Trehalose Glycopolymer Enhances Both Solution Stability and Pharmacokinetics of a Therapeutic Protein

Biocompatible polymers such as poly(ethylene glycol) (PEG) have been successfully conjugated to therapeutic proteins to enhance their pharmacokinetics. However, many of these polymers, including PEG, only improve the in vivo lifetimes and do not protect proteins against inactivation during storage and transportation. Herein, we report a polymer with trehalose side chains (PolyProtek) that is capable of improving both the external stability and the in vivo plasma half-life of a therapeutic protein. Insulin was employed as a model biologic, and high performance liquid chromatography and dynamic light scattering confirmed that addition of trehalose glycopolymer as an excipient or covalent conjugation prevented thermal or agitation-induced aggregation of insulin. The insulin-trehalose glycopolymer conjugate also showed significantly prolonged plasma circulation time in mice, similar to the analogous insulin-PEG conjugate. The insulin-trehalose glycopolymer conjugate was active as tested by insulin tolerance tests in mice and retained bioactivity even after exposure to high temperatures. The trehalose glycopolymer was shown to be non-toxic to mice up to at least 1.6 mg/kg dosage. These results together suggest that the trehalose glycopolymer should be further explored as an alternative to PEG for long circulating protein therapeutics

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

Utilization of Various Industrial Wastes in Ordinary Concrete Under Normal Manufacturing Conditions

Abstract The main objective of the present work is to evaluate using alkaline wastewater from pot factories (recycled NaOH solutions with variant concentrations and pH values) along with waste powders possessing pozzolanic properties, such as supplementary cementitious materials and stone waste dust in concrete under normal manufacturing conditions. An extensive analysis of the chemical components and the physical properties of the used materials was achieved. Both supplementary cementitious materials and stone waste dust materials were used as 0%, 10%, 20%, or 30% partial cement replacements using either tap water or alkaline wastewater to make samples for physical, mechanical, and microstructure testing. Thermodynamic modeling was used to evaluate the effect of the flushed alkaline industrial water and the powders on the hydration products. The results showed an increase in the workability of the mixes made with alkaline wastewater, an increase in water absorption for samples made with alkaline wastewater at the age of 28 days, and a relative decrease in compressive strength at 3 and 28 days, respectively. Despite the reduction in mechanical strength, most samples made with alkaline wastewater and 10%, 20% supplementary cementitious materials, or stone waste dust materials gave an accepted concrete grade. The microstructure analysis showed a slight change in pores distribution, pores values, and hydration products at 3 and 28 days. The thermodynamic analysis provided insight into data on the effect of supplementary cementitious materials, stone waste dust materials, and alkaline wastewater on hydration products. Finally, the combination of these wastes in concrete production showed satisfactory conclusions

The renin-angiotensin system modulates endotoxic postconditioning of exacerbated renal vasoconstriction in preeclamptic offspring

Abstract We recently reported exacerbated endotoxic signs of neuroinflammation and autonomic defects in offspring of preeclamptic (PE) dams. Here, we investigated whether PE programming similarly modifies hemodynamic and renal vasoconstrictor responsiveness to endotoxemia in PE offspring and whether this interaction is modulated by gestational angiotensin 1–7 (Ang1-7). Preeclampsia was induced by gestational treatment with L-NAME. Adult offspring was challenged with lipopolysaccharides (LPS, 5 mg/kg) and systolic blood pressure (SBP) and renal vasoconstrictions were assessed 4 h later. Male, but not female, offspring of PE rats exhibited SBP elevations that were blunted by LPS. Renal vasoconstrictions induced by angiotensin II (Ang II), but not phenylephrine, were intensified in perfused kidneys of either sex. LPS blunted the heightened Ang II responses in male, but not female, kidneys. While renal expressions of AT1-receptors and angiotensin converting enzyme (ACE) were increased in PE offspring of both sexes, ACE2 was upregulated in female offspring only. These molecular effects were diminished by LPS in male offspring. Gestational Ang1-7 caused sex-unrelated attenuation of phenylephrine vasoconstrictions and preferentially downregulated Ang II responses and AT1-receptor and nuclear factor-kB (NFkB) expressions in females. Together, endotoxemia and Ang1-7 offset in sexually-related manners imbalances in renal vasoconstriction and AT1/ACE/ACE2 signaling in PE offspring

