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Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Background: Antimicrobial resistance (AMR) has evolved into a severe public health issue that defies all current control strategies and needs multidisciplinary, creative solutions. Antimicrobial stewardship (AMS) activities demand a set of tools and abilities that can be used by health systems. In view of the growing AMR and the difficulty for the surveillance of it in the developing country, this study was conducted to incorporate pharmacovigilance (PV) in the AMS program., Materials and Methods: A cross-sectional pilot study was conducted to collect the PV database of antimicrobials induced adverse drug reactions (ADR) from the Adverse Drug Reactions Monitoring Center (AMC) of the institute for a period of 2 months from August 2022 to September 2022. The information from the database was analyzed to estimate the usage of antibiotics from the PV database from AMC and classified it under the Anatomical Therapeutic Chemical, to assess the rationality of the antimicrobial's usage based on "Access," "Watch," and "Reserve" (AWaRe) classification, and to assess the ADR of the antibiotics. The analysis was done by using the SPSS version 20.0 for Windows., Results: The results showed that the prevalence of ADRs were more in adults' population with preponderance in female. The antibiotics usage was as per with World Health Organization standard and most of the antibiotics used were from the Access group of AWaRe classifications. Tetracyclines and penicillins were the most used antibiotic group of drugs. The number of patients included in the study was 70. Most of the causality assessment was "possible" (62.85%). In the study, almost 90% of the drug was withdrawn and 70% of the patients were in the recovering stage., Conclusion: Using existing PV approaches to address usage of antibiotics and AMR issues would allow PV to progress as a field, and governments will get a stronger return on their PV investments., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Introduction and Importance: Purtscher retinopathy is the rare form of occlusive microvasculopathy, characterized by multiple retinal white areas around the optic nerve head and fovea with paravascular clearing and may be related to intraretinal hemorrhages. Acute Pancreatitis (AP) is one of the most common gastrointestinal reasons for hospital admissions globally. The complications of Acute Pancreatitis may include Purtscher's-like retinopathy, which has a low incidence rate of less than 0.24 instances per million cases. This case report highlights the value of thorough medical history taking and examination, and it apprises the consideration of ophthalmological manifestation in patients of Acute Pancreatitis., Case Presentation: A 34-year-old female came to the emergency room due to intense abdominal pain associated with nausea and vomiting, which worsened over the last 24 h. The pain was described as continuous, sharp, and cramping-like in the upper abdomen, radiating to the back. Lab tests revealed elevated serum amylase and lipase levels, indicating pancreatitis, along with slight leukocytosis. A contrast-enhanced CT scan confirmed acute pancreatitis with mild inflammation and enlargement of the pancreas. Two days after admission, the patient experienced a sudden and painless loss of central vision in both eyes. There was no history of trauma or any other significant relevant history, other than pancreatitis. The ophthalmologist's examination found reduced visual acuity (6/60 in the right eye, 3/60 in the left eye), normal corneas, and anterior chambers., Discussion: Inkeles and Walsh established the first link between acute pancreatitis and Purtscher-like retinopathy when they reported three cases of the distinctive retinal appearance in individuals with acute pancreatitis in 1975., Conclusion: The recovery and prognosis in cases of Purtscher-like retinopathy is variable and further research is required to ascertain the usage of corticosteroids and pentoxifylline in improving the course of a patient's with Purtscher's-like retinopathy., Competing Interests: Conflict of interest statement None to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study examines the fundamental chemical mechanisms responsible for capsaicin's advantageous impact on cancer, specifically investigating its influence on several biological processes such as inflammation in cancer metastasis, apoptosis, angiogenesis, and cellular proliferation. This entity's connections with other signaling pathways, including PI3K/AKT, NF-B, and TRPV channels, which have been linked to tumor growth, are thoroughly examined in this work. This study presents a thorough analysis of preclinical studies and clinical trials investigating the efficacy of capsaicin in treating many forms of cancer, such as breast, prostate, colorectal, pancreatic, and others. Through tests conducted in both live organisms and laboratory settings, it has been determined that capsaicin has the ability to inhibit tumor growth and induce apoptosis in cancer cells. ( in vitro and in vivo ). Researchers have also looked at the results of combining capsaicin with chemotherapy medications in traditional treatment. The efficacy and bioavailability of capsaicin as a viable medicinal drug are being studied, along with ways to improve its clinical value. The present investigation carefully assesses the challenges and potential options for maximizing the therapeutic benefits of capsaicin, including customized drug delivery and personalized therapeutic strategies. In finalization, this comprehensive investigation brings together the evidence currently obtainable on the anticancer properties of capsaicin, underscoring its potential as an autonomous treatment option in the struggle against cancer. Capsaicin is a compound of significant relevance for continuing research and clinical exploration in the field of cancer treatment due to its diverse mechanisms of action and ability for boosting prevailing therapy approaches., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide. Bromocriptine is a partial antagonist for D1 dopamine receptors while also serving as a selective agonist on D2 dopamine receptors as a dopamine receptor agonist. Apart from prolactin inhibiting action, bromocriptine has some beneficial effects on the blood pressure, plasma norepinephrine levels and vascular resistance. Dopamine D2 receptor activation of bromocriptine is associated with the antihypertensive effect, which lowers blood pressure via inhibiting sympathetic nerve activity and Na/K ATPase activity. Plasma levels of the pro-inflammatory cytokines such as interleukin (IL)-1B and IL-18, chemokine CCL2/ MCP-1/, and the pro-inflammatory hormone prolactin, all of which are elevated and linked to accelerated cardiometabolic illness, were decreased because of bromocriptine therapy. The most common side effects of Bromocriptine use are dizziness, nausea, headache, vomiting and hypotension. Bromocriptine is mainly contraindicated in patients with syncope with hypotension, psychosis, and type I diabetes mellitus. The authors suggest that developing therapies directed to increase D2 receptor expression and function by drugs like Bromocriptine can provide practical and novelistic approaches to prevent and manage myocardial and renal injury in the cardiovascular disease patients., Competing Interests: There are no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells., Competing Interests: The authors declare that, there is no conflict of interest., (Thieme. All rights reserved.)

