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The importance of developing effective assays to diagnose, monitor and evaluate human lymphatic filariasis has been emphasized by the World Health Organization. Presently, few immunodiagnostics are available for filarial monitoring programmes. The Wuchereria bancrofti (Wb) SXP-1 parasite protein, with 84% homology to Brugia malayi (Bm) SXP-1, was found to be highly immunogenic. WbSXP-1 is one among the diagnostic candidate molecules that were used for developing a rapid-antibody-flow-through diagnostic kit for filariasis. Studies were initiated with the aim of developing monoclonal antibodies against recombinant WbSXP-1 and prospective applications for the detection of both circulating Wb and Bm antigens in serum samples from infected individuals. The monoclones 1A6C2 of subclass IgG1k, and 2A12F8 of class IgM, specifically detected Wb and Bm microfilaria isolated from patients and did not show cross-reactivity with other filarial recombinant antigens. We anticipate that this work will address the problems faced in the rapid diagnosis of human lymphatic filariasis in endemic areas in developing countries. [ABSTRACT FROM AUTHOR]

Microglia are key immune cells in the brain that maintain homeostasis and defend against immune threats. Targeting the dysfunctional microglia is one of the most promising approaches to inhibit neuroinflammation. In the current study, a diverse series of molecular hybrids were designed and screened through molecular docking against two neuroinflammatory targets, namely HMGB1 (2LY4) and HMGB1 Box A (4QR9) proteins. Based on the outcomes of docking scores fifteen compounds; ten furanyl-pyrazolyl acetamides 11(a-j), and five 2,4-thiazolidinyl-furan-3-carboxamide 15(a-e) derivatives were selected for further synthesis, followed by biological evaluation. The selected compounds, 11(a-j) and 15(a-e) were successfully synthesized with moderate to good yields, and structures were confirmed by IR, NMR, and mass spectra. The in-vitro cytotoxicity was evaluated on microglial cells namely BV-2, N-9, HMO6, leukemic HAP1, and human fibroblast cells. Further western-blot analysis revealed that 11h, 11f, 11c, 11j, 15d, 15c, 15e, and 15b compounds significantly suppressed anti-inflammatory markers such as TNF-α, IL-1, IL-6, and Bcl-2. All derivatives were moderate in potency compared to reference doxorubicin and could potentially act as novel anti-neuroinflammatory agents. This study can act as a beacon for further research in the application of furan-pyrazole and furan-2,4-thiazolidinediones as lead moieties for anti-neuroinflammatory and related diseases., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: Our objective was to evaluate the incidence of urinary tract infections (UTIs) in low birth weight (LBW) neonates and to evaluate the compliance of neonatal intensive care unit (NICU) providers in performing urine cultures as a part of late-onset sepsis (LOS) evaluations following an educational intervention., Study Design: A retrospective chart review for all LBW infants undergoing LOS evaluations was performed. An educational intervention was conducted to encourage NICU providers to perform urine cultures in LOS evaluations. Prospective chart reviews were conducted following the intervention to assess compliance with the urine culture directive and the incidence of UTIs before and after the intervention., Results: Rate of UTIs among LBW neonates was 1.3% for the entire study period and typical uropathogens were the cause. UTIs were found concurrently with bacteremia in only 33.3% of cases and showed a predilection for male infants when analyzing based on the number of infections. Urine cultures were performed in 20% of LOS evaluations prior to our educational intervention and increased to 57% ( p  < 0.0001) postintervention., Conclusion: An educational intervention is effective at increasing the rate of obtaining urine cultures with LOS evaluations. Performing these cultures reveals that UTIs in LBW neonates are common without bacteremia and can be missed if they are omitted from LOS evaluations., Key Points: · UTIs occur often in preterm infants, especially boys.. · Education increases the performance of urine cultures.. · UTIs in preterm infants occur often without bacteremia.., Competing Interests: None declared., (Thieme. All rights reserved.)

