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Bacterial biofilm is a structured bacterial community enclosed within a three-dimensional polymeric matrix, governed by complex signaling pathways, including two-component systems, quorum sensing, and c-di-GMP, which regulate its development and resistance in challenging environments. The genetic configurations within biofilm empower bacteria to exhibit significant pollutant remediation abilities, offering a promising strategy to tackle diverse ecological challenges and expedite progress toward Sustainable Development Goals (SDGs). Biofilm-based technologies offer advantages such as high treatment efficiency, cost-effectiveness, and sustainability compared to conventional methods. They significantly contribute to agricultural improvement, soil fertility, nutrient cycling, and carbon sequestration, thereby supporting SDG 1 (No poverty), SDG 2 (Zero hunger), SDG 13 (Climate action), and SDG 15 (Life on land). In addition, biofilm facilitates the degradation of organic-inorganic pollutants from contaminated environments, aligning with SDG 6 (Clean water and sanitation) and SDG 14 (Life below water). Bacterial biofilm also has potential applications in industrial innovation, aligning SDG 7 (Affordable and clean energy), SDG 8 (Decent work and economic growth), and SDG 9 (Industry, innovation, and infrastructure). Besides, bacterial biofilm prevents several diseases, aligning with SDG 3 (Good health and well-being). Thus, bacterial biofilm-mediated remediation provides advanced opportunities for addressing environmental issues and progressing toward achieving the SDGs. This review explores the potential of bacterial biofilms in addressing soil pollution, wastewater, air quality improvement, and biodiversity conservation, emphasizing their critical role in promoting sustainable development., 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 © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Hypopharyngeal squamous cell carcinoma, stage III has poor prognosis with only 25% chance of 5 years of relative survival in such patients in spite of conventional treatment including radical surgery, radiotherapy, and concurrent chemotherapy., Case Presentation: A chronic tobacco-betel nut chewer 62-year-old male patient had dysphagia with hoarseness of voice diagnosed with stage III, grade II malignant pyriform fossa. The patient underwent 9 cycles of neoadjuvant chemotherapy with Inj Paclitaxel 100 mg and Inj Cisplatin 40 mg. He was then referred to our institute for Radical Radiotherapy with concurrent chemotherapy with adjunct Ayurvedic treatment. A total dose of 70 Gy of radiation with cobalt 60 source was administered to the bilateral face and neck, in 35 fractions. Patient also received 6 cycles of concurrent weekly chemotherapy with Inj Cisplatin 40 mg. He received well-planned adjunct Ayurvedic treatment in the form of oral Ayurvedic medicines (OAM) and detoxifying treatment, Panchakarma. All the measured adverse effects of radiotherapy such as Stomatitis, Xerostomia, Taste Alteration, Dysphagia, and Nausea were observed to be remarkably low during and post radiotherapy in this patient. Karnofsky and Quality of Life (QoL) scores revealed patient's well-being throughout the treatment course. After 5 years, PET CT scan revealed no FDG avid locoregional recurrence or distant organ involvement implying disease-free survival (DFS). Various chemokines, cytokines, and oxidative stress markers were assessed during the course of treatment to observe tumour microenvironment., Conclusion: The present case of Head & Neck Cancer (HNC), stage III, and grade II belonged to high-grade, high-risk hypopharyngeal cancer with poor prognosis. The patient opted for Ayurvedic treatment besides radiotherapy, which continued thereafter for 5 years. We therefore emphasize that in this case, minimum side effects of radiotherapy, immunomodulation, and reduction in inflammation and oxidative stress along with good quality of life can be attributed to OAM and repeated detoxifying Panchakarma treatment supported with healthy diet and good lifestyle. The highlight of the study is the marked effect on the patient's immune response and reduction in oxidative stress, leading to 5 years and beyond of DFS., (© 2024 S. Karger AG, Basel.)

