X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, and 1 H nuclear magnetic resonance techniques to unravel the pretreatment mechanisms. Combined application of various physico-chemical/biological pretreatment may be a promising approach for proficient bioconversion of rice straw biomass., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quest for renewable/eco-friendly energy sources has received immense focus in recent years. Current study involved consolidated bioprocessing of Saccharum spontaneum biomass (SSB) for biofuel-ethanol generation in a 'one pot consolidated bioprocess' (OPCB). SSB was pretreated with protic ionic liquid, triethylamine-bisulfate ([TEA][HSO 4 ]), saccharified in-situ with cellulase/xylanase enzymes, and the released sugars were fermented to ethanol. Pretreatment and saccharification processes were optimized under OPCB to achieve 2.70-fold increased sugar yield i.e. from 196.56 to 531.00 mg/g biomass. Fermentation of sugars yielded ethanol at 209.6 mg/g biomass at a bioconversion efficiency of 72.56 %. The pretreated SSB was comprehensively examined by/for XRD, NMR, SEM, FT-IR, and properties such as water retention capacity, surface area and cellulase adsorption ability to elucidate functional mechanisms of [TEA][HSO 4 ] pretreatment., 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.)

Benign positional vertigo (BPV) occurs when freely floating otoconia which are normally attached to the utricular macula, enter the posterior semicircular canal and move under the influence of gravity. It is the most common cause of peripheral vertigo. Migraine is a common headache disorder which is characterized by hemicranial, throbbing pain and may be preceded by aura. The relation between vertigo and migraine is intriguing and in day to day practice, often not clear. 100 diagnosed patients of BPV, aged more than 20 years, were evaluated for presence of headache specifically migraine based on International Headache Classification 3rd Edition, beta version. We also compared the success of epley's manoeuvre in patients having BPV & headache as compared to patients with complaints of vertigo alone. Overall seventy-four patients had successful epley's manoeuver and the rest did not show improvement even after four trials. Thirty-four patients reported headache and migraine was diagnosed in only ten patients. 67.6% of patients with headache had successful epley's maneuver however fifty-one of the 66 patients without headache had successful epley's manoeuver. Prevalence of migraine was only 10% in patients with BPV in our population and we observed that presence of headache does not suggest success or failure of epley's manoeuvre., Competing Interests: Conflict of interestNil., (© Association of Otolaryngologists of India 2020.)

