Preparation and optimization of glyceryl monooleate-low molecular weight chitosan nanoparticles for delivery of morpholinopyrrolizine derivative

Purpose: To develop and optimize glyceryl monooleate–low-molecular-weight chitosan (GMO-LMWC) nanoparticles loaded with morpholinopyrrolizine derivative (NPM). Methods: Molecular mechanics was used to determine the main driving force for the complexation between glyceryl monooleate (GMO) and chitosan. Nanoparticles were fabricated using a modified film-rehydration method. Optimization was carried out using a statistical design approach. The effects of formulation factors (concentrations of GMO, LMWC and Tween 80) on zeta potential and particle size were investigated using a 23 factorial design. Results: A steady increase in binding energy was observed when chitosan length was increased from 22 to 142 Å, and thereafter it remained almost constant. The examined independent variables had significant effects on particle size and zeta potential. The particle size of the nanoparticles varied from 265 to 1270 nm while zeta potential was in the range of 3 – 12 mV. The optimized preparation showed a significantly low half-maximal inhibitory concentration (IC50) when compared to a free anticancer agent in the hepatocellular carcinoma (HePG-2) cell line. Conclusion: A nanoparticulate system composed of GMO and LMWC is a potential nanocarrier for delivery of morpholinopyrrolizine derivative

A Multi-Criteria Model for Sustainable Development Goals Using Fuzzy Goal Programming-Application for Egypt

This article proposes fuzzy goal programming model that combines optimal resource allocation with prospective goals for economic development, electricity consumption, employment, and greenhouse gas emission reduction in Egypt’s primary economic sectors. The presented model analyses the prospects for improvement, the effort required, and the implementation of sustainable development strategies. The model also offers valuable insights to decision makers for both strategic planning and investment allocations towards sustainable development. We validate the model by applying it to Egypt’s important economic sectors to meet the country’s 2030 sustainable development goals

The Role of PCR in the Diagnosis of Dermatophytes in Onychomycosis

Background:  Onychomycosis is a critical medical problem. This fungal infection of the nails leads to disfigurement, pain and impaired quality of life.  Given that it requires long-term expensive therapy; a proper diagnosis of this infection is greatly demanded.  Hence, study aimed at investigating the different laboratory methods used in the identification of dermatophytes implicated in onychomycosis including conventional laboratory methods (KOH preparation), Culture and PCR (multiplex). Subjects and Methods: This cross-section study included sixty-one (61) patients [ 82% females and 18% males]. All collected samples were investigated using microscopic examination and cultivation of samples. In addition, DNA extraction and PCR amplification were evaluated. Results: Distal and lateral subungual onychomycosis(DLSO) was the most common clinical types of onychomycosis represented 70 % of total cases. Pain was the most common presenting symptoms. Among the studied group, the most common fungal infections encountered were chronic paronychia, tinea pads and tinea manum (37.7%, 16.4%, and 8.2%) respectively. The 67.2% of the studied group by PCR were +ve, by culture 60.7% were +ve and finally, 73.8% were +ve by direct smear. The sensitivity of PCR in the diagnosis of lesions was 100% specificity was 83.3% and accuracy was 93.4%. Conclusion: The dermatophyte responsible for a majority of cases of onychomycosis. However, the role of NDMs should not be ignored and this may be now a consideration in evaluating and treating onychomycosis. PCR is highly sensitive methods for diagnosis of fungal infection. The application of PCR technology directly to the clinical specimens will allow early and accurate diagnosis of onychomycosis. This will permit prompt and targeted initiation of antifungal therapy. So, it is recommended to be used in the rapid diagnosis of onychomycosis. &nbsp

Evaluation of calcium magnesium silicate-date palm cellulose as a potential tablet excipient

A novel excipient was prepared from natural resources and bio-wastes such as sodium silicate, brine and date palm cellulose. The prepared excipient was water-insoluble silicate salt precipitated in date palm cellulose (WISS-DPC). The aim of this study was to evaluate the potential of this new substance as a tablet excipient. Diclofenac sodium and paracetamol tablets were manufactured using direct compression and wet granulation methods, respectively. The surface of the tablets was studied using AFM and SEM. FTIR and DSC provided a guarantee of compatibility of the excipient with the model drugs. The prepared tablets passed Pharmacopeial and Non-Pharmacopeial tests. Tablets prepared from WISS-DPC were harder, had rapid disintegration and rapidly dissolved compared to those produced from microcrystalline cellulose. The compactability of WISS-DPC was not affected by dilution with drugs or wet granulation. This new excipient could be used in pharmaceutical industry