Objectives: To evaluate if vaginal metronidazole for 5 days before hysterectomy decreases postoperative infections and patient issues., Design: This randomized trial compared vaginal metronidazole for 5 days before a scheduled hysterectomy to no intervention. Sample size calculation was based on a 20% difference in issues and infection (30% incidence and 10% in the intervention arm) with 80% power and an alpha error of 0.05 and indicated 62 subjects needed in each arm., Setting: Outpatient gynecology clinics at a single academic institution., Participants: 154 subjects were screened for eligibility between July 2020 and September 2022. 133 underwent hysterectomy including 68 subjects (51.1%) randomized to the metronidazole and 65 (48.9%) controls. Overall, the population was racially and ethnically diverse. There was no significant difference in characteristics between the two groups., Interventions: Vaginal metronidazole for 5 days before hysterectomy., Main Outcome Measures: Postoperative patient issues and documented postoperative infections at 4-8 weeks after surgery., Results: There was no difference in the composite rate of patient-reported issues and/or documented postoperative infection (53/133 (39.8%) with no difference between groups (29/68 (42.6%) vs 24/65 (36.9%), p=0.50). There was no difference in patient-reported issues which was 51/133 (38.3%) with no difference between groups (28/68 (41.2%) vs 23/65 (33.8%), p=0.49) or in documented infections with a rate of 25/133 (18.8%) with no significant difference between groups (15/68 (22.0%) vs 10/65 (15.4%), p=0.33). In the intervention arm, the compliance rate was 73.5% for all 5 days of vaginal metronidazole, and a per-protocol analysis was performed which resulted in no significant difference between groups., Conclusions: There is insufficient evidence to suggest a significant benefit of preoperative vaginal metronidazole to prevent surgical site infections and postoperative patient issues in patients undergoing hysterectomy., Trial Registration Number: ClinicalTrials.gov, NCT04478617., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research. Oxadiazole is a five-membered heterocyclic organic compound containing two nitrogen atoms and one oxygen atom in its ring. Oxadiazole hybrids have shown the ability to improve glucose tolerance, enhance insulin sensitivity, and reduce fasting blood glucose levels. The mechanisms underlying the antidiabetic effects of oxadiazole involve the modulation of molecular targets such as peroxisome proliferator-activated receptor gamma (PPARγ), α-glucosidase, α-amylase and GSK-3β which regulate glucose metabolism and insulin secretion. The present review article describes the chemical structure and properties of oxadiazoles and highlights the antidiabetic activity through action on different targets. The SAR for the oxadiazole hybrids has been discussed in this article, which will pave the way for the design and development of new 1,3,4-oxadiazole derivatives as promising antidiabetic agents in the future. We expect that this article will provide comprehensive knowledge and current innovation on oxadiazole derivatives with antidiabetic potential and will fulfil the needs of the scientific community in designing and developing efficacious antidiabetic agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Competing Interests: There are no conflicts of interest.

Diabetes is a chronic, and metabolic disorder that has gained epidemic proportions in the past few decades creating a threat throughout the globe. It is characterized by increased glucose levels that may be due to immune-mediated disorders (T1DM), insulin resistance or inability to produce sufficient insulin by β-pancreatic cells (T2DM), gestational, or an increasingly sedentary lifestyle. The progression of the disease is marked by several pathological changes in the body like nephropathy, retinopathy, and various cardiovascular complications. Treatment options for T1DM are majorly focused on insulin replacement therapy. While T2DM is generally treated through oral hypoglycemics that include metformin, sulfonylureas, thiazolidinediones, meglitinides, incretins, SGLT-2 inhibitors, and amylin antagonists. Multidrug therapy is often recommended when patients are found incompliant with the first-line therapy. Despite the considerable therapeutic benefits of these oral hypoglycemics, there lie greater side effects (weight variation, upset stomach, skin rashes, and risk of hepatic disease), and limitations including short half-life, frequent dosing, and differential bioavailability which inspires the researchers to pursue novel drug targets and small molecules having promising clinical efficacy posing minimum side-effects. This review summarizes some of the current emerging novel approaches along with the conventional drug targets to treat type 2 diabetes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Obstetric cholestasis is one of the most frequent hepatic disorders specific to pregnancy. It occurs commonly during the latter half of pregnancy. The data regarding this issue is rare in our settings. The aim of this study was to find out the prevalence of obstetric cholestasis among pregnant women visiting a tertiary care centre., Methods: A descriptive cross-sectional study was conducted among pregnant women, who attended a tertiary care centre from 24 July 2022 to 24 January 2023. Ethical approval was taken from the Institutional Review Committee of the same institute. Convenience sampling method was used. The point estimate was calculated at a 99% Confidence Interval., Results: The prevalence of obstetric cholestasis was 80 (1.38%) (1-1.80, 99% Confidence Interval). A total of 40 (50%) were in the age group 21-30 years, with a mean age of 28.06±6.39 years. A total of 48 (60%) were multigravida and 73 (91.30%) had singleton pregnancies. Pruritus of the whole body was complained of by 56 (70%) patients. Previous history of obstetric cholestasis was present in 21 (26.30%)., Conclusions: The prevalence of obstetric cholestasis among pregnant women is lower than other studies done in similar settings., Keywords: Nepal; obstetric cholestasis; pregnancy.

