Partial synthetic PPARƳ derivative ameliorates aorta injury in experimental diabetic rats mediated by activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR expression

Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPARα/Ƴ partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 ± 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPARƳ agonist pioglitazone and the partial synthetic PPARƳ (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPARƳ derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPARƳ derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta

Large Ascites in a Cirrhotic Patient Reveal an Isolated and Late Metastasis of Ductal Breast Cancer: A Case Study

Breast cancer is the most prevalent cancer in women worldwide, and its prevalence has increased since the introduction of screening programs. Most cases are discovered at an early stage; however, despite effective treatment, some cases progress to metastasis. The most common breast cancer metastatic locations are the bone, liver, and lungs. Ascites malignant due to peritoneal involvement is a rare manifestation of metastatic breast cancer. After 8 years of well-controlled breast cancer, we report a 54-year-old woman who presents with malignant ascites and is known to have cirrhosis of the liver

Metabolomic profile, anti-trypanosomal potential and molecular docking studies of <i>Thunbergia grandifolia</i>

Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90 μg/mL within 72 h. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves

Accuracy and Reproducibility of Voxel Based Superimposition of Cone Beam Computed Tomography Models on the Anterior Cranial Base and the Zygomatic Arches

Superimposition of serial Cone Beam Computed Tomography (CBCT) scans has become a valuable tool for three dimensional (3D) assessment of treatment effects and stability. Voxel based image registration is a newly developed semi-automated technique for superimposition and comparison of two CBCT scans. The accuracy and reproducibility of CBCT superimposition on the anterior cranial base or the zygomatic arches using voxel based image registration was tested in this study. 16 pairs of 3D CBCT models were constructed from pre and post treatment CBCT scans of 16 adult dysgnathic patients. Each pair was registered on the anterior cranial base three times and on the left zygomatic arch twice. Following each superimposition, the mean absolute distances between the 2 models were calculated at 4 regions: anterior cranial base, forehead, left and right zygomatic arches. The mean distances between the models ranged from 0.2 to 0.37 mm (SD 0.08–0.16) for the anterior cranial base registration and from 0.2 to 0.45 mm (SD 0.09–0.27) for the zygomatic arch registration. The mean differences between the two registration zones ranged between 0.12 to 0.19 mm at the 4 regions. Voxel based image registration on both zones could be considered as an accurate and a reproducible method for CBCT superimposition. The left zygomatic arch could be used as a stable structure for the superimposition of smaller field of view CBCT scans where the anterior cranial base is not visible

Viral Gastroenteritis Associated with Genogroup II Norovirus among U.S. Military Personnel in Turkey, 2009

The present study demonstrates that multiple NoV genotypes belonging to genogroup II contributed to an acute gastroenteritis outbreak at a US military facility in Turkey that was associated with significant negative operational impact. Norovirus (NoV) is an important pathogen associated with acute gastroenteritis among military populations. We describe the genotypes of NoV outbreak occurred at a United States military facility in Turkey. Stool samples were collected from 37 out of 97 patients presenting to the clinic on base with acute gastroenteritis and evaluated for bacterial and viral pathogens. NoV genogroup II (GII) was identified by RT-PCR in 43% (16/37) stool samples. Phylogenetic analysis of a 260 base pair fragment of the NoV capsid gene from ten stool samples indicated the circulation of multiple and rare genotypes of GII NoV during the outbreak. We detected four GII.8 isolates, three GII.15, two GII.9 and a sole GII.10 NoV. Viral sequences could be grouped into four clusters, three of which have not been previously reported in Turkey. The fact that current NoV outbreak was caused by rare genotypes highlights the importance of norovirus strain typing. While NoV genogroup II is recognized as causative agent of outbreak, circulation of current genotypes has been rarely observed in large number of outbreaks

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

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

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

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe