Assessing the feasibility of employing a combination of a bacteriophage-derived endolysin and spore germinants to treat relapsing clostridioides difficile infection

Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacillus and is a major cause of healthcare-associated infections. Whereas the vegetative form of the pathogen is susceptible to treatment with antibiotics, its ability to persist in the gut as antibiotic-resistant spores means that reinfection can occur in cases were the individual fails to re-establish a protective microflora. Bacteriophages and their lysins are currently being explored as treatment options due to their specificity, which minimizes the disruption to the other members of the gut microflora that are protective. The feasibility of employing recombinant endolysins to target the vegetative form of C. difficile has been demonstrated in animal models. In this study, we cloned and expressed the enzyme active domain of LysCD6356 and confirmed its ability to lyse the vegetative forms of a diverse range of clinical isolates of C. difficile, which included members of the hypervirulent 027 ribotype. Lytic activity was adversely affected by calcium, which is naturally found in the gut and is released from the spore upon germination. Our results suggests that a strategy in which the triggering of spore germination is separated in time from the application of the lysin could be developed as a strategy to reduce the risk of relapsing C. difficile infections

Post-tonsillectomy hemorrhage after bipolar diathermy vs. cold dissection surgical techniques in Alahsa region, Saudi Arabia

Introduction: Tonsillectomy is a common surgical procedure done by  totolaryngologists. Tonsillectomy is a relatively simple procedure. The concept of implementing it as a day case operation has become increasingly popular.Material and Methods: This is a cross sectional study done in Alahsa city, eastern province, Saudi Arabia during the period from January 2014 to March 2015,This study reported the postoperative hemorrhage after Bipolar diathermy and Cold dissection surgical techniques to evaluate the incidence of the hemorrhage and to identify the possible risk factors associated with its occurrence.Results: Postoperative bleeding occurred in 45 (3.6%) out of 1232 patients. Post-tonsillectomy hemorrhage according to operation technique was significantly higher among patients who underwent bipolar diathermy than cold dissection technique (p< 0.05).Conclusion: Bleeding after operation by bipolar diathermy technique was occurring more frequently within the first five days. Hemoglobin level was significantly decreased in posttonsillectomy hemorrhage

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Empowerment and human capital utilization deficit in public sector organizations: Gulf states in comparative perspective

This study of bureaucracy and organizational leadership behavior examined the strategic importance of power-influence sharing (participation) and organizational culture to human capital resource utilization and organizational effectiveness in work organizations. The analysis is based on a recent survey of Saudi public administrators (n = 390). The findings expose a disturbing “competence utilization-empowerment deficit” in the public sector. The most significant outcome of participatory decision making is a reduction in underutilization of competence and thus the attainment of cost-effective human resource development. Both participation and skill utilization were significant predicators of job satisfaction, effectiveness of decision-making, and predictability and acceptability of new policy changes. Under favorable conditions, this may lead to more effective public organizations and contribute to good governance. ^ At the same time, the study depicted a slight shift in managerial values and attitudes towards modern management and democratic institutions. This may be consistent with the theory of an emerging trend leading to a more international convergence of managerial values as suggested by universalist-convergence hypotheses. Contrary to previous studies conducted in the Middle East, the data demonstrates that respondents have greater interest in and support for participation and involvement in decision making than the popular system of consultation provides. This might coincide with improvement in management training and knowledge acquisition, growing role of private sector, and local management exposure to workings of modern and global management. ^ The implications for institutional modernization and policy human capital development are profound. The effectiveness of human capital and management development is related to effective practices and structures that support de-concentration of power-authority and knowledge-skill utilization necessary for improved performance. The problem in many institutions may not be the lack of skills/capabilities, but the absence of appropriate mechanisms to utilize them. Without such important utilization schemes, investments in capacity development do little to improve organizational performance and (sustainable) administrative development. At advanced stages of capacity development, it is essential for modernizing bureaucracies to increase influenceinformation sharing found to enhance the recognition and utilization of workforce\u27s skills and capabilities and the effectiveness/success of decision making. Without changes in bureaucratic culture and structures, additional development and knowledge building might prove inadequate and largely irrelevant to performance improvements and institutional modernization.

Effect of Exposure of RAW264.7 Macrophages to Salmonella typhimurium Components on Cell Viability, Cytoskeleton Re-arrangement and Cytokine Secretion