Introduction: Induction of labour is the artificial initiation of uterine contraction by various means such as medical, surgical or mechanical with the aim of achieving vaginal delivery. Misoprostol, a prostaglandin E1 analogue is used popularly for the induction of labour in resource-limited health centres. The aim of the study was to find out the prevalence of induction of labour among pregnant women in the Department of Obstetrics and Gynaecology in a tertiary care centre., Methods: A descriptive cross-sectional study was conducted among pregnant women in a tertiary care centre from 3 February 2022 to 31 July 2022. Ethical approval was taken from the Institutional Review Committee. The women with a singleton pregnancy, reactive non-stress test, and adequate pelvis were included. Women with malpresentation, previous cesarean section, placenta previa, and cephalopelvic disproportion were excluded. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval., Results: Among 1355 pregnant women, the prevalence of induction of labour was found to be 135 (9.96%) (8.37-11.55, 95% Confidence Interval)., Conclusions: The prevalence of induction of labour among pregnant women was found to be similar to other studies done in similar settings., Keywords: induction of labour; misoprostol; pregnancy.

Systemic antibody light chain (AL) amyloidosis is characterized by deposition of amyloid fibrils. Prior to fibril formation, soluble oligomeric AL protein has a direct cytotoxic effect on cardiomyocytes. We focus on the patient derived λ-III AL variable domain FOR005 which is mutated at five positions with respect to the closest germline protein. Using solution-state NMR spectroscopy, we follow the individual steps involved in protein misfolding from the native to the amyloid fibril state. Unfavorable mutations in the complementary determining regions introduce a strain in the native protein structure which yields partial unfolding. Driven by electrostatic interactions, the protein converts into a high molecular weight, oligomeric, molten globule. The high local concentration of aggregation prone regions in the oligomer finally catalyzes the conversion into fibrils. The topology is determined by balanced electrostatic interactions in the fibril core implying a 180° rotational switch of the beta-sheets around the conserved disulfide bond., (© 2023. The Author(s).)

Competing Interests: Conflicts of interest None disclosed.

Background: Solefinacin and Tolterodine are new generation antimuscarinics claimed to have bladder specific action and less adverse effect like dry mouth. The objective of the study was to compare the improvement in urinary symptoms among patients using solefinacin and tolterodine with overactive bladder symptoms., Methods: A hospital based cross-sectional comparative study was done for one year duration. All patients with overactive bladder symptoms were included and in every alternate patient's solefinacin and tolterodine were given after taking note of baseline OAB symptoms, PPBC score and UPS score. Participants were followed up after one month and noted improvement in endpoint OAB symptoms. Comparison of baseline to end-point symptoms changes among each group of participants were analyzed for statistical significance., Results: Among 101 participants included in the study, 49 participants were in solefinacin group and 52 participants were in tolterodine group. The end-point comparison of urgency symptoms were improved by 20.1±6.76 (mean ± SD) units in solefinacin group and by 17.0 ± 9.18 units in tolterodine group. Urgency perception score improved to 2.1±0.66 for patients under solefinacin and 2±0.73 for tolterodine. Patient perception of bladder condition (PPBC) showed improvement in solefinacin group by 3.2±1.26 units and in tolteradine by 2.8±1.54 units (p = 0.165). Comparing the patient's perception of treatment outcome, massive improvement was reported by 81.6% of those receiving Solefinacinand 65.4% receiving tolterodine, though not statistically significant ( p = 0.131)., Conclusions: Solefinacin and Tolterodine showed improvement in urinary symptoms, UPS and PPBC. Both showed comparable efficacy without significant superiority over one another.

The thiazolidine-4-one scaffold has recently emerged as a potential pharmacophore having clinical significance for medicinal chemists. This heterocyclic ring has been reported to possess a plethora of biological activities, including antidiabetic activity that has inspired researchers to integrate this core with different pharmacophoric fragments to design novel and effective antidiabetic leads. The antidiabetic activity has been observed due to the ability of the thiazolidine-4-one nucleus to interact with different biological targets, including peroxisome proliferator-activated receptor γ, protein tyrosine phosphatase 1B, aldose reductase, α-glucosidase, and α-amylase. The present review discusses the mode of action of thiazolidine-4-ones through these antidiabetic drug targets. This review attempts to summarize and analyze the recent developments with regard to the antidiabetic potential of thiazolidine-4-ones covering different synthetic strategies, structure-activity relationships, and docking studies reported in the literature. The significance of various structural modifications at C-2, N-3, and C-5 of the thiazolidine-4-one ring has also been discussed in this manuscript. This comprehensive compilation will provide an inevitable scope for the design and development of potential antidiabetic drug candidates having a thiazolidine-4-one core., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Recent global health concern motivated the exploration of natural medicinal plant resources as an alternative target for treating COVID-19 infection and associated inflammation. In the current study, a phytochemical, 6-shogaol [1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one; 6-SHO] was investigated as a potential anti-inflammatory and anti-COVID-19 agent. In virus release assay, 6-SHO efficiently (94.5%) inhibited SARS-CoV2 replication. When tested in the inflammasome activation model, 6-SHO displayed mechanistic action by regulating the expression of the inflammasome pathway molecules. In comparison to the existing drugs, remdesivir and hydroxy-chloroquine, 6-SHO was not only found to be as effective as the standard anti-viral drugs but also much superior and safe in terms of predicted physicochemical properties and clinical toxicity. Comparative molecular dynamics simulation demonstrated a stable interaction of 6-SHO with NLRP3 (the key inflammasome regulator) in the explicit water environment. Overall, this study provides important cues for further development of 6-SHO as potential anti-inflammatory and anti-viral therapeutic agents., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Recently, proton-detected magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectroscopy has become an attractive tool to study the structure and dynamics of insoluble proteins at atomic resolution. The sensitivity of the employed multidimensional experiments can be systematically improved when both transversal components of the magnetization are transferred simultaneously after an evolution period. The method of preservation of equivalent pathways has been explored in solution-state NMR; however, it does not find widespread application due to relaxation issues connected with increased molecular size. We present here for the first time heteronuclear transverse mixing sequences for correlation experiments at moderate and fast MAS frequencies. Optimal control allows to boost the signal-to-noise ratio (SNR) beyond the expected factor of 2 for each indirect dimension. In addition to the carbon-detected sensitivity-enhanced 2D NCA experiment, we present a novel proton-detected, doubly sensitivity-enhanced 3D hCANH pulse sequence for which we observe a 3-fold improvement in SNR compared to the conventional experimental implementation. The sensitivity gain turned out to be essential to unambiguously characterize a minor fibril polymorph of a human lambda-III immunoglobulin light chain protein that escaped detection so far.