Finger millet ( Eluesine coracana L.) is gaining importance as a food crop with the increasing emphasis on nutritional aspects and drought resilience. However, the average productivity of the crop has stagnated at around 2,000 kg ha -1 in India. Recently released nutrient responsive high yielding varieties are reported to respond better to application of fertilizers/manures. Further, substitution of chemical fertilizers with organic manures to maintain sustainable yields and improve soil health is gaining attention in recent years. Therefore, identifying the appropriate rate and source of nutrition is important to enhance the productivity of finger millet while improving the soil health. A field experiment was conducted during two rainy seasons (July-November, 2018 and 2019) to study the response of finger millet varieties to chemical fertilizers and farmyard manure (FYM) on growth, yields, N use efficiency, N uptake and on soil properties. Two varieties MR-1 and MR-6 were tested with four nutrient management practices viz. , unamended control, 100% recommended dose of fertilizers (RDF; 40-20-20 kg NPK ha -1 ), 50% RDF + 50% recommended dose of nitrogen (RDN) as FYM and 100% RDN as FYM. Among the varieties, MR-6 outperformed MR-1 in terms of growth, yield, N use efficiency and N uptake. The yield enhancement was up to 22.6% in MR-6 compared to MR-1 across the nutrient management practices. Substituting FYM completely or half of the fertilizer dose increased the growth and yield of finger millet compared to application of chemical fertilizers alone. Similarly, the average biomass yield, ears m -2 , grain yield, total N uptake and N use efficiency in response to nutrient management practices followed the order of 100% RDN as FYM > 50% RDF + 50% RDN as FYM > 100% RDF. The soil organic carbon, available N, P, K, and S improved by 25.0, 12.9, 5.7, 6.1, and 22.6%, respectively in the plots under higher rate of FYM application (8 Mg ha -1 ) compared to plots under chemical fertilizers alone. We conclude that substituting chemical fertilizers either completely or by up to 50% with organic manures supplies adequate amounts of nutrients, improves the yield of finger millet, economic returns, and soil properties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor AC declared a past co-authorship with the author VS., (Copyright © 2023 Prabhakar, Gopinath, Sai Sravan, Srasvan Kumar, Thirupathi, Samba Siva, Meghalakshmi, Ravi Kumar and Singh.)

Malaria is an acute fever sickness caused by the Plasmodium parasite and spread by infected Anopheles female mosquitoes. It causes catastrophic illness if left untreated for an extended period, and delaying exact treatment might result in the development of further complications. The most prevalent method now available for detecting malaria is the microscope. Under a microscope, blood smears are typically examined for malaria diagnosis. Despite its advantages, this method is time-consuming, subjective, and requires highly skilled personnel. Therefore, an automated malaria diagnosis system is imperative for ensuring accurate and efficient treatment. This research develops an innovative approach utilizing an urgent, inception-based capsule network to distinguish parasitized and uninfected cells from microscopic images. This diagnostic model incorporates neural networks based on Inception and Imperative Capsule networks. The inception block extracts rich characteristics from images of malaria cells using a pre-trained model, such as Inception V3, which facilitates efficient representation learning. Subsequently, the dynamic imperative capsule neural network detects malaria parasites in microscopic images by classifying them into parasitized and healthy cells, enabling the detection of malaria parasites. The experiment results demonstrate a significant improvement in malaria parasite recognition. Compared to traditional manual microscopy, the proposed system is more accurate and faster. Finally, this study demonstrates the need to provide robust and efficient diagnostic solutions by leveraging state-of-the-art technologies to combat malaria., (© 2023. Springer Nature Limited.)

