Enhanced vermicomposting of rice straw and pressmud with biogas slurry employing Eisenia fetida: Production, characterization, growth, and toxicological risk assessment.

The biogas plant plays a dual role: it directly provides energy and indirectly promotes organic farming through outlet slurry. However, agricultural biomass wastes such as rice straws (RS) and pressmud (PM), which can't be used as fertilizers on their own, were vermicomposted (60 days) with biogas slurry (BS), using earthworm, into four blends: T1(BS, 100%), T2(3:2, BS: RS), T3(3:2, BS: PM), and T4(3:1:1, BS: RS: PM). The characterization, elemental analysis, and toxicological risk assessment of derived vermimanure were carried out using various analytical tools, such as an organic elemental analyzer such as CHNS, FT-IR, FESEM-EDXA, XPS, and ICP-OES. The pH, electrical conductivity, and C/N values were within 7.1-7.8, 3.2-6.0 dSm-1, and 12-15, respectively, for all treatments. The proportions of N (38%), P (70%), K (58%), Mg (67%), Ca (42%), and ash (44%), increased significantly (P < 0.05) over the initial feedstocks. The ecological risks of heavy metals (Zn, Cu, Ni, Pb, Cd, and Cr) in all feedstocks were found to be under WHO-permitted levels. The growth performance of earthworms was also considerably higher (P < 0.05) over the control feedstock group. The analytical methods verified that feedstock T4 (3:1:1, BS: RS: PM) was more porous, containing NH4+, PO43-, K+, and other nutrients. Pellets of all vermimanure groups keep 65-75% of the original volume. As well, when these pellets have been employed for agronomy and dispersed in the field, they will cause less dust than traditional or powdered compost or manure. In comparison to the control group, the synergistic approach of RS, PM, and BS in vermimanure significantly (P < 0.05) enhanced seed germination (83%), vigour index (42.5%), and decreased mean germination time by 27%. Furthermore, pot trials with Abelmoschus esculentus seed indicated that seedlings cultivated with 40% vermimanure of T4 (3:1:1, BS: RS: PM) mixed soil showed high growth in shoot, root, and plant yield.

Effect of an Antacid (Aluminum Hydroxide/Magnesium Hydroxide/Simethicone) or a Proton Pump Inhibitor (Omeprazole) on the Pharmacokinetics of Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Adult Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label, 3-period, fixed sequence study evaluated the effect of gastric acid-reducing agents, aluminum hydroxide/magnesium hydroxide/simethicone, and omeprazole on the pharmacokinetics (PK) of tebipenem (TBP), the active moiety, following coadministration with immediate release TBP-PI-HBr during fasting. In Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets). In Period 2, subjects received a single oral dose of aluminum hydroxide 800 mg/magnesium hydroxide 800 mg/simethicone 80 mg suspension co-administered with a single dose of TBP-PI-HBr 600 mg. In Period 3, subjects received a single oral dose of omeprazole 40 mg once daily over 5 days, followed by single dose administration of TBP-PI-HBr 600 mg on day 5. In each period, whole blood samples were obtained prior to, and up to 24 h, following TBP-PI-HBr dose administration in order to characterize TBP PK. A 7-day washout was required between periods. Twenty subjects were enrolled and completed the study. Following co-administration of TBP-PI-HBr with either aluminum hydroxide/magnesium hydroxide/simethicone or omeprazole, total TBP exposure (area under the curve [AUC]) was approximately 11% (geometric mean ratio 89.2, 90% confidence interval: 83,2, 95.7) lower, and Cmax was 22% (geometric mean ratio 78.4, 90% confidence interval: 67.9, 90.6) and 43% (geometric mean ratio 56.9, 90% confidence interval: 49.2, 65.8) lower, respectively, compared to administration of TBP-PI-HBr alone. Mean TBP elimination half-life (t1/2) was generally comparable across treatments (range: 1.0 to 1.5 h). Concomitant administration of TBP-PI-HBr with omeprazole or aluminum hydroxide/magnesium hydroxide/simethicone is not expected to impact the efficacy of TBP-PI-HBr, as there is minimal impact on TBP plasma AUC, which is the pharmacodynamic driver of efficacy. Co-administration was generally safe and well tolerated.

