Efficacy and Safety of Erbium-YAG Laser Ablation Therapy in Superficial Dermatoses: The Workhorse of Dermatology.

Background: Erbium-YAG laser has been the working horse in dermatology for years. Surprisingly, data on the efficacy and adverse effects of this novel resurfacing and ablative technique of erbium-YAG laser for superficial dermatoses in Indian skin is limited. Aim and Objective: To evaluate the efficacy and safety profile of erbium-YAG laser ablation in superficial cutaneous lesions. Materials and Methods: Two hundred and fifty patients of various superficial dermatoses, treatable by erbium-YAG laser, were recruited in the study. All the patients were subjected to erbium-YAG laser sessions. The number of laser sessions, fluence, frequency and other parameters were individualized as per the respective dermatosis. The clinical response was evaluated as grade 4 (100% lesion clearance), grade 3 (75-99%), grade 2 (50-75%) or grade 1 (<50%). Results: The overall mean age of our study group was 37.70 years. In our study, 52.38% cases of verruca plana, 36.84% cases of seborrheic keratosis, 56.4% cases of xanthelasma palpebrarum, 22% cases of acquired melanocytic nevus, 23.8% cases of plantar wart and 40% cases of sebaceous hyperplasia showed complete clearance. The most common adverse effect was post-laser erythema in 50.4% of cases, followed by pain in 36.8%. Besides this, scarring and dyspigmentation were observed in 11.6% and 12% of cases, respectively. The rate of recurrence on 3 months follow-up was 9 (23.07%) cases in xanthelasma palpebrarum, 11 (28.9%) cases in seborrheic keratosis, 10 (23.8%) cases in verruca plana and 9 (42.8%) cases in plantar warts. Conclusion: This study suggested that erbium-YAG ablation achieved good results for superficial lesions like verruca plana, seborrheic keratosis, xanthelasma palpebrarum, plantar wart, sebaceous hyperplasia and acquired melanocytic nevus. Thus, Er: YAG laser can offer a one-step procedure with better cosmetic results and a lesser rate of recurrence.

Characterization and Biological Studies of the Terpenoids from Ganoderma resinaceum and Serpula similis (Agaricomycetes).

Mycochemical properties and bioactivities of Ganoderma resinaceum and Serpula similis remain unexplored. The present study assessed antioxidant, cytotoxicity, and cell migration abilities of Ganoderma and Serpula extracts, followed by their phytochemical analyses. The MTT assay was conducted to determine the cytotoxicity along with the cell migration studies in human cancer cell lines. The antioxidant profiles were evaluated through DPPH and FRAP assays. Furthermore, LC-MS/MS analysis was performed to elucidate the phytochemicals responsible for anticancer and antioxidant activities. Significant concentration-dependent cytotoxicities of 12.7% and 13.7% were observed against HCT 116 cell lines at 1% and 5% concentrations of the G. resinaceum extract, respectively. Similarly, significant concentration-dependent cytotoxicities of 6.7% and 25.5% were observed at 1% and 5% concentrations of the S. similis extract, respectively. The extracts of G. resinaceum and S. similis both shows better anti-migration potential in lung cancer cells. Both extracts demonstrated good scavenging activity on DPPH and ferric ion free radicals. LC-MS analysis revealed 11 compounds from S. similis and 15 compounds from G. resinaceum fruiting bodies. Compounds such as terpenoids, alkaloids, cytotoxic peptides, and other metabolites were identified as major components in both extracts. These extracts exhibited cytotoxic activity against HCT 116 cancer cells, along with moderate antioxidant activity. This implies that the extracts might be used as bioactive natural sources in the pharmaceutical and food industries.

Biocompatible polysaccharide fabricated graphene oxide nanoparticles: A versatile nanodrug carrier to deliver κ- carrageenan against cancer cells.