Background and Purpose: Metal nanoparticles are essential due to their unique catalytic, electrical, magnetic, and optical characteristics, as well as their prospective use in sensing, catalysis, and biological research. In recent years, researchers have focused on developing cost-effective and eco-friendly biogenic practices using the green synthesis of metal nanoparticles (AgNP)., Experimental Approach: In the present study, the aqueous extracts prepared from the leaf, stem, bark, and flower of Neolamarkia cadamba were used for the synthesis of silver nanoparticles. Synthesized silver nanoparticles were characterized using UV-Visible spectroscopy, zeta potential, dynamic light scattering, scanning electron microscope (SEM), and EDAX., Key Results: The current study showed absorption of synthesized AgNPs at 425, 423, 410, and 400 nm. Dynamic light scattering of AgNPs Showed size distribution of AgNPs synthesized from leaf, stem, and flower aqueous extracts ranges from 80-200 nm and AgNPs prepared from bark extract ranges from 100-700 nm. Zeta-potential of the biosynthesized AgNPs was found as a sharp peak at -23.1 mV for the leaf, -27.0 mV for the stem, -34.1 mV for the bark, and -20.2 mV for the flower. Silver nanoparticles and crude extracts of Neolamarkia cadamba showed effective antibacterial, antifungal, and antioxidant activities., Conclusion: Silver nanoparticles have substantial antibacterial activity against Gram-positive bacteria and also exhibit the utmost antifungal activity against Aspergillus niger . The study concludes that the green synthesis of silver nanoparticles from N. cadamba leaf, stem, bark, and flower extract is a reliable and eco-friendly technique., Competing Interests: Conflicts of interest: The authors declared no conflicts of interest., (Copyright © 2023 by the authors.)

With continuous advancements in Internet technology and the increased use of cryptographic techniques, the cloud has become the obvious choice for data sharing. Generally, the data are outsourced to cloud storage servers in encrypted form. Access control methods can be used on encrypted outsourced data to facilitate and regulate access. Multi-authority attribute-based encryption is a propitious technique to control who can access encrypted data in inter-domain applications such as sharing data between organizations, sharing data in healthcare, etc. The data owner may require the flexibility to share the data with known and unknown users. The known or closed-domain users may be internal employees of the organization, and unknown or open-domain users may be outside agencies, third-party users, etc. In the case of closed-domain users, the data owner becomes the key issuing authority, and in the case of open-domain users, various established attribute authorities perform the task of key issuance. Privacy preservation is also a crucial requirement in cloud-based data-sharing systems. This work proposes the SP-MAACS scheme, a secure and privacy-preserving multi-authority access control system for cloud-based healthcare data sharing. Both open and closed domain users are considered, and policy privacy is ensured by only disclosing the names of policy attributes. The values of the attributes are kept hidden. Characteristic comparison with similar existing schemes shows that our scheme simultaneously provides features such as multi-authority setting, expressive and flexible access policy structure, privacy preservation, and scalability. The performance analysis carried out by us shows that the decryption cost is reasonable enough. Furthermore, the scheme is demonstrated to be adaptively secure under the standard model.

A mild method for an efficient synthesis of C3-naphthyl indoles from o -alkynylacetophenones has been developed. This Ag-catalyzed transformation is assisted by the acetal formed under the reaction condition employing trimethyl orthoformate (TMOF). The role of acetal in promoting the reaction under ambient conditions has been established with control experiments. A range of C3-naphthyl indole derivatives have been synthesized in moderate to very good yields.

The reactivity of o -propargyl alcohol benzaldehydes has been increased tremendously toward Brønsted acid-catalyzed intramolecular electrophile intercepted Meyer-Schuster (M-S) rearrangement under acetalization conditions using trimethyl orthoformate (TMOF). The in situ formed acetal transfers the methoxy group intramolecularly to generate the M-S intermediate in even less reactive substrates, and the formed oxocarbenium ion makes the carbonyl more electrophilic for an effective intramolecular trapping of the M-S intermediate to furnish the indanone derivatives.

An efficient protocol for the synthesis of indole-substituted indanes from o -alkenylbenzaldehydes under acetalization conditions has been presented. The cyclization occurs via a nucleophilic addition of indole on the oxacarbenium ion generated from acetal formed under the reaction condition followed by a conrotatory 4π-electrocyclization reaction, which takes care of the exclusive diastereoselectivity observed during the cyclization step. Olefin geometry of o -alkenylbenzaldehyde and the amount of indole play a decisive role in the success of this cyclization process.

Sloshing in fuel tanks has become a new source of noise in hybrid and high-end vehicles in the wake of reduced noise from major sources like the engine. It occurs due to the interactions of fluid inside the tank under various driving conditions of the vehicle. Interactions of fluid with the tank walls cause hit noise, and the fluid-fluid interactions cause splash noise. As the generation mechanism is different, the hit and splash noises demand different noise controlling strategies. Thus, identifying these noises during the design stage is important for implementing effective solutions in designing a quieter fuel tank. This paper presents a convolutional neural network (CNN) based methodology for the identification of sloshing noises under different conditions of fill level, excitation, baffle configuration, etc. Data for training and testing the network are collected using a reciprocating test setup, which facilitates the generation of hit and splash noises in a rectangular tank. The identification accuracy of the features learned by CNN is compared with the hand-crafted features using support vector machines. The applicability of the proposed CNN model is tested for practical scenarios like vehicle braking, where different types of sloshing noises occur in quick succession.

