Modified Corneosurfametry as a new accelerated high-throughput ex vivo methodology for predicting cleanser effects towards human skin.

BACKGROUND: Corneosurfametry (CSM) was originally developed as a tool to predict irritation potential of cleansers. In this method, surface skin stripped using cyanoacrylate is contacted with surfactants/products, rinsed and stained with toluidine blue and basic fuschin dyes. The intensity of staining increases with increases in irritation potential of surfactant. Our objective was to modify the CSM technique to achieve better control of the tape stripping process. Another objective was to correlate the modified CSM (MCSM) with a traditional in-vivo forearm controlled application test (FCAT) for mildness and to explore its utility to assess the state of corneum after a clinical test. METHODS: Surface skin cells were tape stripped from forearms of volunteers with D-Squame Adhesive Discs. Discs were treated with a 10% solution of the product in a 96-plate well for 10 min, rinsed, dried and treated with basic fuschin-toluidine blue dye solution, rinsed and dried again. Forearm Controlled Application Test (FCAT) was based on a published protocol. Tape strips obtained after product treatment were also analyzed by the MCSM procedure without additional product treatment. RESULTS: Mildness/barrier damage assessed from in-vivo FCAT showed a similar ranking to the MCSM results. MCSM, TEWL and Erythema analysis of between-treatment differences showed a good correlation indicating that barrier damage seen in in-vivo studies can be predicted from ex-vivo MCSM studies. MCSM analysis of tape strips after the FCAT study showed that the damage decreased with increase in tape strip number. A moisturizing body wash (MBW) with mild surfactants showed the least damage in all layers. In contrast, harsh dish washing liquid showed significantly higher damage down to several layers. Another MBW with petrolatum in a harsher base showed damage almost similar to that of the harsh dish washing liquid in the surface layers. Thus, the MCSM was able to show underlying damage which would have been normally masked by the deposited petrolatum. CONCLUSION: The MCSM assay was shown to be a valuable tool for accelerated high throughput evaluation of mildness of surfactants and fully formulated products. MCSM can also be used to assess the state of the corneum after a product treatment.

Optimisation of radiolysis of Reactive Red 120 dye in aqueous solution using ionising (60)Co gamma radiation by response surface methodology.

In recent years, employing radiation technology is gaining great interest in degradation of industrial effluents. In this work the possibility of using gamma irradiation to degrade Reactive Red 120 (C.I.292775) was explored. The effects of pH, dose of gamma irradiation and concentration of dye were examined and their interaction were also established based on their response. For the analysis and optimisation of variables, three factor three level Box-Wilson face centred central composite design (CCF) was used. Analysis of variance with R(2) = 0.9988, adjusted R(2) = 0.9981 and the adequate precision value of 122.303 indicates that the CCF model can be used. The coefficient of variation (0.54%) indicates the reliability of the model. The dose of gamma irradiation (kGy) and the concentration of dye (mg/L) showed significant effects on the degradation of RR 120, while a difference of 6 to 10% degradation was observed in extending the pH towards the acid or alkali range from pH 7.00. The maximum concentration of dye degraded was observed as 347.509 mg/L at initial pH: 7.0, dose of gamma irradiation: 5.94 kGy and initial concentration of dye: 500 mg/L. This predicted value was found to be in agreement with the experimental value on the optimised conditions.

Impact of CYP polymorphisms, ethnicity and sex differences in metabolism on dosing strategies: the case of efavirenz.