Absorption, Metabolism, and Excretion of [14C]-Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Male Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral prodrug of pharmacologically active moiety tebipenem (TBP), which is a carbapenem with activity against multidrug-resistant Gram-negative pathogens. Conversion from the prodrug to the active moiety, namely, TBP, occurs in the enterocytes of the gastrointestinal tract via intestinal esterases. The absorption, metabolism, and excretion in humans were evaluated, following the administration of a single oral dose of [14C]-TBP-PI-HBr. Healthy male subjects (n = 8) received a single 600 mg oral dose of TBP-PI-HBr containing approximately 150 µCi of [14C]-TBP-PI-HBr. Blood, urine, and fecal samples were collected to determine the total radioactivity, concentrations of TBP (plasma only), and metabolite profiling and identification. The overall mean recovery of the total radioactivity in urine (38.7%) and feces (44.6%) combined was approximately 83.3% of the administered dose, with individual recoveries ranging from 80.1% to 85.0%. Plasma TBP LC-MS/MS and metabolite profiling data suggest that TBP was the main circulating component in plasma and that it accounts for approximately 54% of the total plasma radioactivity, based on the plasma AUC ratio of TBP/total radioactivity. The ring-open metabolite LJC 11562 was another major component in plasma (>10%). TBP (M12), LJC 11562, and four trace to minor metabolites were identified/characterized in the urine. TBP-PI, TBP (M12), and 11 trace to minor metabolites were identified/characterized in the feces. The renal and fecal routes are major clearance pathways in the elimination of [14C]-TBP-PI-HBr, with a mean combined recovery of 83.3%. TBP and its inactive ring-open metabolite LJC 11562 were the major circulating metabolites in the plasma.

Plasma and Intrapulmonary Concentrations of Tebipenem following Oral Administration of Tebipenem Pivoxil Hydrobromide to Healthy Adult Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral carbapenem prodrug being developed for the treatment of serious bacterial infections. The active moiety, tebipenem, has broad-spectrum activity against common Enterobacterales pathogens, including extended-spectrum-ß-lactamase (ESBL)-producing multidrug-resistant strains. This study evaluated the intrapulmonary pharmacokinetics (PK) and epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations of tebipenem relative to plasma levels in nonsmoking, healthy adult subjects. Thirty subjects received oral TBP-PI-HBr at 600 mg every 8 h for five doses. Serial blood samples were collected following the last dose. Each subject underwent one standardized bronchoscopy with bronchoalveolar lavage (BAL) 1, 2, 4, 6, or 8 h after the fifth dose of TBP-PI-HBr. The tebipenem area under the concentration-time curve for the 8-h dosing interval (AUC0-8) values in plasma, ELF, and AMs were calculated using the mean concentration at each BAL sampling time. Ratios of AUC0-8 values for total ELF and AMs to those for unbound plasma were determined, using a plasma protein binding value of 42%. Mean values ± standard deviations (SD) of tebipenem maximum (Cmax) and minimum (Cmin) total plasma concentrations were 11.37 ± 3.87 mg/L and 0.043 ± 0.039 mg/L, respectively. Peak tebipenem concentrations in plasma, ELF, and AMs occurred at 1 h and then decreased over 8 h. Ratios of tebipenem AUC0-8 values for ELF and AMs to those for unbound plasma were 0.191 and 0.047, respectively. Four (13.3%) subjects experienced adverse events (diarrhea, fatigue, papule, and coronavirus disease 2019 [COVID-19]); all resolved, and none were severe or serious. Tebipenem is distributed into the lungs of healthy adults, which supports the further evaluation of TBP-PI-HBr for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT04710407.).