Background: Periodontal Disease (PD) is associated with complications of diabetes. Control of the PD reduces glycated hemoglobin (HbA1c) level. This study aimed to evaluate the relationship of PD with duration, severity of diabetes and eGFR., Material and Method: A Prospective observational study conducted at Sidhi Vinayaka Hospitals (SVH) Sangareddy during the period of January 2014 to December 2019. Total 1436 patients with a definite diagnosis of type 2 diabetes (T2DM), between the ages of 45-60 years were included. They were classified according to CPITN score for PD and compared against the variables., Results: A total of 1436 consecutive outpatients attending to SVH were included. Among them 662 (46.1%) were males and 774(53.9%) were females. The mean age of the patients was 48.3(SD ± 10.62) and mean duration of diabetes was 2.9(SD ± 4.18). The mean fasting blood glucose was 198.5(SD ± 85), mean post prandial blood glucose was 277.2 (SD ± 107.7) and mean HBA1c was 9.98% (SD ± 2.6). Among the study group 1198 (83.4%) had none/mild (Grade I) PD, 192(13.4%) had moderate/severe (Grade II) PD and 46(3.2%) were completely edentulous (Grade III)., Conclusion: There is a linear correlation between PD and age of patient, duration of diabetes, eGFR and level of glycemic status among rural population with T2DM., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Laccase, a multicopper oxidoreductase (EC: 1.10.3.2), is a widely used enzyme in bioremediation of textile dye effluents. Fungal Laccase is preferably used as a remediating agent in the treatment and transformation of toxic organic pollutants. In this study, crude laccase from a basidiomycetes fungus, Phanerochaete sordida, was able to decolorize azo, antroquinone and indigoid dyes. In addition, interactions between dyes and enzyme were analysed using molecular docking studies., Methods: In this work, a white rot basidiomycete's fungus, Phanerochaete sordida, was selected from forest soil isolates of Eastern Ghats, and Tirumala and lignolytic enzymes production was assayed after 7 days of incubation. The crude enzyme was checked for decolourisation of various synthetic textile dyes (Vat Brown, Acid Blue, Indigo, Reactive Blue and Reactive Black). Molecular docking studies were done using Autodock-4.2 to understand the interactions between dyes and enzymes., Results: Highest decolourisation efficiency was achieved with the crude enzyme in case of vat brown whereas the lowest decolourisation efficiency was achieved in Reactive blue decolourisation. Similar results were observed in their binding affinity with lignin peroxidase of Phanerochaete chrysosporium through molecular docking approach., Conclusion: Thus, experimental results and subsequent in silico validation involving an advanced remediation approach would be useful to reduce time and cost in other similar experiments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The use of phytochemicals in control of human diseases have been considerable public and scientific interest in current days. Syringic acid (SA), a phenolic compound often found in fruits and vegetables and which is synthesized via shikimic acid pathway in plants. It shows a wide range of therapeutic applications in prevention of diabetes, CVDs, cancer, cerebral ischemia; as well as it possess anti-oxidant, antimicrobial, anti-inflammatory, antiendotoxic, neuro and hepatoprotective activities. It has an effective free radical scavenger and alleviates the oxidative stress markers. The therapeutic property of SA is attributed by the presence of methoxy groups onto the aromatic ring at positions 3 and 5. The strong antioxidant activity of SA may confer its beneficial effects for human health. SA has the potential to modulate enzyme activity, protein dynamics and diverse transcription factors involved in diabetes, inflammation, cancer and angiogenesis. In vivo experimental data and histopathological studies on SA activity has delineated its possible therapeutic mechanisms. Besides usage in biomedical field, SA has greater industrial applications in bioremediation, photocatalytic ozonation, and laccase based catalysis. The present review deals about SA natural sources, biosynthesis, bioavailability, biomedical applications (in vivo and in vito. The review addresses basic information about molecular mechanisms, therapeutic and industrial potential of SA., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: Hepatitis C virus (HCV) infection in end stage renal disease (ESRD) is associated with increased mortality. Recently, numerous directly acting antiviral agents have been approved for the management of HCV. Ledipasvir along with Sofosbuvir has been approved for management of genotype 1 infection in patients with eGFR ≥30 mL/min. However, there is paucity of data regarding its role in the management of patients on dialysis., Material and Methods: This is a single center prospective open label observational study to assess the safety and efficacy of Ledipasvir and Sofosbuvir in hemodialysis (HD) patients who were diagnosed with HCV genotype 1 infection. Eligibility criteria were treatment naive HD patients with normal liver histology. We administered Ledipasvir and Sofosbuvir combination tablet on alternate days for a period of 12 weeks. Primary efficacy end point was the assessment of sustained virological response (SVR12), and the safety end point was the discontinuation of therapy secondary to adverse drug effects., Results: A total of 21 patients were treated with this regimen. Two patients expired during the study period and are not related to the therapy. SVR12 was achieved in all the 19 patients. None of the patients in our study discontinued the therapy or had severe adverse drug effects. One patient had head ache and another patient had giddiness which were managed symptomatically., Conclusion: Ledipasvir and Sofosbuvir combination therapy on alternate days, is effective even in ESRD patients, with excellent SVR12 rates, and it is as safe as in other population groups, without any major adverse reactions., (© 2017 International Society for Hemodialysis.)