Justification: Osteoarticular infections are fairly common in children but often these are associated with underdiagnosis, delayed diagnosis and improper management. This leads to an increased incidence of complications and poor outcomes. Given the paucity of standard protocols for the management of these children in the Indian context, Indian Academy of Pediatrics (IAP) has taken the initiative to formulate guidelines for the early diagnosis and rational management of bone and joint infections (BJIs)., Objectives: To critically evaluate the current evidence and formulate consensus guidelines for the diagnosis and management of BJIs in children., Process: A committee comprising of eminent national faculty from different parts of the country who are experts in the field of Pediatric Infectious Diseases, Pediatric Orthopedics and Musculoskeletal Radiology was constituted and duly approved by the IAP. On Jan 16, 2021, a virtual meeting was held and a detailed discussions were carried out regarding the need to formulate these guidelines. Subsequently, the expert group defined the key questions in the first stage followed by collection and review of scientific evidences including available national and international recommendations or guidelines. This was followed by detailed deliberation among group members and presentation of their recommendations. The same were finalized in an online meeting on Aug 01, 2021, and a consensus statement was developed and adopted by the group., Statement: BJIs are medical emergencies that need early diagnosis and appropriate therapy to prevent long term sequelae like limb deformities. Bacterial infections like Staphylococcus aureus is the most common etiological agent. Nonspecific and subtle clinical manifestations make the diagnosis of pediatric BJIs more challenging. Diagnosis of BJIs is primarily clinical, supplemented by laboratory and radiological investigations. The choice of antibiotic(s), mode of administration and duration of therapy requires individualization depending upon the severity of infection, causative organism, regional sensitivity patterns, time elapsed between onset of symptoms and the child's presentation, age, risk factors and the clinical and laboratory response to treatment. There is paucity of appropriate guidelines regarding the diagnosis and management of BJIs in children in Indian context. Hence, the need for this expert consensus guidelines in Indian settings.

Within the scope of their practice, advanced practice providers provide similar patient care as physicians, but in some cases have outperformed physicians in terms of health outcomes, satisfaction, and cost-effectiveness. At an academic medical center, hepatology trained advanced practice providers, who were also certified in obesity management, led an interprofessional team to develop the Weight Intervention in Liver Disease pathway. In September 2018, patients who were seen in the hepatology practice and met criteria for enrollment were referred to the Weight Intervention in Liver Disease program for comprehensive care of obesity and related metabolic disorders. A program evaluation was conducted in 2021 to identify whether the effectiveness of the advanced practice provider-led structure and process, and the Weight Intervention in Liver Disease pathway, supported weight loss goals as well as improvement in alanine aminotransferase levels, patient satisfaction, and provider satisfaction. Results found that the structure of the pathway and the implementation are resulting in positive outcomes of 100% patient satisfaction, 80% provider satisfaction, and a total average sustained weight loss of 5.05% ( SD = 7.98, p < .01). A weight loss pathway led by trained advanced practice providers proves successful in long-term weight loss goals., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Society of Gastroenterology Nurses and Associates.)

Competing Interests: The authors have no conflicts to report.

Background: Degeneration of Lumbar muscle in chronic low back pain (CLBP) is characterized by an increase in fat infiltration of paraspinal muscle, decrease in the cross-sectional area (CSA) of lumbar multifidus muscle (LMM) and increased thickness of Thoracolumbar fascia (TLF) by 25%. The study objective is to compare the effects of yoga and dynamic neuromuscular stabilization (DNS) exercise on CSA, fat infiltration of LMM with magnetic resonance imaging (MRI), and TLF thickness using musculoskeletal ultrasound imaging (MSK-USI) in CLBP., Methods: One hundred and forty-four participants with CLBP, which persisted longer than three months, will be recruited for this trial. Both group interventions focused on LMM. The experimental group will receive structured yoga sessions, and the Control Group will receive exercise based on DNS. In each group, exercises will be performed for 3-5 days/week and progressed for 12 weeks. Baseline data will be collected, followed by the recording of primary outcome measure (MRI) and secondary outcome measures (MSK-USI, Oswestry disability index, visual analogue score, optimism, self-efficacy, mood, physical activity, fear of movement, pain catastrophizing, and coping) at baseline and the end of 12th weeks. The normality of data will be verified. Based on the data distribution, within-group analysis and between-group analysis will be performed., Discussion: This will be the first RCT to compare the effect of yoga and DNS exercise among chronic low back pain participants. This will provide evidence of these interventions' impact on CSA, fat infiltration of LMM, and thickness of TLF in CLBP., Registration Number: CTRI/2021/08/035984 (This trial was registered prospectively)., Competing Interests: 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., (© 2022 Published by Elsevier Inc.)

