Publications by authors named "Nazrul Islam"

199 Publications

Does anthropogenic upstream water withdrawal impact on downstream land use and livelihood changes of Teesta transboundary river basin in Bangladesh?

Environ Monit Assess 2022 Jan 6;194(2):59. Epub 2022 Jan 6.

Department of Economics, Shahjalal University of Science & Technology, Sylhet-3114, Bangladesh.

This article evaluates the impact of upstream water withdrawal on downstream land use and livelihood changes in the Teesta River basin, using a combination of geospatial and social data. Results show that water bodies gradually decreased, indicating a low volume of water discharge from upstream of the Teesta River basin due to the construction of several barrages. During the study period, a significant change in the area of water bodies was observed between 2012 and 2016, from 881 to 1123 Ha, respectively. The cropland area increased because farmers changed their cropping practice due to water scarcity and floods. Trend analyses of riverbank erosion and accretion patterns suggest an increase in accretion rates compared to the rate of riverbank erosion. A household survey was conducted using a self-administered questionnaire where 450 respondents have participated (farmers: 200 and fishermen: 250). Survey results show that most of the farmers (65.5%) and fishermen (76.8%) think that the construction of upstream barrages caused harm to them. The majority of farmers and fishermen feel water scarcity, mainly in the dry season. We found that a large number of participants in the study area are willing to change their occupations. Furthermore, participants observed that many local people are migrating or willing to migrate to other places nowadays. Our study also found that farmers who face water scarcity in their area are more likely to change their location than their counterparts, while those who face problems in their cultivation are less likely to move. On the other hand, upstream barrages, fishing effects, and getting support in crisis significantly predict fishermen's occupation changes. We believe our results provide essential information on the significance of transboundary water-sharing treaties, sustainable water resource management, and planning.
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http://dx.doi.org/10.1007/s10661-021-09726-3DOI Listing
January 2022

Recent advances on chitosan as an adjuvant for vaccine delivery.

Int J Biol Macromol 2021 Dec 30. Epub 2021 Dec 30.

Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; Centre for Immunology and Infection Control (CIIC), Queensland University of Technology (QUT), Brisbane, QLD, Australia.

Chitosan (CS) is a natural polymer derived from chitin that has wide applications in drugs, vaccines, and antigen delivery. The distinctive mucoadhesive, biocompatibility, biodegradable, and less toxic properties of chitosan compared to the currently used vaccine adjuvants made it a promising candidate for use as an adjuvant/carrier in vaccine delivery. In addition, chitosan exhibits intrinsic immunomodulating properties making it a suitable adjuvant in preparing vaccines delivery systems. Nanoparticles (NPs) of chitosan and its derivatives loaded with antigen have been shown to induce cellular and humoral responses. Versatility in the physicochemical properties of chitosan can provide an excellent opportunity to engineer antigen-specific adjuvant/delivery systems. This review discusses the recent advances of chitosan and its derivatives as adjuvants in vaccine deliveryand the published literature in the last fifteen years. The impact of physicochemical properties of chitosan on vaccine formulation has been described in detail. Applications of chitosan and its derivatives, their physicochemical properties, and mechanisms in enhancing immune responses have been discussed. Finally, challenges and future aspects of chitosan use has been pointed out.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.12.129DOI Listing
December 2021

Multilevel Deep Feature Generation Framework for Automated Detection of Retinal Abnormalities Using OCT Images.

Entropy (Basel) 2021 Dec 8;23(12). Epub 2021 Dec 8.

Department of Electronics and Computer Engineering, Ngee Ann Polytechnic, Singapore 599489, Singapore.

Optical coherence tomography (OCT) images coupled with many learning techniques have been developed to diagnose retinal disorders. This work aims to develop a novel framework for extracting deep features from 18 pre-trained convolutional neural networks (CNN) and to attain high performance using OCT images. In this work, we have developed a new framework for automated detection of retinal disorders using transfer learning. This model consists of three phases: deep fused and multilevel feature extraction, using 18 pre-trained networks and tent maximal pooling, feature selection with ReliefF, and classification using the optimized classifier. The novelty of this proposed framework is the feature generation using widely used CNNs and to select the most suitable features for classification. The extracted features using our proposed intelligent feature extractor are fed to iterative ReliefF (IRF) to automatically select the best feature vector. The quadratic support vector machine (QSVM) is utilized as a classifier in this work. We have developed our model using two public OCT image datasets, and they are named database 1 (DB1) and database 2 (DB2). The proposed framework can attain 97.40% and 100% classification accuracies using the two OCT datasets, DB1 and DB2, respectively. These results illustrate the success of our model.
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http://dx.doi.org/10.3390/e23121651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700736PMC
December 2021

Inhaled ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) nanoparticles from dry powder inhaler formulation for the potential treatment of lower respiratory tract infections.

PLoS One 2021 23;16(12):e0261720. Epub 2021 Dec 23.

Faculty of Health, Pharmacy Discipline, School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.

Lower respiratory tract infections (LRTIs) are one of the fatal diseases of the lungs that have severe impacts on public health and the global economy. The currently available antibiotics administered orally for the treatment of LRTIs need high doses with frequent administration and cause dose-related adverse effects. To overcome this problem, we investigated the development of ciprofloxacin (CIP) loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) for potential pulmonary delivery from dry powder inhaler (DPI) formulations against LRTIs. NPs were prepared using a straightforward co-assembly reaction carried out by the intermolecular hydrogen bonding among PEtOx, tannic acid (TA), and CIP. The prepared NPs were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The CIP was determined by validated HPLC and UV spectrophotometry methods. The CIP loading into the PEtOx was between 21-67% and increased loading was observed with the increasing concentration of CIP. The NP sizes of PEtOx with or without drug loading were between 196-350 nm and increased with increasing drug loading. The in vitro CIP release showed the maximum cumulative release of about 78% in 168 h with a burst release of 50% in the first 12 h. The kinetics of CIP release from NPs followed non-Fickian or anomalous transport thus suggesting the drug release was regulated by both diffusion and polymer degradation. The in vitro aerosolization study carried out using a Twin Stage Impinger (TSI) at 60 L/min air flow showed the fine particle fraction (FPF) between 34.4% and 40.8%. The FPF was increased with increased drug loading. The outcome of this study revealed the potential of the polymer PEtOx as a carrier for developing CIP-loaded PEtOx NPs as DPI formulation for pulmonary delivery against LRTIs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261720PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699692PMC
January 2022

Personality and travel intentions during and after the COVID-19 pandemic: An artificial neural network (ANN) approach.