The threat of zika virus looms throughout the world and the use of allethrin-based mosquito coils to prevent mosquito bites during and postpregnancy is on the rise. The aim of this study was to analyze the toxic effects of exposure to allethrin-based mosquito coil smoke in rats under conditions that reflect human settings. Pregnant female rats were exposed to mosquito coil smoke and same was continued to the male pups up to 111 days postparturition (21-day weaning plus up to 90 days postweaning). Increased oxidative stress, distorted antioxidant enzyme status, downregulation of genes involved in spermatogenesis, sperm maturation and steroidogenesis was observed. Daily sperm production, total sperm count and acrosome reaction was compromised. Results of our study indicate the toxic effects of exposure to allethrin-based mosquito coil smoke in male offspring and calls for preventing mosquito coil use during pregnancy and postnatal development. Community-based programs that will encourage general population to use classical methods such as use of mosquito nets, keeping the surroundings clean and use of natural mosquito repellents should be conducted.

Pyrethroids are widely used for domestic and agricultural purposes and their use is increasing, especially in developing countries. Uncontrolled use of these insecticides resulted in their entry into the food chain thereby causing toxicity to different organ systems. Allethrin is one of the widely used pyrethroids, but its toxicological effects are underreported when compared to other pyrethroids. Further, its effects on the male reproductive tract remain uncharacterized. In this study, its toxicity on the male reproductive tract was evaluated by administering 25-150 mg/kg body weight allethrin to adult rats for 60 days. The mRNA expression of factors that are important in spermatogenesis (Scf, c-Kit, Hsf2, Ovol1, Brdt, Kdm3A, Ybx-2, and Grth) and steroidogenesis (StAR, 3β-HSD, 17β-HSD) was significantly downregulated. Decreased levels of testosterone, reduced sperm count and daily sperm production was also observed due to allethrin toxicity. However, sperm quality parameters assessed by computer-assisted sperm analyzer were not affected. Spermatozoa obtained from allethrin-treated rats failed to undergo acrosome reaction. Results of this study indicate that allethrin affects spermatogenesis and sperm function, thus lending further support to the growing evidence of its toxicity., (© 2017 Wiley Periodicals, Inc.)