PURPOSE: Differences in drug metabolism due to cytochrome P450 (CYP) polymorphisms may be significant enough to warrant different dosing strategies in carriers of specific cytochrome P450 (CYP) polymorphisms, especially for drugs with a narrow therapeutic index. The impact of such polymorphisms on drug plasma concentrations and the resulting dosing strategies are presented in this review, using the example of efavirenz (EFV). METHODS: A structured literature search was performed to extract information pertaining to EFV metabolism and the influence of polymorphisms of CYP2B6, ethnicity, sex and drug interactions on plasma concentrations of EFV. The corresponding dosing strategies developed for carriers of specific CYP2B6 genotypes were also reviewed. RESULTS: The polymorphic CYP2B6 enzyme, which is the major enzyme in the EFV metabolic pathway, is a key determinant for the significant inter-individual differences seen in EFV pharmacokinetics and pharmacodynamics (PKPD). Ethnic differences and the associated prevalence of CYP2B6 polymorphisms result in significant differences in the PKPD associated with a standard 600 mg per day dose of EFV, warranting dosage reduction in carriers of specific CYP2B6 polymorphisms. Drug interactions and auto-induction also influence EFV PKPD significantly. CONCLUSION: Using EFV as an example of a drug with a narrow therapeutic index and a high inter-patient variability in plasma concentrations corresponding to a standard dose of the drug, this review demonstrates how genotyping of the primary metabolising enzyme can be useful for appropriate dosage adjustments in individuals. However, other variables such as drug interactions and auto-induction may necessitate plasma concentration measurements as well, prior to personalising the dose.

Boundaries tuned support vector machine (BT-SVM) classifier for cancer prediction from gene selection.

In recent days, the identified genes which are detecting cancer-causing diseases are plays a crucial part in the microarray data analysis. Huge volume of data required since the disease changed often. Conventional data mining techniques are lacking in space concern and time complexity. Based on big data the proposed work is executed. Using the ISPCA - Improved Supervised Principal Component Analysis, feature extraction is developed in this study. For gene expression, co-variance matrix is generated and through feature selection cancer classification is performed by IPSCA. Further feature selection process by boundaries tuned support vector machines (BT-SVM) classifier and modified particle swarm optimization with novel wrapper model algorithm are performed. The experimentation is carried out by utilizing different datasets like leukaemia, breast cancer dataset, brain cancer, colon, and lung carcinoma from the UCI repository. The proposed work is executed on six benchmark dataset for DNA microarray data in terms of accuracy, recall, and precision to evaluate the performance of the proposed work. For evaluating the proposed work effectiveness, it is compared with various traditional techniques and resulted in optimum accuracy, recall, precision and training time with and without feature selection effectively.

Communication of Autonomous Vehicles in Road Accidents for Emergency Help in Healthcare Industries.

Autonomous cars like driverless motors are considered solely in science fiction films; however, in 2019, they are turning into a veracity and reality. People all around the world are excited to see the driverless automobile in reality. Selfless vehicles do not want human intervention. A completely driverless car is nonetheless at a superior trying out stage; however, in part due to computerized technological know-how, it has been around for the last few years. A partly computerized car has points such as lane keeping, automatic braking, and adaptive cruise control. With a self-sustaining automobile device, the vehicle has to feel the environment and discover objects, and with the assistance of GPS, it should run on the right navigation course even while obeying site visitors and transportation rules. In addition to that, the safety of passengers and pedestrians is also very important. This capability to keep away from collisions with barriers and accidents during assemble is important. To forestall the self-sufficient vehicle, this autonomous system helps a lot. The sensor used in this gadget identifies the objects in front of the car and stops the car, directing it to go on a specific course to keep away from accidents and communicate with each other. This accident-avoidance gadget and communication system help the self-sustaining car to attain the vacation spot via coaching the vehicle with synthetic intelligence. By making the motors smartest the lifestyles fashion additionally turns into smartest.

Potential benefit of vitamin D supplementation in people with respiratory illnesses, during the COVID-19 pandemic.

This review describes the evidence for the potential benefit of vitamin D supplementation in people with respiratory diseases who may have a higher susceptibility to coronavirus disease 2019 (COVID-19) infection and its consequences. Clinical evidence indicates that vitamin D may reduce the risk of both upper and lower respiratory tract infections and offers benefit particularly in people with vitamin D deficiency. Some evidence exists for a higher incidence of active tuberculosis (TB) in patients who are deficient in vitamin D. An association between low levels of 25(OH)D (the active form of vitamin D) and COVID-19 severity of illness and mortality has also been reported. In addition, low 25(OH)D levels are associated with poor outcomes in acute respiratory distress syndrome (ARDS). The cytokine storm experienced in severe COVID-19 infections results from excessive release of pro-inflammatory cytokines. Due to its immunomodulatory effects, adequate vitamin D levels may cause a decrease in the pro-inflammatory cytokines and an increase in the anti-inflammatory cytokines during COVID-19 infections. Vitamin D deficiency was found in 82.2% of hospitalized COVID-19 cases and 47.2% of population-based controls (p < 0.0001). The available evidence warrants an evaluation of vitamin D supplementation in susceptible populations with respiratory diseases, such as TB, and particularly in those who are deficient in vitamin D. This may mitigate against serious complications of COVID-19 infections or reduce the impact of ARDS in those who have been infected.

