ALOE IRAFENSIS AN ENDEMIC PLANT OF YEMEN: PHYTOCHEMICAL SCREENING, ANTIBACTERIAL, ANTIOXIDANT, AND WOUND-HEALING ACTIVITIES

Objectives: The objectives of the study were to determine the phytochemical constituents and assess the antibacterial, antioxidant, and wound-healing properties of the methanol extracts of Aloe irafensis. Methods: Methanol extracts of A. irafensis’s latex, gel, and green skin were screened for their phytochemical constituents. All three extracts were investigated regarding their antibacterial potential using disc diffusion and microdilution assays, and their antioxidant activity using 2,2-diphenyl-1- picrylhydrazyl free-radical scavenging assay. Histopathological study of wound healing area was performed for the latex extract in male albino rats. Results: The methanol extracts of A. irafensis revealed the presence of carbohydrates, steroids, phenols, tannins, and anthrones. The latex extract showed greater inhibition zones against Staphylococcus aureus and Pseudomonas aeruginosa (24 and 17 mm, respectively) and minimum inhibitory concentration values of 1.25 and 2.50 mg/ml, respectively. The latex extract showed the highest antioxidant activity (IC50 of 65.54 μg/ml), followed by green skin (IC50 of 89.48 μg/ml). The latex extract significantly accelerated the rate of wound healing in rats (p<0.01), compared to fucidin ointment, a reference control. Histological findings showed remarkably less scar width at wound closure site in the latex extract-treated wounds. Granulation tissue contained fewer inflammatory cells and more fibroblasts in wounds treated with the latex extract compared to those treated with the vehicle. Conclusion: A. irafensis latex extract is a potential source of bioactive compounds that can be used as antioxidant, antibacterial, and wound healing agents

PHYTOCHEMICAL, ANTI-INFLAMMATORY, ANTIOXIDANT, CYTOTOXIC AND ANTIBACTERIAL STUDY OF CAPPARIS CARTILAGINEA DECNEFROM YEMEN

Objective: To investigate phytochemicals and biological activities of Capparis cartilaginea extracts.Methods: The methanolic extracts of leaves, stem and twigs of C. cartilaginea were screened for their phytochemicals. The essential oil of the leaves was hydrodistilled by a Clevenger apparatus and analyzed by gas chromatography-mass spectrometry (GC-MS). The leaves extract of C. cartilaginea was evaluated for its anti-inflammatory effect, using formalin-induced paw edema. The leaves, stem and twig extracts were assessed for their antioxidant activity, using free radical scavenging assay, cytotoxic activity, using 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and antibacterial activity, using the microdilution method.Results: All extracts of C. cartilaginea contained alkaloids, carbohydrates, protein, coumarin, phytosterols, bitter principles, phenols and tannins. The essential oil of the leaves was mainly composed of isopropyl isothiocyanate (69.4%), butane,1-isothiocyanate (26.97%) and isobutyl isothiocyanate (3.26%). The leaves extract at doses of 200 and 400 mg/kg, significantly inhibited paw edema at the 3rd h (49.1%, 54.0%, respectively) and this effect was comparable to that of diclofenac (58.87%). The leaves extract showed the highest antioxidant activity with IC50 value of 91.71 µg/ml. The twigs extract exhibited the highest cytotoxic activity against human lung carcinoma (A549) with IC50 of 57.5 µg/ml. The leaves and stem extracts exhibited antibacterial activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) of 5.0 mg/ml. Conclusion: The leaves extract of C. cartilaginea is a potential source of bioactive compounds that could have a role in anti-inflammation. Twigs extract of the C. cartilaginea possesses a potential cytotoxic effect on human lung cell line

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

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

PHYTOCHEMICAL, ANTI-INFLAMMATORY, ANTIOXIDANT, CYTOTOXIC AND ANTIBACTERIAL STUDY OF CAPPARIS CARTILAGINEA DECNEFROM YEMEN

Objective: To investigate phytochemicals and biological activities of Capparis cartilaginea extracts.Methods: The methanolic extracts of leaves, stem and twigs of C. cartilaginea were screened for their phytochemicals. The essential oil of the leaves was hydrodistilled by a Clevenger apparatus and analyzed by gas chromatography-mass spectrometry (GC-MS). The leaves extract of C. cartilaginea was evaluated for its anti-inflammatory effect, using formalin-induced paw edema. The leaves, stem and twig extracts were assessed for their antioxidant activity, using free radical scavenging assay, cytotoxic activity, using 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and antibacterial activity, using the microdilution method.Results: All extracts of C. cartilaginea contained alkaloids, carbohydrates, protein, coumarin, phytosterols, bitter principles, phenols and tannins. The essential oil of the leaves was mainly composed of isopropyl isothiocyanate (69.4%), butane,1-isothiocyanate (26.97%) and isobutyl isothiocyanate (3.26%). The leaves extract at doses of 200 and 400 mg/kg, significantly inhibited paw edema at the 3rd h (49.1%, 54.0%, respectively) and this effect was comparable to that of diclofenac (58.87%). The leaves extract showed the highest antioxidant activity with IC50 value of 91.71 µg/ml. The twigs extract exhibited the highest cytotoxic activity against human lung carcinoma (A549) with IC50 of 57.5 µg/ml. The leaves and stem extracts exhibited antibacterial activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) of 5.0 mg/ml. Conclusion: The leaves extract of C. cartilaginea is a potential source of bioactive compounds that could have a role in anti-inflammation. Twigs extract of the C. cartilaginea possesses a potential cytotoxic effect on human lung cell line.</jats:p