A graphene oxide mediated hybrid nano system for pH stimuli-responsive and in vitro drug delivery targeted for cancer was described in this study. Graphene oxide (GO) functionalized Chitosan (CS) mediated nanocarrier capped with xyloglucan (XG) was fabricated with and without Kappa carrageenan (κ-C) from red seaweed, Kappaphycus alverzii, as an active drug. FTIR, EDAX, XPS, XRD, SEM and HR-TEM studies were carried out for GO-CS-XG nanocarrier loaded with and without active drugs to understand the physicochemical properties. XPS (C1s, N1s and O1s) confirmed the fabrications of XG and functionalization of GO by CS via the binding energies at 284.2 eV, 399.4 eV and 531.3 eV, respectively. The amount of drug loaded in vitro was 0.422 mg/mL. The GO-CS-XG nanocarrier showed a cumulative drug release of 77 % at acidic pH 5.3. In contrast to physiological conditions, the release rate of κ-C from the GO-CS-XG nanocarrier was considerably higher in the acidic condition. Thus, a pH stimuli-responsive anticancer drug release was successfully achieved with the GO-CS-XG-κ-C nanocarrier system for the first time. The drug release mechanism was carried out using various kinetic models that showed a mixed release behavior depending on concentration and diffusion/swelling mechanism. The best-fitting model which supports our release mechanism are zero order, first order and Higuchi models. GO-CS-XG and κ-C loaded nanocarrier biocompatibility were determined by in vitro hemolysis and membrane stabilization studies. MCF-7 and U937 cancer cell lines were used to study the cytotoxicity of the nanocarrier by MTT assay, which indicates excellent cytocompatibility. These findings support the versatile use of a green renewable biocompatible GO-CS-XG nanocarrier as targeted drug delivery and potential anticancer agent for therapeutic purposes.

Histopathological Spectrum of Cutaneous Reactions following COVID-19 Vaccine - An Observational Study.

Background: Owing to the myriad clinical presentations of COVID-19 vaccine-induced adverse events, clinicopathological correlation is the key to understanding the underlying pathophysiology of these reactions. However, there is still a dearth of such systematic studies across a wide spectrum of vaccine reactions. Aim and Objectives: This study provides a clinical and histopathological correlation of COVID-19 vaccine-induced mucocutaneous reactions. Materials and Methods: The study population included all the individuals developing any form of self-reported mucocutaneous adverse events within 4 weeks of receiving the COVID-19 vaccine. The clinical and histopathological features were recorded. Results: A total of 126 cases were identified. Seven histopathological patterns were recognized. The most common histopathological feature was spongiotic dermatitis, seen in all the patients with "vaccine-related eruption of papules and plaques" (VREPP). Other patterns included lichenoid or interface dermatitis, dermal hypersensitivity reaction, leukocytoclastic vasculitis, subepidermal blistering, psoriasiform hyperplasia, and dermal granulomatous reaction. Conclusion: Owing to such myriad clinical presentations, utilizing a histopathological classification could ease categorizing the vaccine-induced mucocutaneous eruptions.

Anticoagulation Strategies in Non-Critically Ill Patients with Covid-19.

Anticoagulation in Non-Critically Ill Covid-19 PatientsMcQuilten et al. conducted a randomized clinical trial comparing low-dose, intermediate-dose, low-dose plus aspirin, and therapeutic-dose anticoagulation in patients with Covid-19 of diverse ethnicities in high-, low-, and middle-income countries.

A Randomized Control Trial of 20% Glycolic Acid Versus 30% Salicylic Acid in the Management of Molluscum Contagiosum.

Background: Molluscum contagiosum (MC) is a common self-limiting viral infection of the skin. Many therapeutic agents have been used for it with varying success rates. Objective: To evaluate and compare the efficacy and safety profile of topical 20% glycolic acid and 30% salicylic acid in the treatment of MC in pediatric patients. Materials and Methods: All patients of MC between 1 and 15 years of age attending the outpatient department of dermatology were randomized into two treatment groups A and B. Group A was treated with 20% glycolic acid solution, and group B was treated with 30% salicylic acid solution daily for 4 weeks. Parents of patients were instructed to apply the medication once daily at night for 1 h on the lesions only. The assessment of response and side effects were analyzed in all the patients weekly for 4 weeks during the daily treatment protocol. Follow-up was done monthly for 3 months after the completion of therapy. Results: At the end of 4 weeks, group A patients (60 patients) were treated with 20% glycolic acid out of which 34 (56.66%) patients had a complete clearance of lesions. Group B patients were treated with 30% salicylic acid out of which 38 (63.33%) had a complete clearance of lesions. Secondary bacterial infection was the most common side effect followed by postinflammatory hyperpigmentation in both groups. Conclusion: 30% salicylic acid was found to be more effective and has less side-effect profile in the treatment of MC than 20% glycolic acid.

Enhancement of landfill leachate treatment using extracellular polymeric substances as bio-flocculants.

Fermentation of Klebsiella pneumoniae was conducted using crude glycerol fortified with secondary paper mill sludge as a carbon source in 5 L fermenter. After 96 hours of fermentation, the fermented broth contained mostly microbial cells surrounded by extracellular polymeric substances (EPS) and other particulate residues from paper mill sludge and glycerol. When this fermented broth is used as it is, it is called broth EPS (B-EPS). When the fermented broth is centrifuged, the supernatant solution is separated from the rest of the microbial cells and from sludge residues. This supernatant is called Slime-EPS (S-EPS). Both types of EPS were used for treatment of landfill leachate. S-EPS showed better flocculation activity (85%) than B-EPS (70%). EPS was also used in combination of Al2(SO4)3 or FeSO4. The removal efficiency of COD with use of S-EPS combined with FeSO4 (more than 80% of COD removal) was higher than with S-EPS alone (48% of COD removal). Better results were recorded when S-EPS (0.015 g/L) was combined with FeSO4 (2 g/L) at pH 8. A remarkable reduction of the following parameters was recorded: COD (82%), total nitrogen (44%), phosphorus (50%) and removal of metals such as Ca (64.3%) and Mg (62.4%).

Investigations on substituted (2-aminothiazol-5-yl)(imidazo[1,2-a]pyridin-3-yl)methanones for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease majorly affecting old age populations. Various factors that affect the progression of the disease include, amyloid plaque formation, neurofibrillary tangles, inflammation, oxidative stress, etc. Herein we report of a new series of substituted (2-aminothiazol-5-yl)(imidazo[1,2-a]pyridin-3-yl)methanones. The designed compounds were synthesized and characterized by spectral data. In vivo anti-inflammatory activity was carried out for screening of anti-inflammatory potential of synthesized compounds. All the compounds were tested for acute inflammatory activity by using carrageenan induced acute inflammation model. Compounds 10b, 10c, and 10o had shown promising acute anti-inflammatory activity and they were further tested for formalin induced chronic inflammation model. Compound 10c showed both acute and chronic anti-inflammatory activity. Compound 10c also showed promising results in AlCl3 induced AD model. Studies on various behavioral parameters suggested improved amnesic performance of compound 10c treated rats. Compound 10c treated rats also exhibited excellent antioxidant and neuroprotective effect with inherent gastrointestinal safety.

Pharmacological investigation of quinoxaline-bisthiazoles as multitarget-directed ligands for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent disease of old age leading to dementia. Complex AD pathogenesis involves multiple factors viz. amyloid plaque formation, neurofibrillary tangles and inflammation. Herein we report of a new series of quinoxaline-bisthiazoles as multitarget-directed ligands (MTDLs) targeting BACE-1 and inflammation concurrently. Virtual screening of a library of novel quinoxaline-bisthiazoles was performed by docking studies. The most active molecules from the docking library were taken up for synthesis and characterized by spectral data. Compounds 8a-8n showed BACE-1 inhibition in micro molar range. One of the compounds, 8n showed BACE-1 inhibition at IC50 of 3 ±â€¯0.07 µM. Rat paw edema inhibition in acute and chronic models of inflammation were obtained at 69 ±â€¯0.45% and 55 ±â€¯0.7%, respectively. Compound 8n also showed noteworthy results in AlCl3 induced AD model. The treated rats exhibited excellent antiamnesic, antiamyloid, antioxidant, and neuroprotective properties. Behavioural parameters suggested improved cognitive functions which further validates the testimony of present study. Moreover, compound 8n was found to have inherent gastrointestinal safety. This new string of quinoxaline-bisthiazoles were identified as effective lead for the generation of potent MTDLs and compound 8n was found to showcase qualities to tackle AD pathogenesis.

Thiazolyl-thiadiazines as Beta Site Amyloid Precursor Protein Cleaving Enzyme-1 (BACE-1) Inhibitors and Anti-inflammatory Agents: Multitarget-Directed Ligands for the Efficient Management of Alzheimer's Disease.

Alzheimer's disease (AD) is associated with multiple neuropathological events including ß-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.

A Quality Improvement Initiative to Reduce "Out-of-ICU" Cardiopulmonary Arrests in a Tertiary Care Hospital in India: A 2-Year Learning Experience.