Pullulan is a microbial polymer, commercially produced from Aureobasidium pullulans. Downstream processing of pullulan involves a multi-stage process which should be efficient, safe and reproducible. In liquid-liquid separations, firstly cell free extract is separated. Cell biomass can be separated after fermentation either by centrifugation or filtration. Due to practically insolubility of pullulan in organic solvents, ethanol and isopropanol are the most commonly used organic solvents for its recovery. Pullulan can also be purified by chromatographic techniques, but these are not cost effective for the purification of pullulan. Efficient aqueous two-phase system can be used for the purification of pullulan. The current review describes the methods and perspectives used for solid-liquid separation, liquid-liquid separations and finishing steps for the recovery of pullulan. Techniques used to determine the structural attributes of pullulan have also been highlighted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) is a chronic autoimmune disorder and the treatment involves the use of traditional and biological disease modifying anti-rheumatic drugs (DMARDs). Recent studies have shown JAK/STAT signaling pathway as potential target for the treatment of RA. Novel JAK/STAT inhibitors viz tofacitinib and baricitinib have been recently approved by FDA for RA treatment and have attained substantial importance. However, the discernible risks of thromboembolism, gastrointestinal (GIT) perforations, hepatotoxicity and serious infections including tuberculosis, herpes zoster associated with their administration cannot be overlooked. Furthermore, these are highly expensive which limits their application for a broader use. These limitations provide the basis of exploring novel JAK/STAT inhibitors of natural origin with increased tolerability, safety and cost-effectiveness. In this review we confer an account of various natural compounds/phytochemicals that have proved to be beneficial in attenuating inflammation in RA via modulation of JAK/STAT signaling pathway. Some of these natural compounds including resveratrol have clearly indicated biochemical and clinically significant therapeutic effects in ameliorating RA both in vivo and in clinical settings. We further discuss the physicochemical challenges of poor solubility and absorption coupled with the use of natural JAK/STAT inhibitors. We thereafter discuss and summarize various drug delivery systems (DDS) to confront the physicochemical limitations of natural JAK/STAT inhibitors with the aim to enhance the therapeutic efficacy. Overall the review unveils the potential of natural JAK/STAT inhibitors as a cost-effective approach in ameliorating RA without incorporating the risks of adverse repercussions, thus setting the stage for clinical exploration of these compounds that may possibly complement the present RA therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This work aimed to study the hydrolysis of ionic liquid (IL) pretreated sugarcane tops (SCT) biomass with in-house developed IL-stable enzyme preparation, from a fungal isolate Aspergillus flavus PN3. Maximum reducing sugar yield (181.18 mg/g biomass) was obtained from tris (2-hydroxyethyl) methylammonium-methylsulfate ([TMA]MeSO 4 ) pretreated biomass. Pretreatment parameters were optimized to attain enhanced sugar yield (1.57-fold). Functional mechanism of IL mediated pretreatment of SCT biomass was elucidated by SEM, XRD, FTIR and 1 H NMR studies. Furthermore, nanobiocatalysts prepared by immobilization of enzyme preparation by covalent coupling on magnetic nanoparticles functionalized with amino-propyl triethoxysilane, were assessed for their hydrolytic efficacy and reusability. Nanobiocatalysts were examined by SEM and FTIR analysis for substantiation of immobilization. This is the first ever report of application of magnetic nanobiocatalysts for saccharification of IL-pretreated sugarcane tops biomass., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The use of biologically active compounds derived from plants i.e. phytochemicals, have been known for ages for their pharmacological activities in the treatment of autoimmune disorders like rheumatoid arthritis (RA). Besides enormous scientific evidence, the therapeutic potential of phytochemicals is often undervalued. The treatment in RA involves the use of synthetic and biological disease modifying anti-rheumatic drugs (DMARDs). However, the long-term treatment in RA is associated with the risk of gastrointestinal, liver, pulmonary and renal toxicities and serious infections including latent tuberculosis, pneumococcus influenza, herpes zoster and hepatitis. These adverse effects sometimes lead to discontinuation of the therapy. A relatively new vision based on the combination of DMARDs with phytochemicals exhibiting anti-inflammatory, anti-arthritic, anti-oxidant, hepatoprotective and nephroprotective properties for the treatment of RA has achieved substantial importance in the last decade. From this perspective, the present review focuses on the combination of DMARDs (primarily MTX) with phytochemicals that have shown synergistic therapeutic effects while decreasing the toxic repercussions of current RA therapy. The review covers recent evidences of such combination studies that have shown promising results both in experimental arthritic models and clinical arthritis. Few of the combinations including resveratrol, sinomenine, coenzyme Q10 exhibited considerable interest because of their efficacy as an adjuvant to the MTX/standard DMARDs therapy in clinical trials. Besides giving an overview of such combination studies the review also critically discusses the limitations with the use of phytochemicals (e.g. solubility, permeability and bioavailability) compromising their clinical application. Additionally, it stresses upon the need of novel delivery systems and pharmaceutical technologies to increase the therapeutic efficacy of the combination therapy. Overall, the review unveils the potential of phytochemicals in combination with DMARDs with increased tolerability and superior efficacy in further refining the future of the RA therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A novel strategy involving sodium dodecylsulfate (SDS) (SDS assisted tris (2-hydroxyethyl) methyl- ammonium methyl sulphate ([TMA][MeSO 4 ], ionic liquid) pretreatment of Saccharum spontaneum biomass (SSB) following its enzymatic saccharification, and conversion into ethanol-biofuel in a consolidated bioprocess (CBP) was developed. Ionic liquid stable enzyme preparation developed from Bacillus subtilis G 2 was used for saccharification. Optimized pretreatment and saccharification variables enhanced the sugar yield (2.35-fold), which was fermented to ethanol content of 104.42 mg/g biomass with an efficiency of 35.73%. The pretreated biomass was examined for textural/ultrastructural alterations by scanning electron microscopy (SEM), 1 H/ 13 C nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), surface area measurements, water retention value, and cellulase adsorption isotherms. The combined [TMA][MeSO 4 ] and SDS pretreatment disrupted the lignocellulosic microfibrils, and increased the porosity and surface area. The study provides new mechanistic insights on combined IL and surfactant pretreatment of biomass for its efficient conversion to biofuel., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lactic acid bacteria (LAB) isolates possessed functional probiotic attributes, such as high hydrophobicity and autoaggregation ability, coaggregation capability with bacterial pathogens, antimicrobial activity, antioxidant potential, and hypocholesterolemic effects. Selected potential probiotic LAB, i.e. Lactobacillus paracasei M3, L. casei M5, L. paracasei M7, and few others were studied for their ability to lower cholesterol using a number of methods viz. cholesterol assimilation, bile salt deconjugation, cholesterol co-precipitation, cholesterol adhesion to probiotic cell wall, and miceller sequestration of cholesterol. L. casei M5 showed maximum bile salt hydrolase (BSH) activity, and released 57.63 nmol of glycine/min, and was closely followed by LAB isolate M9 which generated 52.12 nmol of glycine/min. Sodium glycocholate was deconjugated by L. casei M5 to produce 27.77 μmol/mL of cholic acid, while other isolates produced 20-26 μmol/mL of cholic acid. Cholesterol was assimilated significantly by isolate M6 (82.15%) and L. casei M5 (76.51%). L. casei M5 showed higher cholesterol co-precipitation ability (50.16 μg/mL) as compared to other LAB isolates (33-44 μg/mL). Miceller cholesterol concentration was reduced maximally by LAB isolate M8 (87.5%), followed by isolates M5 (84.75%), M9 (84%), M10 (80%), and M37 (79%). Higher cell wall adhesion of cholesterol was realized by L. casei M5 (42.48 μg/mL) than other LAB isolates (30-40 μg/mL). Selected LAB probiotics demonstrated short chain fatty acid (acetate, propionate, and butyrate) producing ability, yet another way of probiotics-mediated cholesterol lowering., Competing Interests: Conflict of interestAll authors declare that there is no conflict of interest., (© King Abdulaziz City for Science and Technology 2020.)