Pharmacokinetics of Oral Tebipenem Pivoxil Hydrobromide in Subjects with Various Degrees of Renal Impairment.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral carbapenem prodrug antimicrobial agent with broad-spectrum activity that includes multidrug-resistant (MDR) Enterobacterales. This study evaluated the safety, tolerability, and pharmacokinetics of TBP-PI-HBr in healthy subjects with normal renal function (cohort 1) and subjects with various degrees of renal impairment (RI [cohorts 2 to 4]) or end-stage renal disease (ESRD) receiving hemodialysis (HD) (cohort 5). Subjects in cohorts 1 to 4 received a single oral dose of TBP-PI-HBr (600 mg). Subjects in cohort 5 received single-dose administration (600 mg) in 2 separate periods: pre-HD (period 2) and post-HD (period 1). Pharmacokinetic (PK) parameters for TBP, the active moiety, were determined using noncompartmental analysis. Compared with cohort 1, the TBP plasma area under the curve (AUC) increased 1.4- to 4.5-fold among cohorts 2 to 4, the maximum concentration of drug in plasma (Cmax) increased up to 1.3-fold and renal clearance (CLR) decreased from 13.4 L/h to 2.4 L/h as the severity of RI increased. Plasma TBP concentrations decreased over 8 to 12 h in cohorts 1 to 4, and apparent total body clearance (CL/F) correlated (R2 = 0.585) with creatinine clearance (CLCR). TBP urinary excretion ranged from 38% to 64% of the administered dose for cohorts 1 to 4. Subjects in cohort 5 had an approximately 7-fold increase in TBP AUC and elimination half-life (t1/2) versus cohort 1. After 4 h of HD, mean TBP plasma exposure decreased by approximately 40%. Overall, TBP plasma exposure increased with increasing RI, highlighting the renal route importance in TBP elimination. A dose reduction of TBP-PI-HBr may be needed in patients with RI (CLCR of ≤50 mL/min) and those with ESRD on HD. TBP-PI-HBr was well tolerated across all cohorts. (This study has been registered at ClinicalTrials.gov under registration no. NCT04178577.).

Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug of tebipenem (TBP), the active moiety, currently in development for treating serious bacterial infections. This study assessed the bioequivalence (BE) of the clinical trial and registration tablet formulations of TBP-PI-HBr and evaluated the effect of food on the pharmacokinetics (PKs) of tebipenem. This was a single center, open-label, randomized, single-dose, three-sequence, four-period crossover, BE, and food-effect study. Subjects received single 600 mg oral doses of TBP-PI-HBr as the reference clinical trial tablet (treatment A) and test registration tablet (treatment B) formulations in alternating sequence while fasting, and then the test formulation under fed conditions. Whole blood samples were collected predose and at specified intervals up to 24 h postdose to evaluate TBP PK parameters. Safety and tolerability were monitored. Thirty-six healthy, adult subjects were enrolled and completed the study. The criteria for BE were met for the TBP-PI-HBr test (registration tablet) and reference (clinical trial tablet) formulations as the 90% confidence intervals for the geometric mean ratios for TBP area under the curve (AUC)0-t , AUC0-inf , and maximum plasma concentration (Cmax ) fell within the established 80% to 125% BE limits. Dosing with food had no meaningful effect on TBP PK parameters. Five (14%) subjects reported adverse events (AEs) of mild severity. No deaths, serious AEs, or discontinuations due to AEs were reported, and no clinically relevant electrocardiograms, vital signs, or safety laboratory findings were observed. The study results demonstrate the BE of oral TBP-PI-HBr registration and clinical trial tablet formulations and indicate that TBP-PI-HBr can be administered without regard to meals.

The effects of dietary immunostimulants on the innate immune response of Indian major carp: A review.