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells-together with data from the literature-suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function, characterized by slowing of fast inactivation, acceleration of its recovery or increased persistent sodium current. Further, a good response to sodium channel blockers clinically was found to be associated with a relatively small gain-of-function. In contrast, mutations in patients with late-onset forms and an insufficient response to sodium channel blockers were associated with loss-of-function effects, including a depolarizing shift of voltage-dependent activation or a hyperpolarizing shift of channel availability (steady-state inactivation). Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Cyclooxygenase (COX-2) inhibitors have been developed to provide better anti-inflammatory and analgesic efficacy than those of traditional NSAIDs. Several compounds having selective COX-2 inhibitors such as SC-558, Celecoxib, Rofecoxib, Valdecoxib and Etoricoxib are marketed as new generation NSAIDs and block the production of prostaglandins (PGs) in inflammatory cells. New anti-inflammatory agents with improved potency and safety profile are still needed., Objective: As a part of our continuation research work towards new anti-inflammatory agents, the synthesis of N-substituted aryl/heteroaryl-pyrazole-1yl benzene sulfonamide (Celecoxib) derivatives, their anti-inflammatory activity in both methods in vitro and in vivo and molecular docking study on COX-2 enzyme will be discussed in this study., Methods: A series of N-substituted (aryl/heteroarylpyrazol-1-yl)benzenesulfonamide (Celecoxib) derivatives was synthesized and characterized them using IR, NMR (1H and 13C), mass and elemental analyses. Anti-inflammatory activity of the title compounds was evaluated by in vitro initially using albumin denaturation and membrane stabilization methods, enzymatic activity against COX-2 enzyme using colorimetric assay and then in vivo by carrageenan induced paw oedema and cotton pellet induced granuloma methods. The docking study was performed, to find the binding mode of the title compounds with the binding site of the COX-2 enzyme., Results: The biological activity screening data disclosed that some of the compounds 5b, 5e, 5f and 5i exhibited potent anti-inflammatory activity in both methods, in vitro and in vivo. The enzymatic assay on COX-2 enzyme demonstrated that few compounds potently inhibit COX-2 enzyme activity with IC50 of &lt;0.89 &#956;M. Unexpectedly, compound 5e (IC50, 0.62±0.17 &#956;M) showed more potent COX-2 inhibited activity than that of parent drug, celecoxib (IC50, 0.62±0.25 &#956;M) and the standard, flufenamic acid (IC50, 0.71±0.12 &#956;M)., Conclusion: The bio-screening data, in vitro and in vivo anti-inflammatory activity and COX-2 enzymatic assay revealed that few N-substituteed aryl/heteroaryl-pyrazol-1-yl) benzene sulfonamides showed potent activity and compound 5e showed more potent COX-2 inhibit activity than that of parent drug, celecoxib and the standard, flufenamic acid. Moreover, all the newly synthesized title products were bonded well with good binding energies in the sight of COX-2 enzyme. Therefore, the described study might provide sustained information to the development of new series of derivatives with potent drug like activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Xylanses are hydrolytic enzymes with wide applications in several industries like biofuels, paper and pulp, deinking, food, and feed. The present study was aimed at hitting at high yield xylanase producing fungi from natural resources. Two highest xylanase producing fungal isolates-Q12 and L1 were picked from collection of 450 fungal cultures for the utilization of xylan. These fungal isolates-Q12 and L1 were identified basing on ITS gene sequencing analysis as Fusarium sp. BVKT R2 (KT119615) and Fusarium strain BRR R6 (KT119619), respectively with construction of phylogenetic trees. Fusarium sp. BVKT R2 was further optimized for maximum xylanase production and the interaction effects between variables on production of xylanase were studied through response surface methodology. The optimal conditions for maximal production of xylanase were sorbitol 1.5%, yeast extract 1.5%, pH of 5.0, Temperature of 32.5°C, and agitation of 175 rpm. Under optimal conditions, the yields of xylanase production by Fusarium sp. BVKT R2 was as high as 4560 U/ml in SmF. Incubation of different lignocellulosic biomasses with crude enzyme of Fusarium sp. BVKT R2 at 37°C for 72 h could achieve about 45% saccharification. The results suggest that Fusarium sp. BVKT R2 has potential applications in saccharification process of biomass.

A Gram-positive bacterium was isolated from mangrove soil and was identified as Bacillus licheniformis (KC710973). The potential of a mangrove microorganism to utilize different natural waste carbon substrates for biosurfactant production and biodegradation of hydrocarbons was evaluated. Among several substrates used in the present study, orange peel was found to be best substrate of biosurfactant yield with 1.796 g/L and emulsification activity of 75.17 % against diesel. Fourier transform infrared spectroscopy analysis of biosurfactant compound revealed that the isolated biosurfactant is in lipopeptide nature. The 1 H-NMR of the extracted biosurfactant from B. licheniformis has a doublet signal at 0.8-0.9 ppm corresponding to six hydrogen atoms suggests the presence of a terminal isopropyl group. The spectra showed two main regions corresponding to resonance of α-carbon protons (3.5-5.5 ppm) and side-chain protons (0.25-3.0 ppm). All the data suggests that the fatty acid residue is from lipopeptide. From the biodegradation studies, it concluded that the biosurfactant produced by B. licheniformis further can add to its value as an ecofriendly and biodegradable product.

We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40-70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur &61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88-124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39-4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6-3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV.

Background and Objective: Pradigastat, a novel diacylglycerol acyltransferase 1 inhibitor, is under development to treat familial chylomicronemia syndrome. The potential impact of hepatic impairment on the pharmacokinetics of pradigastat was evaluated in this study., Methods: In this study, a single oral dose of 20 mg pradigastat was administered first to patients with mild and moderate hepatic impairment (n = 10/group) and subsequently to patients with severe hepatic impairment (n = 6). The pharmacokinetics of pradigastat were compared between each patient group and the respective matched healthy subjects., Results: As compared with the respective matched healthy groups, the geometric mean ratios of the area under the plasma concentration-time curve from time zero to infinity (AUC inf) (h · ng/mL) were 1.49, 1.06 and 1.99 in mild, moderate and severe hepatic impairment patients, respectively; the observed maximum plasma concentration (C max) (ng/mL) values were 0.97, 1.28 and 2.74, respectively; and the total body clearance of the drug from plasma (CL/F) (L/h) values were 0.67, 0.95 and 0.50, respectively. The elimination half-life and plasma protein binding of pradigastat were comparable among all the patients. There were no apparent relationships between AUC inf or C max and albumin or bilirubin levels (R (2) < 0.3; p > 0.05). Overall, 19 adverse events (AEs) were reported in 13 patients. The incidence of AEs appeared to increase with increasing severity of hepatic impairment., Conclusion: No clinically significant differences in the pharmacokinetics of pradigastat were observed in mild and moderate hepatic impairment patients compared with healthy subjects. However, the systemic exposure of pradigastat doubled while the clearance decreased by half in patients with severe hepatic impairment compared with healthy subjects. All treatments were well tolerated in the study.

