Modelling Psychopathology: Towards a Transdiagnostic Understanding of Psychopathology

The scope of the current body of work addresses the matter of the paradigm of the empirically derived structure(s) of psychopathology in adults. The discussion addresses how the comorbidity or the co-occurrence of symptoms influences how the nosology of mental ill health is organized and tabulated. The first part of the thesis is a systematic literature review of empirically defined models of psychopathology that have been derived using latent modeling techniques. The narrative of over 40 years’ worth of research is discussed in terms of the nosological conceptualization of how patterns of discrete mental health symptoms occur and co-occur. Specifically, efforts were made to look into the over-arching ‘multifactorial models’ of psychopathology. In the second part of thesis a concept known as the general factor of psychopathology denoted as p, that represents a statistical summary of comorbid patterns of psychological ill health is taken further and explored in a mixed sample of patient and control participants. The hope is that this work will be taken forward in support of the current zeitgeist in the fields of psychiatry and clinical psychology which favour transdiagnsotic concepts in nosology and guide research efforts into the aetiology of mental ill health and applications thereof in the clinic

Overexpression, purification and characterization of the Aspergillus niger endoglucanase, EglA, in Pichia pastoris>/i>

Cellulases are industrially important hydrolytic enzymes applicable in the bioconversion of cellulosic biomass to simple sugars. In this work, an endoglucanase from Aspergillus niger ATCC 10574, EglA, was expressed in the methylotrophic yeast Pichia pastoris and the properties of the recombinant protein were characterized. The full length cDNA of eglA has been cloned into a pPICZαC expression vector and expressed extracellularly as a ~30 kDa recombinant protein in P. pastoris X-33. Pure EglA displayed optimum activity at 50°C and was stable between 30 and 55°C. The pH stability of this enzyme was shown to be in the range of pH 2.0 to 7.0 and optimum at pH 4.0. EglA showed the highest affinity toward β-glucan followed by carboxymethyl cellulose (CMC) with a specific activity of 63.83 and 9.47 U/mg, respectively. Very low or no detectable hydrolysis of cellobiose, laminarin, filter paper and avicel were observed. Metal ions such as Mn2+, Co2+, Zn2+, Mg2+, Ba2+, Fe2+, Ca2+ and K+ showed significant augmentation of endoglucanase activity, with manganese ions causing the highest increase in activity to about 2.7 fold when compared with the control assay, whereas Pd2+, Cu2+, SDS and EDTA showed inhibition of EglA activity.Key words: Cellulase, endoglucanase, recombinant, Aspergillus niger, Pichia pastoris

Optimizing the drying conditions of date plum (Diospyros lotus L.) to conserve its phenolic content and antioxidants for preparing a highly bioaccessible polyphenol-rich tea

This is the final version. Available from Springer via the DOI in this record. Data availability: All data supporting this study are included in this manuscript.Date plum (Diospyros lotus L.) fruits are a good source of bioactive compounds and antioxidants. Drying can increase the shelf life of the fruit and its applications in the food development industry. Optimizing the drying conditions can help to produce prime-quality dried date plum fruits and conserve nutrients including phytochemicals. This study used a two-factor graphics-optimal design to optimize convective drying considering the air velocity and drying temperature of date plum fruits. The independent factors considered included drying temperature (43.78–86.21 °C) and air velocities (0.54–1.96 m/s), and the responses included total phenolic content (TPC), total favonoid content (TFC), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazy (DPPH) radical scavenging activity of date plum fruit. The optimized drying conditions (68 °C and 1.75 m/s) resulted in desirable TPC, TFC, FRAP, and DPPH values. The fndings indicated that long drying time at low temperatures signifcantly decreased the phenolics and antioxidants. Date plum tea with diferent decoction times (5, 10, and 15 min) was prepared from fruits dried at optimum conditions. A decoction time of 5 min resulted in the highest catechin, vanillic, epicatechin, syringic acid, and quercetin-3-glucoside content, which were 2.45±0.04, 11.06±0.11, 22.03±0.11, 12.95±0.08, and 9.37±0.10 mg/L; respectively. In vitro gastrointestinal digestion revealed that the tea product can be a source of highly bioaccessible (>80%) gallic acid, catechin, vanillic acid, and quercetin-3-glucoside. Applying optimized drying conditions to dehydrate date plum fruit can be useful in preparing a highly bioaccessible polyphenol-rich tea

Drying date plum (Diospyros lotus L.) fruit: Assessing rehydration properties, antioxidant activity, and phenolic compounds

