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Nevin Manimala Statistics

Optimization of Microbial Rennet Encapsulation in Alginate – Chitosan Nanoparticles

Food Chem. 2021 Feb 19;352:129325. doi: 10.1016/j.foodchem.2021.129325. Online ahead of print.

ABSTRACT

The milk-coagulating enzyme, rennet, is widely used in cheese making. Recently stabilization of rennet, especially in accelerated cheese ripening, has received considerable interest. As we know encapsulation is one of the enzyme immobilization methods, which could increase enzyme stability. In this study, the effects of alginate, chitosan and, CaCl2 on rennet encapsulation were evaluated and optimized using RSM. Under the optimal conditions alginate, chitosan, and CaCl2 were 0.04%, 0.1%, and 0.1% respectively. At the optimum point, encapsulation efficiency, particle size, and zeta potential were evaluated to be 61.8%, 323 nm, and 25 mV, respectively. The effect of temperature and pH on the enzyme activity was evaluated, and the results showed that encapsulated enzyme had higher activity at various pH and temperature in comparison with the free enzyme. Also, the enzyme release data in all pH values were fitted to Korsmeyer-Peppas model and the n exponent indicated that the release mechanism was Fickian. The electrostatic interactions between enzyme, alginate, and chitosan were confirmed by infrared spectroscopy. No statistical difference was found between the Km and Vmax of encapsulated and free enzymes.

PMID:33691212 | DOI:10.1016/j.foodchem.2021.129325

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Nevin Manimala Statistics

Democracy, governance, and road safety

Accid Anal Prev. 2021 Mar 7;154:106067. doi: 10.1016/j.aap.2021.106067. Online ahead of print.

ABSTRACT

Countries scoring high on the Democracy Index developed by The Economist Intelligence Unit have fewer traffic fatalities per 100,000 inhabitants than countries scoring low on this index. The statistical relationship between democracy score and fatalities per 100,000 inhabitants is statistically highly significant and robust with respect to control for potentially confounding factors. A similar relationship exists between democracy score and the number of traffic fatalities per 100,000 motor vehicles. The statistical relationship between level of democracy and level of road safety is strong, although the analyses reported in this paper do not justify a causal interpretation of the relationship. Changes over time in government effectiveness (one of the indicators of the World Governance Index developed by the World Bank) are weakly associated with changes in road safety performance.

PMID:33691228 | DOI:10.1016/j.aap.2021.106067

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Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution

EBioMedicine. 2021 Mar 7;65:103262. doi: 10.1016/j.ebiom.2021.103262. Online ahead of print.

ABSTRACT

BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic has cost lives and economic hardships globally. Various studies have found a number of different factors, such as hyperinflammation and exhausted/suppressed T cell responses to the etiological SARS coronavirus-2 (SARS-CoV-2), being associated with severe COVID-19. However, sieving the causative from associative factors of respiratory dysfunction has remained rudimentary.

METHODS: We postulated that the host responses causative of respiratory dysfunction would track most closely with disease progression and resolution and thus be differentiated from other factors that are statistically associated with but not causative of severe COVID-19. To track the temporal dynamics of the host responses involved, we examined the changes in gene expression in whole blood of 6 severe and 4 non-severe COVID-19 patients across 15 different timepoints spanning the nadir of respiratory function.

FINDINGS: We found that neutrophil activation but not type I interferon signaling transcripts tracked most closely with disease progression and resolution. Moreover, transcripts encoding for protein phosphorylation, particularly the serine-threonine kinases, many of which have known T cell proliferation and activation functions, were increased after and may thus contribute to the upswing of respiratory function. Notably, these associative genes were targeted by dexamethasone, but not methylprednisolone, which is consistent with efficacy outcomes in clinical trials.

INTERPRETATION: Our findings suggest neutrophil activation as a critical factor of respiratory dysfunction in COVID-19. Drugs that target this pathway could be potentially repurposed for the treatment of severe COVID-19.

FUNDING: This study was sponsored in part by a generous gift from The Hour Glass. EEO and JGL are funded by the National Medical Research Council of Singapore, through the Clinician Scientist Awards awarded by the National Research Foundation of Singapore.

PMID:33691247 | DOI:10.1016/j.ebiom.2021.103262

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Evaluation of ten cone-beam computed tomography devices for endodontic assessment of fine anatomical structures

J Endod. 2021 Mar 7:S0099-2399(21)00150-3. doi: 10.1016/j.joen.2021.02.013. Online ahead of print.

