Modular Multilevel Converter-Based Hvdc Transmission Systems

High-Voltage Direct Current (HVDC) transmission systems based on Voltage Source Converter (VSC) technology has attracted significant interest recently for transmitting large amounts of power over long distances using back-to-back or point-to-point configurations. VSC-HVDC has been addressed for various HV applications such as DC interconnections, Multi-Terminal HVDC Transmission (MT-HVDC), installation of offshore wind power generation such as Europe super DC grid and installation of other renewable energy sources. Several classes of VSC topologies can be employed in HVDC systems including the conventional two and three-level converters, multilevel converters, and Modular Multilevel Converters (MMCs) that has been recently introduced and investigated for HVDC applications. MMC is penetrating the modern HVDC transmission market, due to its inherent features such as scalability, modularity, and fault ride through capability. Therefore, this thesis investigates and models a point-to-point VSC-based HVDC transmission system using nine-level MMC transient model, and 25-level MMC averaged model using MATLAB/Simulink platform to meet the requirements of HVDC systems such as HV requirements and fault ride through capability. However, a point-topoint HVDC system using conventional two-level converter is modeled and simulated using MATLAB/Simulink as a starting and benchmarking model. MMC transient model employed in this study is based on Half-Bridge Sub-Modules (HB-SMs) due to its simple structure, yet, other structures are discussed. Nevertheless, balancing of the floating capacitors is one of the challenges associated with MMCs. Therefore, capacitor voltage balancing and its modeling is addressed. Then the average model of the MMC-based HVDC system is investigated. Moreover, the behavior during DC side faults is investigated, and the employment of hybrid DC circuit breakers and Hybrid Current Limiting Circuit (HCLC) are introduced for protection and limiting the DC fault current. This introduces a platform for studying large MMC-based HVDC systems in normal operation and during faults

Comparative Evaluation of Marginal Adaptation of Two Sealers with Two Different Obturation Techniques Using SEM (AN IN VITRO STUDY)

Objective To evaluate and compare the marginal adaptation of epoxy resin-based sealer (AH Plus) versus Bioceramic-based sealer (Total fill BC Sealer) to root canals that were filled by single cone technique & Cold Lateral compaction technique and utilizing scanning electron microscope (SEM). Methods Sixty recently extracted single-rooted mandibular premolars were disinfected. Access cavity preparation was performed followed by cleaning and shaping, using 2.6% NaOCl as final irrigation protocol. Samples were then equally divided into 4 different groups as follows; Group A: AH Plus with CLC technique, Group B: AH Plus with SC technique, Group C: Totalfill BC with CLC technique, and Group D: Total fill Bioceramic sealer with single cone technique. After cleaning and shaping, each sample was obturated with Gutta percha and the sealer according to group of allocation. Afterwards, Transverse sectioning of each root was done at three, six, nine millimeters from the root apex corresponding to the three thirds of the root (apical, middle and coronal thirds). The specimens have been examined under scanning electron microscope (SEM). A commercially accessible software programme (SPSS Chicago, IL, USA) was used for the statistical analysis. The mean and standard deviation were used to describe numerical data. According to data normality, the Kruskall Wallis or ANOVA test was used to compare the data. A P 0.05 significance threshold was used. Every test had two tails. Results BC sealer presented better marginal adaptation than AH Plus sealer. However, On marginal adaption, there was no discernible difference between the two examined obturation techniques. Conclusion BC sealer is a reliable and promising material that improves marginal adaptation. Keywords: AH Plus sealer, BC sealer, Cold lateral condensation, Marginal adaptation, Single cone obturation

Phenotypic detection of resistance in Staphylococcus aureus isolates: Detection of (mec A and fem A) gene in methicillin resistant Staphylococcus aureus (MRSA) by Polymerase Chain Reaction

Background: The drug resistant phenomenon is being worldwide concern especially in the last 20 years. Among the most threatening antibiotic-resistant pathogens known are strains of methicillin-resistant S. aureus ? (MRSA), they are resistant to ß-lactams and other cell-wall-active agents. In many developing countries, the situation appears gloomy due to inadequate or poor implementation of policy on infection control, lack of political will, inadequate resources including shortage of skilled manpower, poor motivation of health care workers and researchers. Objective: The present study tries to describe an accurate and quick detection for of clinically relevant antibiotic resistance gene of Staphylococcus aureus using PCR technique. Methodology: The mec A gene was amplified to characterize MRSA isolates at species level. The S. aureus ? isolates were analyzed for their susceptibility to different classes of antibiotics using the disk diffusion method. Results: Of the total 429 Staphylococcus aureus isolated, 114 (26.54%) strains were MRSA. MSRA strains were selected for PCR assay. Eighty one MRSA strains (71.05%) were mecA gene positive and thirty three (28.95%) MRSA strains were mecA negative visualized on 1% agarose gel electrophoresis. Conclusions: The PCR assay was rapid and accurate procedure for the detection mec A gene of MRSA strains as compared to the conventional methods like cutler, biochemical and microscopically since the time was taken is less and can help efficiently in infection management. Keywords: mec A, fem A, MRSA, SCC, PBP2a, PCR, genes, Staphylococcus aureu

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand. We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as inactive due to several factors. This includes lack of accurate and specific quantification methods, sample collection techniques that are inherently inaccurate and inappropriate, and a general perception that DPP4 cleavage inactivates its ligand substrates. Increasing evidence points towards many DPP4-cleaved ligands having their own bioactivity. For example, GLP-1 can work through a different receptor than GLP-1R, DPP4-cleaved GIP can function as a GIP receptor antagonist at high doses, and DPP4-cleaved PYY, NPY, and CXCL12 can have different receptor selectivity, or can bind novel, previously unrecognized receptors to their intact ligands, resulting in altered signaling and functionality. We believe that more rigorous research in this area could lead to a better understanding of DPP4’s role and the biological importance of the generation of novel cryptic ligands. This will also significantly impact our understanding of the clinical effects and side effects of DPP4-inhibitors as a class of anti-diabetic drugs that potentially have an expanding clinical relevance. This will be specifically relevant in targeting DPP4 substrate ligands involved in a variety of other major clinical acute and chronic injury/disease areas including inflammation, immunology, cardiology, stroke, musculoskeletal disease and injury, as well as cancer biology and tissue maintenance in aging

Evaluation of The Genoprotective Effect of Curcumin Against Methotrexate in Bone Marrow and Spleen Cells in Mice

Curcumin is a yellow pigment produced from the rhizomes of the Curcuma longa plant and a primary chemo preventive component of turmeric is used as a spice and food coloring ingredient. Curcumin has a large number of pharmacological activities, such as anticancer, anti-diabetic, antioxidant, anti-infectious, and anti-inflammatory properties.Investigation of the geno-protective effect of curcumin on methotrexate induces chromosomal aberrations of spleen and bone marrow cells. In this study, 32 mice were used and divided into four groups (eight mice at each group) as follows: Group1 (negative control): Dimethyl sulfoxide was given intraperitoneally to mice every day for ten days.Group2 (positive control): Mice were received a single dose (20mg/kg) of methotrexate intraperitoneally Group3: Mice were received (200mg/kg) of curcumin solution intraperitoneally for ten successive days.Group4: Mice were received (200mg/kg) of curcumin solution intraperitoneally for ten successive days and on the day 11, a single dose  of methotrexate ( 20 mg/kg ) was injected intraperitoneally . In animals treated with methotrexate, significant elevations of the chromosomal aberrations were observed along with a decline in the mitotic index. Meanwhile, there was a considerable elevation of the mitotic index and no detectable chromosomal changes in the curcumin-supplemented mice. The number of abnormal cells was reduced significantly in the curcumin-treated group in comparison with the methotrexate-treated group. The ability of curcumin to inhibit methotrexate's cytotoxic effects was shown by the compound's ability to raise the mitotic index. According to this finding, curcumin approved to be a protective agent against genotoxic effects of methotrexate. Keywords: Curcumin, Chromosomal aberrations, Methotrexate, Mitotic index, Mic

Age-related increase of kynurenine enhances miR29b-1-5p to decrease both CXCL12 signaling and the epigenetic enzyme Hdac3 in bone marrow stromal cells

Mechanisms leading to age-related reductions in bone formation and subsequent osteoporosis are still incompletely understood. We recently demonstrated that kynurenine (KYN), a tryptophan metabolite, accumulates in serum of aged mice and induces bone loss. Here, we report on novel mechanisms underlying KYN's detrimental effect on bone aging. We show that KYN is increased with aging in murine bone marrow mesenchymal stem cells (BMSCs). KYN reduces bone formation via modulating levels of CXCL12 and its receptors as well as histone deacetylase 3 (Hdac3). BMSCs responded to KYN by significantly decreasing mRNA expression levels of CXCL12 and its cognate receptors, CXCR4 and ACKR3, as well as downregulating osteogenic gene RUNX2 expression, resulting in a significant inhibition in BMSCs osteogenic differentiation. KYN's effects on these targets occur by increasing regulatory miRNAs that target osteogenesis, specifically miR29b-1-5p. Thus, KYN significantly upregulated the anti-osteogenic miRNA miR29b-1-5p in BMSCs, mimicking the up-regulation of miR-29b-1-5p in human and murine BMSCs with age. Direct inhibition of miR29b-1-5p by antagomirs rescued CXCL12 protein levels downregulated by KYN, while a miR29b-1-5p mimic further decreased CXCL12 levels. KYN also significantly downregulated mRNA levels of Hdac3, a target of miR-29b-1-5p, as well as its cofactor NCoR1. KYN is a ligand for the aryl hydrocarbon receptor (AhR). We hypothesized that AhR mediates KYN's effects in BMSCs. Indeed, AhR inhibitors (CH-223191 and 3',4'-dimethoxyflavone [DMF]) partially rescued secreted CXCL12 protein levels in BMSCs treated with KYN. Importantly, we found that treatment with CXCL12, or transfection with an miR29b-1-5p antagomir, downregulated the AhR mRNA level, while transfection with miR29b-1-5p mimic significantly upregulated its level. Further, CXCL12 treatment downregulated IDO, an enzyme responsible for generating KYN. Our findings reveal novel molecular pathways involved in KYN's age-associated effects in the bone microenvironment that may be useful translational targets for treating osteoporosis

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

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

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

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112