2,4-Thiazolidinedione (2,4-TZD), commonly known as glitazone, is a ubiquitous heterocyclic pharmacophore possessing a plethora of pharmacological activities and offering a vast opportunity for structural modification. The diverse range of biological activities endowed with a novel mode of action, low cost, and easy synthesis has attracted the attention of medicinal chemists. Several researchers have integrated the TZD core with different structural fragments to develop a wide range of lead molecules against various clinical disorders. The most common sites for structural modifications at the 2,4-TZD nucleus are the N-3 and the active methylene at C-5. The review covers the recent development of TZD derivatives such as antimicrobial, anticancer, and antidiabetic agents. Various 2,4-TZD based agents or drugs, which are either under clinical development or in the market, are discussed in the study. Different synthetic methodologies for synthesizing the 2,4-TZD core are also included in the manuscript. The importance of various substitutions at N-3 and C-5 and the mechanisms of action and structure-activity relationships are also discussed. We hope this study will serve as a valuable tool for the scientific community engaged in the structural exploitation of the 2,4-TZD core for developing novel drug m\olecules for life-threatening ailments., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Several studies recently showed that ex vivo fibrils from patient or animal tissue were structurally different from in vitro formed fibrils from the same polypeptide chain. Analysis of serum amyloid A (SAA) and Aβ-derived amyloid fibrils additionally revealed that ex vivo fibrils were more protease stable than in vitro fibrils. These observations gave rise to the proteolytic selection hypothesis that suggested that disease-associated amyloid fibrils were selected inside the body by their ability to resist endogenous clearance mechanisms. We here show, for more than twenty different fibril samples, that ex vivo fibrils are more protease stable than in vitro fibrils. These data support the idea of a proteolytic selection of pathogenic amyloid fibril morphologies and help to explain why only few amino acid sequences lead to amyloid diseases, although many, if not all, polypeptide chains can form amyloid fibrils in vitro .

Leishmaniasis is a parasitic neglected tropical disease caused by various species of Leishmania parasite. Despite tremendous advancements in the therapeutic sector and drug development strategies, still the existing anti-leishmanial agents are associated with some clinical issues like drug resistance, toxicity and selectivity. Therefore, several research groups are continuously working towards the development of new therapeutic candidates to overcome these issues. Many potential heterocyclic moieties have been explored for this purpose including triazoles, chalcones, chromone, thiazoles, thiosemicarbazones, indole, quinolines, etc. It is evident from the literature that the majority of anti-leishmanial agents act by interacting with key regulators including PTR-I, DHFR, LdMetAP1, MAPK, 14 α-demethylase and pteridine reductase-I, etc. Also, these tend to induce the production of ROS which causes damage to parasites. In the present compilation, authors have summarized various significant synthetic procedures for anti-leishmanial agents reported in recent years. A brief description of the pharmacological potentials of synthesized compounds along with important aspects related to structural activity relationship has been provided. Important docking outcomes highlighting the possible mode of interaction for the reported compounds have also been included. This review would be helpful to the scientific community to design newer strategies and also to develop novel therapeutic candidates against leishmaniasis., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