ABSTRACT

AIM: To classify ten CBCT devices, by using a ranking model, according to the detection of fine endodontic structures.

METHODS: A dedicated dentate anthropomorphic phantom was scanned two times using ten CBCT devices: without any metal (metal-free condition) and with an endodontically treated tooth containing a metallic post (metal condition). A reference image acquired on an industrial micro-CT scanner was used to register all CBCT images, yielding corresponding anatomic slices. Afterwards, three experienced observers assessed all acquired CBCT images for their ability to assess narrow canal, isthmus and apical delta ramification following a categorical rank from 1 (best) to 10 (worst). Fleiss Kappa statistics were used to calculate intra- and interobserver agreements for each CBCT device separately. Based on the observers` scores, general linear mixed models were applied to compare image quality among different CBCTs for performing endodontic diagnostic tasks (α = .05).

RESULTS: The ten CBCT devices performed differently for the evaluated endodontic tasks (P < .05), with three devices performing better for endodontic feature detection. Yet, in the presence of metal, only two devices were able to keep a high level of endodontic feature detection.

CONCLUSIONS: The evaluated endodontic tasks were CBCT device-dependent, and its detection was influenced by the presence of metal.

PMID:33691170 | DOI:10.1016/j.joen.2021.02.013

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Early receptive and expressive lexicons and language and pre-literacy skills at 5;0 years – A longitudinal study

Early Hum Dev. 2021 Mar 3;156:105345. doi: 10.1016/j.earlhumdev.2021.105345. Online ahead of print.

ABSTRACT

BACKGROUND: The long-term associations between early receptive/expressive lexical skills and later language/pre-literacy skills require clarification.

AIMS: To study the association between and predictive values of early receptive/expressive lexical skills and language/pre-literacy skills at 5;0 years, and to examine the language profiles at 5;0 years of children with weak receptive language/expressive lexical skills at 2;0 years.

PARTICIPANTS AND METHODS: The participants were 66 monolingual children. Their lexical skills were measured using the Finnish short-form version of the MacArthur-Bates Communicative Development Inventories at 1;6 and 2;0 years. Receptive language skills were measured at 2;0 years using the Reynell Developmental Language Scales III. A broader assessment at 5;0 years measured lexical, phonological, morphological and pre-literacy skills.

RESULTS: Significant associations between receptive/expressive lexical skills at 1;6 years and language and pre-literacy skills at 5;0 years were found. Both receptive language and expressive lexical development measured at 2;0 years were greatly and relatively evenly associated with language and pre-literacy skills at 5;0 years. Lexicon/language variables at 1;6 years and 2;0 years had statistically significant predictive values for general language and pre-literacy scores at 5;0 years. The best models that included early lexical predictors explained 20-34% of later language/literacy outcome. Weak skills at 2;0 years proposed vulnerability in language and pre-literacy skills at 5;0 years.

CONCLUSIONS: Language and pre-literacy skills at 5;0 years can to some extent be explained by early receptive language and/or expressive lexical development. Further assessment and/or follow-up is important for children who have had weak language/lexical skills at 2;0 years.

PMID:33691196 | DOI:10.1016/j.earlhumdev.2021.105345

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Comparative analysis of chemical components in different parts of Epimedium Herb

J Pharm Biomed Anal. 2021 Feb 17;198:113984. doi: 10.1016/j.jpba.2021.113984. Online ahead of print.