Immunostimulants, as feed additives, play an important role in maintaining fish health and enhancing their overall growth by providing resistance against diseases in cultured fish. At the initial stages of life of fish, innate immunity is the essential mechanism in their survival. Later, innate immunity has an instructive role in adapting acquired immune response and homeostasis through different receptor proteins. Several studies have been conducted to analyze the effect of dietary immunostimulants like algae, plant extracts, vitamins, herbs, probiotics, and prebiotics-containing diets in Indian major carps. Many bacterial, fungal and viral pathogens are responsible for high death rates in both wild and cultured fish. It's a major limiting factor for world aquaculture industries. Recognition of invading pathogens by different pathogen recognition receptor plays an important role for the activation of different pathways to initiate protective immune responses. Hence, there is a growing need to control the devastating effects of diseases without recourse to toxic chemicals or antibiotics. Keeping with alternative approaches without using toxic chemicals to control fish diseases in mind, many immunostimulants are used, which enhance immune responses along with their gene expression level through different signaling pathway. The objective of this review is to summarize and evaluate the current knowledge of various immunostimulants and their immune responses in three Indian major carps namely Catla catla, Labeo rohita and Cirrhinus mrigala, which are preferred by the people.

HRNET: AI-on-Edge for Mask Detection and Social Distancing Calculation.

The purpose of the paper is to provide innovative emerging technology framework for community to combat epidemic situations. The paper proposes a unique outbreak response system framework based on artificial intelligence and edge computing for citizen centric services to help track and trace people eluding safety policies like mask detection and social distancing measure in public or workplace setup. The framework further provides implementation guideline in industrial setup as well for governance and contact tracing tasks. The adoption will thus lead in smart city planning and development focusing on citizen health systems contributing to improved quality of life. The conceptual framework presented is validated through quantitative data analysis via secondary data collection from researcher's public websites, GitHub repositories and renowned journals and further benchmarking were conducted for experimental results in Microsoft Azure cloud environment. The study includes selective AI models for benchmark analysis and were assessed on performance and accuracy in edge computing environment for large-scale societal setup. Overall YOLO model outperforms in object detection task and is faster enough for mask detection and HRNetV2 outperform semantic segmentation problem applied to solve social distancing task in AI-Edge inferencing environmental setup. The paper proposes new Edge-AI algorithm for building technology-oriented solutions for detecting mask in human movement and social distance. The paper enriches the technological advancement in artificial intelligence and edge computing applied to problems in society and healthcare systems. The framework further equips government agency, system providers to design and construct technology-oriented models in community setup to increase the quality of life using emerging technologies into smart urban environments.

Quantum algorithm for quicker clinical prognostic analysis: an application and experimental study using CT scan images of COVID-19 patients.

BACKGROUND: In medical diagnosis and clinical practice, diagnosing a disease early is crucial for accurate treatment, lessening the stress on the healthcare system. In medical imaging research, image processing techniques tend to be vital in analyzing and resolving diseases with a high degree of accuracy. This paper establishes a new image classification and segmentation method through simulation techniques, conducted over images of COVID-19 patients in India, introducing the use of Quantum Machine Learning (QML) in medical practice. METHODS: This study establishes a prototype model for classifying COVID-19, comparing it with non-COVID pneumonia signals in Computed tomography (CT) images. The simulation work evaluates the usage of quantum machine learning algorithms, while assessing the efficacy for deep learning models for image classification problems, and thereby establishes performance quality that is required for improved prediction rate when dealing with complex clinical image data exhibiting high biases. RESULTS: The study considers a novel algorithmic implementation leveraging quantum neural network (QNN). The proposed model outperformed the conventional deep learning models for specific classification task. The performance was evident because of the efficiency of quantum simulation and faster convergence property solving for an optimization problem for network training particularly for large-scale biased image classification task. The model run-time observed on quantum optimized hardware was 52 min, while on K80 GPU hardware it was 1 h 30 min for similar sample size. The simulation shows that QNN outperforms DNN, CNN, 2D CNN by more than 2.92% in gain in accuracy measure with an average recall of around 97.7%. CONCLUSION: The results suggest that quantum neural networks outperform in COVID-19 traits' classification task, comparing to deep learning w.r.t model efficacy and training time. However, a further study needs to be conducted to evaluate implementation scenarios by integrating the model within medical devices.

QbD-driven development of dissolving microneedle patch loaded with ultradeformable liposomes encapsulated Noopept: Exploring a patient friendly, once-daily option to manage dementia.