J Bus Res 2022 Mar 8;142:400-411. Epub 2021 Dec 8.

Department of Management, School of Business & Law, University of Agder, Kristiansand, Norway.

The tourism sector has been deeply ravaged by the COVID-19 pandemic as many individuals abstained entirely from travel. Thus, before contemplating the trajectory of the sector's recovery, it is essential to understand individuals' travel intentions both during and after the pandemic. The present study contributes in this regard by examining the impact of individuals' personality traits categorised by the five-factor model, or the Big Five, on their leisure travel intentions during and after the pandemic. To this end, we utilised an artificial neural network (ANN) approach to analyse 500 responses from individuals residing in Japan. The results reveal that extraversion has the strongest relative influence on intentions to travel during the pandemic, whereas openness to experience has the strongest influence on travel intentions after the pandemic. This study is the first of its kind to examine the influence of the Big Five personality traits on travel intentions in the context of a pandemic.
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http://dx.doi.org/10.1016/j.jbusres.2021.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669890PMC
March 2022

Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19.

Heart 2021 Dec 15. Epub 2021 Dec 15.

Leicester Real World Evidence Unit, Leicester General Hospital, Leicester, UK.

Objective: Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death.

Methods: A multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death.

Results: Of 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication.

Conclusions: In hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.
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http://dx.doi.org/10.1136/heartjnl-2021-320047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678560PMC
December 2021

COVID-19 and black fungus: Analysis of the public perceptions through machine learning.

Eng Rep 2021 Nov 14:e12475. Epub 2021 Nov 14.

Department of Computer Science and Engineering Military Institute of Science and Technology (MIST) Dhaka Bangladesh.

While COVID-19 is ravaging the lives of millions of people across the globe, a second pandemic "black fungus" has surfaced robbing people of their lives especially people who are recovering from coronavirus. Thus, the objective of this article is to analyze public perceptions through sentiment analysis regarding black fungus during the COVID-19 pandemic. To attain the objective, first, a support vector machine (SVM) model, with an average AUC of 82.75%, was developed to classify user sentiments in terms of anger, fear, joy, and sad. Next, this SVM model was used to predict the class labels of the public tweets ( = 6477) related to COVID-19 and black fungus. As outcome, this article found public perceptions towards black fungus during COVID-19 pandemic belong mostly to sad (= 2370, 36.59%), followed by joy ( = 2095, 32.34%), fear ( = 1914, 29.55%) and anger ( = 98, 1.51%). This article also found that public perceptions are varied to some critical concerns like education, lockdown, hospital, oxygen, quarantine, and vaccine. For example, people mostly exhibited fear in social media about education, hospital, vaccine while some people expressed joy about education, hospital, vaccine, and oxygen. Again, it was found that mass people have an ignorance tendency to lockdown, COVID-19 restrictions, and prescribed hygiene rules although the coronavirus and black fungus infection rates broke the previous infection records.
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http://dx.doi.org/10.1002/eng2.12475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646461PMC
November 2021

Diabetes, obesity, hypertension and risk of severe COVID-19: a protocol for systematic review and meta-analysis.

BMJ Open 2021 11 26;11(11):e051711. Epub 2021 Nov 26.

Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Introduction: Previous evidence from several countries, including China, Italy, Mexico, UK and the USA, indicates that among patients with confirmed COVID-19 who were hospitalised, diabetes, obesity and hypertension might be important risk factors for severe clinical outcomes. Several preliminary systematic reviews and meta-analyses have been conducted on one or more of these non-communicable diseases, but the findings have not been definitive, and recent evidence has become available from many more populations. Thus, we aim to conduct a systematic review and meta-analysis of observational studies to assess the relationship of diabetes, obesity and hypertension with severe clinical outcomes in patients with COVID-19.

Method And Analysis: We will search 16 major databases (MEDLINE, Embase, Global Health, CAB Abstracts, PsycINFO, CINAHL, Academic Research Complete, Africa Wide Information, Scopus, PubMed Central, ProQuest Central, WHO Virtual Health Library, Homeland Security COVID-19 collection, SciFinder, Clinical Trials and Cochrane Library) for articles published between December 2019 and December 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2016 guidelines for the design and reporting the results. We will include observational studies that assess the associations of pre-existing diabetes, obesity and hypertension in patients with COVID-19 with risk of severe clinical outcomes such as intensive care unit admission, receiving mechanical ventilation or death. Stata V.16.1 and R-Studio V.1.4.1103 statistical software will be used for statistical analysis. Meta-analysis will be used to estimate the pooled risks and to assess potential heterogeneities in risks.

Ethics And Dissemination: The study was reviewed for human subjects concerns by the US CDC Center for Global Health and determined to not represent human subjects research because it uses data from published studies. We plan to publish results in a peer-reviewed journal and present at national and international conferences.

Prospero Registration Number: CRD42021204371.
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http://dx.doi.org/10.1136/bmjopen-2021-051711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628113PMC
November 2021

Quantitative proteomic analyses reveal the dynamics of protein and amino acid accumulation during soybean seed development.