The current study presents the first ever report of surfactant (Tween-20) assisted ionic liquid IL, (1-ethyl-3-methylimidazolium methane sulphonate [Emim][MeSO 3 ]) pretreatment of Parthenium hysterophorus biomass, its saccharification by in-house developed enzyme cocktail from Aspergillus aculeatus PN14, and fermentation of sugars to bioethanol under consolidated bioprocess. Optimization of pretreatment process variables viz. biomass loading, temperature and time, resulted in enhanced sugar yield (40.1%) upon saccharification of pretreated biomass with IL-stable cellulase and xylanase enzymes from an IL-tolerant newly isolated fungus Aspergillus aculeatus PN14. Physicochemical analysis of surfactant assisted IL-pretreated biomass by SEM, FT-IR and XRD provided molecular insights into inter/intra molecular ultrastructural changes in the biomass that eased the saccharification. Thorough understanding of chemical/molecular structure of biomass may help developing customized pretreatment regimes of apt severity which might result in enhanced accessibility of enzymes to biomass, and hence more sugar content., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ionic liquid (IL) pretreatment represents an effective strategy for effective fractionation of lignocellulosic biomass (LB) to fermentable sugars in a biorefinery. Optimization of combinatorial pretreatment of sugarcane bagasse (SCB) with IL (1-butyl-3-methylimidazolium chloride [Bmim]Cl) and surfactant (PEG-8000) resulted in enhanced sugar yield (16.5%) upon enzymatic saccharification. The saccharification enzymes (cellulase and xylanase) used in the current study were in-house produced from a novel IL-tolerant fungal strain Aspergillus assiutensis VS34, isolated from chemically polluted soil, which produced adequately IL-stable enzymes. This is the first ever report of IL-stable cellulase/xylanase enzyme from Aspergillus assiutensis. To get the mechanistic insights of combinatorial pretreatment physicochemical analysis of variously pretreated biomass was executed using SEM, FT-IR, XRD, and 1 H NMR studies. The combined action of IL, surfactant and ultrasound had very severe and distinct effects on the ultrastructure of biomass that subsequently resulted in enhanced accessibility of saccharification enzymes to biomass, and increased sugar yield., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Visual misperceptions (VMs) and hallucinations (VHs) often go unreported in patients with Parkinson's disease (PD). We assessed the utility of single and bistable visual percepts as testing tools for visual perceptual abnormalities in PD., Aim: To assess VM in patients with PD using single and bistable percepts as testing tools., Settings and Design: This was a case-control study conducted at a movement disorders clinic., Materials and Methods: Thirty patients with PD and 30 age and sex-matched controls were assessed for motor severity and stage using Unified Parkinson's Disease Rating Scale-III (UPDRS-III) and modified Hoehn and Yahr scale. Higher mental functions were assessed by Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Trail making tests (TMT-A and B) scores. The participants were presented with monochromatic images representing either "single" or "bistable percepts" and the misperceptions were recorded. VM scores of patients and controls were compared. The correlation between disease duration, treatment period, motor severity, frontal executive functions, and VMs were determined., Results: Twenty-six patients had mild-to-moderate PD. Patients with PD had higher mean VM scores (P < 0.0005). None of the patients reported VHs. TMT-A, TMT-B, TMT-B - A scores were significantly lower in the control group (P < 0.0005). Cases showed significant positive correlation of VM with disease duration, treatment duration, UPDRS-III score, H and Y stage, and TMT A and B and an inverse correlation with MMSE and FAB scores. The patients with VM score greater than the upper limit of normal (Mean + 1.5 standard deviation [SD]), calculated from the control group, showed similar correlation of VM with motor and cognitive parameters., Conclusions: VMs are frequent in patients with PD when assessed using single and bistable visual percepts. VM correlates with frontal executive dysfunction, disease duration, and severity., Competing Interests: None

Considerable variations among probiotics with respect to their health benefitting attributes fuel the research on bioprospecting of proficient probiotic strains from various ecological niches especially the poorly unexplored ones. In the current study, kalarei, an indigenous cheese-like fermented milk product, and other dairy-based sources like curd and raw milk were used for isolation of lactic acid bacteria (LAB). Among 34 LAB isolates, 7 that could withstand simulated gastrointestinal (GI) conditions were characterized for functional probiotic attributes, viz. adhesion ability, aggregation and coaggregation, extracellular enzyme producing capability, antibacterial activity against pathogens and antibiotic resistance. The isolate M-13 (from kalarei) which exhibited most of the desirable probiotic functional properties was identified as Lactobacillus plantarum based on 16S ribosomal DNA sequence analysis and designated as L. plantarum M-13. The sequence was submitted to GenBank (accession number KT592509). The study presents the first ever report of isolation of potential probiotic LAB, i.e. L. plantarum M-13 from indigenous food kalarei, and its application for development of potential probiotic fermented oat flour (PFOF). PFOF was analysed for parameters like viability of L. plantarum M-13, acidity and pH. Results show that PFOF serves as a good matrix for potential probiotic L. plantarum M-13 as it supported adequate growth of the organism (14.4 log cfu/ml after 72 h of fermentation). In addition, appreciable acid production by L. plantarum M-13 and consequential pH reduction indicates the vigorous and active metabolic status of the potential probiotic organism in the food matrix. Thus, study shows that fermented oat flour may possibly be developed as a potential probiotic carrier especially in view of the problems associated with dairy products as probiotic vehicles.