Methotrexate (MTX) is used in the treatment of several childhood cancers and is a main component of the treatment regimen for osteosarcoma. MTX has been linked with side effects of varying severity; headaches, nausea, emesis, lethargy, blurred vision, aphasia, hemiparesis, paresis, convulsions, leukoencephalopathy, and arachnoiditis are symptoms of MTX toxicity. MTX-induced neurotoxicity can occur in up to 15% of patients receiving high-dose MTX. The effects may be transient but can have life-threatening implications, sometimes requiring intubation for respiratory support and airway protection. Elevated homocysteine levels in the cerebrospinal fluid are documented in cases of MTX-induced neurotoxicity; dextromethorphan is used as an initial treatment for MTX-induced neurotoxicity as it works as a noncompetitive antagonist for the N-methyl D-aspartate receptors and suppresses homocysteine activity. In severe cases requiring intubation, medications for sedation are utilized. Ketamine is also an N-methyl D-aspartate receptor antagonist, and as such, may be considered as an optimal treatment choice when sedation is required. We describe the use of ketamine in a pediatric patient with MTX-induced neurotoxicity. The use of ketamine in the treatment of MTX-induced neurotoxicity has not been described in the literature., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

There is an underlying tension between the goals of trade liberalisation and a nation's sovereign right to regulate on matters of public health. In terms of trade in goods, Article XX(b) of the General Agreement on Tariffs and Trade (GATT) allows for measures necessary to protect human health, as one of the general exceptions. The increasing proliferation of comprehensive Free Trade Agreements (FTA) also contains general exception clauses to protect human health. International Investment Agreements contain provisions carving out an exception for tobacco products, from the scope of Investor State Dispute Settlement (ISDS) claims against the host State. The aim of this article is to examine if the public health exceptions in FTAs differ from those under the GATT, and whether they can be used as an avenue for effective regulation. In the context of investment, the article examines if a 'carve-out' from ISDS is a feasible option. The article concludes by observing that it may be difficult for FTAs to provide for broader regulatory autonomy to States, given the resort to the World Trade Organization (WTO) jurisprudence in FTA dispute settlement. Effectively, measures to regulate alcohol for the protection of public health may have to be designed and structured in a WTO compatible manner. In terms of ISDS, a 'carve-out' from dispute settlement may provide increased regulatory space but would depend on whether consensus can be achieved in this regard. States should approach the regulation of alcohol in a comprehensive manner addressing potential challenges under the trade and investment regimes., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

A new series of 1,2,3-triazole tethered chalcone acetamide derivatives (7a-c &8a-r) have been synthesized in excellent yields and their structures were determined by analytical and spectral (FT-IR, 1 H NMR, 13 C NMR & HRMS) studies. The newly synthesized derivatives were evaluated for their cytotoxic activity against four human cancer cell lines, such as HeLa (Human cervical cancer), A549 (Human alveolar adenocarcinoma), MCF-7 (Human breast adenocarcinoma) and SKNSH (Human brain cancer). Among them, compound 7c exhibited good anti-proliferation activity with HeLa (IC 50 7.41 + 0.8 μM), SKNSH (IC 50 8.68 + 1.1 μM), MCF-7 (IC 50 9.76 + 1.3 μM) and MDA-MB-231, while compounds 7a and 7b showed promising anti-proliferation against above four human cancer cell lines with IC 50 7.95-11.62 μM, respectively, compared with the standard drug Doxorubicin. We explored the probable key active site and binding mode interactions in HDAC8 (PDB ID:3SFH) and EHMT2 (PDB ID:3K5K) proteins. The docking results are complementary to the experimental observations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An estimated 60% of the world's population lives in Asia, where the incidence of neural tube defects is high. Aware that tethered cord syndrome (TCS) is an important comorbidity, the purpose of this systematic review was to explore the treatment of TCS among individuals living with spina bifida (SB) in Asia. MEDLINE and Embase databases were searched for relevant studies published from January 2000 to June 2018. Search terms such as 'spinal dysraphism,' 'spinabifida,' 'diastematomyelia,' 'lipomeningocele,' 'lypomyelomeningocele,' 'meningomyelocele,' and 'tethered cord syndrome' were used in diverse combinations. Of the 1,290 articles that were identified in accordance with PRISMA (Preferred Items for Systematic Reviews and Meta-Analyses) guidelines, 15 Asia-based studies met the inclusion criteria. Significant differences in the diagnostic criteria and management of TCS were documented. As the surgical techniques for prenatal closure of the spinal defect continue to evolve, their adoption internationally is likely to continue. In this setting, a clear and evidence-based approach to the definition and management of TCS is essential. The recent publication by the Spina Bifida Association of America of their updated care guidelines may serve as a tool used to promote a systematized approach to diagnosing and treating TCS among individuals with SB in the region, as well as globally.