This is the final version. Available on open access from Wiley via the DOI in this recordDate plum (Diospyrus lotus L.) is an edible fruit from the Ebenaceae family, rich in nutrients, and having tremendous medicinal properties. This paper attempted to show the influence of different parameters of convective drying such as temperature (50, 60, 70, and 80°C) and air velocity (0.5, 1.0, and 1.5 m/s) on the shrinkage and microstructure, rehydration properties, antioxidant activity, and phenolic compounds of date plum. The drying caused significant changes in the color, actual size, and distribution of the fruit cells of date plum. The total phenolic content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) of fresh date plum were 0.81 ± 0.00 mg GAE/g, 0.23 ± 0.10 mg ECE/g, 7.15 ± 1.09 mmol ISE/g, and 14.92 ± 0.88 mmol/TE, respectively. The drying at 70°C had the highest values of TPC, TFC, gallic acid, chlorogenic and syringic acids, catechin, quercetin-3-glucoside, resveratrol, and DPPH. The drying air velocities showed no significant effects on the antioxidant contents and the antioxidant activity. Of the models applied to the drying kinetics, the Midilli model was found as the best model to describe the drying kinetics of date plum. In addition, the Weibull model was found as the most successful among the models applied to the rehydration kinetics of date plum. According to the achieved findings, the convective drying temperature of 70°C is the optimum temperature to produce the dehydrated date plum. Practical Application This work has revealed the drying conditions responsible for preserving the phenolic compounds, total flavonoid content, and antioxidant features of D. lotus L. The study found the optimum drying conditions, and Midilli and Weibull models were the most fitted models to describe the drying and rehydration behaviors of D. lotus L. fruits, respectively. The drying provides a reasonable value of the possibility of continuous consumption of the fruits dried afforded on off-seasons. The dried fruits are widely used for multipurpose and have been extensively used in food industries due to their rich nutraceutical and antioxidant compounds

Development and assessment of cement and concrete made of the burning of quinary by-product

The aim of this study is to evaluate the usability of new cement (NC) made by the burning of quinary by-product to make commercial binders. Chemical analysis of the by-products and NC as well as X-ray diffraction (XRD) analysis of NC, fineness, density, consistency, and setting time of NC paste, and slump in addition to compressive strength (CS) and splitting tensile strength (STS) of NC concrete (NCC) were conducted. The results suggested that chemical composition of by-products is suitable to make NC binder. The NC contains Ca3SiO5, Ca2SiO5, Ca3Al2O6, and Ca3Al2FeO10. The particles passing through the 200 um Sieve were 56% compared with 52% for Portland cement (PC). The density of the of NC was similar to that of PC. The NC needed 48% more water than PC for normal consistency. The initial and final setting-time of NC was 105 min and 225 min respectively which is much higher than that of PC (15 and 45 min). The slump, compressive strength and splitting tensile strength were slightly lower for concrete containing NC compared with that pf PC concrete. Although the CS and STS of NCC are the lowest, the rate of the CS and STS gain of NCC is greater than that of PCC. It was concluded that NC is a viable alternative to PC for the production of greener concrete

Trends in future health financing and coverage: future health spending and universal health coverage in 188 countries, 2016–40

Background: Achieving universal health coverage (UHC) requires health financing systems that provide prepaid pooled resources for key health services without placing undue financial stress on households. Understanding current and future trajectories of health financing is vital for progress towards UHC. We used historical health financing data for 188 countries from 1995 to 2015 to estimate future scenarios of health spending and pooled health spending through to 2040. Methods: We extracted historical data on gross domestic product (GDP) and health spending for 188 countries from 1995 to 2015, and projected annual GDP, development assistance for health, and government, out-of-pocket, and prepaid private health spending from 2015 through to 2040 as a reference scenario. These estimates were generated using an ensemble of models that varied key demographic and socioeconomic determinants. We generated better and worse alternative future scenarios based on the global distribution of historic health spending growth rates. Last, we used stochastic frontier analysis to investigate the association between pooled health resources and UHC index, a measure of a country's UHC service coverage. Finally, we estimated future UHC performance and the number of people covered under the three future scenarios. Findings: In the reference scenario, global health spending was projected to increase from US$10 trillion (95$20 trillion (18 trillion to 22 trillion) in 2040. Per capita health spending was projected to increase fastest in upper-middle-income countries, at 4·2% (3·4–5·1) per year, followed by lower-middle-income countries (4·0%, 3·6–4·5) and low-income countries (2·2%, 1·7–2·8). Despite global growth, per capita health spending was projected to range from only $40 (24–65) to$413 (263–668) in 2040 in low-income countries, and from $140 (90–200) to$1699 (711–3423) in lower-middle-income countries. Globally, the share of health spending covered by pooled resources would range widely, from 19·8% (10·3–38·6) in Nigeria to 97·9% (96·4–98·5) in Seychelles. Historical performance on the UHC index was significantly associated with pooled resources per capita. Across the alternative scenarios, we estimate UHC reaching between 5·1 billion (4·9 billion to 5·3 billion) and 5·6 billion (5·3 billion to 5·8 billion) lives in 2030. Interpretation: We chart future scenarios for health spending and its relationship with UHC. Ensuring that all countries have sustainable pooled health resources is crucial to the achievement of UHC. Funding: The Bill & Melinda Gates Foundation

Global burden of peripheral artery disease and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures. Methods Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed. Findings In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99·2–128·4), with a global prevalence of 1·52% (95% UI 1·33–1·72), of which 42·6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14·91% [12·41–17·87] in those aged 80–84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69·4% (64·2–74·3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles. Interpretation The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors. Funding Bill & Melinda Gates Foundation

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

Sayed M Ahmed,1 Adel Ahmed Ali,2 Ahmed MA Ali,2,3 Omiya A Hassan2,4 1Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 2Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, El-Minia Gadida, Egypt Purpose: The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Materials and methods: Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results: In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031).The pharmacokinetic results indicated that the area under the curve (AUC0–∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022). Conclusion: The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. Keywords: itopride HCl, oral drug delivery, stability study, bioavailabilit