Oleuropein attenuates the nephrotoxic effect of sunitinib in rats: Unraveling the potential role of SIRT6/Notch-1/NLRP-3/IL-1ß axis.

Sunitinib (SUN) is a chemotherapeutic agent clinically approved for treatment of metastatic renal carcinoma. Despite its remarkable benefits, various renal toxicities have been reported that limit its clinical uses. Oleuropein (OLE) is the main polyphenolic constituent of olive tree and mediates the majority of its valuable pharmacological activities. The current study examined the probable renoprotective effects of OLE against SUN-induced nephrotoxicity. Adult male albino rats were co-treated by SUN (25 mg/kg, 3 times/week, PO) with either a drug vehicle or OLE (60 mg/kg/day, daily, PO) for four weeks. A control group comprising of age-matched rats was used. Four weeks later, blood specimens were collected to assess kidney functions. Kidneys were harvested for biochemical and histopathological analyses. Administration of SUN induced kidney dysfunction, along with marked rises in endothelin-1 (ET-1) and monocyte chemotactic protein-1 (MCP-1) levels in renal tissues. Histological abnormalities were also detected in kidneys of SUN-treated rats including glomerular and tubular interstitial congestion along with interstitial fibrosis. On molecular levels, there was a decline in renal SIRT6 expression along with significant up-regulation of Notch-1, NLRP-3, interleukin -1ß (IL-1ß) and cleaved caspsase-3. All these changes were almost alleviated by OLE co-treatment. These findings suggest the implication of SIRT6/Notch-1/NLRP3/IL-1ß axis in the pathogenesis of SUN-induced nephrotoxicity and highlight OLE as a prospective renoprotective agent during SUN chemotherapy to halt its renal toxicity likely through promotion of SIRT6 and suppression of Notch-1/NLRP3/IL-1ß signaling pathway.

Increasing Antimicrobial Resistance in World Health Organization Eastern Mediterranean Region, 2017-2019.

To better guide the regional response to antimicrobial resistance (AMR), we report the burden of AMR over time in countries in the World Health Organization Eastern Mediterranean Region. To assess the capacities of national infection prevention and control and antimicrobial stewardship programs, we analyzed data on bloodstream infections reported to the Global Antimicrobial Resistance Surveillance System during 2017-2019, data from 7 countries on nationally representative surveys of antimicrobial prescriptions, and data from 2 regional surveys. The median proportion of bloodstream infections was highest for carbapenem-resistant Acinetobacter spp. (70.3%) and lowest for carbapenem-resistant Escherichia coli (4.6%). Results of the regional assessments indicate that few countries have capacities for infection prevention and control and antimicrobial stewardship programs to prevent emergence and spread of AMR. Overall, the magnitude of the problem and the limited capacity to respond emphasize the need for regional political leadership in addressing AMR.

Management of Spontaneous Labor in Primigravidae: Labor Scale versus WHO Partograph (SLiP Trial) Randomized Controlled Trial.

OBJECTIVE: We aimed to compare maternal and neonatal outcomes of spontaneous term labor among primigravidae who were monitored by the novel labor scale versus the World Health Organization (WHO) partograph. STUDY DESIGN: A single center, double-blinded randomized trial had been conducted between July 2015 and June 2016. Nulliparous women in spontaneous labor with singleton term pregnancies were randomized to either labor scale or the WHO partograph for management of labor. Primary outcome was successful vaginal delivery. Secondary outcome included low APGAR scores, birth injuries, postpartum hemorrhage, and infection. RESULTS: One hundred ten patients were randomized (55 in each arm). Women managed with labor scale had significantly lower rate of cesarean deliveries than women managed with the partograph arm (3.6% versus 18.2%, P=0.03). There was a significant reduction in the rate and duration of oxytocin administration for augmentation of labor (21.8% versus 69.1%, P < 0.0001) and a significant increase in average 1-minute APGAR score in the labor scale group. CONCLUSION: Labor monitoring with the labor scale is associated with lower rate of cesarean section, less and shorter use of oxytocin for augmentation of labor. Monitoring of labor progress starting at 5 cm or more is also associated with lower rate of cesarean delivery.

Modeling-driven materials by design for conjugated polymers: insights into optoelectronic, conformational, and thermomechanical properties.