ABSTRACT

Epimedium herb is a well-known traditional Chinese medicine (TCM) that is used for treating kidney-yang deficiency, impotence and rheumatism, and flavonoids are the main active ingredients. The leaves and rhizomes of Epimedium herb are two separate kinds of medicinal materials with different functional indications and clinical applications. This study aimed to comprehensively analyze the chemical components of different parts of the herb from three Epimedium species (Epimedium sagittatum, E. pubescens and E. myrianthum) by using ultra high-performance liquid chromatography coupled with photo-diode array and quadrupole time-of-flight mass spectrometry (UHPLC-PDA-Q-TOF/MS) and multivariate statistical analysis to clarify the differences. Firstly, the workflow of UHPLC-Q-TOF/MS combined with UNIFI informatics was developed for characterizing the chemical compounds in different parts of Epimedium herb. Based on the exact mass information, the fragmentation characteristics and the retention times of compounds, all chromatographic peaks (74 chemical components) were identified. Secondly, 21 potential chemical markers for differentiating different parts of Epimedium herb were selected through PCA and PLS-DA analysis. The characteristic components in the leaves included flavonoids with Anhydroicaritin (type A, C-4′ linked methoxy) as the backbone, and the characteristic components in the stems and rhizomes were Magnoline and flavonoids with Demethylanhydroicaritin (type B, C-4′ linked hydroxyl) as the backbone. Thirdly, the UHPLC-PDA combined with heatmap visualization was employed to clarify the distribution of chemical components with high content in different parts of Epimedium herb. The results showed clear differences in the contents of chemical components in leaves, stems and rhizomes. The levels of flavonoids with Anhydroicaritin backbone were high in the leaves, and levels of flavonoids with Demethylanhydroicaritin backbone were high in the rhizomes. The levels of Magnoline in stems and rhizomes were higher than that in leaves. The contents of most of the compounds in stems remained low. The leaves and the other two parts (stems and rhizomes) can be distinguished by qualitative and semi-quantitative analysis of Magnoline and Epimedoside A (type B backbone). These results indicated that the different plant parts of Epimedium herb can be quickly and accurately distinguished by this method, establishing a foundation for the application of Epimedium herb.

PMID:33691203 | DOI:10.1016/j.jpba.2021.113984

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The methodological quality is insufficient in clinical practice guidelines in the context of COVID-19: systematic review

J Clin Epidemiol. 2021 Mar 7:S0895-4356(21)00077-9. doi: 10.1016/j.jclinepi.2021.03.005. Online ahead of print.

ABSTRACT

KEY FINDINGS: Despite clear scope, most guidelines for SARS CoV-2 infections and for other care in the context of COVID-19 fell short of basic methodological standards. Only 4% were based on a systematic literature search and a structured consensus process by representative experts (classified as the highest methodological quality). Patients were included in the development of one guideline. A process for regular updates was described in 14%. What this adds to what is known: Our study explored if basic methodological standards of guideline development have been met in the published clinical practice guidelines related to COVID-19. What is the implication/what should change now: An insufficient consideration of appropriate methodologies in the guideline development process could lead to misleading information, uncertainty among the professionals, and potentially harmful actions for patients. This paper provides an important benchmark for the future assessment of the quality of COVID-19 guidelines. Abstract Objective: The number of published clinical practice guidelines related to COVID-19 has rapidly increased. This study explored if basic methodological standards of guideline development have been met in the published clinical practice guidelines related to COVID-19.

STUDY DESIGN AND SETTING: Rapid systematic review from February 1st until April 27th, 2020 using MEDLINE [PubMed], CINAHL [Ebsco], Trip and manual search, including all types of healthcare workers providing any kind of healthcare to any patient population in any setting.

RESULTS: There were 1342 titles screened and 188 guidelines included. The highest average AGREE II domain score was 89% for scope and purpose, the lowest for rigor of development (25%). Only eight guidelines (4%) were based on a systematic literature search and a structured consensus process by representative experts (classified as the highest methodological quality). The majority (156; 83%) was solely built on an informal expert consensus. A process for regular updates was described in 27 guidelines (14%). Patients were included in the development of only one guideline.

CONCLUSION: Despite clear scope, most publications fell short of basic methodological standards of guideline development. Clinicians should use guidelines that include up-to-date information, were informed by stakeholder involvement, and employed rigorous methodologies.

PMID:33691153 | DOI:10.1016/j.jclinepi.2021.03.005

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Evaluation of the In-Vitro Dissolution Permeation Systems 1 (IDAS1) as a potential tool to monitor for unexpected changes in generic medicaments in poorly regulated markets

Eur J Pharm Sci. 2021 Mar 7:105791. doi: 10.1016/j.ejps.2021.105791. Online ahead of print.