QUALITY PROBLEM OR ISSUE: To assess impact of medical emergency team (MET) in reducing "out-of-ICU" cardiopulmonary arrests and identify barriers to its optimal utilization. INITIAL ASSESSMENT: Frequently observed critical clinical signs and laboratory values of "out-of-ICU" crashes were used to develop Amrita Early Warning Criteria. CHOICE OF SOLUTION: A physician-led MET was established to respond to code MET, activated by a primary nurse. IMPLEMENTATION: Rates of "out-of-ICU" cardiopulmonary arrests per 1000 admissions were compared in pre-MET (2013-2014) and post-MET periods (2014-2016) along with disposition following MET and mortality. Descriptive statistics and logistic regression were used for comparative analysis. EVALUATION: For continued quality improvement, a Likert agreement scale questionnaire collated the nurse's feedback on MET. 386 Code MET were recorded with an activation rate of 18.8 per 1000 inpatients for 2014-2016. Common MET triggers were desaturation (53%), seizure (10%), and syncope (9%). Seventy-one percent of activations were attended within 5 minutes, with 45% reported during nurse's night shift hours. Medical emergency team interventions resulted in 59% being shifted to ICU. In the "post-MET" period, "Cold Blue" dose reduced from 6.9 in 2013-2014 to 2.6 (P = .0002) in 2014-2015 and 3.2 (P = .01) in 2015-2016. Ninety-three percent of the Code Blues with prior MET calls were "delayed MET" and 28% of the Code Blues without prior MET activation were "missed MET." Nurse's feedback revealed that 46% lacked knowledge of correct MET activation process while 31% expressed a fear of reprisal for inappropriate activation. LESSONS LEARNED: Although MET intervention was successful in significantly reducing "out-of-ICU" Code Blues, focused training of nurses is required for continued quality improvement.

Drosophila adult muscle development and regeneration.

Myogenesis is a highly orchestrated, complex developmental process by which cell lineages that are mesodermal in origin generate differentiated multinucleate muscle cells as a final product. Considerable insight into the process of myogenesis has been obtained for the embryonic development of the larval muscles of Drosophila. More recently, the postembryonic development of the muscles of the adult fly has become a focus of experimental investigation of myogenesis since specific flight muscles of the fly manifest remarkable similarities to vertebrate muscles in their development and organization. In this review, we catalog some of the milestones in the study of myogenesis in the large adult-specific flight muscles of Drosophila. The identification of mesoderm-derived muscle stem cell lineages, the characterization of the symmetric and asymmetric divisions through which they produce adult-specific myoblasts, the multifaceted processes of myoblast fusion, and the unexpected discovery of quiescent satellite cells that can be activated by injury are discussed. Moreover, the finding that all of these processes incorporate a plethora of signaling interactions with other myogenic cells and with niche-like neighboring tissue is considered. Finally, we briefly point out possible future developments in the area of Drosophila myogenesis that may lead to of new avenues of genetic research into the roles of muscle stem cells in development, disease and aging.

Identification and functional characterization of muscle satellite cells in Drosophila.

Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly, however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study, we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells observed at the surface and in close proximity to the mature muscle fibers. Normally quiescent, following muscle fiber injury, we show that these cells express Zfh1 and engage in Notch-Delta-dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of strikingly similar morphological and functional features, we consider these novel cells to be the Drosophila equivalent of vertebrate muscle satellite cells.

Positional Asphyxia: Death Due to Unusual Head-Down Position in a Narrow Space.

Death due to a head-down position with hyperflexion of the neck is a rare event. A person accidentally falling into a narrow space and remaining in an upside-down position with no timely recovery may experience positional or postural asphyxia. It is a critical condition arising out of particular body positions, leading to mechanical obstruction of respiration. The precipitating factors are intoxication due to alcohol, drugs, obesity, psychiatric illnesses, and injuries. A 30-year-old unmarried woman, weighing 82 kg and with a body mass index of 31.24, was found in a narrow space between the bed and the wall in a naked state and in a head-down position with hyperflexion of the neck. The distribution of lividity was consistent with the position of the body at the scene. Blood was oozing from the mouth and nostrils, and signs of asphyxia were present. The toxicological analyses of viscera, blood, and urine were negative for alcohol, drugs, and poisons. Glucose levels in the blood (86 mg/dL) as well as urine and vitreous humor levels (68 mg/dL) were within normal limits. On microscopic examination, there were no findings of coronary atherosclerosis, whereas the brain and lung were edematous. After meticulous examination, we ruled out sexual assault, autoerotic asphyxia, epilepsy, psychiatric illness, diabetes, toxicity, and coronary artery disease. Death was attributed to the accidental fall of the obese individual being stuck in a narrow space, resulting in positional asphyxia. It is imperative to recognize the precipitating or risk factors before labeling positional asphyxia as a cause of death.