Proteomics 2021 Nov 26:e2100143. Epub 2021 Nov 26.

Soybean Genomics and Improvement Laboratory, USDA Agricultural Research Service, Beltsville, Maryland, USA.

Using high throughput tandem mass tag (TMT) based tagging technique, we identified 4172 proteins in three developmental stages: early, mid, and late seed filling. We mapped the identified proteins to metabolic pathways associated with seed filling. The elevated abundance of several kinases was observed from the early to mid-stages of seed filling, indicating that protein phosphorylation was a significant event during this period. The early to late seed filling stages were characterized by an increased abundance of proteins associated with the cell wall, oil, and vacuolar-related processes. Among the seed storage proteins, 7S (β-subunit) and 11S (Gy3, Gy4, Gy5) steadily increased in abundance during early to late stages of seed filling, whereas 2S albumin exhibited a decrease in abundance during the same period. An increased abundance of proteases, senescence-associated proteins, and oil synthesis proteins was observed from the mid to late seed filling stages. The mid to late stages of seed filling was also characterized by a lower abundance of transferases, transporters, Kunitz family trypsin, and protease inhibitors. Two enzymes associated with methionine synthesis exhibited lower abundance from early to late stages. This study unveiled several essential enzymes/proteins related to amino acid and protein synthesis and their accumulation during seed development. All data can be accessed through this link: https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=38784ecbd0854bb3801afc0d89056f84. (Accession MSV000087577).
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http://dx.doi.org/10.1002/pmic.202100143DOI Listing
November 2021

Brain morphometry and diminished physical growth in Bangladeshi children growing up in extreme poverty: A longitudinal study.

Dev Cogn Neurosci 2021 Dec 26;52:101029. Epub 2021 Oct 26.

Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Department of Medicine, Boston Children's Hospital, Boston, MA, United States; Harvard Graduate School of Education, Cambridge, MA, United States; Harvard Medical School, Boston, MA, United States.

Diminished physical growth is a common marker of malnutrition and it affects approximately 200 million children worldwide. Despite its importance and prevalence, it is not clear whether diminished growth relates to brain development and general cognitive ability. Further, diminished growth is more common in areas of extreme poverty, raising the possibility that it may mediate previously shown links between socioeconomic status (SES) and brain structure. To address these gaps, 79 children growing up in an extremely poor, urban area of Bangladesh underwent MRI at age six years. Structural brain images were submitted to Mindboggle software, a Docker-compliant and high-reproducibility tool for tissue segmentation and regional estimations of volume, surface area, cortical thickness, sulcal depth, and mean curvature. Diminished growth predicted brain morphometry and mediated the link between SES and brain morphometry most consistently for subcortical and white matter subcortical volumes. Meanwhile, brain volume in left pallidum and right ventral diencephalon mediated the relationship between diminished growth and full-scale IQ. These findings offer malnutrition as one possible pathway through which SES affects brain development and general cognitive ability in areas of extreme poverty.
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http://dx.doi.org/10.1016/j.dcn.2021.101029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605388PMC
December 2021

Mobile apps for SME business sustainability during COVID-19 and onwards.

J Bus Res 2021 Oct 17;135:28-39. Epub 2021 Jun 17.

Indian Institute of Technology, Dhanbad, India.

Small and Medium-Sized Enterprises (SMEs) are struggling to cope with the business uncertainty caused by the COVID-19 pandemic. This study examines how SMEs in developing economies have used mobile apps to improve their business efficiency during the pandemic. We aim to recognize effective measures and actions taken by SMEs that have turned to mobile-app-based business to improve their sustainability during the crisis. The study bridges a literature gap by extending the Theory of Consumption Values and the Theory of Planned Behavior to SMEs that incorporate mobile-app-based business. Data was collected from 343 SMEs from three Industrial Development Corporations (IDCs) in India. Using the covariance-based structural equation modeling method, we investigated the efficiency of a conceptual model of mobile-app-based business for SMEs. The results revealed that consumer choice behavior, perceived behavior control, subjective behavior control and attitude towards the mobile app all influence SMEs' decision-making and business strategy. As such, SMEs need a powerful mobile-app-based business network to succeed in the entrepreneurial business process. Using instrumental variable analysis, we discovered that increased mobile app usage significantly improves SMEs' long-term efficiency. The analysis provides several theoretical and managerial ramifications.
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http://dx.doi.org/10.1016/j.jbusres.2021.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567207PMC
October 2021

Effects of covid-19 pandemic on life expectancy and premature mortality in 2020: time series analysis in 37 countries.

BMJ 2021 11 3;375:e066768. Epub 2021 Nov 3.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, UK.

Objective: To estimate the changes in life expectancy and years of life lost in 2020 associated with the covid-19 pandemic.

Design: Time series analysis.

Setting: 37 upper-middle and high income countries or regions with reliable and complete mortality data.

Participants: Annual all cause mortality data from the Human Mortality Database for 2005-20, harmonised and disaggregated by age and sex.

Main Outcome Measures: Reduction in life expectancy was estimated as the difference between observed and expected life expectancy in 2020 using the Lee-Carter model. Excess years of life lost were estimated as the difference between the observed and expected years of life lost in 2020 using the World Health Organization standard life table.