Conjugated polymers (CPs) have emerged as pivotal functional materials in the realm of flexible electronics and optoelectronic devices due to their unique blend of mechanical flexibility, solution processability, and tunable optoelectronic properties. This review synthesizes the latest molecular simulation-driven insights obtained from various multiscale modeling techniques, including quantum mechanics (QM), all-atomistic (AA) molecular dynamics (MD), coarse-grained (CG) modeling, and machine learning (ML), to elucidate the optoelectronic, structural, and thermomechanical properties of CPs. By integrating findings from our recent computational work with key experimental studies, we highlight the molecular mechanisms influencing the multifunctional performance of CPs. This comprehensive understanding aims to guide future research directions and applications in the modeling assisted design of high-performance CP-based materials and devices.

A portable elliptical dichroism spectrometer targeting secondary structural features of tumorous protein for pancreatic cancer detection.

Stereochemical analysis is essential for understanding the complex function of biomolecules. Various direct and indirect approaches can be used to explore the allosteric configuration. However, the size, cost, and delicate nature of these systems limit their biomedical usage. Here, we constructed elliptical dichroism (ED) spectrometer for biomedical applications, whose performance is validated by experiment and theoretical simulation (Jones/Mueller calculus and time-dependent density-functional theory). Instead of complicated control of circular polarization, ED spectrometer adopted the absorbance of left- and right-oriented elliptically polarized light. With a simplified design, we demonstrated the potential of ED spectrometry as an alternative for secondary structural analysis of biomolecules, their conformation and chirality. It not only provides a portable, low-cost alternative to the sophisticated instruments currently used for structural analysis of biomolecules but also provides superior translational features: low sample consumption(200 µl), easy operation, and multiple working modes, for noninvasive cancer detection.

Molecular Structure and Conformational Design of Donor-Acceptor Conjugated Polymers to Enable Predictable Optoelectronic Property.

Tuning the optoelectronic properties of donor-acceptor conjugated polymers (D-A CPs) is of great importance in designing various organic optoelectronic devices. However, there remains a critical challenge in precise control of bandgap through synthetic approach, since the chain conformation also affects molecular orbital energy levels. Here, D-A CPs with different acceptor units are explored that show an opposite trend in energy band gaps with the increasing length of oligothiophene donor units. By investigating their chain conformation and molecular orbital energy, it is found that the molecular orbital energy alignment between donor and acceptor units plays a crucial role in dictating the final optical bandgap of D-A CPs. For polymers with staggered orbital energy alignment, the higher HOMO with increasing oligothiophene length leads to a narrowing of the optical bandgap despite decreased chain rigidity. On the other hand, for polymers with sandwiched orbital energy alignment, the increased band gap with increasing oligothiophene length originates from the reduction of bandwidth due to more localized charge density distribution. Thus, this work provides a molecular understanding of the role of backbone building blocks on the chain conformation and bandgaps of D-A CPs for organic optoelectronic devices through the conformation design and segment orbital energy alignment.

Over-Prescription and Overuse of Antimicrobials in the Eastern Mediterranean Region: The Urgent Need for Antimicrobial Stewardship Programs with Access, Watch, and Reserve Adoption.

Excessive antimicrobial use contributes to the development of antimicrobial resistance. In the Eastern Mediterranean region (EMR), there is dearth of information on the prevalence of antimicrobial use in patients hospitalized in acute healthcare settings, clinical indications, types of antimicrobials prescribed, and quality indicators for prescriptions. Between September and December 2019, seven countries in the EMR conducted a standardized point prevalence survey. All patients present in the hospital wards at 8 a.m. on the day of the survey constituted the sample population. We collected data, including patient characteristics, antimicrobials received, therapeutic indication according to predefined lists, and markers of prescribing quality. The survey included data from 139 hospitals in seven countries. Among the 19,611 inpatients surveyed, 11,168 patients received at least one antimicrobial {crude prevalence: 56.9% (95%CI: 56.2-57.6%). The top three classes of antimicrobials prescribed were third-generation cephalosporins (26.7%), beta-lactam penicillins (18.1%), and imidazole derivatives (n = 1655, 9.8%). Carbapenems were most frequently prescribed for the treatment of healthcare-associated infections. Compliance with quality indicators of antimicrobial use was limited where treatment guidelines were available for 41% of antimicrobial prescriptions and targeted antimicrobial treatment represented 21% of therapeutic indications. Overall hospital antimicrobial use was high in countries of the EMR, pointing to the need to design and implement context-specific antimicrobial stewardship programs to optimize antimicrobial use and reduce antimicrobial resistance.