12 research outputs found
Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver
Introduction. High-fructose, high-fat diet consumption (HFHF) is one of the primary causes of non-alcoholic fatty liver disease (NAFLD), which is due to impaired beta-oxidation or apolipoprotein secretion by hepatocytes. Activation of autophagy in hepatocytes could be a therapeutic method against hepatic complications. This study was designed to compare effects of rapamycin and intermittent fasting-inducing autophagy in rats with experimentally induced nonalcoholic fatty liver.
Material and methods. Male rats were divided into five groups: C (control, n = 6), the experimental group (EX) subdivided, EXIa (HFHF, n = 6), EXIb (recovery, n = 6), EXII (rapamycin, n = 6) and EXIII (intermittent fasting, n = 6). All rats in the experimental group received HFHF diet for 8 weeks to induce nonalcoholic-fatty liver and obesity. Then, for the next 8 weeks the animals received either a daily oral dose of rapamycin (EXII group) or to intermittent fasting (IF) for 16 hours daily (EXIII group). Blood samples were drawn, and serum TG concentration as well as ALT and AST activities were determined. Hepatic sections were examined by light and electron microscopy. LC3B immunohistochemical staining, morphometric and statistical studies were performed.
Results. Subgroups EXIa (HFHF subgroup) and EXIb (Recovery subgroup) showed marked increase in TG, ALT, and AST levels associated with loss of normal hepatic architecture, cytoplasmic vacuolations and faint LC3B immunoreactivity. Ultrathin sections exhibited many autophagosomes in hepatocytes. On the other hand, rapamycin (EXII) and IF (EXIII) showed significant improvement to a variable extent in comparison to EXI.
Conclusions. It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes
Adaptive Fuzzy Supplementary Controller for SSR Damping in a Series-Compensated DFIG-Based Wind Farm
Although using a series compensation technique in a long transmission line effectively increases the transmittable power; it may cause a sub-synchronous resonance (SSR) phenomenon. Gate-controlled series capacitor (GCSC) is an effective method for SSR damping by controlling the turn-off angle. In the previous studies, a constant supplementary damping controller (SDC) was used for controlling the turn-off angle, which can mitigate the SSR phenomenon. However, these methods can not capture the maximum transmittable power at different operating points. In this paper, a fuzzy logic controller (FLC) is proposed to compute the gain of SDC based on the wind speed and the error between the measured and reference line currents for transferring as much power as possible and damping the SSR phenomenon simultaneously. Using the MATLAB/SIMULINK program, the proposed method is tested at different operating points to validate its effectiveness and robustness. Compared to the traditional method (constant SDC), the maximum transmittable power, as well as SSR damping, is achieved in all studied cases by the proposed method (variable SDC)
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
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
Data_Sheet_2_Comparing the therapeutic potentials of Lactobacillus johnsonii vs. Lactobacillus acidophilus against vulvovaginal candidiasis in female rats: an in vivo study.xlsx
BackgroundVulvovaginal candidiasis (VVC) is a highly prevalent illness affecting women globally. Lactobacilli, which make up the majority of healthy vaginal microbiota (VMB), serve as a powerful barrier against infections. Probiotic therapy has been recommended for the treatment or prevention of VVC.Aim of workTo compare the in vivo therapeutic effects of Lactobacillus johnsonii (B-2178) vs. Lactobacillus acidophilus (LA-5®) on VVC in a rat model, particularly highlighting the immune response of the host vaginal epithelium.MethodsIn total, 30 female Sprague-Dawley rats were divided into 5 groups; Group 1: no intervention, Group 2: ovariectomy group, while animals in Groups 3–5 were subjected to ovariectomy and an intravaginal inoculation of Candida albicans (C. albicans) to establish VVC. The animals in Groups 4 and 5 received intravaginal lactobacilli treatment with L. acidophilus (LA-5®) and L. johnsonii (B-2178) strains, respectively, for 7 days. C. albicans load was measured in a vaginal lavage 1, 3, and 7 days after the stoppage of the treatment. Histological, morphometric, and immunohistochemical studies of the vaginal tissues were done. IFN-γ, IL-4, and IL-17 were measured