Results: Reduction in life expectancy in men and women was observed in all the countries studied except New Zealand, Taiwan, and Norway, where there was a gain in life expectancy in 2020. No evidence was found of a change in life expectancy in Denmark, Iceland, and South Korea. The highest reduction in life expectancy was observed in Russia (men: -2.33, 95% confidence interval -2.50 to -2.17; women: -2.14, -2.25 to -2.03), the United States (men: -2.27, -2.39 to -2.15; women: -1.61, -1.70 to -1.51), Bulgaria (men: -1.96, -2.11 to -1.81; women: -1.37, -1.74 to -1.01), Lithuania (men: -1.83, -2.07 to -1.59; women: -1.21, -1.36 to -1.05), Chile (men: -1.64, -1.97 to -1.32; women: -0.88, -1.28 to -0.50), and Spain (men: -1.35, -1.53 to -1.18; women: -1.13, -1.37 to -0.90). Years of life lost in 2020 were higher than expected in all countries except Taiwan, New Zealand, Norway, Iceland, Denmark, and South Korea. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million (95% confidence interval 26.8m to 29.5m) years of life lost more than expected (17.3 million (16.8m to 17.8m) in men and 10.8 million (10.4m to 11.3m) in women). The highest excess years of life lost per 100 000 population were observed in Bulgaria (men: 7260, 95% confidence interval 6820 to 7710; women: 3730, 2740 to 4730), Russia (men: 7020, 6550 to 7480; women: 4760, 4530 to 4990), Lithuania (men: 5430, 4750 to 6070; women: 2640, 2310 to 2980), the US (men: 4350, 4170 to 4530; women: 2430, 2320 to 2550), Poland (men: 3830, 3540 to 4120; women: 1830, 1630 to 2040), and Hungary (men: 2770, 2490 to 3040; women: 1920, 1590 to 2240). The excess years of life lost were relatively low in people younger than 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was >2000 per 100 000.

Conclusion: More than 28 million excess years of life were lost in 2020 in 31 countries, with a higher rate in men than women. Excess years of life lost associated with the covid-19 pandemic in 2020 were more than five times higher than those associated with the seasonal influenza epidemic in 2015.
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http://dx.doi.org/10.1136/bmj-2021-066768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564739PMC
November 2021

PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells.

Pharmaceutics 2021 Oct 2;13(10). Epub 2021 Oct 2.

School of Chemistry and Physics, Science and Engineering Faculty, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD 4000, Australia.

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.
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http://dx.doi.org/10.3390/pharmaceutics13101605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540390PMC
October 2021

Naturally Occurring Species and Mycotoxins in Oat Grains from Manitoba, Canada.

Toxins (Basel) 2021 09 18;13(9). Epub 2021 Sep 18.

Agriculture and Agri-Food Canada (AAFC), Morden Research and Development Centre, 101 Route 100, Morden, MB R6M 1Y5, Canada.

head blight (FHB) can lead to dramatic yield losses and mycotoxin contamination in small grain cereals in Canada. To assess the extent and severity of FHB in oat, samples collected from 168 commercial oat fields in the province of Manitoba, Canada, during 2016-2018 were analyzed for the occurrence of head blight and associated mycotoxins. Through morphological and molecular analysis, was found to be the predominant species affecting oat, followed by , , , and . Deoxynivalenol (DON) and nivalenol (NIV), type B trichothecenes, were the two most abundant mycotoxins detected in oat. Beauvericin (BEA) was also frequently detected, though at lower concentrations. Close clustering of and NIV/BEA, and DON, and and HT2/T2 (type A trichothecenes) was detected in the principal component analysis. Sampling location and crop rotation significantly impacted the concentrations of mycotoxins in oat. A phylogenetic analysis of 95 strains from Manitoba was conducted using the concatenated nucleotide sequences of , , and genes. The results indicated that all strains belong to a monophyletic lineage. Four subgroups of strains were identified; however, no correlations were observed between the grouping of strains and sample locations/crop rotations.
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http://dx.doi.org/10.3390/toxins13090670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473195PMC
September 2021

Inhaled Edoxaban dry powder inhaler formulations: Development, characterization and their effects on the coagulopathy associated with COVID-19 infection.

Int J Pharm 2021 Oct 21;608:121122. Epub 2021 Sep 21.

Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; Centre for Immunology and Infection Control (CIIC), Queensland University of Technology (QUT), Brisbane, Queensland, Australia. Electronic address:

Herein, we demonstrated the development and characterization of a dry powder inhaler (DPI) formulation of edoxaban (EDX); and investigated the in-vitro anticoagulation effect for the management of pulmonary or cerebral coagulopathy associated with COVID-19 infection. The formulations were prepared by mixing the inhalable micronized drug with a large carrier lactose and dispersibility enhancers, leucine, and magnesium stearate. The drug-excipient interaction was studied using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) methods. The drug and excipients showed no physical inter particulate interaction. The in-vitro drug aerosolization from the developed formulation was determined by a Twin Stage Impinger (TSI) at a flow rate of 60 ± 5 L /min. The amount of drug deposition was quantified by an established HPLC-UV method. The fine particle fraction (FPF) of EDX API from drug alone formulation was 7%, whereas the formulations with excipients increased dramatically to almost 7-folds up to 47%. The developed DPI formulation of EDX showed a promising in-vitro anticoagulation effect at a very low concentration. This novel DPI formulation of EDX could be a potential and effective inhalation therapy for managing pulmonary venous thromboembolism (VTE) associated with COVID-19 infection. Further studies are warranted to investigate the toxicity and clinical application of the inhaled EDX DPI formulation.
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http://dx.doi.org/10.1016/j.ijpharm.2021.121122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463814PMC
October 2021

Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K.

BMC Infect Dis 2021 Sep 4;21(1):908. Epub 2021 Sep 4.

Leicester Real World Evidence Unit, Diabetes Research Centre, Leicester General Hospital, University of Leicester, Leicester, UK.

Background: Pre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection.

Methods: We used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: (1) angina; (2) asthma; (3) atrial fibrillation; (4) cancer; (5) chronic kidney disease; (6) chronic obstructive pulmonary disease; (7) diabetes mellitus; (8) heart failure; (9) hypertension; (10) myocardial infarction; (11) peripheral vascular disease; (12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation/death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein.

