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Background: Gaps in Tuberculosis Preventive Treatment (TPT) cascade among household contacts (HHCs) of Tuberculosis patients are often attributed to the knowledge gaps among the HHCs. Objectives: To examine the factors affecting the uptake of IGRA testing among HHCs of drug-susceptible, pulmonary TB patients registered between January and May 2023 in Kolar district, Karnataka using Health Belief model and qualitative interviews. Methodology: Between April and June 2023, 196 HHCs of 70 registered TB patients were included in the mixed methods study. Using a four-point Likert scale questionnaire, adult HHCs were interviewed regarding their knowledge of TB disease, perceived susceptibility and severity of TB Infection, benefits, and barriers in testing for TB Infection (IGRA) and cues for action. Mann Whitney U test was used to compare the scores of those who were tested and those who were not. Further, reasons for not undergoing IGRA testing were also assessed qualitatively. Results: Among 196 HHC, 45 were children under 5 years. IGRA testing had been done in 47% (71/151) of eligible HHCs. Among adult HHC, self- perceived and Index case-attributed susceptibility score was significantly associated with testing; while perceived severity scores, knowledge and perceived benefit scores were not. Major themes in barriers to testing were misinterpretation of ‘TB Infection’, selective testing of HHCs, delayed contact tracing, lack of logistics and lack of planning and coordination. TPT was given to 84% (38/45) under five HHCs. Major cue for TPT provision was availability of TPT, followed by caregiver’s perceived susceptibility. Conclusion: Perceived susceptibility of HHC to TB infection is often misinformed. Group counselling of HHCs, provision of IGRA at doorstep and a well-established referral system will improve the uptake of IGRA.

Spinal disorders are the major cause of disability and poor Quality Of Life (QoL). This study attempted to measure Health Related Quality Of Life (HRQoL) Spinal disorders using a brief, generic scale. Consecutive subjects with spinal disorders (n=102) were interviewed using two scales Karnofsky Performance Status, Euro QoL EQ-5D and two statements from WHOQoL-Bref. The study found that the overall HRQoL in spinal disorders is not so good in most of the patients. Pain and impaired mobility maximally contributed to the poor HRQoL. Socio demographic factors like age, education, habitat had significant relationship with HRQoL scores. Average time taken for HRQoL measurement was less than 5 minutes. In conclusion HRQoL in spinal disorders is generally not so good and brief generic scales to measure HRQOL can prove to be useful for routine use.

Background: Community-acquired (CA) pyodermas are one of the most common infections encountered in the dermatology outpatient clinics. A significant number of these conditions are caused by Staphylococcus aureus . CA-methicillin-sensitive Staphylococcus aureus (MSSA) and CA-methicillin-resistant Staphylococcus aureus (MRSA) have specific virulence genes which are associated with these diseases, particularly the Panton-Valentine leukocidin ( PVL ) genes. The presence of the PVL gene as a virulence factor may be associated with recurrent and severe skin infections., Materials and Methods: A prospective study was conducted with 205 cases of CA pyodermas, of which five were discarded due to mixed isolates. Clinical details were taken and wound exudate was sent for bacteriological examination. Further, the molecular study was performed on all MRSA (7) isolates and 13 randomly selected MSSA isolates using polymerase chain reaction for mecA and PVL genes., Results: Staphylococcus aureus was the most common organism (90%) isolated from primary or secondary CA pyodermas. The prevalence of CA-MRSA among all pyodermas was 3.5% in our community. The PVL gene was not detected in all tested CA-MRSA and CA-MSSA isolates., Conclusion: While pyodermas are common, the prevalence of MRSA is low in the CA pyodermas in our region. PVL does not appear to be a virulence factor among the isolated MRSA. Larger, multicentric, and periodic studies are, however, required to further justify these claims., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Dermatology Online Journal.)

Introduction: Melasma is a common pigmentary disorder affecting the face. Although a few risk factors have been identified, the exact pathogenesis remains elusive. Many treatment modalities have been tried, but none have been completely successful., Aim: To compare safety and efficacy of microneedling with Tranexamic acid versus microneedling with Vitamin C in the treatment of melasma., Materials and Methods: It was a split face, comparative study conducted on 30 female melasma patients. After obtaining informed consent, microneedling with Tranexamic acid was done on left side and microneedling with Vitamin C was done on right side of face. The improvement was evaluated on the basis of clinical photographs, MASI, Physician Global Assessment (PGA) and Patient Global Assessment (PtGA) at each visit (0, 4 and 8 weeks). Z test was used to test the significant difference in the means of the 2 groups at 4 weeks and at 8 weeks., Results: At the end of 8 weeks, MASI, PGA and PtGA showed improvement with both tranexamic acid and vitamin C. However the improvement was more with tranexamic acid than with vitamin C, although not statistically significant., Conclusion: Both TXA and Vitamin C are effective and safe treatments for melasma. But, TXA was found to be more effective., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Dermatology Online Journal.)

In the pursuit of novel anticancer leads, new bisindole-oxadiazoles were synthesized using propyl phosphonic anhydride as a mild and efficient reagent. The molecule, 3-[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indole (3a) exhibited selective cytotoxicity to MCF-7 cells with a cell cycle arrest in the G1 phase. The mechanism of cytotoxicity of 3a involved caspase-2-dependent apoptotic pathway with characteristic apoptotic morphological alterations as observed in acridine orange/ethidium bromide and Hoechst staining. The wound healing migratory assay exhibited an intense impairment in the motility of MCF-7 cells on incubation with 3a. Docking simulations with anti-apoptotic protein Bcl-2, which is also involved in cancer metastasis displayed good affinity and high binding energy of 3a into the well characterized BH3 binding site. The positive correlation between the Bcl-2 binding studies and the results of in vitro investigations exemplifies compound 3a as a lead molecule exhibiting MCF-7 differential cytotoxicity via apoptotic mode of cell death in addition to its anti-metastatic activity., (© 2017 Wiley Periodicals, Inc.)