Biorefining of lignocellulosic biomass to fuels/chemicals has recently gained immense research momentum. Current study reports sequential pretreatment of sunflower stalk (SFS) biomass in a combinatorial regime involving alkali (NaOH) and ionic liquid 1-butyl-3-methyl imidazolium chloride. The pretreatment enhanced the enzymatic digestibility, and resulted in increased sugar yield (163.42 mg/g biomass) as compared to standalone pretreatment using alkali (97.38 mg/g biomass) or ionic liquid (79.6 mg/g biomass). Ultrastructural and morphological analysis (FTIR and SEM) of pretreated biomass showed that the combined ionic liquid and alkali pretreatment causes more drastic alterations in the biomass ultrastructure as compared to alone ionic liquid or alkali pretreatment. Thus, combined pretreatment led to ease of enzymatic saccharification and consequent increased sugar yield, and this observation was corroborated by physicochemical analysis of the pretreated biomass. The pretreated SFS biomass was subjected to consolidated bioprocessing for its direct conversion to bioethanol in a single vessel., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Huge industrial application potential of xylanases is stalled due to lack of process suitable characteristics like thermostability, broad range pH stability, and high catalytic efficiency in the available enzymes. Current study presents the first ever report of a pH stable (pH 6-11) and thermostable (80-100 °C) xylanase from a novel strain of Aspergillus terreus S9. The xylanase was purified to homogeneity (6.67-fold) by ammonium sulphate precipitation, ion exchange chromatography, and molecular exclusion chromatography. SDS-PAGE analysis revealed an estimated molecular mass of ~33 kDa for the xylanase. Metal ions and surfactants such as K + , Ca 2+ , Mn 2+ , Mg 2+ , CTAB and Tween-80 enhanced the xylanase activity while Cu 2+ and Hg 2+ strongly inhibited the activity. Kinetic parameters i.e. K m , V max, K cat and K cat /K m of A. terreus S9 xylanase were 2.94 mg/ml, 285.71 μmol/min/mg, 1587.28 s -1 and 539.89 ml/mg/s, respectively. The substrate specificity confirmed the true endoxylanolytic nature of xylanase. The conserved domain analysis, and Blastn and Blastx results showed that the xylanase belonged to GH10 family. A. terreus S9 xylanase may be used as model system for understanding the molecular basis of robust nature of enzymes, and the knowledge generated may help designing novel enzymes that are suitable for industrial applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bioprospecting of novel probiotic strains especially from unexplored eco-niches has been a continuous practice. Enterococcus faecium K1, an isolate from indigenously fermented milk product kalarei possesses numerous desirable functional attributes. In current study, E. faecium K1 has been used for EPS production, and it yielded 355 ± 0.019 mg/L EPS. EPS demonstrates remarkable hypocholesterolemic, antioxidant, antibiofilm, and emulsification characteristics. EPS is constituted of mannose, glucose and galactose. SEM analysis reveals flake like compact structure of EPS while TEM and X-ray diffractogram confirms the amorphous structure of EPS. FTIR substantiates the functional groups/bonds typical of polysaccharides. Thermal analysis indicates adequate stability of EPS at 237 °C with average weight loss of 22%. E. faecium K1 EPS possesses unique functional bioactivities and physicochemical characteristics, and may potentially be explored for applications in food/pharmaceutical industries., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Process apt microbial proteases due to their wide range industrial applications have become the focus of intense scientific research during recent years. Considering the hostile process milieu, the proteases intended for application must be robust enough to withstand the extremes of temperature and pH, and presence of organic solvents and other potential enzyme inhibitors. Current study presents the characterization of a robust protease from a previously isolated bacterium Bacillus subtilis K-1 (BSK-1). Purification of BSK-1 protease (5.21-fold) was achieved to homogeneity by salt (ammonium sulfate) precipitation, and ion-exchange (diethyl-aminoethyl-sephadex) and size exclusion chromatography (Sephadex G-100). Molecular weight of BSK-1 protease was determined by SDS-PAGE analysis (42 kDa). Though the optimum temperature and pH for BSK-1 protease activity was 50 °C and 10, respectively, but, the protease exhibited remarkable activity and stability over elevated temperatures (60-80 °C) and a broad pH range (pH 7-11). Protease showed resistance towards several organic solvents/other potential enzyme inhibitors. Drastic activity loss in presence of phenylmethylsulfonyl fluoride indicated that the enzyme is a serine protease. Kinetic parameters (K m and V max ) for BSK-1 protease were found to be 0.14 mg ml -1 and 1176 mg min -1 , respectively. Putative amino acid sequence of BSK-1 protease (derived from nucleotide sequence of protease gene) suggested that the enzyme belonged to peptidases S8/S53 super family with multidomain of S8. BSK-1 protease being stable under harsh conditions may serve a model system for understanding the molecular basis of stability, and may help designing novel proteases that are suitable for industrial applications., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Both depression and low serum levels of folate are common in people with epilepsy (PWE), the latter especially in patients on hepatic enzyme-inducing antiepileptic drugs (AEDs). We did a cross-sectional study and a meta-analysis to assess if lower folate levels have any relation with depression in PWE., Materials and Methods: Two hundred and one PWE were recruited and assessed for depression using the Inventory of Depressive Symptomatology-Self-Rated (IDS-SR) and Inventory of Depressive Symptomatology-Clinician Rated; serum folate levels were measured in them at the same time. Literature search was carried out and studies with data on depression as well as folate levels in PWE were included. Statistical analysis to determine frequency of depression, low folate levels, and relation between them among our cases and the pooled data from the included studies was done., Results: Depression was observed in 65.68% and low serum folate (<4 ng/ml) in 48.75% of PWE (over 80% on older AEDs); there was no statistically significant correlation between them. However, on analyzing the pooled data of six studies including the present, the Fisher's z -transformed correlation coefficient was -0.1690 (95% confidence interval [-0.3175, -0.0124], P = 0.0464)., Conclusions: Depression and low folate levels are common in PWE. Low folate levels have a mild but significant negative correlation with depression in this population, and folate supplementation would be advisable for those on the older AEDs., Competing Interests: There are no conflicts of interest.