Results: Among 360,283 participants, the median age was 68 [range 48-85] years, most were White (94.5%), and 1706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among older age. The highest risk of severe infection was strongly evidenced in those with CKD and diabetes (4.93 [95% CI 3.36, 7.22]).

Conclusion: The multimorbidity index may help identify individuals at higher risk for severe COVID-19 outcomes and provide guidance for tailoring effective treatment.
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http://dx.doi.org/10.1186/s12879-021-06600-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418288PMC
September 2021

Association Between Accelerometer-Assessed Physical Activity and Severity of COVID-19 in UK Biobank.

Mayo Clin Proc Innov Qual Outcomes 2021 Dec 20;5(6):997-1007. Epub 2021 Aug 20.

Diabetes Research Centre, Leicester General Hospital, University of Leicester, Leicester, United Kingdom.

Objective: To quantify the association between accelerometer-assessed physical activity and coronavirus disease 2019 (COVID-19) outcomes.

Methods: Data from 82,253 UK Biobank participants with accelerometer data (measured 2013-2015), complete covariate data, and linked COVID-19 data from March 16, 2020, to March 16, 2021, were included. Two outcomes were investigated: severe COVID-19 (positive test result from in-hospital setting or COVID-19 as primary cause of death) and nonsevere COVID-19 (positive test result from community setting). Logistic regressions were used to assess associations with moderate to vigorous physical activity (MVPA), total activity, and intensity gradient. A higher intensity gradient indicates a higher proportion of vigorous activity.

Results: Average MVPA was 48.1 (32.7) min/d. Physical activity was associated with lower odds of severe COVID-19 (adjusted odds ratio per standard deviation increase: MVPA, 0.75 [95% CI, 0.67 to 0.85]; total, 0.83 [0.74 to 0.92]; intensity, 0.77 [0.70 to 0.86]), with stronger associations in women (MVPA, 0.63 [0.52 to 0.77]; total, 0.76 [0.64 to 0.90]; intensity, 0.63 [0.53 to 0.74]) than in men (MVPA, 0.84 [0.73 to 0.97]; total, 0.88 [0.77 to 1.01]; intensity, 0.88 [0.77 to 1.00]). In contrast, when mutually adjusted, total activity was associated with higher odds of a nonsevere infection (1.10 [1.04 to 1.16]), whereas the intensity gradient was associated with lower odds (0.91 [0.86 to 0.97]).

Conclusion: Odds of severe COVID-19 were approximately 25% lower per standard deviation (∼30 min/d) MVPA. A greater proportion of vigorous activity was associated with lower odds of severe and nonsevere infections. The association between total activity and higher odds of a nonsevere infection may be through greater community engagement and thus more exposure to the virus. Results support calls for public health messaging highlighting the potential of MVPA for reducing the odds of severe COVID-19.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376658PMC
December 2021

Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort.

BMC Infect Dis 2021 Jul 31;21(1):717. Epub 2021 Jul 31.

Diabetes Research Centre, Leicester General Hospital, University of Leicester, Leicester, LE5 4PW, UK.

Background: Although age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched.

Methods: We used data from the Clinical Characterisation Protocol UK (CCP-UK) for Severe Emerging Infection developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC). Patients admitted to hospital with COVID-19 from 6th February to 12th October 2020 were included where there was a coded outcome following hospital admission. Obesity was determined by an assessment from a clinician and chronic disease by medical records. Chronic diseases included: chronic cardiac disease, hypertension, chronic kidney disease, chronic pulmonary disease, diabetes and cancer. Mutually exclusive categories of obesity, with or without chronic disease, were created. Associations with in-hospital mortality were examined across sex and age categories.

Results: The analysis included 27,624 women with 6407 (23.2%) in-hospital deaths and 35,065 men with 10,001 (28.5%) in-hospital deaths. The prevalence of chronic disease in women and men was 66.3 and 68.5%, respectively, while that of obesity was 12.9 and 11.1%, respectively. Association of obesity and chronic disease status varied by age (p < 0.001). Under 50 years of age, obesity and chronic disease were associated with in-hospital mortality within 28 days of admission in a dose-response manner, such that patients with both obesity and chronic disease had the highest risk with a hazard ratio (HR) of in-hospital mortality of 2.99 (95% CI: 2.12, 4.21) in men and 2.16 (1.42, 3.26) in women compared to patients without obesity or chronic disease. Between the ages of 50-69 years, obesity and chronic disease remained associated with in-hospital COVID-19 mortality, but survival in those with obesity was similar to those with and without prevalent chronic disease. Beyond the age of 70 years in men and 80 years in women there was no meaningful difference between those with and without obesity and/or chronic disease.

Conclusion: Obesity and chronic disease are important risk factors for in-hospital mortality in younger age groups, with the combination of chronic disease and obesity being particularly important in those under 50 years of age. These findings have implications for targeted public health interventions, vaccination strategies and in-hospital clinical decision making.
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http://dx.doi.org/10.1186/s12879-021-06466-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324452PMC
July 2021

Comparing Stop Signal Reaction Times in Alzheimer's and Parkinson's Disease.

Can J Neurol Sci 2021 Jul 29:1-10. Epub 2021 Jul 29.

Department of Neurology, RGCM Research Centre, Institute of Neurosciences, Kolkata, India.

Background: To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer's disease (AD) and Parkinson's disease (PD) and compared values with data from healthy controls.

Methods: Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm.

Result: The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022).

Conclusion: Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.
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http://dx.doi.org/10.1017/cjn.2021.184DOI Listing
July 2021

Control of Plant Viral Diseases by CRISPR/Cas9: Resistance Mechanisms, Strategies and Challenges in Food Crops.