Comparative evaluation of decellularized bovine omentum alone and in combination with mitomycin-C in the management of corneal injuries in dogs.

BACKGROUND AND AIM: Ulcerative corneal lesions are common ocular affections encountered in veterinary ophthalmology, having a higher incidence in dogs with brachycephalic conformation. Prompt and effective diagnosis and repair are necessary to avoid corneal perforation and restore vision. Corneal wound healing is a complex phenomenon often resulting in vision impairment as a consequence of corneal fibrosis and pigmentation. The present study investigated the efficacy of decellularized and gamma-irradiated bovine omentum as an extracellular matrix scaffold in the reconstruction of extensive and full-thickness corneal defects, and the cytotoxic effects of mitomycin-C (MMC) to prevent corneal fibrosis and pigmentation. MATERIALS AND METHODS: Twelve injured corneas of eleven dogs irrespective of breed, age, and sex were randomly divided into Groups I and II, consisting of six corneas each. Under general anesthesia, corneal grafting with decellularized and gamma-irradiated bovine omentum was carried out in Group I, whereas Group II corneas underwent single time intra-operative application of topical MMC for 2 min before corneal grafting with the same material. Epithelialization of cornea and observations including corneal edema, neovascularization, the extent of pigmentation, corneal clarity, and scarring was recorded on days 7, 14, 21, and 60 postoperatively. RESULTS: All corneas in Group I showed early epithelialization by day 7 compared to Group II where the MMC delayed epithelialization in 50% of the corneas. Visual function scores improved greatly from 0.17±0.17 in Group II on the day of presentation to 1.0±00 by the end of the observation period compared to Group I (from 0.33±0.15 to 0.88±0.11). Although epithelialization and corneal healing were delayed, 50% of the corneas recovered with undetectable corneal scar and melanosis at the end of the observation period in Group II due to the anti-fibrotic effect of MMC. CONCLUSION: From the present study, it was concluded that re-epithelialization of the cornea was enhanced by corneal grafting with decellularized bovine omentum, and application of MMC was effective in delaying corneal fibrosis and pigmentation.

LNTP-MDBN: Big Data Integrated Learning Framework for Heterogeneous Image Set Classification.

BACKGROUND: With the explosive growth of global data, the term Big Data describes the enormous size of dataset through the detailed analysis. The big data analytics revealed the hidden patterns and secret correlations among the values. The major challenges in Big data analysis are due to increase of volume, variety, and velocity. The capturing of images with multi-directional views initiates the image set classification which is an attractive research study in the volumetricbased medical image processing. METHODS: This paper proposes the Local N-ary Ternary Patterns (LNTP) and Modified Deep Belief Network (MDBN) to alleviate the dimensionality and robustness issues. Initially, the proposed LNTP-MDBN utilizes the filtering technique to identify and remove the dependent and independent noise from the images. Then, the application of smoothening and the normalization techniques on the filtered image improves the intensity of the images. RESULTS: The LNTP-based feature extraction categorizes the heterogeneous images into different categories and extracts the features from each category. Based on the extracted features, the modified DBN classifies the normal and abnormal categories in the image set finally. CONCLUSION: The comparative analysis of proposed LNTP-MDBN with the existing pattern extraction and DBN learning models regarding classification accuracy and runtime confirms the effectiveness in mining applications.

Lost in translation: translational interference from a recurrent mutation in exon 1 of MECP2.