The main objective of this paper is to optimize biosurfactant production by Pseudomonas aeruginosa 2297 with statistical approaches. Biosurfactant production from P. aeruginosa 2297 was carried out with different carbon sources, and maximum yield was achieved with sawdust followed by groundnut husk and glycerol. The produced biosurfactant has showed active emulsification and surface-active properties. From the kinetic growth modeling, the specific growth rate was calculated on sawdust and it was 1.12 day -1 . The maximum estimated value of product yield on biomass growth (Y p/x ) was 1.02 g/g. The important medium components identified by the Plackett-Burman method were sawdust and glycerol along with culture parameter pH. Box-Behnken response surface methodology was applied to optimize biosurfactant production. The obtained experimental result concludes that Box-Behnken designs are very effective statistical tools to improve biosurfactant production. These results may be useful to develop a high efficient production process of biosurfactant. In addition, this type of kinetic modeling approach may constitute a useful tool to design and scaling-up of bioreactors for the production of biosurfactant.

Molecular docking studies of the designed two series (4a-l, 6a-l, 9 and 10) of novel substituted phosphorylated 1, 4-dihydropyridine and 1,2,3,4-tetrahydropyrimidine derivatives against the drug targets of DHFR from Bacillus cereus, LpxC from Pseudomonas aeruginosa, IDH from E. coli and MurB from Staphylococcus aureus were encouraged for their synthesis. These compounds were synthesized from substituted aromatic aldehydes, thiourea/urea and ethyl acetoacetate in the presence of polyphosphoric acid (PPA). These were further phosphorylated with diethyl (2-chloroethoxy) methyl phosphonate to get the desired products. In vitro anti-bacterial activity against the specified bacterial strains related to docked protein exhibited good inhibitory activity at different dose concentrations. Quantitative Structure Activity Relationship (QSAR) descriptors of the designed structures have demonstrated their satisfactory drug like properties. The results from Molecular Docking, QSAR descriptors and in vitro anti-bacterial activities led to the identification of safer and potential antibacterial agents of the title compounds screened. Compounds 4a, 4d, 4i, 6a, 6d, 9 and 10 were found to be potent antibacterial agents.

Over the years, pyrethroids, including D-allethrin, are widely used for domestic and agricultural purposes and are found to be toxic to many organ systems including the male reproductive system. However, the molecular mechanisms of allethrin toxicity are not well understood. In this study, we demonstrate that allethrin exhibited a dose-dependent cytotoxicity on Leydig cell carcinoma cells (LC540) and isolated primary Leydig cells with an IC50 of 125 μM and 59 μM respectively. Cytotoxicity was associated with generation of reactive oxygen species, increased lipid peroxidation and alterations in antioxidant enzyme status. Morphological analyses of LC540 cells treated with allethrin revealed the presence of apoptotic bodies. Using flow cytometry, we observed that the number of cells that displayed early apoptotic features and entering into G0 phase of cell cycle increased significantly with loss of mitochondrial membrane potential. The levels of p53 mRNA and cleaved PARP-1 protein were increased, whereas BCL-2, pro-Caspase-3 and PARP-1 were decreased. Allethrin induced apoptosis was associated with voltage gated calcium channel mediated intracellular calcium release. Results of our study demonstrate that allethrin toxicity in the male reproductive tract may involve Leydig cell apoptotic death., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Pyrethroids are known to be neurotoxic. However, their toxic effects including that of allethrin on the male reproductive tract are not elucidated. Adult male rats were treated orally with 25, 50, 100, and 150 mg/kg body weight allethrin every day for 60 days. Lipid peroxidation was increased (p < 0.001) in the caput, cauda, and testes. Nitric oxide production was increased (p < 0.001) in the caput, but unaltered in the cauda and testes. The activities of catalase, glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase were decreased in the caput and cauda where as a decrease was observed in the testis obtained from allethrin treated rats. In the epididymides and testes, damage to tubular architecture, congestion, degeneration of epithelial cell lining, intestinal edema, and presence of dead or degenerating spermatids were observed in a dose dependent manner. The expression profile of genes involved in spermatogenesis (Tgf-beta1), sperm maturation (Spag11e), and sperm function (Defb22) were reduced (p < 0.001) in allethrin rats. The expression of p53 gene was decreased and increased phosphorylation of MAPK (p42/p44) expression was observed the male reproductive tract tissues of allethrin treated rats. Although earlier studies have reported the effects of allethrin inhalation because of the use of mosquito coils and vaporizers, our results for the first time prove that oral exposure to allethrin could affect fertility and may contribute to deregulation of cell cycle in the male reproductive tract., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: To evaluate the effects of siponimod (BAF312) on the pharmacokinetics (PK) and pharmacodynamics (PD) of a monophasic oral contraceptive (OC)., Materials and Methods: This was a phase 1, single-center, open-label, multipledose, single-sequence study in healthy females. Eligible subjects (n = 23) were exposed sequentially to two treatment periods: period 1 (OC alone) and period 2 (OC + siponimod) in two consecutive menstrual periods. PK parameters were assessed on day 21 of both treatment periods. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone concentrations were measured at baseline and days 3, 6, 8, 11, 14, 16, 19, 21, and 23 of each period. Largest ovarian follicle size and sex hormone-binding globulin (SHBG) concentration were measured and Hoogland score was calculated at baseline and day 21 of each period. Safety and tolerability of siponimod was also assessed., Results: Co-administration (OC + siponimod) increased the AUC(τ,ss) and C(max,ss) of levonorgestrel by 28% and 18%, respectively, but had no effect on the PK of ethinylestradiol. No significant changes in estradiol, FSH, and LH were noted with co-administration vs. OC alone. Progesterone levels < 5 nmol/L, largest follicle size < 10 mm, and Hoogland score of 1 on day 21 indicated lack of ovulation in all subjects during co-administration. Co-administration was well tolerated., Conclusion: In conclusion, PK and PD of the OC were not altered to a clinically significant extent and contraceptive efficacy was maintained with co-administration. Hence, OC as a contraceptive measure can be safely co-administered with siponimod.

Owing to the promising antiviral activity of amino acid ester-substituted phosphorylated nucleosides in the present study, a series of phosphorylated derivatives of emtricitabine and didanosine substituted with bioactive amino acid esters at P-atom were synthesized. Initially, molecular docking studies were screened to predict their molecular interactions with hemagglutinin-neuraminidase protein of Newcastle disease virus and E2 protein of human papillomavirus. The title compounds were screened for their antiviral ability against Newcastle disease virus (NDV) by their in ovo study in embryonated chicken eggs. Compounds 5g and 9c exposed well mode of interactions with HN protein and also exhibited potential growth of NDV inhibition. The remaining compounds exhibited better growth of NDV inhibition than their parent molecules, i.e., emtricitabine (FTC) and didanosine (ddI). In addition, the in vitro anticancer activity of all the title compounds were screenedagainst HeLa cell lines at 10 and 100 μg/mL concentrations. The compounds 5g and 9c showed an effective anticancer activity than that of the remaining title compounds with IC50 values of 40 and 60 μg/mL, respectively. The present in silico and in ovo antiviral and in vitro anticancer results of the title compounds are suggesting that the amino acid ester-substituted phosphorylated FTC and ddI derivatives, especially 5g and 9c, can be used as NDV inhibitors and anticancer agents for the control and management of viral diseases with cancerous condition.

An actinomycete was isolated from mangrove soil collected from Nellore region of Andhra Pradesh, India, and screened for its ability to produce bioactive compounds. The cultural, morphological, and biochemical characters and 16S rRNA sequencing suggest that the isolated strain is Nocardiopsis alba. The bioactive compounds produced by this strain were purified by column chromatography. The in vitro antioxidant capacity of the isolated compounds (fractions) was estimated and fraction F2 showed very near values to the standard ascorbic acid. The potential fraction obtained by column chromatography was subjected to HPLC for further purification, then this purified fraction F2 was examined by FTIR, NMR, and mass spectroscopy to elucidate its chemical structure. By spectral data, the structure of the isolated compound was predicted as "(Z)-1-((1-hydroxypenta-2,4-dien-1-yl)oxy)anthracene-9,10-dione."

Laccases are blue multicopper oxidases, which catalyze the monoelectronic oxidation of a broad spectrum of substrates, for example, ortho- and para-diphenols, polyphenols, aminophenols, and aromatic or aliphatic amines, coupled with a full, four-electron reduction of O2 to H2O. Hence, they are capable of degrading lignin and are present abundantly in many white-rot fungi. Laccases decolorize and detoxify the industrial effluents and help in wastewater treatment. They act on both phenolic and nonphenolic lignin-related compounds as well as highly recalcitrant environmental pollutants, and they can be effectively used in paper and pulp industries, textile industries, xenobiotic degradation, and bioremediation and act as biosensors. Recently, laccase has been applied to nanobiotechnology, which is an increasing research field, and catalyzes electron transfer reactions without additional cofactors. Several techniques have been developed for the immobilization of biomolecule such as micropatterning, self-assembled monolayer, and layer-by-layer techniques, which immobilize laccase and preserve their enzymatic activity. In this review, we describe the fungal source of laccases and their application in environment protection.

Baylis-Hillman adduct-derived N -cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on Mycobacterium tuberculosis H 37 Rv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds ( 3j - l ) have shown significant activity against Mycobacterium strain and the compound 3l has shown specific cytotoxic activity., (© Springer Science+Business Media New York 2013.)