ESAT-6 is a small secreted protein of Mycobacterium tuberculosis involved in the ESAT-6 secretion system (ESX-1)-mediated virulence and pathogenesis. The protein interacts with β2M, causing downregulation of MHC class I Ag presentation, which could be one of the mechanisms by which it favors increased survival of the bacilli inside the host. In an earlier study, we have shown that the C-terminal region of ESAT-6 is crucial for its interaction with β2M. However, the interface of β2M involved in interaction with ESAT-6 and detailed physicochemical changes associated with ESAT-6:β2M complexation are not fully defined. In this study, using computational and site-directed mutagenesis studies, we demonstrate the presence of strong noncovalent hydrophobic interactions between ESAT-6 and β2M in addition to the vital hydrogen bonding between the aspartate residue (Asp53) of β2M and methionine (Met93) of ESAT-6. Docking-based high-throughput virtual screening followed by 16-point screening on microscale thermophoresis resulted in the identification of two potent inhibitors (SM09 and SM15) that mask the critical Met93 residue of ESAT-6 that is required for ESAT-6:β2M interaction and could rescue cell surface expression of β2M and HLA in human macrophages as well as MHC class I Ag presentation suppressed by ESAT-6 in peritoneal macrophages isolated from C57BL/6 mice. Both SM09 and SM15 significantly inhibited intracellular survival of M. tuberculosis in human macrophages. Further, we characterized the physicochemical properties involved in the ESAT-6:β2M complexation, which may help in understanding host-pathogen interactions., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Background: Metabolic disorders comprise a set of different disorders varying from epidemic diseases such as diabetes mellitus to inborn metabolic orphan diseases such as phenylketonuria. Despite considerable evidence showing the importance of the computational methods in discovery and development of new pharmaceuticals, there are no systematic reviews outlining how they are utilized in the field of metabolic disorders. This review aims to discuss the necessity of the development of web-based tools and databases by integration of available information for solving Big Data problems in network pharmacology of metabolic disorders., Methods: We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers was appraised using standard tools., Results: The alterations in metabolic pathways cause various cardiovascular, hematological, neurological, gastrointestinal, immune disorders and cancer. In this regard, informatics, Big Data and modeling techniques aid in the design of novel therapeutic agents for metabolic diseases by addressing various Big Data problems in the network polypharmacology (drugs/pharmaceutical agents, proteins, genes, diseases, bioassays, ADMET and metabolic pathways), identification of privileged scaffolds, developing new diagnostic biomarkers, understanding the pathophysiology of disease and progress in personalized medicine., Conclusion: The recent advances of developing pharmaceutical agents for various metabolic disorders by considering their pathogenesis, mechanisms of action, therapeutic and adverse effects have been summarized. We have highlighted the role of computational techniques, drug repurposing, and network-based polypharmacological approaches in the identification of new/existing medicines with improved drug-likeness properties for the rare metabolic disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In an attempt to develop potential and selective anti-proliferative agents, a series of novel benzothiazine-piperazine derivatives 8a-i and 10a-g were synthesized by coupling of 2H-1,4-benzothiazin-3(4H)-one with various amines 7a-i and 9a-g in excellent yields and evaluated for their in vitro anti-proliferative activity against four cancer cell lines, HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). In vitro inhibitory activity indicated that compounds 8a, 8d, 8g, 10a, 10b, 10e, 10f were found to be good anti-proliferative agents. Among them the derivatives 8g, 10e and 10f were found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking was undertaken to investigate the probable binding mode and key active site interactions in HDAC8 and EHMT2 proteins. The docking results are complementary to the experimental results., (Copyright © 2016 Elsevier Ltd. All rights reserved.)