Aurora kinases are a family of serine/threonine kinases that play a crucial role in cell proliferation through the regulation of mitotic spindles. These kinases are the regulatory proteins localized in the various phases of the cell cycle and are involved in centrosome maturation, chromosome alignment, chromosomal segregation, and cytokinesis. They have emerged as one of the validated drug targets for anticancer drug discovery as their overexpression has been implicated in the pathogenesis of various carcinomas. Inhibitors of Aurora kinases induce growth inhibition and apoptosis in a variety of tumor cells. Hence, the design and development of Aurora kinase inhibitors have been widely explored in recent years by the scientific community as potential anticancer agents. Various Aurora kinase inhibitors have been under preclinical and clinical investigations as antitumor agents. This review summarizes the recent strategies of various researchers for the design and development of Aurora kinase inhibitors belonging to different structural classes. Their bioactivity, SARs, molecular modelling, and mechanistic studies have also been described. The comprehensive compilation of research work carried out in the field will provide inevitable scope for the design and development of novel drug candidates with better selectivity and efficacy. The review is constructed after the exhaustive research in this discipline and includes the papers from 2011 to 2020., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

The discovery of a potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene; however, its molecular associations and role in colorectal oncogenesis are unknown. In this study, we have explored the role of STIL gene in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 and CD44 and drug resistant markers thymidylate synthase , ABCB1 , and ABCG2 both in in-vitro and in-vivo CRC models. In addition, high expression of STIL mRNA was found to be associated with reduced disease-free survival in CRC cases. Interestingly, we observed that STIL -mediated regulation of stemness and drug resistant genes is not exclusively governed by Sonic hedgehog (Shh) signaling. Remarkably, we found STIL regulate β-catenin levels through p-AKT, independent of Shh pathway. This partially answers Shh independent regulatory mechanism of cancer stem cell (CSC) markers by STIL . Our study suggests an instrumental role of STIL in molecular manifestation of CRC and progression., 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., (Copyright © 2021 Pradhan, Kumar, Surya H, Krishna, John, Jissa, Anjana, Chandramohan and Nair.)

The aggregation of antibody light chains is linked to systemic light chain (AL) amyloidosis, a disease where amyloid deposits frequently affect the heart and the kidney. We here investigate fibrils from the λ-III FOR005 light chain (LC), which is derived from an AL-patient with severe cardiac involvement. In FOR005, five residues are mutated with respect to its closest germline gene segment IGLV3-19 and IGLJ3. All mutations are located close to the complementarity determining regions (CDRs). The sequence segments responsible for the fibril formation are not yet known. We use fibrils extracted from the heart of this particular amyloidosis patient as seeds to prepare fibrils for solid-state NMR. We show that the seeds induce the formation of a specific fibril structure from the biochemically produced protein. We have assigned the fibril core region of the FOR005-derived fibrils and characterized the secondary structure propensity of the observed amino acids. As the primary structure of the aggregated patient protein is different for every AL patient, it is important to study, analyze and report a greater number of light chain sequences associated with AL amyloidosis.

Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that are derived from the closest germline (GL) sequence. Both analyzed fibril structures were seeded with ex-vivo amyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. In the germline sequence, this residue is replaced by a glycine. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patient ex-vivo fibrils. Seeded R49G fibrils show an increased heterogeneity in the C-terminal residues 80-102, which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra, show 13 Cα chemical shifts that are highly like patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C terminus in the fibril state, whereas the overall fibril topology is retained. These findings imply that patient mutations in FOR005 can stabilize the fibril structure., Competing Interests: Conflict of interest—The authors declare no competing financial interest., (© 2020 Pradhan et al.)

A library of new phenstatin based indole linked chalcone compounds (9a-z and 9aa-ad) were designed and synthesized. Of these, compound 9a with 1-methyl, 2- and 3-methoxy substituents in the aromatic ring was efficacious against the human oral cancer cell line SCC-29B, spheroids, and in a mouse xenograft model of oral cancer AW13516. Compound 9a exhibited anti-cancer activity through disrupting cellular integrity and affecting glucose metabolism-which is a hallmark of cancer. The cellular architecture was affected by inhibition of tubulin polymerization as observed by an immunofluorescence assay on 9a-treated SCC-29B cells. An in vitro tubulin polymerization kinetics assay provided evidence of direct interaction of 9a with tubulin. This physical interaction between tubulin and compound 9a was further confirmed by Surface Plasmon Resonance (SPR) analysis. Molecular docking experiments and validations revealed that compound 9a interacts and binds at the colchicine binding site of tubulin and at active sites of key enzymes in the glucose metabolism pathway. Based on in silico modeling, biophysical interactions, and pre-clinical observations, 9a consisting of phenstatin based indole-chalcone scaffolds, can be considered as an attractive tubulin polymerization inhibitor candidate for developing anti-cancer therapeutics., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In antibody light chain amyloidosis (AL), mutant light chains (LCs) or their variable domains (V L s) form fibrils, which accumulate in organs and lead to their failure. The molecular mechanism of this disease is still poorly understood. One of the key open issues is whether the mutant V L s and LCs differ in fibril formation. We addressed this question studying the effects of the V L mutations S20N and R61A within the isolated V L domain and in the full-length LC scaffold. Both V L variants readily form fibrils. Here, we find that in the LC context, the S20N variant is protected from fibril formation while for LC R61A fibril formation is even accelerated compared to V L R61A. Our analyses revealed that the partially unfolded state of the V L R61A domain destabilizes the C L domain by non-native interactions, in turn leading to a further unfolding of the V L domain. In contrast, the folded mutant V L S20N and V L wt form native interactions with C L . These are beneficial for LC stability and promote amyloid resistance. Thus the effects of specific mutations on the V L fold can have opposing effects on LC domain interactions, stability and amyloidogenicity., 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.)

