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Nevin Manimala Statistics

A unique view of SARS-COV-2 through the lens of ORF8 protein

Comput Biol Med. 2021 Apr 15;133:104380. doi: 10.1016/j.compbiomed.2021.104380. Online ahead of print.

ABSTRACT

Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host’s interferon-mediated antiviral response. To understand the host’s immune perspective concerning the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.

PMID:33872970 | DOI:10.1016/j.compbiomed.2021.104380

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The effects of different potato dextrose agar media on secondary metabolite production in Fusarium

Int J Food Microbiol. 2021 Mar 26;347:109171. doi: 10.1016/j.ijfoodmicro.2021.109171. Online ahead of print.

ABSTRACT

Potatoes contain several nutrients essential for fungal growth, making them an excellent component of media such as the popular Potato Dextrose Agar (PDA) medium. Commercially, PDA is available from multiple retailers offering virtually the same product. These media, however, could contain small differences in composition of nutrients affecting the expression of secondary metabolites. This study aims to investigate the use of four PDA media from different manufacturers (Fluka, Oxoid, Sigma, and VWR) and their effect on the metabolite profile of four species of Fusarium (F. fujikuroi, F. graminearum, F. pseudograminearum and F. avenaceum). Secondary metabolites were analysed using HPLC-HRMS, from which statistically significant differences in intensities were observed for 9 out of 10 metabolites.

PMID:33872940 | DOI:10.1016/j.ijfoodmicro.2021.109171

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Nevin Manimala Statistics

Smart spectrophotometric methods for the simultaneous determination of newly co-formulated hypoglycemic drugs in binary mixtures

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Apr 1;257:119763. doi: 10.1016/j.saa.2021.119763. Online ahead of print.

ABSTRACT

Achieving good glycemic control in patients with type II diabetes mellitus is essential for preventing both microvascular and macrovascular complications. Combination therapy represents the principle strategy for successful long term control of type II diabetes mellitus with minimal complications. Two sensitive, precise and non-destructive spectroscopic methods were developed for the simultaneous estimation of two new co-formulated hypoglycemic drugs; canagliflozin/metformin (CAG/MEF) and empagliflozin/linagliptin (EMG/LIG) in tablets with no need of previous separation. The first method was amplitude modulation (a normalized spectra-based UV spectrophotometric method) for the analysis of (CAG/MEF) binary mixture. The amplitude of the constant at the plateau region at (264-310 nm) on the ratio spectrum was measured and used for the determination of CAG concentration in the mixture. On the other hand, MEF was estimated by subtracting the previously obtained amplitude from the total amplitude of CAG and MEF at the isosbestic point (λiso) at 250 nm. The second method was chemometric-assisted FTIR spectrophotometric method for the determination of (EMG/LIG) binary mixture. (EMG/LIG) mixture in chloroform was analyzed using FTIR in the region 4000-400 cm-1. The spectral region 3900-2900 cm-1 was selected for (EMG/LIG) determination using principal component regression and partial least squares chemometric methods. The methods were validated according to ICH guidelines. The studied drugs were successfully determined in tablets applying the developed methods. Validation parameters were in agreement with acceptance limits, ensuring methods accuracy and selectivity. Besides, no significant difference was obtained by statistically comparing the obtained results with the reported one.

PMID:33872950 | DOI:10.1016/j.saa.2021.119763

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Autofluorescence spectroscopy and multivariate analysis for predicting the induced damages to other organs due to liver fibrosis

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Mar 24;257:119741. doi: 10.1016/j.saa.2021.119741. Online ahead of print.

ABSTRACT

When our liver does not work well, it can induce damage to other organs causing their dysfunction. With this background, we aim to study the effect of liver fibrosis on other organs such as heart, lungs, kidney and spleen by assessing the variations in the inherent emission property of the tissue, using fluorescence spectroscopy. Fluorescence emission spectra from excised organs of liver fibrosis induced rats were collected at excitation wavelengths 320 and 410 nm. Optical redox ratio derived from the spectral data supported by multivariate statistical analysis, principal component analysis followed by linear discriminant analysis (PCA-LDA) distinguished between control and fibrosis induced groups. The two different excitation wavelength provided variations in the endogenous flurophores collagen, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), lipopigments and porphyrins. Additionally, evaluation of redox ratio provided variations in tissue metabolic activity of different organs. The PCA-LDA modelling yielded a sensitivity of 85 to 97% and specificity of 80 to 96% on 320 nm excitation and a sensitivity of 72 to 100% and specificity of 59 to 100% on 410 nm excitation. Fluorescence emission spectral study along with multivariate analysis paved way to identify the biochemical alterations caused to other organs due to the development of liver fibrosis, which could lead to their damage and dysfunction.