Noopept (NPT), a potent neuroprotective agent, suffers the problem of poor oral bioavailability (~10%) and thus demands exploration of ways of bioavailability improvement. Present work focuses on confronting this issue via development of NPT loaded ultradeformable liposomes (UDL) and its further incorporation in fast dissolving microneedle patch (MNP) for transdermal route. A combination of Phospholipon 90 G and Phospholipon 90H was used as bilayer forming lipids while sodium deoxycholate was used as edge activator to formulate NPT UDL by ethanol injection method. QbD approach was adapted to optimize NPT UDL considering vesicle size and entrapment efficiency as critical quality attributes (CQA). Fractional factorial design established amount of lipids, surfactant and NPT as critical material attributes and their optimum levels were statistically derived using combined D-optimal design. These optimized NPT UDL were fabricated as fast dissolving MNP and exhaustively evaluated to establish their safety, efficacy and stability. NPT UDL MNP possessed axial needle fracture force of 0.688 N which was sufficient enough to breach stratum corneum. Physical stability evaluation revealed that NPT UDL re-dispersion obtained from MNP matrix dissolution possessed identical vesicle shape and size while retaining > 99% NPT when compared to optimized NPT UDL. In vitro viability of HaCaT cells after exposure to NPT UDL MNP matrix was found to be 89.74% supporting the formulation as safe for transdermal application. NPT UDL MNP showed a 6.5-fold increase in steady state flux across full thickness pig ear skin as compared to NPT suspension. A 3-fold increase in relative bioavailability with similar pharmacological response as compared to oral NPT suspension was also observed during PK-PD studies in Sprague Dawley rats. Results were found fairly encouraging and created a scope of reducing both dose and dosing frequency to eventually improve the associated patient compliance.

Supply chain vulnerability assessment for manufacturing industry.

In today's business, environment natural and manmade disasters like recent event (Covid 19) have increased the attention of practitioners and researchers to Supply chain vulnerability. Purpose of this paper is to investigate and prioritize the factors that are responsible for supply chain vulnerability. Extant literature review and interviews with the experts helped to extract 26 supply chain vulnerability factors. Further, the relative criticality of vulnerability factors is assessed by analytical hierarchy process (AHP). Critical part supplier; location of supplier; long supply chain lead times; Fixing process owners and mis-aligned incentives in supply chain are identified as the most critical factors among twenty-six vulnerability factors. Research concludes that not only long and complex supply chain but supply chain practices adopted by firms also increase supply chain vulnerability. Relative assessment of vulnerability factors enables professionals to take appropriate mitigation strategies to make the supply chains more robust. This research adds in building a model for vulnerability factors that are internal to supply chain & controllable.

Vinpocetine loaded ultradeformable liposomes as fast dissolving microneedle patch: Tackling treatment challenges of dementia.

Vinpocetine (VPN) displays poor bioavailability (~7%) and short half-life (2-3 h) justifying the frequent dosing requirement of currently marketed oral tablets (thrice daily) and thus, posing a great challenge to patient compliance. Present work envisaged to achieve an infusion like delivery through transdermal route so as to tackle aforesaid challenges. With this aim, ultradeformable liposomes (UDL) incorporated fast dissolving microneedle patch (MNP) of VPN was developed and optimized for vesicle size and percent drug entrapment (critical quality attributes, CQA) utilizing the quality by design tool. Fractional factorial design followed by combined D-optimal design were applied to identify critical material attributes and obtain their statistically verified optimum levels (Phospholipon 90G, 15.17 mM; Phospholipon 90H, 4.83 mM; sodium deoxycholate, 15 mol% and Vinpocetine, 5 mol%) showing mean vesicle size of 75.65 nm and mean drug entrapment of 87.44%. An insignificant change in CQA of optimized UDL after incorporation in MNP further represented their physical compatibility with MNP components. In vitro characterization of these microneedles revealed rapid dissolution (~2 min) and good skin penetrability with around 0.684 N axial needle fracture force (ANFF). The safety was ascertained in vitro by exposing HaCaT cells to VPN UDL MNP components. A 94.27% cell viability advocated the safe nature of excipients used in formulation. Ex vivo permeation across full thickness pig ear skin revealed a steady state flux of 11.091 µg/cm2/h via VPN UDL MNP with around 9-fold enhancement when compared to flux value achieved through VPN suspension. In vivo pharmacokinetic and pharmacodynamic study in Sprague Dawley rats showed a 3-fold rise in relative bioavailability and a comparable mean escape latency via UDL MNP as compared to its oral suspension. In addition, half-life of 14 h and MRT of 21 h further confirmed the controlled release behavior of UDL MNP for prolonged period of time. In nutshell, the developed fast dissolving microneedle patch of VPN showed promising results with the prospect of lowering dose as well as dosing frequency for improved patient compliance.