Obstructed Hemivagina and Ipsilateral Renal Anomaly syndrome is a rare obstructive uterovaginal anomaly involving both mesonephric and paramesonephric ducts. It usually presents after menarche with non-specific symptoms like pelvic pain, dysmenorrhea, or paravaginal mass and examination findings of paravaginal or pelvic mass. Because of non-specific symptoms and signs, the diagnosis is usually overlooked, which leads to complications like endometriosis, tubo-ovarian abscess compromising patient’s fertility, and quality of life. Therefore, in presence of these nonspecific clinical features along with imaging findings of uterine didelphys and unilateral renal agenesis, this syndrome should be considered in the diagnosis. We present a case of a 17-year-old lady with Obstructed Hemivagina and Ipsilateral Renal Anomaly syndrome, diagnosed by finding of paravaginal mass on examination and uterine didelphys with ipsilateral renal agenesis in USG and managed successfully by resection of vaginal septum. Keywords: ipsilateral renal anomaly;paravaginal mass;uterovaginal anomaly.

Background: The primary health-care center (PHC) and community health center (CHC) are not well equipped with laboratory services. Semiauto analyzer-based reporting could be an effective modality, provided that the performance standard is comparable to that of the fully automatic analyzer. So, the objective of this study was to analyze the test results of biochemical parameters in semiauto and fully automatic analyzer and to compare the quality performance., Materials and Methods: One hundred forty-nine patients undergoing routine biochemical investigations in the department laboratory were enrolled in this study. Two millimeter of venous blood was collected from all the participants and processed for urea, cholesterol, triglyceride (TG), serum glutamate-oxaloacetate transaminase (SGOT) (aspartate aminotransferase), and serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase) by using standard kits (ERBA) in semiauto analyzer (Transasia Erba Chem5X by Calbiotech Inc. USA, semiautomated clinical chemistry analyzer) and the fully automatic analyzer (Cobas Integra 400 Roche, Germany) method., Results: There was high variability in the distribution of urea, TG, SGOT, and SGPT values in both measurement methods, whereas cholesterol data followed a normal distribution (skewness: 1.522, 1.037; kurtosis: 2.373, 0.693 in semiauto and automated methods, respectively). A significant positive correlation between both the methods of assessment was observed in urea, cholesterol, TGs, SGOT, and SGPT. The mean difference for urea was -9.85 ± 23.997 (LOA: 37.189, -56.88), whereas it was highest for TG -24.34 ± 38.513 (LOA: 51.144, -99.829), suggesting that both methods can measure urea with less difference in absolute values, whereas for TG the measurement values are highly variable., Conclusion: The test performance of biochemical parameters such as urea, total cholesterol, TGs, SGOT, and SGPT taken by semiauto analyzer and fully automatic analyzer method of assessment were highly related and comparable., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Objective: Inpatient psychiatric readmission rates are increasingly considered indicators of quality of care. This study builds upon prior research by examining patient-, hospital-, and community-level factors associated with single and multiple readmissions for youth., Method: A retrospective cohort study was conducted using Medicaid claims data from four states supplemented with the American Hospital Association survey, the Area Resource File, and the National Survey of Mental Health Treatment Services. Multinomial logistic regression examined patient-, hospital-, and community-level factors that were associated with inpatient psychiatric readmission for 6,797 Medicaid-eligible youth with a primary diagnosis of mood disorder using a three-level nominal dependent variable coded as no readmission, one readmission, and two or more readmissions within 6 months after discharge., Results: Six months after initial discharge, 941 youth (13.8%) were readmitted once and 471 (6.9%) were readmitted two or more times. The odds of single or multiple readmissions were significantly higher (p < .05) for youth classified as disabled or in foster care, those with multiple psychiatric comorbidities, medical comorbidity, and prior psychiatric hospitalization. Treatment in hospitals with high percentage of Medicaid discharges and a high number of beds was associated with lower odds of readmission. There was a significant interaction between length of stay and outpatient mental health follow-up within 7 days of discharge., Conclusion: Patient- and hospital-level factors are associated with likelihood of both single and multiple youth inpatient psychiatric readmissions, suggesting potential risk markers for psychiatric readmission., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Pathological assessment of excised tumour and surgical margins in colorectal cancer (CRC) play crucial role in prognosis after surgery. Molecular assessment of margins could be more sensitive and informative than conventional histopathological analysis. Considering this view, we evaluated the distal surgical margins for expression of cancer stem cell (CSC) markers. Cellular and molecular assessment of normal, tumour and distal margin tissues were performed by flow cytometry, real-time q-PCR and immuno-histochemical analysis for CRC patients after tumour excision. CRC patients were evaluated for expression of CSC markers in their normal, tumour and distal tissues. Flow cytometry assay revealed CD133 and CD44 enriched cells in distal margin and tumour compared to normal colorectal tissues, which was further confirmed by immunohistochemistry. Most importantly, immunohistochemistry also revealed the enrichment of CSC markers expression in pathologically negative distal margins. Patients with distal margin enriched for CD133 expression showed an increased recurrence rate and decreased disease-free survival. This study proposes that although distal margin seems to be tumour free in conventional histopathological analysis, it could harbour cells enriched for CSC markers. Further CD133 could be a promising molecule to be used in molecular pathology for disease prognosis after surgery in CRC patients., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