PMID:33872953 | DOI:10.1016/j.saa.2021.119741

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Micro-mechanical properties of corneal scaffolds from two different bio-models obtained by an efficient chemical decellularization

J Mech Behav Biomed Mater. 2021 Apr 16;119:104510. doi: 10.1016/j.jmbbm.2021.104510. Online ahead of print.

ABSTRACT

The present study elucidates the impact of detergent-based chemical decellularization on the micro-mechanical properties of porcine and rabbit corneas for the purpose of extracellular matrix (ECM) derived scaffolds. Aiming to optimize the decellularization process, different concentrations of Sodium Dodecyl Sulfate (SDS), Triton X-100 and CHAPS detergents were assessed on their ability to decellularize corneas from both bio-models at incubation periods of 12 and 24h. We evaluated the effect of decellularization on corneal ECM Young’s Modulus and various area’s roughness parameters (topography features) at a microscale by using Atomic Force Microscopy (AFM). Only SDS presented adequate decellularization properties at the selected concentrations (0.2, 0.5 and 1%) and incubation periods. All topography features displayed by native corneas were preserved after SDS treatments, while no statistically significant differences were identified for the average value of Young’s Modulus between the control samples and those treated with 0.2% SDS (rabbit corneas) and 0.5% SDS (porcine corneas) after 12h. In this sense, cornea decellularization procedures can be improved by simultaneously reducing SDS concentration and incubation period. AFM is a useful tool to perform biomechanical analysis of the effect of decellularization on scaffold micro-mechanics. Evaluation of the scaffold mechanical behavior at a microscale could help in understanding cell-scaffold interactions in terms of mechanotransduction, complementing macroscale techniques (e.g. tensile tests) relevant for tissue engineering quality control and decision-making.

PMID:33872923 | DOI:10.1016/j.jmbbm.2021.104510

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Comparison of the effects of corticosteroid and hyaluronic acid-carboxylmethylcellulose (HA-CMC) solution on selective nerve root block (SNRB) for lumbar radiculopathy: A prospective, double-blind, randomized controlled clinical trial

Pain Pract. 2021 Apr 19. doi: 10.1111/papr.13018. Online ahead of print.

ABSTRACT

BACKGROUND: SNRB was shown to effectively control radiating pain and reduce the need for surgical intervention. However, repetitive injections may trigger corticosteroid-induced side effects (hypercorticism, hyperglycemia, or fluid retention). This study aims to compare the potency of hyaluronic acid-carboxymethylcellulose (HA-CMC) solution versus that of corticosteroids regarding lower leg radiating pain (LLRP) improvement and functional outcome.

METHODS: Among 128 patients, 44 patients who complain LLRP due to lumbar spinal stenosis and do not have neurological symptoms requiring surgery were enrolled for this study. Group A with 22 patients injected with cocktail A (local anesthetics, corticosteroid) and group B with 22 patients injected with cocktail B (local anesthetics, HA-CMC). Outcome measures were the visual analog scale (VAS), Oswestry Disability Index (ODI), and short form -36 (SF-36). All patients were asked to fill in the questionnaires during the follow-up assessment period at 3 days, 7 days, 2 weeks, 6 weeks, and 12 weeks.

RESULTS: In all time periods, there were no statistical differences between the two groups for VAS scores and VAS improvement over time, ODI scores and ODI improvement over time, and SF-36 PCS scores and SF-36 MCS scores. Additionally, the 95% confidence interval of the difference in VAS score improvement between the two groups in all time periods was within VAS 5.0, which is the minimum clinically relevant difference.

CONCLUSIONS: Considering the adverse effects of corticosteroids, and the similar LLRP improvements, functional outcome, and quality of life, the HA-CMC solution may be an alternative option to corticosteroid in SNRB.

PMID:33872462 | DOI:10.1111/papr.13018

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Vaccination of Holstein heifers with Mycobacterium bovis BCG strain induces protection against bovine tuberculosis and higher milk production yields in a natural transmission setting

Transbound Emerg Dis. 2021 Apr 19. doi: 10.1111/tbed.14108. Online ahead of print.