Cancer therapeutic potential of thiadiazole hybrids incorporating pharmacologically active indole and coumarin moieties have not been explored much. In the current investigation, three new thiadiazole hybrids with spacers of varying lengths linking indole and thiadiazole units were synthesized and their structures were well-established using various spectroscopic techniques. 3-(1-(5-(3-(1H-indol-3-yl)propyl)-1,3,4-thiadiazol-2-ylimino)ethyl)-6-bromo-2H-chromen-2-one (IPTBC) exhibited dose-dependent cytotoxicity in breast adenocarcinoma (MCF-7) cells. The circumvention of apoptosis is a prominent hallmark of cancer and hence triggering apoptosis in specific cancer cells is one of the convenient and widely used approaches for the development of anticancer chemotherapeutics. The induction of apoptosis upon treatment with IPTBC was confirmed by multiple apoptosis assays like Acridine orange-ethidium bromide, Hoechst staining, TUNEL staining, and colorimetric quantification using APOPercentage™ Apoptosis assay. The apoptosis initialisation through the active involvement of caspases was confirmed by caspase profiling tests. The wound healing assay displayed an intense impairment in the motility of MCF-7 cells suggesting the anti-metastatic potential of IPTBC. The ability of IPTBC to inhibit the antiapoptotic Bcl-2 protein by acting as a small molecule BH3 mimetic was explored through docking simulation studies. Although auxiliary investigations are warranted with this promising thiadiazole hybrid IPTBC, the perspective anticancer potential through programmed cell death, anti-metastatic and probable Bcl-2 inhibitory action will enable its further exploration in oncology., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The limited efficacy of marketed anticancer agents demands the design of novel target-specific hybrid molecules incorporating multiple bioactive pharmacores to combat cancer. In the present study, a one-pot simple and efficient T3P ® mediated procedure for the preparation of twelve new 3-(substituted- [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazolo)-1H-indoles with short reaction times, easy workup procedure, good yields, and purity of products is described. Cytotoxicity assay (MTT), flow-cytometric univariate cell cycle analysis, Annexin V-FITC staining and DNA fragmentation for cell death mechanism suggested that compound 3d with chloro-substituted phenyl ring induced enhanced cytotoxicity by an apoptotic pathway with high differential toxicity to breast adenocarcinoma cells (MCF-7) when compared with normal human dermal fibroblast cells. Additionally, the interaction between the BH3 domain of anti-apoptotic proteins Bcl-2 and Bcl-xL with the pharmacophore 3d was examined by molecular docking simulations to assess its potential to induce apoptosis. The docking solutions were proposed to explain the observed selectivity of 3d to Bcl-xL protein. From the present findings, the lead compound, 3d exhibited better anticancer activity when related to the other synthesized molecules with specific action on MCF-7 cells and hence can be considered as a plausible candidate chemo-therapeutic agent, although this warrants further experimentation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cancer is a multifactorial disease and most of its types still remain incurable, in spite of enormous efforts to explicate various tumor pathophysiology. The anti-cancer drug discovery paradigm "one-compound-one-target" has failed and subsequently shifted to two-drug cocktail and recently the "multi-target approach" in order to design and develop agents able to act simultaneously on multiple intracellular constituents and signaling pathways. Novel hybrid compounds are now designed by incorporating two covalently linked independently acting pharmacores, each efficient at combating cancer. They can deliver synergistic effects from the dual action of both independently acting moieties by interacting with multiple targets. These composite molecules are also less prone to drug resistance, leading to an improved pharmacological potency than each individual moiety. As indole nucleus is a central component of many natural and synthetic molecules with extensive biological activity, this review incorporates a variety of such hybrid compounds with indole moiety as one of the active units, where better therapeutic effect has been successfully achieved, by either simultaneous or sequential action of individual functional pharmacore. The current limitations and challenges encountered in the development of these hybrid agents are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Cancer is one of the most awful lethal diseases all over the world and the success of its current chemotherapeutic treatment strategies is limited due to several associated drawbacks. The exploration of cancer cell physiology and its microenvironment has exposed the potential of various classes of nanocarriers to deliver anticancer chemotherapeutic agents at the tumor target site. These nanocarriers must evade the immune surveillance system and achieve target selectivity. Besides, they must gain access into the interior of cancerous cells, evade endosomal entrapment and discharge the drugs in a sustained manner. Chitosan, the second naturally abundant polysaccharide is a biocompatible, biodegradable and mucoadhesive cationic polymer which has been exploited extensively in the last few years in the effective delivery of anticancer chemotherapeutics to the target tumor cells. Therapeutic agent-loaded surface modified chitosan nanoparticles are established to be more stable, permeable and bioactive., Conclusion: This review will provide an up-to-date evidence-based background on recent pharmaceutical advancements in the transformation of chitosan nanoparticles for smart anticancer therapeutic drug delivery., Highlights: • Efforts to improve cancer chemotherapy by exploiting the intrinsic differences between normal and neoplastic cells to achieve maximum effective drug delivery to target cancer cells through bioengineered chitosan nano delivery vectors are discussed. • The easy manipulation of surface characteristics of chitosan based nanoparticles by various functionalization methods to achieve targeted drug delivery proves its potential to be an essential tool for the advancement of anticancer drug-delivery vectors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