BACKGROUND: Rett syndrome (RTT) is an X linked neuro-developmental disorder affecting mostly girls. Mutations in the coding region of MECP2 are found in 80% of classic RTT patients. Until recently, the region encoding MECP2 was believed to comprise exons 2, 3, and 4 with the ATG start site located at the end of exon 2 (MeCP2_e2). METHODS: Recent reports of another mRNA transcript transcribed from exon 1 (MeCP2_e1) prompted us to screen exon 1 among RNA samples from 20 females with classic or atypical RTT. RESULTS: A previously reported 11 base pair deletion in exon 1 was detected in one subject with a milder phenotype. Although RNA expression for both protein isoforms was detected from the mutant allele, evaluation of MeCP2 protein in uncultured patient lymphocytes by immunocytochemistry revealed that MeCP2 protein production was restricted to only 74-76% of lymphocytes. X chromosome inactivation studies of genomic DNA revealed similar XCI ratios at the HUMARA locus (73:27 with HpaII and 74:26 with McrBC). We have demonstrated that translation but not transcription of the MeCP2_e2 isoform is ablated by the 11 nucleotide deletion, 103 nucleotides upstream of the e2 translation start site. CONCLUSIONS: These findings reveal that nucleotides within the deleted sequence in the 5'-UTR of the MeCP2_e2 transcript, while not required for transcription, are essential for translation.

Do the length-based (Broselow) Tape, APLS, Argall and Nelson's formulae accurately estimate weight of Indian children?

This study was aimed at validating the usefulness of a length based pediatric emergency tape (Broselow) in an Indian population. The secondary objective was to validate age based weight estimation formulae (Nelson, Argalls, APLS) for emergency needs (doses, sizes). This cross sectional study was done at a tertiary teaching hospital on a sample of 500 children attending outpatient clinic. Inclusion criteria was age between 1 month to 12 years. Children who were unstable, uncooperative or critically ill requiring emergency care and those measuring more than 145 cm in length or weighing more than 35 kg weight were excluded from the study. Measurement of actual weights, calculation of weight, adrenaline dose, fluid bolus and endotracheal tube size was done by all four methods. Results indicated good positive correlation between actual measured weights and weights estimated using Broselow Tape (r = 0.974), APLS (r = 0.902), Argalls modification (r = 0.902), and combined Nelson formulae (0.935). However, specific Nelson formulas for 7-12 yr and 3-12 mo were especially poor in correlation. Bland-Altman Plots comparing actual weight showed least mean bias for Broselow Tape estimations in < 15 kg group (0.080 +/- 0.96 kg) and maximum bias with Nelsons formula for 7 to12 yr (5.204 +/- 4.272 kg). For adrenaline doses and fluid bolus calculations, Broselow estimations were valid estimates. Broselow tape did underestimate endotracheal tube size (mean bias -0.53 +/- 0.18). To conclude, length based pediatric emergency tape (Broselow) correlates well with overall emergency decision making process in our setting. This is especially validated in the age group 0.1 to 6.7 yr weighing less than 15 kg.

Potential Co-Relation Between Chronic Periodontitis And Cancer - An Emerging Concept.

Periodontal disease caused chiefly by bacteria is characterized by inflammation, bacteremia, and a strong immune response. It is based on evidence that a continuous long-term exposure to oral bacteremia and bacterial toxins induces inflammatory immune response after immune evasion releases growth factors such as FGF, EGF, TGF-Beta, free radicals such as ROS and NOS, cytokines such as TNFAlfa, IL-1 Beta, IL-6; and matrix metalloproteinase such as MMP-9. Immature myeloid cells such as macrophages, dendritic cells and granulocytes involved in chronic inflammation and tumor progression through immunosuppressive activity against innate and adaptive immunity by factors such as iNOS, Arginase1 and ROS, activate major transcriptional factors such as NF-KB and STAT3 that could contribute to genetic instability, uncontrolled cell proliferation, angiogenesis, resistance to apoptosis, epithelial to mesenchymal transition, immunosuppression, invasion and metastasis. This study is a product of research and analysis on the role of chronic inflammatory mediators of chronic periodontitis in progression to cancer.