ABSTRACT

Panama, like most Latin American countries, has insufficient regulatory safeguards to ensure the safety and efficacy of all pharmaceutical products in the market, a situation that results in a two-tier system, where affluent citizens can afford innovator products while poor citizens must consume ‘generics’ of uncertain quality. Given that one lot of each drug product is analyzed every five years during registration while commercial lots are not, and since most products are not bioequivalent but simply copies or similars, there is a concern that commercial and registration lots of these ‘generics’ may not be of the same quality. The objective of this study was to assess the ability of various in vitro quality control tests to detect difference among five amlodipine products available in the Panamanian market: four ‘generics’, made in various countries, and the innovator, made in Germany and used as reference listed drug in Panama (Pan-RLD). The innovator manufactured in the United States (US-RLD) was used to compare the two RLDs. The Content Uniformity test, 30-min Dissolution test and multiple-pH Dissolution Profiles did not show any difference among the products. However, the in vitro dissolution absorption system 1 (IDAS1) showed a statistically significant difference in the amount dissolved between Pan-RLD and three out of the four ‘generics’, and significantly lower permeated amount for all the ‘generics’ compared with Pan-RLD; only US-RLD was similar to Pan-RLD. Thus, IDAS1 showed promise as a potential tool that authorities in weakly regulated markets can use to monitor for possible lot-to-lot product changes, which can help improve the quality of pharmaceutical products available to their entire populations. The significance of the similarity between the innovators made in Germany and the United States and their difference from the ‘generics’ (manufactured in other countries) is not known but deserves investigation.

PMID:33691154 | DOI:10.1016/j.ejps.2021.105791

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Risk Factors for Major Amputation for Midfoot Ulcers in Hospitalized Patients With Diabetes: A Retrospective Study

J Wound Ostomy Continence Nurs. 2021 Mar-Apr 01;48(2):163-168. doi: 10.1097/WON.0000000000000735.

ABSTRACT

PURPOSE: The purpose of this study was to investigate the risk factors for major amputation in persons hospitalized with diabetic foot ulcers involving the midfoot.

DESIGN: Retrospective study.

SUBJECTS AND SETTING: Between January 2003 and May 2019, a total of 1931 patients with diabetes were admitted to the diabetic wound center for the management of foot ulcers. Among the admitted patients, 169 patients with midfoot ulcers were included in this study. One hundred fifty-four patients (91%) healed without major amputation, while 15 patients (9%) healed post-major amputation.

METHODS: Data related to 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology, and serology were collected from patients in these 2 groups for comparison. Univariate and multivariate logistic regression analyses were performed to analyze risk factors for major amputation.

RESULTS: Among the 88 potential risk factors, 15 showed statistically significant differences between the 2 groups. Using univariate analysis of 88 potential risk factors, 8 showed statistically significant differences. Using stepwise multiple logistic regression analysis, 3 of the 8 risk factors remained statistically significant. Multivariate-adjusted odds ratios for deep ulcers invading bone, cardiac disorders, and Charcot foot were 26.718, 18.739, and 16.997, respectively.

CONCLUSION: The risk factors for major amputation in patients hospitalized with diabetic midfoot ulcers included deep ulcers invading the bone, cardiac disorders, and Charcot foot.

PMID:33690250 | DOI:10.1097/WON.0000000000000735

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The Bayesian reconstruction and the evolutionary history of Salivirus type 1 and type 2: the worldwide spreading

J Infect Dev Ctries. 2021 Mar 7;15(2):280-288. doi: 10.3855/jidc.12141.

ABSTRACT

INTRODUCTION: Salivirus (SalV) represents an emerging problem in public health especially during the recent years. In this study, the Bayesian evolutionary history and the spread of the virus through the different countries have been reported.

METHODOLOGY: a database of 81 sequences of SalV structural VP1 fragment were downloaded from GenBank, aligned and manually edited by Bioedit Software. ModelTest v. 3.7 software was used to estimate the simplest evolutionary model fitting the sequence dataset. A Maximum-Likelihood tree has been generated using MEGA-X to test the “clockliness” signal using TempEst 1.5.1. The Bayesian phylogenetic tree was built by BEAST. Homology modelling was performed by SWISS-Model and protein variability evaluated by ConSurf server.

RESULTS: the phylogenetic tree showed a clade of SalV A2 and three main clades of SalV A1, revealing several infections in humans in South Korea, India, Tunisia, China, Nigeria, Ethiopia and USA. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor dated back the root of the tree to the year 1788 with the probable origin in USA. Selective pressure analysis revealed two positive selection sites, His at 100th and Leu at 116th positions that at the homology modelling resulted important to guarantee protein stability and variability. This could contribute to the development of new mutations modifying the clinical features of this evolving virus.

CONCLUSIONS: Bayesian phylogenetic and phylodynamic represented a useful tool to follow the transmission dynamic of SalV and to prevent new epidemics worldwide.

PMID:33690212 | DOI:10.3855/jidc.12141