In rural communities, primary care providers continue to provide mental health services, and about 70% of children and adolescents identified to have a psychiatric disorder never receive treatment. A telehealth model for providing integrated mental health services in a school-based health clinic has the potential to increase access to specialized care for the most vulnerable youths. This column provides an overview of the strategies used to implement and integrate such a model in West Virginia. Operationalization, barriers, challenges, and judicious resource use are discussed. Appropriate reimbursement for services and state-specific legislation to ensure consistent revenue to sustain the program are considered.

Background: Eclampsia is a multisystem disorder that may lead to deterioration of maternal condition, hypoxia and acidosis of fetus. Objective was to evaluate the risk factors associated with adverse maternal and fetal outcome in patients with eclampsia., Methods: All patients with eclampsia were enrolled after informed consent from February 2013 to February 2014. Questions as per per-forma were asked to the patients and attendants about antenatal visits, parity, number of episodes of seizures, duration from onset of seizure to magnesium sulfate, then the patients were followed as per the hospital protocol, the mode of delivery, outcome of baby, post partum maternal condition and mortality were then noted., Results: Fifty-two patients with eclampsia were admitted in the study period. Thirty-one patients required mechanical ventilator support. Twenty-five (48.07%) patients were delivered by emergency cesarean section and 30(57.6%) babies were low birth weight and there were 11(21.1%) stillbirths. There was one maternal mortality and 45(86.5%) patients were discharged with improvement but 6(11.5%) patients had neurological impairment. Mortality was significantly related with number of seizure episodes and time interval between seizure onset and administration of magnesium sulphate., Conclusions: Early detection of hypertension and management with magnesium sulphate for eclampsia can help to minimize the maternal and fetal adverse outcomes.

Despite their importance for antibody architecture and design, the principles governing antibody domain stability are still not understood in sufficient detail. Here, to address this question, we chose a domain from the invariant part of IgG, the C H 2 domain. We found that compared with other Ig domains, the isolated C H 2 domain is a surprisingly unstable monomer, exhibiting a melting temperature of ∼44 °C. We further show that the presence of an additional C-terminal lysine in a C H 2 variant substantially increases the melting temperature by ∼14 °C relative to C H 2 WT. To explore the molecular mechanism of this effect, we employed biophysical approaches to probe structural features of C H 2. The results revealed that Lys 101 is key for the formation of three secondary structure elements: the very C-terminal β-strand and two adjacent α-helices. We also noted that a dipole interaction between Lys 101 and the nearby α-helix, is important for stabilizing the C H 2 architecture by protecting the hydrophobic core. Interestingly, this interaction between the α-helix and C-terminal charged residues is highly conserved in antibody domains, suggesting that it represents a general mechanism for maintaining their integrity. We conclude that the observed interactions involving terminal residues have practical applications for defining domain boundaries in the development of antibody therapeutics and diagnostics., (© 2018 Weber et al.)

