Pharmacokinetics and bioavailability of ceftiofur following intravenous and intramuscular administrations in broiler chickens

The study focussed on pharmacokinetics and bioavailability of ceftiofur (CFT) after receiving a single dose (2 mg/kg BW) through either intravenous (IV) or intramuscular (IM) injection. Eight broiler chickens, were used in a crossover design with a washout period of two weeks to analyze the behaviour of CFT. Ceftiofur concentrations in the plasma were determined by HPLC with UV detector. The pharmacokinetics of CFT was analyzed using non- compartmental analysis. Following IV injection, CFT elimination half-life (t1/2β) was 2.43 h, volume of distribution at steady state (Vdss) was 0.63 L/kg, and total body clearance (Cl) was 0.24 L/h/kg. Following a single intramuscular (IM) injection of CFT at the same dose, the drug was quickly absorbed into the bloodstream with an absorption half- life (t1/2ab) of 0.31 h. The maximum concentration of the drug in the plasma (Cmax) was 2.85 μg/mL and reached at a time (Tmax) of 0.57 h after injection and the bioavailability (F) of CFT was 96.25%. The results of the study revealed that CFT was absorbed rapidly and showed high bioavailability when administered by IM route. This suggests that CFT has a promising disposition in chickens, and its use could help determine the best dosage regimens for effective eradication of various infections in chickens

Work in Progress – Establishing a Master Program in Cyber Physical Systems: Basic Findings and Future Perspectives

© 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.This paper reports on the basic findings and future perspectives of a capacity building project funded by the European Union. The International Master of Science on Cyber Physical Systems (MS@CPS) is a collaborative project that aims to establish a master program in cyber physical systems (CPS). A consortium composed of nine partners proposed the project. Three partners are European and from Germany, UK and Sweden; while the other six partners are from the South Mediterranean region and include: Palestine, Jordan and Tunisia. The consortium is led by the University of Siegen in Germany who also manages the implementation of the work packages. CPS is an emerging engineering subject with significant economic and societal implications, which motivated the consortium to propose the establishment of a master program to offer educational and training opportunities at graduate level in the fields of CPS. In this paper, CPS as a field of study is introduced with an emphasis on its importance, especially with regard to meeting local needs. A brief description of the project is presented in conjunction with the methodology for developing the courses and their learning outcomes

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

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

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

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Notes on the decorations of central vault mosaic of Galla Placidia chapel in Ravenna, Italy.

The Galla Placidia Chapel in Ravenna, or globally known as the "Mausoleum" of Galla Placidia, is renowned for its exceptional mosaic decorations covering the surfaces of its interior walls. The entrance of the chapel represents a dramatic transition from the humble exterior to the grandeur and majesty of the interior; the chapel has retained its entire interior decoration program, which is uncommon for buildings from late antiquity. This cross-planned chapel still raises many Issues and questions that are difficult to answer decisively as a result of the lack of any contemporary documentation, so it remains purely hypothetical. The interpretation of central vault mosaics of the chapel is one of the most important issues that have long occupied the scholars over the years due to the ambiguity and distinctiveness of its elements with regard to the iconographic traditions of the time, as it is the predecessor of a decorative subject that will continue over time in the early Christian structures. The central vault mosaic consists of 567 golden stars arranged in concentric circles against a dark blue background, all orbiting a Latin gold cross represented at the vault apex, while floating, over the heap of the clouds, in the pendentives area, winged bust-figures represent the four living creatures around the celestial throne. Although the blue dome covered with stars is a decorative element known both from Roman art and even from ancient Egyptian art before it, but its significance here with the inclusion of the golden cross in the middle of the vault was not clear, especially since the meaning of the cross itself is disputed and Its orientation to the east and non-following the axis of the chapel reflects many meanings. Therefore, this paper aims to describe and analyze the artistic composition of the central vault mosaics, try to understand the meanings of its elements, and comparing it with other similar decorative elements, whether earlier from the old Egyptian and Roman times or later from the early Byzantine era

The relationship between the severity of disability and serum IL-8 in acute ischemic stroke patients

Abstract Background Stroke is the third leading cause of death and leading cause of adult disability worldwide. Long-term disability is a significant problem among survivors; post-stroke inflammation is well known to contribute to the expansion of the ischemic lesion resulting in significant morbidity and disability. To study the impact of serum level of IL-8 on severity of disability in patients with acute ischemic stroke in the first 48 h post stroke. Methods A cross-sectional case control study was conducted on 44 patients with acute ischemic stroke (in the first 48 h). The patients were subjected to full neurological examination, computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, and assessment of stroke disability using the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Measurement of the serum levels of IL-8, erythrocyte sedimentation rate, and C-reactive protein (CRP) was done. Forty-four matched control subjects for their age and sex were included for comparison of serum level of IL-8. Results The level of IL-8 was significantly higher in the patients than in the control subjects (p < 0.001).There was a statistically significant positive correlation between serum level of IL-8 and disability assessed by NIHSS (r = 0.42, p = 0.004). The patients with moderate disability showed significant higher IL-8 levels than those with minor disability (p = 0.02). Conclusion The severity of disability in early acute ischemic stroke is highly correlated to the serum level of IL-8

LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS. Expression of the selected RNAs was examined by qPCR in peripheral blood leukocytes obtained from 73 PCOS patients (41 obese and 32 non-obese) and 31 healthy controls. PCOS patients showed significantly higher expression levels of NEAT1, miR-30a-5p, AR, FST and IRS-2, with significantly lower expression levels of MALAT1 and miR-30d-5p relative to controls especially in obese versus non-obese patients. Receiver operating characteristic (ROC) curve analysis indicated that most of the selected RNAs could serve as potential early diagnostic markers for PCOS with the highest efficiency obtained upon combining NEAT1 and miR-30d-5p or MALAT1 and miR-30a-5p with either of PCOS target genes. Moreover, all addressed RNAs had been proved as potential predictors of PCOS. The obtained data of ceRNA network raised the possibility that NEAT1 overexpression may increase the expression levels of AR, FST and IRS-2 by sponging miR-30d-5p, while low expression of MALAT1 may allow higher expression of the above genes via increasing miR-30a-5p, suggesting their involvement in PCOS pathogenesis and promising role for future diagnosis and targeted therapy