Structural Characterization and in Vitro Fermentation of ß-Mannooligosaccharides Produced from Locust Bean Gum by GH-26 endo-ß-1,4-Mannanase (ManB-1601).

Size exclusion chromatography of ß-mannooligosaccharides (ß-MOS) mixtures, obtained from ManB-1601 hydrolysis of locust bean gum, resulted in separation of oligosaccharides with various degrees of polymerization (DP 2, 3, and 5). The oligosaccharides were structurally [ESI-MS, FTIR, XRD, TGA, and NMR (1H and 13C)] and functionally (in vitro fermentation) characterized. DP2 oligosaccharide was composed of two species, (A) mannopyranose ß-1,4 mannopyranose and (B) α-1,6-galactosyl-mannopyranose, while DP3 oligosaccharide showed the presence of only one species, i.e. α-d-galactosyl-ß-d-mannobiose. ManB-1601 was capable of cleaving near the branch points in the substrate, resulting in oligosaccharides with galactose at the terminal position apart from attacking unsubstituted ß-1,4-glycosidic linkages. DP2 and DP3 improved the growth of three out of seven species of Lactobacillus while DP5 resulted in poor growth of all Lactobacillus spp. under in vitro conditions. DP2, DP3, and DP5 were found to inhibit the growth of Escherichia coli, Listeria monocytogenes and Salmonella typhi.

Production, properties, and applications of endo-ß-mannanases.

The present review provides up-to-date information on the occurrence and methodologies used for producing and purifying endo-ß-mannanases and a comprehensive comparison of their biochemical properties. The amalgamation of biochemical, molecular and structural biology approaches which have been used for understanding endo-ß-mannanase families, catalytic mechanism, substrate binding, non-catalytic modules, trans-glycosylation, and multi-functional enzyme complexes has been given critical attention. A separate section entailing the state-of-the-art about thermostable endo-ß-mannanases, which has emerged as an exciting field of both basic and applied research, is also deliberated. The remarkable progress made by endo-ß-mannanases in various industrial sectors like food, feed, detergents, biofuel and oil drilling is also emphasized.

Metal-dependent thermal stability of recombinant endo-mannanase (ManB-1601) belonging to family GH 26 from Bacillus sp. CFR1601.

A GH 26 endo-mannanase from Bacillus sp. CFR1601 was purified to homogeneity (Mw ∼39kDa, specific activity 10,461.5±100IU/mg). Endo-mannanase gene (manb-1601, 1083bp, accession No. KM404299) was expressed in Escherichia coli BL21 (DE3) and showed typical fingerprints of α/ß proteins in the far-UV CD. A high degree of conservation among amino acid residues involved in metal chelation (His-1, 23 and Glu-336) and internal repeats (122-152 and 181-212) was observed in endo-mannanases reported from various Bacillus sp. Thermal inactivation kinetics suggested that metal ions are quintessential for stabilization of ManB-1601 structure as holoenzyme (Ea 87.4kcal/mol, ΔH 86.7kcal/mol, ΔS 186.6cal/k/mol) displayed better values of thermodynamic parameters compared to metal-depleted ManB-1601 (Ea 47kcal/mol, ΔH 45.7kcal/mol, ΔS 64.7cal/k/mol). EDTA treatment of ManB-1601 not only lead to transitions in both secondary and tertiary structure but also promulgated the population of conformational state that unfolds at lower temperature. ManB-1601 followed a three-state process for thermal inactivation wherein loss of tertiary structure preceded the concurrent loss of secondary structure and activity.

Effect of seeds of Achyranthes aspera on the immune responses and expression of some immune-related genes in carp Catla catla.

Evaluation of functional mechanism of immunostimulant in fish is essential for realizing their therapeutic potential. The impact of dietary supplementation of seeds of Achyranthes aspera on the immune system of Catla catla was studied. Catla (37.73 ± 6.7 g) were fed with test diets containing 0.5 (D1) and 1.0% (D2) seeds of A. aspera and control diet (D3) for 50 days. Then fish were immunized with heat-killed Aeromonas hydrophila. Blood and tissue samples were collected after 7 days of immunization. Three fish were sacrificed for each parameter. Respiratory burst activity, bactericidal activity and antibody response were significantly (P < 0.05) higher in test diets fed catla compared to the control one. Nitric oxide synthase and serum lysozyme were significantly (P < 0.05) higher in fish fed with diet D2 compared to the other treatments. There were up-regulations of TNFα, lysozyme c and g gene expressions in kidney and IL-10, lysozyme c and g expressions in hepatopancreas of test diets fed fish compared to the control one. The expression of IL-10 was down-regulated in the kidney of D2 diet fed fish compared to others. In the gill, significantly (P < 0.05) higher expressions of TNFα was found in D1 diet feed fish and lysozyme c and in D2 diet fed fish compared to the other groups. This study showed tissue-specific gene expression pattern in catla. An inverse relationship was found between the expression of TNFα and IL-10 in kidney of catla.

Cost-effective endo-mannanase from Bacillus sp. CFR1601 and its application in generation of oligosaccharides from guar gum and as detergent additive.

The indigenous bacteria Bacillus sp. CFR1601 produced significant levels of endo-mannanase when grown on agro-wastes, namely, green gram husk and sunflower oil cake (25.6 IU/mL), used as sole carbon and nitrogen sources, respectively. Under immobilized cell system, synthetic supports (polyurethane foam, scotch brite, polyester; up to 33.2 IU/mL) were found marginally superior as compared to natural supports (cotton and silk; up to 28.2 IU/mL) for endo-mannanase production. Cooperative interactions between L-lysine HCl (0.3% w/v), Tween 60 (0.3% v/v), and sunflower oil cake (3.0% w/v) in central composite design response surface methodology ameliorated (1.61-fold) endo-mannanase titers to 48.0 IU/mL. Partially purified endo-mannanase was tested for its ability to produce oligosaccharides from guar gum. These oligosaccharides were tested in vitro for their ability to promote growth of Lactobacillus plantarum MTCC 5422 and Lactobacillus salivarius CHS 1E. Results indicated that low-molecular-weight degraded products from guar gum were (1) able to support the growth of tested strains [increased O.D600nm up to 2.3-fold and decrease in pH (<6.3) due to production of short chain fatty acid (SCFA)] when used as sole carbon source; and (2) after purification and analysis by electron spray ionization-mass spectrometry (ESI-MS) were found to be composed of mainly disaccharide and tetrasaccharide. The compatibility of endo-mannanase with various detergents together with wash performance test confirmed its potential applicability for laundry industry.

A sensitive and selective liquid chromatography/tandem mass spectrometry method for quantitative analysis of efavirenz in human plasma.