Growth, spectral, thermal, optical, mechanical and etching studies of l-lysine semi-maleate (l-LSM) single crystals.

Organic nonlinear optical material, l-lysine semi-maleate (l-LSM) single crystals were grown by slow cooling solution growth technique. The crystal system of grown l-LSM was confirmed by single crystal and powder X-ray diffraction analyzes. Functional groups of the grown crystal have been identified by Fourier Transform Infrared spectral analysis. The proton and carbon NMR spectral studies confirm the presence of hydrogen and carbon in the grown l-LSM. The melting and thermal decomposition temperatures of the crystal were determined using thermogravimetric (TG) and differential scanning calorimetry (DSC) analyses. Optical transparency, second harmonic generation efficiency, micro hardness, dielectric constant and loss, refractive index and birefringence have also been measured. Further, the growth patterns and dislocations present in the grown crystal are studied.

Cytomegalovirus necrotizing bronchiolitis with HIV infection.

Cytomegalovirus (CMV) is frequently isolated from respiratory secretions of human immunodeficiency virus (HIV)-infected patients. Even in the presence of histopathologic evidence of CMV cytopathic abnormalities, the true clinical significance of CMV pneumonitis is not well established. Airways disease is increasingly recognized in HIV-infected patients, but its etiology is unclear. We describe an HIV-infected patient who presented with fever, wheeze, and micronodular interstitial infiltrates and developed severe hypercapnic and hypoxemic respiratory failure. Open lung biopsy showed necrotizing bronchiolitis with cytopathic changes characteristic of CMV infection; no other pathogens were isolated. He responded well to treatment with ganciclovir.

Pneumocystis carinii pneumonia. Rare cause of hemoptysis.

Pneumocystis carinii pneumonia is a frequent manifestation of the acquired immunodeficiency syndrome (AIDS). It commonly presents with nonproductive cough, fever, and dyspnea. We report this case of P carinii pneumonia presenting with hemoptysis, since to the best of our knowledge, hemoptysis has not been reported to be a presenting manifestation of P carinii pneumonia. Autopsy revealed multiple lung cavities.

Solvent-free sonochemical preparation of ionic liquids.

[reaction: see text] An ultrasound-assisted preparation of a series of ambient-temperature ionic liquids, 1-alkyl-3-methylimidazolium (AMIM) halides, which proceeds via efficient reaction of 1-methyl imidazole with alkyl halides/terminal dihalides under solvent-free conditions, is described.

Microwave-assisted preparation of dialkylimidazolium tetrachloroaluminates and their use as catalysts in the solvent-free tetrahydropyranylation of alcohols and phenols.

Microwave-assisted preparation of dialkylimidazolium tetrachloroaluminates, [CnMIM][AlCl4] and their application as recyclable catalysts for the efficient and eco-friendly protection of alcohols as tetrahydropyranyl (THP) ethers are described. The same catalyst can also be utilized for the deprotection of THP ethers.

Regional-dependent intestinal absorption and meal composition effects on systemic availability of LY303366, a lipopeptide antifungal agent, in dogs.

Low oral bioavailability and a negative meal effect on drug plasma levels motivated studies on formulation and meal composition effects on the absorption of LY303366, a poorly water-soluble, semisynthetic, cyclic peptide antifungal drug. Solid drug particle size and meal composition studies were evaluated in beagle dogs. Canine regional absorption studies were also carried out utilizing surgically implanted intestinal access ports, and Caco-2 studies were performed to evaluate drug candidate intestinal permeability. Particle size and Caco-2 data indicate that drug permeability limitations to absorption are more important than dissolution rate limits. Caco-2 cell-associated LY303366 approached 10% of incubation concentration that is in the range of the oral bioavailability of the drug. Canine regional absorption studies showed that the extent of LY303366 absorption following duodenal administration was similar to that following oral administration. Significantly lower drug plasma levels were obtained following administration through a colonic access port, a result consistent with poor membrane permeation. Administration of drug with meals of mixed composition, as well as simple fat and protein meals, resulted in significant reductions in AUC(0-48h) compared with results from fasted dogs. In contrast, carbohydrate meals did not reduce drug plasma levels compared to controls. Intravenous pretreatment with devazepide, a cholecystokinin (CCK) antagonist that blocks canine biliary secretion, did not reverse the negative effect of the fat meal on LY303366. Taken together, the results from the present study suggest that membrane-permeability-limited absorption is the cause of the observed regionally dependent absorption of LY303366 in the dog and that the observed negative meal effects depend on composition but are independent of biliary secretion.