Cancer stem cells are cellular subpopulations in tumor, which are highly tumorigenic and drug resistant due to their adaptive molecular mechanism. In the recent years, these cells have attracted researchers' focus because of their unique properties which makes them biologically well evolved than other proliferating tumor cells. We have studied the presence of cancer stem cells in colorectal cancer (CRC) and its surgical margins. We report for the first time the presence of drug-resistant cells in distal resection margins in CRC and showed that a closer distal margin of less than 2 cm could have higher possibility of drug-resistant cells to spread., Competing Interests: Compliance with Ethical StandardsThe study protocol conformed to the guidelines of the ethics committee of each institution and was approved by each institution’s review board; all patients provided written informed consent.The authors declare that they have no conflict of interest.This work was supported by extra mural fund from Department of Biotechnology (DBT), Government of India. (BT/PR3223/BRB/10/964/2011).

The notion of statistical weighted [Formula: see text]-summability was introduced very recently (Kadak et al. in Appl. Math. Comput. 302:80-96, 2017). In the paper, we study the concept of statistical deferred weighted [Formula: see text]-summability and deferred weighted [Formula: see text]-statistical convergence and then establish an inclusion relation between them. In particular, based on our proposed methods, we establish a new Korovkin-type approximation theorem for the functions of two variables defined on a Banach space [Formula: see text] and then present an illustrative example to show that our result is a non-trivial extension of some traditional and statistical versions of Korovkin-type approximation theorems which were demonstrated in the earlier works. Furthermore, we establish another result for the rate of deferred weighted [Formula: see text]-statistical convergence for the same set of functions via modulus of continuity. Finally, we consider a number of interesting special cases and illustrative examples in support of our findings of this paper., Competing Interests: The authors declare that they have no competing interests.

The mechanical properties of extracellular matrix (ECM) and connective tissues is largely dependent on the collagen and elastin structure. Lysyl oxidase (LOX) plays a critical role in the formation and repair of the ECM by oxidizing lysine residues in elastin and collagen, thereby initiating the formation of covalent cross linkages which stabilize these fibrous proteins. Due to its multiple functions both extracellularly and intracellularly, lysyl oxidase is involved in several processes in the tumorigenic pathway, in many different cancer types and stages. Alteration in LOX activity is implicated in many diseases and disorders including inflammation and inflammatory diseases, fibrosis of distinct organs and fibrotic disorders, cancer promotion and progression. There are only sparse reports of mutations or epigenetic alterations in the LOX gene. This review provides the recent clinical developments in the molecular mechanisms and pathologic process, pointing out LOX as a potential therapeutic target in translational medicine.

Background: The concept of generic prescription is widely accepted in various parts of the world. Nevertheless, it has failed to gain popularity in India due to factors such as nonavailability and distrust on the product quality. However, since 2012, the Government of West Bengal, India, has initiated exclusive generic drug outlets called "fair price medicine shop" (FPMS) inside the government hospital premises in a "public-private-partnership" model. This study was undertaken to evaluate the experience and attitude of patients who were consuming generic drugs purchased from these FPMS., Materials and Methods: It was a questionnaire-based cross-sectional study where we have interviewed 100 patients each consuming generic and branded drugs, respectively. The perceived effectiveness, reported safety, medication adherence, cost of therapy, and availability of drugs was compared between two mentioned groups. Medication adherence was estimated through Drug Attitude Inventory-10., Results: 93% of generic and 87% branded drug users believed that their drugs were effective ( P = 0.238) in controlling their ailments. No significant difference (9% generic, 10% branded drug users, P = 1.000) was observed in reported adverse effects between generic and branded drug users. 82% and 77% of patients were adherent generic and branded drugs, respectively ( P = 0.289). As expected, a significantly lower cost of generic drugs was observed compared to its branded counterpart., Conclusion: The policy of FPMS implemented by the Government of West Bengal, India appeared to be promising in terms of perceived effectiveness, safety, and adherence of generic drugs from FPMS compared to drugs purchased from open market retailers. Therefore, this study might act as an impetus for the policy-makers to initiate similar models across the country., Competing Interests: The authors are either employee of Government of West Bengal or students of medical college under the same administration. However, no tangible or intangible support was sought from the concerned department during the designing, conduct, or publication of the study.

Background and Objectives: In females, raising a pectoralis major myocutaneous flap is challenging and primary closure of flap donor site causes breast deformity with medial displacement of nipple areola complex. To avoid this distortion, a new method of donor site closure is devised., Methods: A parasternal skin paddle which has better vascularity is planned while doing a pectoralis major myocutaneous flap in females and a lateral flap planned along the lateral breast curve is used to cover the donor site. The lateral flap donor site is primarily closed. This prevents medial displacement of nipple areola complex., Results: A total of 47 patients underwent donor site flap closure technique. Minor complications in form of marginal necrosis near the tip of the flap were observed in 10.6 % patients. The donor breast of all these PMMC flaps had good contour and aesthetic positioning of nipple areola complex., Conclusion: Donor site morbidity with respect to breast distortion has not been studied so far in case of females so our study stands unique in this aspect. Using this technique of planning PMMC in females ensures a skin paddle of better vascularity and restores the breast aesthetics.