Plants (Basel) 2021 Jun 22;10(7). Epub 2021 Jun 22.

Biotechnology Research Institute, Universiti Malaysia Sabah, Jln UMS, Kota Kinabalu 88400, Malaysia.

Protecting food crops from viral pathogens is a significant challenge for agriculture. An integral approach to genome-editing, known as CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR associated protein 9), is used to produce virus-resistant cultivars. The CRISPR/Cas9 tool is an essential part of modern plant breeding due to its attractive features. Advances in plant breeding programs due to the incorporation of Cas9 have enabled the development of cultivars with heritable resistance to plant viruses. The resistance to viral DNA and RNA is generally provided using the Cas9 endonuclease and sgRNAs (single-guide RNAs) complex, targeting particular virus and host plant genomes by interrupting the viral cleavage or altering the plant host genome, thus reducing the replication ability of the virus. In this review, the CRISPR/Cas9 system and its application to staple food crops resistance against several destructive plant viruses are briefly described. We outline the key findings of recent Cas9 applications, including enhanced virus resistance, genetic mechanisms, research strategies, and challenges in economically important and globally cultivated food crop species. The research outcome of this emerging molecular technology can extend the development of agriculture and food security. We also describe the information gaps and address the unanswered concerns relating to plant viral resistance mediated by CRISPR/Cas9.
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http://dx.doi.org/10.3390/plants10071264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309070PMC
June 2021

Greater Arterial Stiffness in Children with or without Second-generation Antipsychotic Treatment for Mental Health Disorders: Rigidité Artérielle Plus Importante Chez Les Enfants Avec ou Sans Traitement Par Antipsychotiques de la Deuxième Génération Pour des Troubles de Santé Mentale.

Can J Psychiatry 2021 07 2;66(7):667-676. Epub 2020 Dec 2.

Department of Pediatrics, BC Children's Hospital Research Institute, 8166The University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Second-generation antipsychotics (SGAs) are used for a variety of mental disorders and are associated with cardiometabolic side effects in children. The objective of this study was to assess the cardiovascular health of children with mental disorders that are SGA-treated or SGA-naive.

Methods: SGA-treated ( = 47) or SGA-naive ( = 37) children (aged 6 to 18 years) with mental disorders and control children ( = 83, no mental disorder) underwent assessment for cardiac function and morphology by echocardiography, aortic pulse wave velocity (PWV), and carotid intima-media thickness (cIMT). Body mass index (BMI) -scores, waist circumference -scores, systolic and diastolic blood pressure (BP) percentiles for height and sex, and fasting plasma glucose, insulin, triglycerides, and cholesterol were also assessed. Differences between SGA-treated, SGA-naive, and control children were assessed by linear and log-linear regression models.

Results: SGA-treated children had greater BMI -scores and overweight/obesity (BMI ≥ 85th percentile for age and sex) and hypertension than SGA-naive and control children. The PWV geometric mean was 11.1% higher in SGA-treated (95%CI, 3.95 to 18.77) and 12.9% higher in SGA-naive children (95% CI, 5.60 to 20.59) compared to controls in models adjusted for age, sex, BMI, and systolic BP percentile. Left ventricular (LV) end-diastolic dimension/body surface area (BSA), LV end-systolic dimension/BSA, and LV ejection fraction were lower in SGA-treated and SGA-naive children compared to controls in models adjusted for sex and age.

Conclusions: Children with mental disorders have greater arterial stiffness and altered cardiac structure/function than children with no mental health diagnosis. SGA treatment in children is not associated with alterations in cardiovascular structure/function.
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http://dx.doi.org/10.1177/0706743720974838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243168PMC
July 2021

Risk Factors for Developing Posttransplant Diabetes After Pediatric Kidney Transplant in a Canadian Tertiary Care Children's Hospital Between 1995 and 2016.

Can J Diabetes 2021 Jul 19;45(5):481-489. Epub 2021 May 19.

Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Posttransplant diabetes mellitus (PTDM) is a serious complication in kidney transplant recipients (KTRs) due to its negative impact on graft and patient survival. Although reported in 3% to 20% of pediatric KTRs, it has not been as well characterized in adults. In this study we describe incidence and risk factors associated with development of PTDM in pediatric KTRs.

Methods: This work is a retrospective cohort study of nondiabetic pediatric patients, aged 6 months to 19 years, who underwent a first kidney transplant during 1995 to 2016. We estimated the cumulative incidence rate and used multivariable logistic regression to identify the diabetogenic risk factors for PTDM.

Results: A total of 142 KTRs were included in this study. The cumulative incidence of PTDM was 31% and 14.1% in the first and second year posttransplant, respectively. Significant risk factors for PTDM in the first year after transplant included: dysglycemia in the first 8 to 30 days posttransplant (adjusted odds ratio [aOR], 3.02; 95% confidence interval [CI], 1.21 to 7.53; p=0.018) and use of sirolimus in the first 30 days posttransplant (aOR, 5.33; 95% CI, 1.16 to 24.35; p=0.031). No significant association was found with typical diabetogenic factors.

Conclusions: The incidence of PTDM is high among pediatric KTRs. Independent risk factors associated with PTDM included meeting the criteria for dysglycemia or diabetes and sirolimus use in the first month posttransplant. Typical diabetogenic risk factors for type 2 diabetes were not associated with increased risk. This study provides valuable information for posttransplant medical care and future research.
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http://dx.doi.org/10.1016/j.jcjd.2021.05.004DOI Listing
July 2021

Body composition and risk of heart failure: protocol for a systematic review and meta-analysis.

Open Heart 2021 06;8(1)

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.