A selective and a highly sensitive method for the determination of the non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz, in human plasma has been developed and fully validated based on high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Sample preparation involved protein precipitation followed by one to one dilution with water. The analyte, efavirenz was separated by high performance liquid chromatography and detected with tandem mass spectrometry in negative ionization mode with multiple reaction monitoring. Efavirenz and ¹³C6-efavirenz (Internal Standard), respectively, were detected via the following MRM transitions: m/z 314.20243.90 and m/z 320.20249.90. A gradient program was used to elute the analytes using 0.1% formic acid in water and 0.1% formic acid in acetonitrile as mobile phase solvents, at a flow-rate of 0.3 mL/min. The total run time was 5 min and the retention times for the internal standard (¹³C6-efavirenz) and efavirenz was approximately 2.6 min. The calibration curves showed linearity (coefficient of regression, r>0.99) over the concentration range of 1.0-2,500 ng/mL. The intraday precision based on the standard deviation of replicates of lower limit of quantification (LLOQ) was 9.24% and for quality control (QC) samples ranged from 2.41% to 6.42% and with accuracy from 112% and 100-111% for LLOQ and QC samples. The inter day precision was 12.3% and 3.03-9.18% for LLOQ and quality controls samples, and the accuracy was 108% and 95.2-108% for LLOQ and QC samples. Stability studies showed that efavirenz was stable during the expected conditions for sample preparation and storage. The lower limit of quantification for efavirenz was 1 ng/mL. The analytical method showed excellent sensitivity, precision, and accuracy. This method is robust and is being successfully applied for therapeutic drug monitoring and pharmacokinetic studies in HIV-infected patients.

Evaluation of immunostimulatory and growth promoting effect of seed fractions of Achyranthes aspera in common carp Cyprinus carpio and identification of active constituents.

Immunostimulatory and growth promoting properties of Achyranthes aspera seeds were studied with larvae of common carp Cyprinus carpio. Four experimental diets were prepared using raw (D1) and alcohol (D2), petroleum ether (D3) and 50% aqueous alcohol (D4) extracts of A. aspera seeds. Diet without seed served as control (D5). Fish were fed with test/control diet for 30 days and then immunized with 10 µl of c-RBC. Blood samples were collected 7 days after immunization. Survival (93 ± 3%) of fish was significantly (P < 0.05) higher in D1 diet fed group compared to others. Highest specific growth rate was found in fish fed with diet D2. Significantly (P < 0.05) higher levels of serum protein and albumin were found in D1 and D3 compared to others. Highest serum globulin level was found in D1, which was followed by D3, D2, D4 and D5. Hemagglutination titer level was 5-18 folds higher in diet D3 fed fish compared to others. SGOT and SGPT levels were significantly (P < 0.05) higher in control group compared to the treated groups. Myeloperoxidase activity was significantly (P < 0.05) higher in D1 (2.513 ± 0.27 λ 450 nm) and D3 (2.38 ± 0.07 λ 450 nm) diets fed groups compared to others. The best performance of fish was found in raw A. aspera seeds incorporated diet fed group and the active constituents were identified as ecdysterone and two essential fatty acids linolenic acid and oleic acid.

Effectiveness of using teachers to screen eyes of school-going children in Satna district of Madhya Pradesh, India.

AIM: To assess the effectiveness of teachers in a vision screening program for children in classes 5th to 12th attending school in two blocks of a district of north central India. MATERIALS AND METHODS: Ophthalmic assistants trained school teachers to measure visual acuity and to identify obvious ocular abnormalities in children. Children with visual acuity worse than 20/30 in any eye and/or any obvious ocular abnormality were referred to an ophthalmic assistant. Ophthalmic assistants also repeated eye examinations on a random sample of children identified as normal (approximately 1%, n=543) by the teachers. Ophthalmic assistants prescribed spectacles to children needing refractive correction and referred children needing further examination to a pediatric ophthalmologist at the base hospital. RESULTS: Five hundred and thirty teachers from 530 schools enrolled 77,778 children in the project and screened 68,833 (88.50%) of enrolled children. Teachers referred 3,822 children (4.91%) with eye defects for further examination by the ophthalmic assistant who confirmed eye defects in 1242 children (1.80% of all screened children). Myopia (n=410, 33.01%), Vitamin A deficiency (n=143, 11.51%) and strabismus (n=134, 10.79%) were the most common eye problems identified by the ophthalmic assistant. Ophthalmic assistants identified 57.97% referrals as false positives and 6.08% children as false negatives from the random sample of normal children. Spectacles were prescribed to 39.47% of children confirmed with eye defects. CONCLUSIONS: Primary vision screening by teachers has effectively reduced the workload of ophthalmic assistants. High false positive and false negative rates need to be studied further.