A bifunctional α-amylase/trypsin inhibitor from pigeonpea seeds: Purification, biochemical characterization and its bio-efficacy against Helicoverpa armigera.

This paper evaluates α-amylase inhibitor (α-AI) mediated defense of pigeonpea against Helicoverpa armigera. A bifunctional α-amylase/trypsin inhibitor was purified from the seeds of pigeonpea by native liquid phase isoelectric focusing (N-LP-IEF), affinity chromatography and preparative electrophoresis. Its in-vivo and in-vitro interaction with midgut amylases of H. armigera was studied along with growth inhibitory activity. One and two dimensional (2D) zymographic analyses revealed that the purified inhibitor is dimeric glycoprotein (60.2kDa and 56kDa) exist in a multi-isomeric form with five pI variants (pI 5.5 to 6.3). It was found to be heat labile with complete inactivation up to 80°C and stable over a wide range of pH (4-11). The slow binding and competitive type of α-amylase inhibition was observed with 0.08µM of dissociation constant (Ki) for the enzyme-inhibitor complex (EI). The internal protein sequence of two subunits obtained by mass spectrometry matched with cereal-type α-AI, a conserved domain from AAI_LTSS superfamily and sialyltransferase-like protein respectively. In-vivo studies indicated up-regulation of total midgut α-amylase activity with negative effect on growth rate of H. armigera suggesting its suitability for pest control.

Patient and Provider Reported Reasons for Lost to Follow Up in MDRTB Treatment: A Qualitative Study from a Drug Resistant TB Centre in India.

INTRODUCTION: Multidrug-resistant Tuberculosis (MDR TB) is emerging public health concern globally. Lost to follow-up (LTFU) is one of the key challenge in MDRTB treatment. In 2013, 18% of MDR TB patients were reported LTFU in India. A qualitative study was conducted to obtain better understanding of both patient and provider related factors for LTFU among MDR TB treatment. METHODS: Qualitative semi-structured personal interviews were conducted with 20 MDRTB patients reported as LTFU and 10 treatment providers in seven districts linked to Nagpur Drug resistant TB Centre (DRTBC) during August 2012-February 2013. Interviews were transcribed and inductive content analysis was performed to derive emergent themes. RESULTS: We found multiple factors influencing MDR TB treatment adherence. Barriers to treatment adherence included drug side effects, a perceived lack of provider support, patient financial constraints, conflicts with the timing of treatment services, alcoholism and social stigma. CONCLUSIONS: Patient adherence to treatment is multi-factorial and involves individual patient factors, provider factors, and community factors. Addressing issue of LTFU during MDRTB treatment requires enhanced efforts towards resolving medical problems like adverse drug effects, developing short duration treatment regimens, reducing pill burden, motivational counselling, flexible timings for DOT services, social, family support for patients & improving awareness about disease.

Antibody tagged gold nanoparticles as scattering probes for the pico molar detection of the proteins in blood serum using nanoparticle tracking analyzer.

We report a rapid one-step immunoassay to detect protein using antibody conjugated gold nanoparticles (AbGNPs) where the targeted protein concentration was determined by analyzing the gold nanoparticle aggregation caused by antibody-antigen interactions using nanoparticles tracking analysis (NTA) technique. The sandwich structure constituting the binding of the targeted human IgG to the gold nanoparticle conjugates with goat anti human monoclonal IgG (AbGNPs) was confirmed by transmission electron microscopy. The binding of human IgG (antigen, mentioned hence forth as AT) induce AbGNPs to form dimers or trimers through a typical antibody-antigen-antibody sandwich structure that can be analyzed for the sensitive determination on the basis of change in hydrodynamic diameter of AbGNPs. By this method the minimum detectable concentration of AT is found to be below 2pg/ml. We expect that a significant change in the hydrodynamic diameter of AbGNP could form the basis for the rapid one-step immunoassay development.