Introduction: Although there is strong evidence of an association between general adiposity and incidence of heart failure, previous systematic reviews and meta-analyses have not reliably assessed the association of heart failure risk with other aspects of body composition (such as body fat distribution or lean mass), or between body composition and risk of heart failure subtypes. We aim to conduct a systematic review and meta-analysis of prospective studies to address these uncertainties, and inform efforts to prevent and treat heart failure.

Methods And Analysis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols statement was used as a template for this protocol. A systematic search of Medline, Embase and Global Health from database inception to present will be conducted to identify prospective studies reporting on the associations between major measures of body composition (body mass index, waist circumference, waist-hip ratio, total body fat, visceral adiposity tissue and lean mass) and risk of heart failure. Article screening and selection will be performed by two reviewers independently, and disagreements will be adjudicated by consensus or by a third reviewer. Data from eligible articles will be extracted, and article quality will be assessed using the Newcastle-Ottawa Scale. Relative risks (and 95% CIs) will be pooled in a fixed effect meta-analysis, if there is no prohibitive heterogeneity of studies as assessed using the Cochrane Q statistic and I statistic. Subgroup analyses will be by age, sex, ethnicity and heart failure subtypes. Publication bias in the meta-analysis will be assessed using Egger's test and funnel plots.

Ethics And Dissemination: This work is secondary analyses on published data and ethical approval is not required. We plan to publish results in an open-access peer-reviewed journal, present it at international and national conferences, and share the findings on social media.

Prospero Registration Number: CRD42020224584.
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http://dx.doi.org/10.1136/openhrt-2021-001632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231056PMC
June 2021

Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England.

Eur J Epidemiol 2021 Jun 16;36(6):605-617. Epub 2021 Jun 16.

Diabetes Research Centre, University of Leicester, Leicester, UK.

Ethnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves. Using data from the Office for National Statistics Public Health Data Asset, a linked dataset combining the 2011 Census with primary care and hospital records and death registrations, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and the first part of the second wave (from 1st September to 28th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. The study population included over 28.9 million individuals aged 30-100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7-376.2] and 166.8 [141.7-191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4-390.1] and 127.1 [91.1-171.3] in men and women) background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves. Between the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes.
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http://dx.doi.org/10.1007/s10654-021-00765-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206182PMC
June 2021

Development of Thiabendazole-Loaded Mesoporous Silica Nanoparticles for Cancer Therapy.

ACS Biomater Sci Eng 2021 May 30. Epub 2021 May 30.

School of Chemistry and Physics, Science and Engineering Faculty, Queensland University of Technology (QUT), 2 George Street, Brisbane, Queensland 4000, Australia.

Thiabendazole (TBZ) is an anthelmintic drug currently studied for anticancer purposes. However, due to its low solubility, its biomedical application has been limited. Using mesoporous silica nanoparticles (MSNPs), such as Mobil Composition of Matter Number 41 (MCM-41), as a drug carrier, is a promising approach to improve the solubility of low water-soluble drugs. In the present work, we aim to develop TBZ-loaded MCM-41 (TBZ MCM-41) nanoparticles to improve the solubility and the therapeutic efficacy of TBZ against prostate cancer PC-3 cells. TBZ MCM-41 nanoparticles were synthesized with a size of 215.9 ± 0.07 nm, a spherical shape, a hexagonal array of channels, and a drug loading capacity of 19.1%. The biological effects of the nanoformulation on PC-3 cells were then evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), IncuCyte live-cell imaging system, cell migration, and reactive oxygen species (ROS) assays. The results demonstrated that TBZ was released from MCM-41 nanoparticles in a controlled manner at pH values of 1.2 and 6.8. The cell viability measurements revealed that the TBZ MCM-41 nanoparticles caused a considerable 2.8-fold increase in the cytotoxicity of TBZ (IC 127.3 and 46 μM for TBZ and TBZ MCM-41 nanoparticles, respectively). The results of the proliferation assay were in agreement with those of the cell viability measurements, where the MCM-41 increased the cytotoxicity of TBZ in a concentration-dependent manner. Also, the TBZ MCM-41 nanoparticles were found to enhance the potency of the drug and inhibit PC-3 cell migration. In addition, the ROS assay confirmed that TBZ MCM-41 nanoparticles were approximately 15% more potent than TBZ to produce ROS. Overall, the results demonstrated that MCM-41 nanoparticles are a promising carrier to improve the therapeutic efficacy of TBZ against PC-3 cells and suggest evaluating the efficacy of the formulation .
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http://dx.doi.org/10.1021/acsbiomaterials.1c00066DOI Listing
May 2021

Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants.

BMC Public Health 2021 05 27;21(1):963. Epub 2021 May 27.

Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.

Background: Cardiovascular disease accounts for about one-third of all premature deaths (ie, age < 70) in Cuba. Yet, the relevance of major risk factors, including systolic blood pressure (SBP), diabetes, and body-mass index (BMI), to cardiovascular mortality in this population remains unclear.

Methods: In 1996-2002, 146,556 adults were recruited from the general population in five areas of Cuba. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to national death registries until Jan 1, 2017; in 2006-08, 24,345 participants were resurveyed. After excluding all with missing data, cardiovascular disease at recruitment, and those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate cardiovascular mortality rate ratios (RRs) at ages 35-79 years to SBP, diabetes and BMI; RR were corrected for regression dilution to give associations with long-term average (ie, 'usual') levels of SBP and BMI.

Results: After exclusions, there were 125,939 participants (mean age 53 [SD12]; 55% women). Mean SBP was 124 mmHg (SD15), 5% had diabetes, and mean BMI was 24.2 kg/m (SD3.6); mean SBP and diabetes prevalence at recruitment were both strongly related to BMI. During follow-up, there were 4112 cardiovascular deaths (2032 ischaemic heart disease, 832 stroke, and 1248 other). Cardiovascular mortality was positively associated with SBP (>=120 mmHg), diabetes, and BMI (>=22.5 kg/m): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88-2.18]), as did diabetes (2.15, 1.95-2.37), and 10 kg/m higher usual BMI (1.92, 1.64-2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively.