Application of oral bioavailability surrogates in the design of orally active inhibitors of rhinovirus replication.

Previous studies in rats and humans demonstrated poor oral bioavailability of potent in vitro 2-aminobenzimidazole inhibitors of rhinovirus replication due to significant first-pass elimination and possibly also to poor aqueous solubility. Estimations of aqueous solubility, as well as measurements of caco-2 permeability and NADPH dependent compound loss in rat liver microsomal incubations were employed alongside traditional in vivo experiments in rats to guide subsequent chemistry efforts. Retention of activity upon replacement of the metabolically labile vinyl oxime in the lead molecule with a vinyl carboxamide was a major breakthrough; however, oral bioavailability among the latter compounds was variable. Based on the ability to independently measure solubility, permeability, and metabolic stability of new compounds, variable solubility across the series (ranging from approximately 1 to 10 microg/mL) was identified as the cause of the inconsistent performance. Subsequent efforts to improve solubility led to the discovery of highly soluble (>10 mg/mL) and potent dessulfonyl vinyl carboxamide benzimidazoles. Determination of the metabolic stability of these compounds as a surrogate of the extent of their first-pass elimination supported a prediction of excellent oral bioavailability. In comparison to the sulfonyl-containing vinyl carboxamides, caco-2 permeabilities were reduced 5 to 10-fold; however, these were considered to be in the range of well-absorbed compounds based on comparison to a series of reference compounds of known percentage absorption in humans. Subsequent experiments in the rat verified the oral bioavailability of these N-alkyl compounds, with one compound (368177) having an absolute oral bioavailability of 89.4%. The application of solubility and caco-2 permeability as surrogates for oral absorption potential, in conjunction with the use of microsomal incubations as a surrogate for first-pass metabolism, was shown to augment a rational chemistry approach to discover orally bioavailable inhibitors of rhinovirus replication. Future expanded use of these surrogates is planned.

Rabson-Mendenhall syndrome.

Rabson-Mendenhall syndrome is a rare, autosomal recessive disorder affecting insulin receptor. This disorder is characterized by insulin-resistant diabetes mellitus, hyperinsulinemia, deficiency of subcutaneous fat, acanthosis nigrican, growth retardation, coarse and senile appearance, precocious puberty, and dental prematurity, enlarged genitalia, and pineal hyperplasia. Mutations of the insulin receptor gene affecting insulin action appear to be the basic mechanism underlying this syndrome. Herein, we present a case report on Rabson-Mendenhall syndrome in a 9-year-old girl.

Synthesis, growth and characterization of L-lysinium(+)...L-lysinium(2+) dichloride perchlorate (LLDP) single crystals by Sankaranarayanan-Ramasamy method.

L-lysinium(+)...L-lysinium(2+) dichloride perchlorate was synthesized at ambient temperature and bulk single crystals were grown by conventional and Sankaranarayanan-Ramasamy methods. Crystals grown by these methods were subjected to single crystal X-ray diffraction, Fourier transform infrared, high resolution X-ray diffraction, Vickers microhardness and thermogravimetric/differential scanning calorimetric/differential thermal analyses. Further, the cut-off wavelength and optical transmittance of the grown crystals were determined by UV-vis-NIR spectrum. Linear refractive index (n(x)) of the crystal was measured using minimum deviation method for different wavelengths. Optical quality of the grown crystals was analyzed by conoscopic interference pattern and the birefringence was calculated using interferometric technique. Surface laser damage threshold of the crystal was determined using Nd:YAG laser. The nonlinear refractive index n(2) was measured through the Z-scan technique using low power continuous wave HeNe laser. Frequency and temperature dependent dielectric constant (ε(r)) and dielectric loss (tanδ) were measured.