A wide number of marketed drugs and drug candidates in cancer clinical development contain halogen substituents. The aim of the present study was to synthesize a series of halogen incorporated indole-coumarin hybrid schiff bases - N'-((2-(2-oxo-2H-chromen-3-yl)-1H-indol-3-yl)methylene)benzohydrazides and to investigate their apoptotic and anti-migratory potential in human breast adenocarcinoma cells as well as to examine their Bcl-2 and Bcl-xL protein binding ability via in silico docking. Hybrid 5g with a bromine atom in position-7 of coumarin ring displayed significant dose dependent cytotoxic activity with high selectivity to MCF-7 cells in MTT assay. Cell cycle progression analysis of 5g treated cells using flow cytometer exhibited a cell cycle arrest in the S phase and accumulation of cells in the subG1 phase. The apoptotic mode of cell death induced by 5g was further confirmed by Annexin-V staining assay. The wound healing assay revealed a profound impairment in the migration of MCF-7 cells presumably due to down-regulation of Bcl-2 and Bcl-xL proteins induced by 5g as observed in immunoblotting analysis. SAR studies of these hybrid molecules based on cell viability and docking were also probed. The most active pharmacophore 5g was found to bind favourably to Bcl-2 and Bcl-xL in docking simulation analysis suggesting it to be a probable small molecule Bcl-2/Bcl-xL inhibitor and a potential lead for breast cancer chemotherapy with apoptotic and anti-metastatic properties., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The exploration of cancer microenvironment and its physiology have exposed a number of potential molecular targets for selective therapeutic intervention by anti-cancer agents. Microtubules are basic cell components formed by polymerization of αβ heterodimers which play a pivotal role in cellular functions as well as cell division. Drugs that can control the microtubule assembly either by hindering tubulin polymerization or by obstructing microtubule disassembly are of great importance in anti-cancer therapy. Diverse classes of naturally occurring as well as synthetic and semi-synthetic compounds with an indole nucleus induce microtubule polymerization and depolymerization and thereby change tubulin dynamics. Rapid development of several novel tubulin polymerization inhibitors has been observed over the past few years and some of them have associated vascular disrupting properties too. The present review starts with the structure, function and importance of microtubules in a eukaryotic cell. The well characterized tubulin binding domains and the corresponding inhibitors including their mechanism of action is also a part of this article. The report mainly focuses on the brief synthetic methodology with the relevant SAR studies of different indole derived molecules that have been reported in the past few years as potential inhibitors of tubulin polymerization is discussed. This review will provide the up-to-date evidence-base for synthetic chemists as well as biologists to design and synthesize new active molecules to inhibit tubulin polymerization.

Hybrid molecules have attracted attention for their improved biological activity, selectivity and lesser side effects profile, distinct from their individual components. In the quest for novel anticancer drug entities, three series of indole-coumarin hybrids - 3-(1-benzyl-1H-indol-2-yl)-2H-chromen-2-ones, 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carbaldehydes and 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carboxylic acids were synthesized. All the synthesized compounds were characterized by spectral techniques like IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analysis. In silico docking studies of synthesized molecules with apoptosis related gene Bcl-2 that is recognized to play an important role in tumerogenesis were carried out. Dose-dependent cytotoxic effect of the compounds in human breast adenocarcinoma (MCF-7) and normal cell lines were assessed using MTT assay and compared with that of the standard marketed drug, Vincristine. Compound 4c had a highly lipophilic bromine substituent capable of forming halogen bond and was identified as a potent molecule both in docking as well as cytotoxicity studies. Flow cytometric cell cycle analysis of 4c exhibited apoptotic mode of cell death due to cell cycle arrest in G2/M phase. Structure activity relationship of these hybrid molecules was also studied to determine the effect of steric and electronic properties of the substituents on cell viability., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the current communication, we report the synthesis, spectroscopic, crystal structure, DFT and photophysical studies of a new nicotinonitrile derivative, viz. 2-methoxy-6-(4-methoxy-phenyl)-4-p-tolyl-nicotinonitrile (2) as a potential blue light emitting material. The compound 2 was synthesized in good yield via a simple route. The acquired spectral and elemental analysis data were in consistent with the chemical structure of 2. The single crystal study further confirms its three dimensional structure, molecular shape, and nature of short contacts. Its DFT calculations reveal that compound 2 possesses a non-planar structure and its theoretical IR spectral data are found to be in accordance with experimental values. In addition, its UV-visible and fluorescence spectral measurements prove that the compound exhibits good absorption and fluorescence properties. Also, it shows positive solvatochromic effect when the solvent polarity was varied from non-polar to polar., (Copyright © 2014 Elsevier B.V. All rights reserved.)