Conclusions: This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.
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http://dx.doi.org/10.1186/s12889-021-10911-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157418PMC
May 2021

Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries.

BMJ 2021 05 19;373:n1137. Epub 2021 May 19.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To estimate the direct and indirect effects of the covid-19 pandemic on mortality in 2020 in 29 high income countries with reliable and complete age and sex disaggregated mortality data.

Design: Time series study of high income countries.

Setting: Austria, Belgium, Czech Republic, Denmark, England and Wales, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, the Netherlands, New Zealand, Northern Ireland, Norway, Poland, Portugal, Scotland, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, and United States.

Participants: Mortality data from the Short-term Mortality Fluctuations data series of the Human Mortality Database for 2016-20, harmonised and disaggregated by age and sex.

Interventions: Covid-19 pandemic and associated policy measures.

Main Outcome Measures: Weekly excess deaths (observed deaths versus expected deaths predicted by model) in 2020, by sex and age (0-14, 15-64, 65-74, 75-84, and ≥85 years), estimated using an over-dispersed Poisson regression model that accounts for temporal trends and seasonal variability in mortality.

Results: An estimated 979 000 (95% confidence interval 954 000 to 1 001 000) excess deaths occurred in 2020 in the 29 high income countries analysed. All countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The five countries with the highest absolute number of excess deaths were the US (458 000, 454 000 to 461 000), Italy (89 100, 87 500 to 90 700), England and Wales (85 400, 83 900 to 86 800), Spain (84 100, 82 800 to 85 300), and Poland (60 100, 58 800 to 61 300). New Zealand had lower overall mortality than expected (-2500, -2900 to -2100). In many countries, the estimated number of excess deaths substantially exceeded the number of reported deaths from covid-19. The highest excess death rates (per 100 000) in men were in Lithuania (285, 259 to 311), Poland (191, 184 to 197), Spain (179, 174 to 184), Hungary (174, 161 to 188), and Italy (168, 163 to 173); the highest rates in women were in Lithuania (210, 185 to 234), Spain (180, 175 to 185), Hungary (169, 156 to 182), Slovenia (158, 132 to 184), and Belgium (151, 141 to 162). Little evidence was found of subsequent compensatory reductions following excess mortality.

Conclusion: Approximately one million excess deaths occurred in 2020 in these 29 high income countries. Age standardised excess death rates were higher in men than women in almost all countries. Excess deaths substantially exceeded reported deaths from covid-19 in many countries, indicating that determining the full impact of the pandemic on mortality requires assessment of excess deaths. Many countries had lower deaths than expected in children <15 years. Sex inequality in mortality widened further in most countries in 2020.
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http://dx.doi.org/10.1136/bmj.n1137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132017PMC
May 2021

Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization.

PLoS One 2021 13;16(4):e0249683. Epub 2021 Apr 13.

Queensland University of Technology, Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Brisbane, Queensland, Australia.

This study aims at developing and characterizing the puerarin dry powder inhaler (DPI) formulations for pulmonary delivery. The inhalable particles size (<2 μm) was accomplished by micronization and its morphology was examined by scanning electron microscopy (SEM). The puerarin-excipient interaction in powder mixtures was analyzed by using Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder Diffraction (XRD), and differential scanning calorimetry (DSC) methods. Using a Twin stage impinger (TSI), the in-vitro aerosolization of the powder formulations was carried out at a flow rate of 60 L/min and the drug was quantified by employing a validated HPLC method. No significant interactions between the drug and the excipients were observed in the powder formulations. The fine particle fraction (FPF) of the drug alone was 4.2% which has increased five to six-fold for the formulations with aerosolization enhancers. Formulation containing lactose as large carriers produced 32.7% FPF, which further increased with the addition of dispersibility enhancers, leucine and magnesium stearate (40.8% and 41.2%, respectively). The Raman and FTIR techniques are very useful tool for understanding structural integrity and stability of the puerarin in the powder formulations. The puerarin was found to be compatible with the excipients used and the developed DPI formulation may be considered as an efficient formulation for pulmonary delivery for the management of various diseases at a very low dose.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249683PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043385PMC
September 2021

Novel Pulmonary Delivery of Antiviral Drugs for Treating COVID-19 in Patients with Parkinson's Disease.

Curr Drug Deliv 2021 Mar 31. Epub 2021 Mar 31.

Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007. United States.

The COVID-19 pandemic has caused a significant burden on public health worldwide. Currently, there are limited medications for the treatment of COVID-19 in patients with Parkinson's disorder (PD). Several antiviral drugs and other pharmacotherapies have shown promise and are used by various delivery methods. Among the antiviral drugs, amantadine alone was reported to provide therapeutic benefit against COVID-19 in patients with PD. Here we propose novel strategies for pulmonary drug delivery technology of antiviral drug amantadine. As such pulmonary delivery of this drug or combination with the additional antiviral drugs could be a more effective strategy for the treatment of COVID-19-related complications in patients with PD. Furthermore, the important benefits and limitations of this novel delivery technology will be discussed.
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http://dx.doi.org/10.2174/1567201818666210331121803DOI Listing
March 2021

Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults.

EClinicalMedicine 2021 Mar 17;33:100692. Epub 2021 Mar 17.

Nuffield Department of Population Health (NDPH), University of Oxford, UK.

Background: The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba.

Methods: In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35-79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08.

Findings: After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (<1 bottle/week), but this association was almost completely attenuated on exclusion of early follow-up.

Interpretation: In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba.

Funding: Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).
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http://dx.doi.org/10.1016/j.eclinm.2020.100692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980059PMC
March 2021
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