ABSTRACT

Bovine tuberculosis (TB) is a chronic disease caused mainly by Mycobacterium bovis, a zoonotic pathogen that has a worldwide distribution causing serious economic losses for milk and meat producers. In Chile the disease in dairy cattle has a heterogeneous distribution, where the Metropolitan Region concentrates the highest animal prevalence and the main challenge for the national control and eradication program. In this epidemiological context, vaccination with the M. bovis Bacillus Calmette-Guerin (BCG) vaccine might be a useful strategy for disease prevention and control. The objective of this study was to assess the efficacy and impacts on productivity and fertility of vaccination with the BCG Russia strain in 11-month-old heifers from a dairy farm, under a natural transmission condition. Sixty-two animals were vaccinated via the subcutaneous route with the equivalent of 1 human dose of BCG and 60 control animals received saline. Subsequently, blood sampling was performed at 3, 6, 9, 12, 15 and 18 months post inoculation, and infection status was determined using the IFNγ release assay (IGRA)with the DIVA (Differentiate Infected from Vaccinated Animals) antigens ESAT-6, CFP-10 and Rv3615c. Efficacy was calculated as the percentage of reduction in the incidence of infection attributable to vaccination, which showed a statistically significant level of overall protection of 66.5%. No adverse effects on fertility and production were recorded. In contrast, we observed beneficial effects of vaccination on several milk production parameters, with the milk yield in the first 100 days after calving in the BCG group significantly higher compared to unvaccinated heifers( p <0.05).These results suggest that BCG vaccination of heifers in a natural transmission setting might result in both sanitary and productive benefits, supporting its implementation as a new strategy for TB prevention in a high prevalence area of Chile.

PMID:33872473 | DOI:10.1111/tbed.14108

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Systemic photoprotection in 2021

Clin Exp Dermatol. 2021 Apr 19. doi: 10.1111/ced.14697. Online ahead of print.

ABSTRACT

Systemic photoprotection aims to negate the negative effects of ultraviolet radiation-induced DNA damage. Systemic supplements might be used as a monotherapy or in combination with topical sunscreens. Using the keywords ‘carotenoids,’ ‘flavonoids,’ ‘systemic photoprotection,’ ‘polyphenols’ and ‘polypodium leucotomos extract,” we searched the databases MEDLINE and EMBASE to find relevant English-language articles. Few trials have supported the use of any of these supplements as a monotherapy, impeding the recommendation of these systemic supplements as an alternative to sunscreen for photoprotection. Nicotinamide has exhibited clinically relevant benefits in reducing non-melanoma skin cancers in trials and could be recommended as an adjunctive therapy in those most vulnerable. Further research is required that is of higher statistical power, using more clinically meaningful outcome measures with comparison to the current gold standard of care, topical photoprotection, to support the use of alternative therapies in clinical practice.

PMID:33872410 | DOI:10.1111/ced.14697

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Environmental factors in non-syndromic orofacial clefts: A review based on meta-analyses results

Oral Dis. 2021 Apr 19. doi: 10.1111/odi.13880. Online ahead of print.

ABSTRACT

Non-syndromic orofacial clefts (NSOFCs) are prevalent birth defects with a complex etiology where several interacting genetic and environmental factors have been observed. This narrative review describes maternal exposures which have been significantly associated to protective effects or risk factors. The statistically significant information reported here was found in meta-analysis studies, taking advantage of their precision in defining intervention effects and their management of heterogeneity between studies. In addition, I propose a hypothesis explaining the biological basis for the results of the meta-analyses. This review aims to improve the evidence available in parent counseling, to prevent the occurrence of orofacial clefts by suggesting lifestyle changes.

PMID:33872445 | DOI:10.1111/odi.13880

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Heparin-induced thrombocytopenia: construction of a pre-test diagnostic score derived from the analysis of a prospective multinational database, with internal validation

J Thromb Haemost. 2021 Apr 19. doi: 10.1111/jth.15344. Online ahead of print.

ABSTRACT

BACKGROUND: Diagnosis of heparin-induced thrombocytopenia (HIT) requires pre-test probability assessment and dedicated laboratory assays.

OBJECTIVE: To develop a pre-test score for HIT.

DESIGN: Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839).

SETTING: Thirty-one tertiary hospitals in France, Switzerland, and Belgium.

PATIENTS: Patients tested for HIT antibodies (2,280 evaluable), randomly allocated to derivation and validation cohorts.

MEASUREMENTS: Independent adjudicators diagnosed HIT based on the prospectively collected data and Serotonin Release Assay results.

RESULTS: HIT was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); ≥ 40% decrease in platelet count over ≤ six days (3); thrombotic event, arterial (3) or venous (3). The C-statistic was 0.79 [95% CI, 0.76-0.82]. In the validation cohort, the area under the receiver operating characteristic curve was 0.77 [95% CI, 0.74-0.80]. Three groups of scores were defined; HIT prevalence reached almost 30% in the high-probability group.

LIMITATION: The performance of the score may depend on settings and practices.

CONCLUSION: The objective, easy-to-collect, clinical features of HIT we evidenced were incorporated into a pre-test score, which may guide clinical decisions regarding diagnostic testing and anticoagulation.

PMID:33872452 | DOI:10.1111/jth.15344