Innate immune system plays an important role in individual\u27s protection against pathogens and in activation of adaptive immune system. Utilizing RAW 264.7 murine macrophages as an innate immune response representative in this study, we analyzed the effect of invasive pathogen\u27s components (e.g. flagellin) on the arrangement of macrophage\u27s cytoskeleton, on viability of immune cells and on secretion of pro-inflammatory and anti-inflammatory cytokines and on fluorescence intensity of cytoskeleton after rearrangement. Additionally, we studied the similarity and differences between bacterial (Salmonella typhimurium) and synthetic TLR4 agonist (synthetic lipid-A) on viability, fluorescence intensity, cytokine secretion, and cytoskeleton rearrangements. Similarly, we studied the differences between TLR2 receptor agonist from gram-negative and the TLR2/6 receptor agonist from gram-positive bacteria. Flagellin at highest concentration (10 [micro]g/ml) decreased the macrophages viability significantly and increased the tubulin fluorescence intensity significantly. S. typhimurium\u27s LPS and highest concentration of synthetic lipid A (10 [micro]g/ml) decreased the cell viability dramatically. However, the intensity of microtubules was dramatically lower in the S. typhimurium\u27s LPS compared to synthetic lipid A at 5 and 10 [micro]g/ml concentrations. Both bacterial and synthetic TLR4 agonists elevate fluorescence intensity of microfilaments significantly. TLR2/6 agonists from grampositive bacteria decrease the cell viability more than TLR2 agonist from gram negative but not significantly; however, the fluorescence intensity of microtubules was significantly increased in TLR2 agonist in compared to TLR2/6 agonists at all concentrations. S. typhimurium at a concentration (106 cell/ml) that activates TLR4 induced production of IL-6, IL-10, and TNF-[alpha] significantly. Additionally, di-acylated lipoprotein at 5[micro]l induced very high levels of IL-10 secretion compared to control

Effect of Exposure of Raw264.7 Macrophages to Salmonella typhimuriumComponents on Cell Viability, Cytoskeleton Re-arrangement and Cytokine Secretion

Innate immune system plays an important role in individual\u27s protection against pathogens and in activation of adaptive immune system. Utilizing RAW 264.7 murine macrophages as an innate immune response representative in this study, we analyzed the effect of invasive pathogen\u27s components (e.g. flagellin) on the arrangement of macrophage\u27s cytoskeleton, on viability of immune cells and on secretion of pro-inflammatory and anti-inflammatory cytokines and on fluorescence intensity of cytoskeleton after rearrangement. Additionally, we studied the similarity and differences between bacterial (Salmonella typhimurium) and synthetic TLR4 agonist (synthetic lipid-A) on viability, fluorescence intensity, cytokine secretion, and cytoskeleton rearrangements. Similarly, we studied the differences between TLR2 receptor agonist from gram-negative and the TLR2/6 receptor agonist from gram-positive bacteria. Flagellin at highest concentration (10 [micro]g/ml) decreased the macrophages viability significantly and increased the tubulin fluorescence intensity significantly. S. typhimurium\u27s LPS and highest concentration of synthetic lipid A (10 [micro]g/ml) decreased the cell viability dramatically. However, the intensity of microtubules was dramatically lower in the S. typhimurium\u27s LPS compared to synthetic lipid A at 5 and 10 [micro]g/ml concentrations. Both bacterial and synthetic TLR4 agonists elevate fluorescence intensity of microfilaments significantly. TLR2/6 agonists from grampositive bacteria decrease the cell viability more than TLR2 agonist from gram negative but not significantly; however, the fluorescence intensity of microtubules was significantly increased in TLR2 agonist in compared to TLR2/6 agonists at all concentrations. S. typhimurium at a concentration (106 cell/ml) that activates TLR4 induced production of IL-6, IL-10, and TNF-[alpha] significantly. Additionally, di-acylated lipoprotein at 5[micro]l induced very high levels of IL-10 secretion compared to control

Depression and anxiety among high school student at Qassim Region

Background: Adolescence is a stage of changes in body and behaviour that may affect mental health. We found that no study measures the depression and anxiety in adolescence in our region, so we want to measure it and then try to improve our community. Aim: We aim to estimate the prevalence of depression and anxiety among high school students at Qassim region. Methods: A cross-sectional study done in al-Qassim region. A targeted population was secondary school students. The sample size was 1245 students. We used the questionnaire tool the Patient Health Questionnaire (PHQ-9) to assess depression in the students and the GAD7 for anxiety. The data had been gathered through MS Excel then exported to the Statistical Packages for Social Sciences (SPSS) for analyses. A P value cut-off point of 0.05 at 95% confidence interval (CI) was used to determine statistical significance. The analyses measure the association between socio-demographic and other related variables in the survey by using a Chi-square test. Result: Our study shows that depression by using (PHQ-9) among the 1245 students, 325 (26.0%) were not depressed, 423 (34%) were mildly depressed, 306 (24.6%) were moderately depressed, whereas 129 (10.4%) were moderately severe depressed and 62 (5.0%) were severely depressed. Anxiety by using the GAD-7 questionnaire, it was revealed that out of 1245 students, 455 (36.5%) of them were without anxiety, 425 (34.1%) of them were having mild anxiety, 243 (19.5%) of them were having moderate anxiety and 122 (9.8%) were having severe anxiety. Depression and anxiety, according to gender (P value <0.001), show a significant relationship. Conclusion: We have to raise the awareness of the mental health in our community as the prevalence of mental disorder has significantly increased over time. Health services should make health education for students on how they deal with stress and depression through exercise and good sleep