Evaluation of calcium magnesium silicate-date palm cellulose as a potential tablet excipient

A novel excipient was prepared from natural resources and bio-wastes such as sodium silicate, brine and date palm cellulose. The prepared excipient was water-insoluble silicate salt precipitated in date palm cellulose (WISS-DPC). The aim of this study was to evaluate the potential of this new substance as a tablet excipient. Diclofenac sodium and paracetamol tablets were manufactured using direct compression and wet granulation methods, respectively. The surface of the tablets was studied using AFM and SEM. FTIR and DSC provided a guarantee of compatibility of the excipient with the model drugs. The prepared tablets passed Pharmacopeial and Non-Pharmacopeial tests. Tablets prepared from WISS-DPC were harder, had rapid disintegration and rapidly dissolved compared to those produced from microcrystalline cellulose. The compactability of WISS-DPC was not affected by dilution with drugs or wet granulation. This new excipient could be used in pharmaceutical industry

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Elsayed A Usage and Knowledge of the Over- the- Counter Medicines Among Patient Visiting Ophthalmic Hospital in Wad Medani, Sudan

Objective The aim of this work is to determine the usage pattern and knowledge of OTC medicines among Sudanese attending Ophthalmic hospital in Wad-Medani/Sudan. Methods It is a cross-sectional study in which 500 patients were surveyed. Results Participants had taken OTC medicines to treat headache, pain, allergy, heart pain, etc. General knowledge of participants is poor. Majority of respondents admitted having no knowledge about the active ingredient, the maximum dose or side effects of paracetamol. One-third of respondents had taken a dose lower or higher than the recommended one. The main reason of taking larger dose was the intensive pain. More than a half (59.0%) of respondent reported using more than one OTC medications when they had multiple symptoms. The results showed that knowledge is associated with the level of education. Regarding the sources of information, two third of respondents (68.8) get information about the non-prescription medicine from the pharmacist. Only 10.4% read information about the OTC medicines from the leaflet in the package. Conclusions In Sudan, pharmacists play major role in OTC medication safety as the illiteracy comprises high percentage.&nbsp

Formulation, characterization and in-vitro evaluation of solid lipid nanoparticles for the delivery of a new anticancer agent, 1H-pyrazolo[3,4-d] pyrimidine derivative

Purpose: To investigate the physicochemical properties and in vitro cytotoxic effect of a potent epidermal growth factor receptor-tyrosine kinase (EGFRWT-TK) inhibitor, 1H-pyrazolo [3,4-d] pyrimidine (FEP) derivative and formulated as solid lipid nanoparticles (SLNs) using stearic acid (ST) or glycerylmonostearate (GMS). Methods: The SLNs were prepared by hot homogenization and sonication method. The effect of formulation variables on particle size, zeta potential and polydispersity index (PDI) of SLNs were studied, and an optimized formulation selected. Drug-excipient interactions were assessed by differential scanning calorimetry (DSC) and Fourier Transform Infrared (FTIR). Mammary gland breast cancer (MCF-7) and human colon cancer (HCT116) human cell lines were used to evaluate the cytotoxic activity of the free and FEP-loaded SLNs. Results: The particle size of the SLNs was in the range of 138 - 819 nm, while zeta potential varied from -15 to -20 nm. FEP-loaded SLNs exhibited significant cytotoxic effect compared to the free drug and doxorubicin in the two cell lines (p < 0.05). The activity was higher in HCT116 compared with MCF-7 cells (p < 0.007). The concentration of FEP loaded SLNs, free drug and doxorubicin that showed 50 % inhibition (IC50) for breast cancer cells were 1.06 ± 0.09, 2.58 ± 0.16 and 3.75 ± 0.4 μg/ml, respectively. Conclusion: The findings show that FEP-loaded SLNs have greater in-vitro cytotoxic activity than the free FEP, and thus, might improve cancer therapy in humans