in the vaginal tissue.ResultsBoth L. johnsonii and L. acidophilus significantly reduced C. albicans vaginal load (250 ± 77.46 and 133.33 ± 40.82 CFU/mL) compared to the count before treatment in both groups (4,850 ± 1419.51 and 4966.67 ± 852.45 CFU/mL) even after 7 days of stoppage of lactobacilli treatment. A statistically significant reduction of the pro-inflammatory cytokines IL-17 and IFN-γ was reported in both treated groups compared to the infected untreated group. L. johnsonii has a significant effect on the reduction of hyphae formation of C. albicans as well as the nuclear factor kappa B (NF-κB) immunostaining density of vaginal tissue compared to L. acidophilus. Moreover, treatment with L. johnsonii significantly minimized the epithelium damage triggered by C. albicans infection and restored normal vaginal architecture as evidenced by the histologic and morphometric studies when compared to L. acidophilus.ConclusionThrough maintaining an immune tolerant state in the vaginal epithelium and ameliorating the undesirable uncontrolled inflammatory response in the vaginal tissue, L. johnsonii (B-2178) has the potential to be utilized alone or in combination with other lactobacilli species in probiotic clinical trials to treat or prevent VVC.</p
Table_1_Comparing the therapeutic potentials of Lactobacillus johnsonii vs. Lactobacillus acidophilus against vulvovaginal candidiasis in female rats: an in vivo study.DOCX
BackgroundVulvovaginal candidiasis (VVC) is a highly prevalent illness affecting women globally. Lactobacilli, which make up the majority of healthy vaginal microbiota (VMB), serve as a powerful barrier against infections. Probiotic therapy has been recommended for the treatment or prevention of VVC.Aim of workTo compare the in vivo therapeutic effects of Lactobacillus johnsonii (B-2178) vs. Lactobacillus acidophilus (LA-5®) on VVC in a rat model, particularly highlighting the immune response of the host vaginal epithelium.MethodsIn total, 30 female Sprague-Dawley rats were divided into 5 groups; Group 1: no intervention, Group 2: ovariectomy group, while animals in Groups 3–5 were subjected to ovariectomy and an intravaginal inoculation of Candida albicans (C. albicans) to establish VVC. The animals in Groups 4 and 5 received intravaginal lactobacilli treatment with L. acidophilus (LA-5®) and L. johnsonii (B-2178) strains, respectively, for 7 days. C. albicans load was measured in a vaginal lavage 1, 3, and 7 days after the stoppage of the treatment. Histological, morphometric, and immunohistochemical studies of the vaginal tissues were done. IFN-γ, IL-4, and IL-17 were measured in the vaginal tissue.ResultsBoth L. johnsonii and L. acidophilus significantly reduced C. albicans vaginal load (250 ± 77.46 and 133.33 ± 40.82 CFU/mL) compared to the count before treatment in both groups (4,850 ± 1419.51 and 4966.67 ± 852.45 CFU/mL) even after 7 days of stoppage of lactobacilli treatment. A statistically significant reduction of the pro-inflammatory cytokines IL-17 and IFN-γ was reported in both treated groups compared to the infected untreated group. L. johnsonii has a significant effect on the reduction of hyphae formation of C. albicans as well as the nuclear factor kappa B (NF-κB) immunostaining density of vaginal tissue compared to L. acidophilus. Moreover, treatment with L. johnsonii significantly minimized the epithelium damage triggered by C. albicans infection and restored normal vaginal architecture as evidenced by the histologic and morphometric studies when compared to L. acidophilus.ConclusionThrough maintaining an immune tolerant state in the vaginal epithelium and ameliorating the undesirable uncontrolled inflammatory response in the vaginal tissue, L. johnsonii (B-2178) has the potential to be utilized alone or in combination with other lactobacilli species in probiotic clinical trials to treat or prevent VVC.</p
Data_Sheet_1_Comparing the therapeutic potentials of Lactobacillus johnsonii vs. Lactobacillus acidophilus against vulvovaginal candidiasis in female rats: an in vivo study.xlsx