Intravascular thrombosis is one of the major causes of variety of cardiovascular disorders leading to high mortality worldwide. Fibrinolytic enzymes from microbial sources possess ability to dissolve these clots and help to circumvent these problems in more efficient and safer way. In the present study, fibrinolytic protease with higher fibrinolytic activity than plasmin was obtained from Serratia sp. KG-2-1 isolated from garbage dump soil. Response surface methodology was used to study the interactive effect of concentration of maltose, yeast extract + peptone (1:1), incubation time, and pH on enzyme production and biomass. Maximum enzyme production was achieved at 33 °C after 24 h at neutral pH in media containing 1.5% Maltose, 4.0% yeast extract + peptone and other trace elements resulting in 1.82 folds increased production. The enzyme was purified from crude extract using ammonium sulfate precipitation and DEAE-Sephadex chromatography resulting in 12.9 fold purification with 14.9% yield. The purified enzyme belongs to metalloprotease class and had optimal activity in conditions similar to physiological environment with temperature optima of 40 °C and pH optima of 8. The enzyme was found to be stable in various solvents and its activity was enhanced in presence of Na + , K + , Ba 2+ , Cu 2+ , Mn 2+ , Hg 2+ but inhibited by Ca 2+ and Fe 3+ . Hence, the obtained enzyme may be used as potential therapeutic agent in combating various thrombolytic disorders.

Cost-effective production of proteases, which are robust enough to function under harsh process conditions, is always sought after due to their wide industrial application spectra. Solid-state production of enzymes using agro-industrial wastes as substrates is an environment-friendly approach, and it has several advantages such as high productivity, cost-effectiveness, being less labor-intensive, and less effluent production, among others. In the current study, different agro-wastes were employed for thermoalkali-stable protease production from Bacillus subtilis K-1 under solid-state fermentation. Agricultural residues such as cotton seed cake supported maximum protease production (728 U ml(-1)), which was followed by gram husk (714 U ml(-1)), mustard cake (680 U ml(-1)), and soybean meal (653 U ml(-1)). Plackett-Burman design of experiment showed that peptone, moisture content, temperature, phosphates, and inoculum size were the significant variables that influenced the protease production. Furthermore, statistical optimization of three variables, namely peptone, moisture content, and incubation temperature, by response surface methodology resulted in 40% enhanced protease production as compared to that under unoptimized conditions (from initial 728 to 1020 U ml(-1)). Thus, solid-state fermentation coupled with design of experiment tools represents a cost-effective strategy for production of industrial enzymes.

Objective: Poor sleep quality contributes to the inferior quality of life of patients with Parkinson's disease (PD) despite appropriate treatment of motor symptoms. The literature about the impact of sleep quality on quality of life of patients with PD is as yet sparse., Material and Methods: One hundred patients of PD diagnosed as per UK Brain Bank criteria were assessed for severity and stage of PD using UPDRS and modified Hoehn &Yahr scales. The quality of sleep was assessed by Pittsburgh Sleep Quality Index and excessive daytime somnolence (EDS) was evaluated using Epworth Sleepiness Scale. Parkinson's Disease Questionnaire -39 (PDQ-39) was used to determine quality of life of the patients. Comorbid depression and anxiety were assessed using Inventory of Depressive Symptoms-Self Rated and Hamilton Anxiety Rating Scale. Pearson's correlation and multiple linear regressions were used to analyze relation of sleep quality with quality of life of patients., Results: Fifty patients had poor sleep quality. EDS was present in only 9 patients. Co-morbid depression and anxiety were present in 52 and 34 patients respectively. While the motor severity assessed by UPDRS-III was observed to adversely affect quality of life, it did not negatively impact quality of sleep. Higher score on UPDRS-total and UPDRS IV suggesting advanced disease correlated with poor sleep quality. Depression and anxiety were significantly more frequent in patients with poor sleep quality (p<0.01). Patients with poor sleep quality had worse quality of life (r=0.338, p<0.05). Depression and anxiety were also observed to have significant negative impact on quality of life of PD patients (p<0.01). Poor sleep quality was not found to be an independent predictor of quality of life using multiple linear regression analysis., Conclusion: Poor sleep quality along with comorbid depression, anxiety and advanced stage of disease is associated with poor quality of life., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Wide variations among multifaceted-health benefitting attributes of probiotics fueled investigations on targeting efficacious probiotics. In the current study, lactic acid bacteria (LAB) isolated from poultry gut, feces of rat, chicken, human infants, and fermented foods were characterized for desired probiotic functional properties including the phytase-producing ability which is one of the wanted characteristics for probiotics for potential applications for upgrading animal nutrition, enhancing feed conversion, and minimizing anti-nutritional properties. Among 62 LAB isolates Weissella kimchii R-3 an isolate from poultry gut exhibited substantial phytase-producing ability (1.77 U/ml) in addition to other functional probiotic characteristics viz. hydrophobicity, autoaggregation, coaggregation with bacterial pathogens, and antimicrobial activity against pathogens. Survival of W. kimchii R-3 cells (in free and calcium alginate encapsulated state) was examined sequentially in simulated gastric and intestinal juices. Encapsulated cells exhibited better survival under simulated gut conditions indicating that encapsulation conferred considerable protection against adverse gut conditions. Furthermore, simulated gastric and intestinal juices with pepsin and pancreatin showed higher survival of cells than the juices without pepsin and pancreatin. W. kimchii R-3 due to its significant functional probiotic attributes may have prospective for commercial applications in human/animal nutrition.