Photoresponse of porous silicon for potential optical sensing

In this work, porous silicon (P-Si) structures were fabricated by anodizing n-type monocrystalline Si into an ethanoic-HF solution. Anisotropic electrochemical etching with constant time and current density was carried out to fabricate pores and their average diameter was found to be ${\sim}700\ \text{nm}$ . Raman spectra exhibited widened peaks for red, blue, and green wavelengths. The widened photoluminescence (PL) spectrum was blue-shifted owing to the quantum confinement effect. The P-Si exhibited an energy gap of 1.80 eV and manifested a direct bandgap. The photoresponse of the fabricated P-Si based device was studied at different laser irradiation wavelengthsin the range of 400–1100 nm. The best photoresponse was observed for 785 nm wavelength and the corresponding sensitivity was determined to be 9.4%. Hence, the P-Si can potentially be used for visible range photodetectors

New <i>ent</i>-kaurane diterpenoid dimer from <i>Pulicaria inuloides</i>

<p>A new naturally occurring <i>ent</i>-kaurane diterpenoid dimer, 15β, 15′β-oxybis (<i>ent</i>-kaur-16-en-19-oic acid) (<b>1</b>) along with six known compounds, 15β-hydroxy-<i>ent</i>-kaur-16-en-19-oic acid (<b>2</b>), 15β-hydroxy-<i>ent</i>-kaur-16-en-19-oate-β-d-glucopyranoside (<b>3</b>), 6-hydroxykaempferol-3, 7-dimethyl ether (<b>4</b>), quercetagetin 3, 7, 3′-trimethyl ether (<b>5</b>), β-sitosterol (<b>6</b>) and β-sitosterol glucoside (daucosterol) (<b>7</b>) were isolated from the aerial parts of <i>Pulicaria inuloides</i> DC. Compounds <b>2</b>–<b>5</b> were isolated for the first time from genus <i>Pulicaria.</i> The structures of compounds <b>1</b>–<b>7</b> were established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with ESI-MS. The antimicrobial activity of the isolated compounds was evaluated against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i> and <i>Candida albicans</i>. Sulphorhodamine B cytotoxic assay against HepG2 (liver cancer) cell line and ABTS antioxidant assay were carried out.</p

Knowledge, Attitude, and Practice in a Sample of the Lebanese Population Regarding Cholera

The evaluation of knowledge, attitude, and practices towards an emerging disease is an essential component of public health preventive measures during an outbreak. In October 2022, an outbreak of cholera was reported in Lebanon, which is the first to be reported in the Middle Eastern country for 30 years. This study aimed to explore the level of knowledge as well as attitude and practice of the general public in Lebanon towards cholera. A self-administered structured questionnaire was distributed via an online link to individuals living in Lebanon during October&ndash;November 2022. The survey instrument comprised items to assess the sociodemographic data; questions on knowledge about cholera symptoms, transmission, and prevention; as well as attitude and practice questions. Our study involved 553 participants, with a median age of 24 years and a majority of females (72.5%). The results showed that the majority of respondents correctly identified diarrhea as a symptom of cholera and recognized the spread via contaminated water and food. Having a university level education compared with secondary school or less (adjusted odds ratio (aOR) = 2.09), being married compared with single (aOR = 1.67), and working in the medical field compared with unemployed (aOR = 4.19) were significantly associated with higher odds of having good cholera knowledge. Having good knowledge compared with having a poor level of cholera knowledge (aOR = 1.83) and older age (aOR = 1.03) were significantly associated with higher odds of having a good attitude towards cholera. The current study showed an overall high knowledge score on cholera among the Lebanese population. Nevertheless, gaps in cholera knowledge were identified and should be addressed, particularly among workers in the medical field. Thus, we recommend targeted health education to the general population that aims to strengthen the health resilience in the community