Molecular docking studies of an isolated angucycline of Stereospermum fimbriatum, a novel anti-MRSA agent

A novel angucycline, C1 isolated from Stereospermum fimbriatum stem bark was subjected to molecular docking studies on five main targets of penicillin-binding protein 2a (PBP2a), β-lactamase, DNA topoisomerase IV, dehydrosqualene synthase (CrtM) and sortase A (SrtA) for anti-MRSA activity. The binding sites and docking scores of known inhibitors (positive control) were compared with C1. Docking analysis was carried out by AutoDock 4.0 package. The binding site of C1 closely resembled the positive control in all screened receptors. Inhibition constant of C1 was lower than the positive control tested for PBP2a, β-lactamase, dehydrosqualene synthase and sortase A except against DNA Topoisomerase IV. Structure-activity relationship (SAR) analysis of C1 showed that 7-CO was the most significant contributor to its activity since it formed hydrogen bonds with four of the five screened receptors. Molecular docking of C1 indicated that C1 can be a good candidate for new anti-MRSA drug development

Ethical issues on using invertebrates in environmental and biomedical practices – a case study on living fossil horseshoe crab

Increasing utilization of living animals in ecological and biomedical research has drawn serious concerns in terms of animal welfare and ethical practices in animal handling. Significant attention has been given to animals of higher taxonomical hierarchy especially vertebrates such as fishes, rodents, reptiles and mammals, while ethical framework on invertebrate handling and welfare is less addressed (except for cephalopods). The definition of ‘Animal’ itself by any international consortia or Animal Research Act (ARA) does not include invertebrates as an animal entity. This is due to the lack of standard ethical framework to understand the pain and other physiological stress experienced by the invertebrate test animal. One such example would be the living fossil ‘horseshoe crab’ which is extensively bled to obtain its blue blood that is used for endotoxin quantification in biological samples. The biomedical bleeding itself leads to 15-30% post bleeding mortality of crabs, while pain and stress caused by the bleeding practice is not studied. Hence, this paper discusses the technicality of establishing standard framework for invertebrate handling. The paper also highlights the shari’ah (Islamic law) principles on scientific experimentations on animal subjects, particularly the norms related to the adoption of invertebrates in environmental and biomedical practice. Comprehensive review of ethical regulations in animal experiments, especially invertebrates, would be beneficial for revising and improving existing animal ethical practice

Pattern of Neurological Disorders among Patients Evaluated in the Emergency Department; Cross–Sectional Study

Introduction: Neurologic disorders are common reasons for emergency consultations. Most neurologic disorders seen in the emergency department (ED) are life-threatening and require urgent treatment. The goal of this study is to investigate the pattern of neurological disorders among patients evaluated in the ED. Methods: This is a cross-sectional study conducted in the ED of Mogadishu Somali Turkish Training and Research Hospital, from July 2021 to February 2022.  The clinical and epidemiological characteristics of adult patients with neurologic manifestations in the ED were evaluated. Age, gender, distribution of neurological disease manifestations, neurological examination findings, and neurological diagnoses made by consultant neurologists were assessed. Results: During the study period, 321 patients were assessed (3.7 % of all ED admissions). The majority of the patients in the study were above 50 years of age (62.6% male). Hypertension was the most common comorbidity among these patients with 122 (38%) cases, followed by diabetes mellitus with 65 (20.2%), and heart diseases with 26 (8.1%) cases. The main reasons for neurology consultations were altered mental status with 141 (44%) cases, motor weakness with 102 (31.8%), seizures with 33 (10%), headache with 17 (5.3%), and vertigo with 9 (2.8%) cases. 196 (61%) had hemiplegia, 60 (18.7%) had consciousness impairment, and 38 (11.8%) had normal neurological examination. The most frequent neurological diagnoses were ischemic strokes with 125 (39%) cases, hemorrhagic strokes with 65 (20.2%), epileptic seizures with 28 (8.7%), and metabolic encephalopathies with 13 (4%) cases. The median duration of the neurology consultations was 20 minutes. 251 (78%) of the patients were admitted to the hospital, while 70 (22%) were discharged from the emergency department. After neurology consultation, the neurology department made the most admissions with 226 (90%) cases, while 25 (10%) were admitted by other departments. Of those admitted, 186 (74.2%) were admitted to the neurology ward, and 65 (25.8%) were admitted to the intensive care unit. Conclusion: In our study, neurologic emergencies accounted for 3.7% of all emergency admissions. Stroke, epileptic seizures, cerebral venous thrombosis, encephalopathies, and acute spinal cord diseases were the most common neurological disorders.  The admission rate was very high following neurologic assessment by neurologists

Medicinal potentials of Strobilanthes crispus (l.) and Orthosiphon stamineus benth. in the management of kidney stones: a review and bibliometric analysis

Introduction In Malaysia, the consumption of tea made from the leaves of Strobilanthes crispus, Orthosiphon stamineus, and their combination is believed by the local people to alleviate kidney stone disease. Therefore, this review was conducted to validate the traditional claims based on the scientific evidences of kidney stones remedies using S crispus and O stamineus. The scientific progress that has evolved over a period of time will be examined using bibliometric analysis. Methodology The data for S crispus and O stamineus related to kidney stones were searched using the Scopus database. A total of 59 publications from 2009 to 2022 were retrieved and analysed using visualisation of similarities viewer software based on the keywords, authors, countries, institutions, and journals. The World Flora Online was used to confirm the identity of the plant species. Results The publications related to O stamineus (50) were found to be higher than S crispus (9). ‘Strobilanthes crispus, Orthosiphon stamineus, and diuretic’ were identified as the most frequently mentioned keywords. Ahmad, M. and Malaysia were the most productive author and country, respectively. Whereas Université de Metz in France and Universiti Putra Malaysia were identified as the most prominent institutions. A number of isolated compounds, including rosmarinic acid and sinensetin, were identified as diuretic agents. While eupatorine and 3′-hydroxy-5,6,7,4′-tetramethoxyflavone were discovered to prevent the formation of calcium oxalate crystals. Conclusions This study offers fresh insights into S crispus and O stamineus plants as a herbal combination for future studies in the treatment of kidney stones

Calophyllum canum : antibacterial and anticancer plant

Human have used plants as a source of medicine throughout the world since time immemorial. Today there are at least 120 distinct chemical substances derived from plants that are considered as important drugs currently in use in one or more countries in the world. In particular, 60% drugs currently in clinical use for treatment of cancer were found to be of natural origin. Calophyllum canum is a large tree which grows in South East Asia and which is popular for its timber. This plant belongs to the family Guttiferae; a family that boasts species which are rich in bioactive phytochemicals. Some species are believed to having medicinal values and are used against several diseases including anti-inflammatory, anti infectious, astringent and antipyretic. We have successfully isolated two compounds from the methanol extract of Calophyllum canum stembarks that active inhibit the growth of Staphylococcus aureus (ATCC 29213 and ATCC 25923). The cytotoxic study on the extracts revealed that the n-hexane extract had the strongest antiproliferation activity, followed by the methanol extract. n-hexane strongly inhibited the growth of TE1 and MCF7 cell lines. IC50 for n-hexane and methanol extract activity on the A549 cell line was found to be 27.96 μg/mL and 78.9 μg/mL respectively.The compounds (CE0 - CE5) isolated from ethyl acetate extract of C. canum are active to inhibit cell proliferation of human cervix adenocarcinoma cells

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)