Eight thermophilic bacterial strains were isolated from Tattapani Hot spring and screened for various hydrolytic enzymes including cellulases. The isolated bacterial strains were identified as Geobacillus thermodenitrificans IP&#95;WH1(KP842609), Bacillus licheniformis IP&#95;WH2(KP842610), B. aerius IP&#95;WH3(KP842611), B. licheniformis IP&#95;WH4(KP842612), B. licheniformis IP&#95;60Y(KP842613), G. thermodenitrificans IP&#95;60A1(KP842614), Geobacillus sp. IP&#95;60A2(KP842615) and Geobacillus sp. IP&#95;80TP(KP842616) after 16S ribotying. Out of the eight isolates Geobacillus sp. IP&#95;80TP grew best at 80 °C whereas rest of the isolates showed optimal growth at 60 °C. G. thermodenitrificans IP&#95;WH1 produced a thermotolerant cellulase with maximum activity at 60 °C.

Usage of renewable raw materials for production of fully degradable bioplastics (bacterial poly-3-hydroxybutyrate, PHB) has gained immense research impetus considering recalcitrant nature of petroleum based plastics, dwindling fossil fuel feed stocks, and associated green house gas emissions. However, high production cost of PHB is the major bottleneck for its wide range industrial applications. In current study, Bacillus cereus PS 10, a recent isolate, efficiently utilized molasses, an abundantly available by-product from sugar industries as sole carbon source for growth and PHB production. Most influential bioprocess variables i.e. molasses, pH and NH4Cl were identified based on Plackett-Burman-designed experiments. Design of experiment approach (response surface methodology) was further employed for optimization of these bioprocess variables, and an enhanced PHB yield (57.5%) was obtained. PHB produced by Bacillus cereus PS 10 was investigated using various physico-chemical approaches viz. thermogravimetric analysis, proton and carbon NMR ((1)H and (13)C) spectroscopy, melting point, elemental analysis and polarimetry for its detail characterization, and assessment for industrial application potential., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Poly-β-hydroxybutyrate (PHB) may serve as one of the imperative substitutes for petroleum derived plastics because of their close functional analogy and biodegradation quality. In the present study, PHB producing ability of bacterial isolates was examined on low-cost agro industrial residues. Isolate PS-10 from domestic waste landfills, identified as Bacillus cereus PS-10 produced and accumulated appreciable amount of PHB. Bacillus cereus PS-10 was capable of using a wide variety of agro-based residues viz. maize bran, rice husk, wood waste, molasses, whey etc. as cost-effective carbon sources for PHB production. Molasses at 3% (w/v) supported maximum PHB production (9.5 gl(-1)) and was followed by glycerol (8.9 gl(-1)) at 2% (w/v). Certain carbon sources like almond shell powder and walnut shell powder are being reported for the first time for PHB production and supported reasonable PHB yield i.e. 6.6 and 4.6 gl(-1), respectively. Different cost-effective nitrogen sources like corn steep liquor, chick pea bran, soy bean meal, mustard cake etc. were used for PHB production. Highest PHB production was observed at pH 7 (9.6 gl(-1)) after 48 hrs of fermentation, although B. cereus PS-10 grew and produced PHB over pH range of 5-9. Optimum inoculum level for maximum PHB production was found to be 5% v/v (A600 0.9; approximately 10(8) cfu ml(-1)). Fourier transform infrared spectroscopy (FT-IR) analysis of the extracted PHB showed characteristic peaks (1721.95, 1632.19 and 2926.43 cm(-1)) similar to standard PHB. Melting point of PHB was found to be 185°C. Bacillus cereus PS-10 may be a sound PHB producer, especially by exploiting low cost substrates.

Poly-β-hydroxybutyrate (PHB) has attracted a great deal of attention in recent years due to its potential use for production of fully degradable bioplastics, however, high cost of PHB production is the major bottleneck for its wide range industrial applications. In the current study rice straw hydrolysate (RSH) was employed as a cost-effective substrate for PHB production. RSH was prepared based on biphasic acid-pretreatment of rice straw i.e. first phase treatment with 1% sulphuric acid at 121 °C for 45 min, followed by second phase treatment using 5% sulphuric acid at 121 °C for 60 min (solid:liquid ratio, 1:10). RSH turned out be an efficient substrate for PHB production from a recently isolated Bacillus cereus PS 10, and yielded higher PHB amount than that obtained with glucose (8.6g/L in glucose based medium vs 10.61 g/L in RSH based medium) after response surface methodology (RSM) based optimization. Design of experiments based on RSM was used to optimize three process variables i.e. amount of RSH and NH4Cl, and medium pH, and enhanced PHB yield (23.3%) was obtained. PHB produced was investigated by differential scanning calorimetry and X-ray diffraction powder analysis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The understanding and management of neurological disorders is undergoing revolutionary changes over the last three decades in the background of ever increasing advances in medical technologies, diagnostic techniques, therapeutic processes and, molecular and genetic medicine. The fruits of these advances can reach patients only if the psychosocial hurdles in their delivery are identified, acknowledged and addressed., Aim: To explore the beliefs and practices of patients with neurological disorders in a tertiary care center in the eastern Nepal., Materials and Methods: One hundred patients attending neurology/medicine outpatient for neurological disorders were interviewed about their beliefs regarding the triggering factors, causation and treatment-seeking behavior particularly from traditional healers., Result: Of the 100 patients (49 males, 51 females) recruited in the study, 51% expressed having 'no idea' about their illness. Only 20% patients gave medically congruent explanation for their illness. Psychological factors were attributed as triggering factors by 16% of patients, of which two-thirds were females. Chance, destiny and 'jadu tona' topped the list of triggering factors. Forty-four percent patients had sought help of traditional faith healers ('Dhami Jhakri') before seeking medical help. Traditional faith healers were approached by patients irrespective of their educational background. Fifty-nine percent of patients who first sought traditional faith healers, believed in 'jadu-tona'. Of those interviewed, 16% were planning to go to a faith healer in near future., Conclusion: The beliefs of patients with neurological disorders frequently do not conform to current medical opinion. There is need for greater communication and education of patients by their treating physicians.

The killer phenomenon of yeast may have technological implications in many areas like beverage fermentation, food technology, biological control in agriculture, and in medicine. In the present study the killer phenomenon in Pichia kudriavzevii (P. kudriavzevii RY55) is being reported for the first time. The P. kudriavzevii RY55 toxin exhibited excellent antibacterial activity against several pathogens of human health significance such as Escherichia coli, Enterococcus faecalis, Klebsiella sp., Staphylococcus aureus, Pseudomonas aeruginosa and Pseudomonas alcaligenes. Killer toxin was purified to homogeneity by using ammonium sulphate precipitation and ion exchange chromatography and characterized for few properties. P. kudriavzevii RY55 killer toxin may be of vast significance in the development of novel antimicrobial chemotherapeutic agents, new bio-based safer candidates for food preservation and biocontrol, and starter cultures for fermentation industries., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Of six alkalitolerant, extracellular protease producing bacterial strains isolated, DP2 displayed maximum activity. This organism was designated as Streptomyces sp. DP2 and identified as Streptomyces ambofaciens. Maximum protease yield was observed after 48hours of submerged fermentation using various carbon and nitrogen sources. Fructose was found to be the best substrate for protease production, followed by maltose, lactose and wheat bran. Mustard cake is reported for the first time as the most ideal nitrogen source although soybean meal also gave comparable yield. The protease produced by Streptomyces sp. DP2 exhibited extensive activity over a broad pH range (4-12) with maximum activity at pH 8, and was active over a broad range of elevated temperatures (50-100°C), and possessed thermostability at 60-90°C for up to 1 hour. Enzyme activity was reduced by EDTA (25%), SDS (16%), and PMSF (6%). This novel alkaline protease has both alkali- and thermostability that may have industrial significance., (Copyright © 2011 Elsevier B.V. All rights reserved.)

An alkalitolerant fungus, Aspergillus fumigatus strain MA28 produced significant amounts of cellulase-free xylanase when grown on a variety of agro-wastes. Wheat bran as the sole carbon source supported higher xylanase production (8,450 U/L) than xylan (7,500 U/L). Soybean meal was observed to be the best nitrogen source for xylanase production (9,000 U/L). Optimum medium pH for xylanase production was 8 (9,800 U/L), though, significant quantities of the enzyme was also produced at pH 7 (8,500 U/L), 9 (8,200 U/L) and 10 (4,600 U/L). The xylanase was purified by ammonium sulphate precipitation and carboxymethyl cellulose chromatography, and was found to have a molecular weight of 14.4 kDa with a V(max) of 980 μmol/min/mg of protein and a K(m) of approximately 4.9 mg/mL. The optimum temperature and pH for enzyme activity was 50 °C and pH 8, respectively. However, the enzyme also showed substantial residual activity at 60-70 °C (53-75%) and at alkaline pH 8-9 (56-88%).

Thermostable and alkalitolerant xylanases have got intense research focus due to their vast applications in various industries including pulp and paper, food, feed, textile, biofuel, etc. In the present investigation, a Penicillum sp. SS1 isolated from degrading woody material was found to produce moderately thermoactive and alkalistable endo-β-1,4-xylanase (xylanase). Maximum xylanase production was observed after fourth day of fermentation (43.84 IU/ml). The organism produced substantial quantities of xylanase using agricultural residues like wheat bran (20.6 IU/ml), rice bran (21.8 IU/ml) and sawdust (10.7 IU/ml) as carbon sources. The enzyme preparation was totally free of filter paper activity (FPase) and possessed negligible carboxymethyl cellulase (CMCase) activity; this could be an important feature of enzyme if the intended application of enzyme is in pulp and paper industries. Among nitrogen sources examined, yeast extract supported maximum xylanase production (45.74 IU/ml), and was followed by soybean meal (22.2 IU/ml) and ammonium sulphate (20 IU/ml). Maximum xylanase production was observed at initial medium pH 9 (25.6 IU/ml); however, at pH 8 and 10 also significantly high enzyme titre was observed (24 and 21.2 IU/ml, respectively). Thus, Penicillium sp. SS1 displayed capability of growing and producing xylanase at high alkaline pH (8-10). Maximum xylanase activity was reported at 50 °C, however, significantly high activity was observed at 60 °C (65.4%), however, at 70-80 °C activity was lost considerably. At 50-60 °C the enzyme retained very high activity up to 30-60 min (91-100%), however, prolonged incubation (90 min) caused considerable activity reduction (residual activity 63-68%).