BackgroundVulvovaginal candidiasis (VVC) is a highly prevalent illness affecting women globally. Lactobacilli, which make up the majority of healthy vaginal microbiota (VMB), serve as a powerful barrier against infections. Probiotic therapy has been recommended for the treatment or prevention of VVC.Aim of workTo compare the in vivo therapeutic effects of Lactobacillus johnsonii (B-2178) vs. Lactobacillus acidophilus (LA-5®) on VVC in a rat model, particularly highlighting the immune response of the host vaginal epithelium.MethodsIn total, 30 female Sprague-Dawley rats were divided into 5 groups; Group 1: no intervention, Group 2: ovariectomy group, while animals in Groups 3–5 were subjected to ovariectomy and an intravaginal inoculation of Candida albicans (C. albicans) to establish VVC. The animals in Groups 4 and 5 received intravaginal lactobacilli treatment with L. acidophilus (LA-5®) and L. johnsonii (B-2178) strains, respectively, for 7 days. C. albicans load was measured in a vaginal lavage 1, 3, and 7 days after the stoppage of the treatment. Histological, morphometric, and immunohistochemical studies of the vaginal tissues were done. IFN-γ, IL-4, and IL-17 were measured in the vaginal tissue.ResultsBoth L. johnsonii and L. acidophilus significantly reduced C. albicans vaginal load (250 ± 77.46 and 133.33 ± 40.82 CFU/mL) compared to the count before treatment in both groups (4,850 ± 1419.51 and 4966.67 ± 852.45 CFU/mL) even after 7 days of stoppage of lactobacilli treatment. A statistically significant reduction of the pro-inflammatory cytokines IL-17 and IFN-γ was reported in both treated groups compared to the infected untreated group. L. johnsonii has a significant effect on the reduction of hyphae formation of C. albicans as well as the nuclear factor kappa B (NF-κB) immunostaining density of vaginal tissue compared to L. acidophilus. Moreover, treatment with L. johnsonii significantly minimized the epithelium damage triggered by C. albicans infection and restored normal vaginal architecture as evidenced by the histologic and morphometric studies when compared to L. acidophilus.ConclusionThrough maintaining an immune tolerant state in the vaginal epithelium and ameliorating the undesirable uncontrolled inflammatory response in the vaginal tissue, L. johnsonii (B-2178) has the potential to be utilized alone or in combination with other lactobacilli species in probiotic clinical trials to treat or prevent VVC.</p
Surgical site infection after gastrointestinal surgery in children : an international, multicentre, prospective cohort study
Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.Peer reviewe
Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries
Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars (216 compared with 6 (95% confidence interval [CI]: −1) difference in costs. In India, the average cost for high FiO2 was 195 for low FiO2 leading to a −15 to −1164 compared with 93 (95% CI: −65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this
Use of Telemedicine for Post-discharge Assessment of the Surgical Wound: International Cohort Study, and Systematic Review with Meta-analysis
Objective: This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardised assessment tools are needed. Summary background data: Surgical site infection is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery. Methods: The primary outcome of this study was surgical site infection reported up to 30-days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analysed primary data from an international cohort study of adult patients undergoing abdominal surgery who were discharged from hospital before 30-days after surgery. The second part combined this data with the results of a systematic review to perform a meta-analysis of all available data conducted in accordance with PRIMSA guidelines (PROSPERO:192596). Results: The cohort study included 15,358 patients from 66 countries (8069 high, 4448 middle, 1744 low income). Of these, 6907 (45.0%) were followed up using telemedicine. The SSI rate reported using telemedicine was slightly lower than with in-person follow-up (13.4% vs. 11.1%, P<0.001), which persisted after risk adjustment in a mixed-effects model (adjusted odds ratio: 0.73, 95% confidence interval 0.63-0.84, P<0.001). This association was consistent across sensitivity and subgroup analyses, including a propensity-score matched model. In nine eligible non-randomised studies identified, a pooled mean of 64% of patients underwent telemedicine follow-up. Upon meta-analysis, the SSI rate reported was lower with telemedicine (odds ratio: 0.67, 0.47-0.94) than in-person (reference) follow-up (I2=0.45, P=0.12), although there a high risk of bias in included studies. Conclusions: Use of telemedicine to assess the surgical wound post-discharge is feasible, but risks underreporting of SSI. Standardised tools for remote assessment of SSI must be evaluated and adopted as telemedicine is upscaled globally