We report the case of a 30-year-old woman with a rare presentation of early adulthood Huntington's disease (HD) with hypersexuality. It is not known if sexual dysfunction in HD patients is due to a specific brain lesion or adverse psychosocial factors associated with HD. Although there are no evidence-based treatment guidelines for hypersexuality in HD, our patient exhibited significant improvement with olanzapine and haloperidol.

Streptomyces sp. 7b showed highest xylanase activity among 41 bacterial isolates screened under submerged fermentation. The organism grew over broad pH (5-11) and temperatures range (25-55 degrees C) and displayed maximum xylanase production on wheat bran (1230 U/g) under solid-state fermentation. Xylanase production was enhanced substantially (76%-77%) by inclusion of trypton (2180 U/g) or beef extract (2170 U/g) and moderately (36%-46%) by yeast extract (1800 U/g) or soybean meal (1670 U/g). Inclusion of readily utilizable sugars such as glucose, maltose, fructose, lactose or xylose in the substrate repressed the xylanase production. The optimum initial pH of the medium for maximum enzyme production was 7 to 8; however, appreciable level of activity was obtained at pH 6 (1,680 U/g) and 9 (1,900 U/g). Most appropriate solid to liquid ratio for maximum xylanase production in solid-state fermentation was found to be 1:2.5. The organism produced a single xylanase of molecular weight of approximately 30 kDa as analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis after purification with ammonium sulfate precipitation, and carboxy methyl sephadex chromatography. The enzyme was purified to the extent of 5.68-fold by salt precipitation and ion-exchange chromatography. Optimum temperature and pH for maximum xylanase activity were 50 degrees C and 6, respectively.

Saccharomyces cerevisiae HAU-1, a time tested industrial yeast possesses most of the desirable fermentation characteristics like fast growth and fermentation rate, osmotolerance, high ethanol tolerance, ability to ferment molasses, and to ferment at elevated temperatures etc. However, this yeast was found to be sensitive against the killer strains of Saccharomyces cerevisiae. In the present study, killer trait was introduced into Saccharomyces cerevisiae HAU-1 by protoplast fusion with Saccharomyces cerevisiae MTCC 475, a killer strain. The resultant fusants were characterized for desirable fermentation characteristics. All the technologically important characteristics of distillery yeast Saccharomyces cerevisiae HAU-1 were retained in the fusants, and in addition the killer trait was also introduced into them. Further, the killer activity was found to be stably maintained during hostile conditions of ethanol fermentations in dextrose or molasses, and even during biomass recycling.

Introduction: This study was conducted to explore cardiovascular autonomic neuropathy and its pattern in chronic kidney disease patients., Methods: Autonomic function using five standard tests was examined in 20 diabetic patients with CKD, 20 age and sex matched diabetic patients without CKD and 20 age and sex matched controls. Analysis of difference between the autonomic function was done in the three groups using Chi-square test or Fischer's test., Results: Total 20 (100%) diabetic CKD patients were found to have autonomic neuropathy. Of these, 2 (10%) patients had early parasympathetic damage, 8 (40%) patients had definite parasympathetic damage, and 10 (50%) patients had combined damage. Heart rate response to standing was statistically significant (p = 0.014) among diabetic CKD patients when compared with diabetic patients without CKD. Combined form of autonomic dysfunction was more frequent in advanced stages of diabetic CKD. Three (42.85%) patients in stage 3 CKD, 4 (66.66%) patients in stage 4 CKD and 5 (71.42%) patients in stage 5 CKD, had combined autonomic failure., Conclusions: Autonomic neuropathy is common in native Nepalese diabetic CKD patients. Heart rate response to standing is significantly abnormal in diabetic CKD patients in comparison with diabetes mellitus patient without CKD. Severity of autonomic dysfunction increases with severity of CKD..

Monoclonal gammopathy of undetermined significance (MGUS) and peripheral neuropathy may be causally linked. In most cases, the M-protein is of IgG or IgM type. Peripheral neuropathy associated with IgA MGUS is uncommon, and there are limited reports. Here, we report a case of a 55-year-old male who was diagnosed to have symmetrical sensorimotor peripheral neuropathy associated with IgA MGUS with deposits of IgA-monoclonal protein in the myelin sheath.

Aim: To report paradoxical response, i.e. recurrence of appearance of fresh symptoms, physical and radiological signs in a patient who had previously shown improvement with appropriate anti-tubercular medicines., Material and Methods: Ten out of 58 patients of CNS tuberculosis, diagnosed on basis of clinical, laboratory and radiological data that initially showed clinical response to therapy only to deteriorate later were included in the study., Results: Out of ten, three were males and seven were female with age range 13 to 28 years. The duration of time between initiation of therapy and worsening of patient was from one to seven months. Nine out of ten patients developed fresh intracranial tuberculoma while one case otherwise showing improvement developed expansion of tuberculoma and other one of empyema developed tuberculoma while on therapy. All these cases responded to addition of second line therapy or increase in dose of drugs previously prescribed and introduction or increased dose of steroid., Conclusions: Clinical judgement, regular follow up, guarded reassurance of patient is required to detect parodoxial response in CNS tuberculosis.