Microparticles (MPs) are small vesicles shed from the cytoplasmic membrane of healthy, activated, or apoptotic cells. MPs are very heterogeneous in size (100–1,000 nm), and they harbor proteins and surface antigens specific to cells they originate from. Virtually, all cells can shed MPs, and therefore, they can be found in all body fluids, but also entrapped in tissues. Of interest and because of their easy detection using a variety of techniques, circulating MPs were recognized as biomarkers for cell activation. MPs were also found to mediate critical actions in intercellular communication and transmitting biological messages by acting as paracrine vehicles. High plasma numbers of MPs were reported in many cardiovascular and metabolic disturbances that are closely associated with insulin resistance and low-grade inflammation and have been linked to adverse actions on cardiovascular function. This review highlights the involvement of MPs in cardiovascular complications associated with diabetes and discusses the molecular mechanisms that underpin the pathophysiological role of MPs in the onset and progression of cellular injury in diabetes.

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Brucellosis is a zoonotic disease of major concern in Kuwait and the Middle East. Human brucellosis can be caused by several Brucella species with varying degree of pathogenesis, and relapses are common after apparently successful therapy. The classical biochemical methods for identification of Brucella are time-consuming, cumbersome, and provide information limited to the species level only. In contrast, molecular methods are rapid and provide differentiation at intra-species level. In this study, four molecular methods [16S rRNA gene sequencing, real-time PCR, enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus variable-number tandem-repeat analysis (MLVA)-8, MLVA-11 and MLVA-16 were evaluated for the identification and typing of 75 strains of Brucella isolated in Kuwait. 16S rRNA gene sequencing of all isolates showed 90–99% sequence identity with B. melitensis and real-time PCR with genus- and species- specific primers identified all isolates as B. melitensis. The results of ERIC-PCR suggested the existence of 75 ERIC genotypes of B. melitensis with a discriminatory index of 0.997. Cluster classification of these genotypes divided them into two clusters, A and B, diverging at ~25%. The maximum number of genotypes (n = 51) were found in cluster B5. MLVA-8 analysis identified all isolates as B. melitensis, and MLVA-8, MLVA-11 and MLVA-16 typing divided the isolates into 10, 32 and 71 MLVA types, respectively. Furthermore, the combined minimum spanning tree analysis demonstrated that, compared to MLVA types discovered all over the world, the Kuwaiti isolates were a distinct group of MLVA-11 and MLVA-16 types in the East Mediterranean Region.

Background: Antibiotic misuse is a worldwide public health problem and has been associated with increased morbidity, length of hospital stay, mortality, healthcare costs, and most importantly antibiotic resistance. Aims: We aimed to evaluate the compliance of antibiotic prescribing with national guidelines, assess how educational interventions can best be utilized to make impact and fill gaps for optimal antibiotic utilization, and to identify facilitators and barriers to implementing ASPs in Qatar. Methods: Six cross-sectional baseline audits of antibiotic prescribing were conducted over a two-week period at a tertiary care teaching hospital. A sub-analysis of prescriptions with follow up has followed. An educational intervention utilizing the PDSA (Plan-Do-Study-Act) tool was implemented to address gaps identified. A repeated audit was done to assess the impact of change. Lastly, interviews were conducted to recognize perceived facilitators and barriers for ASP implementation, identify strategies to overcome barriers, and evaluate the effectiveness of educational interventions. Results: The most common indication for antibiotic prescribing was febrile neutropenia (20.7%). The most frequently used class of antibiotics was carbapenems (21.4%). Sixty percent of prescriptions complied with guidelines. The rationale behind choosing not to adhere to guidelines was not documented in 37.2% of cases. Suboptimal documentation in records was targeted through our intervention. The audit post intervention showed slight improvement in documentation. Facilitators and barriers included: collaboration and communication among teams, compliance with guidelines, interventions documented by clinical pharmacists, and electronic system errors. Conclusions: Effective communication, continuous documentation in records, and repetitive education promote rational antibiotic prescribing and enhance ASPs.

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Circulating extracellular vesicles (EVs) are recognized as biomarkers and effectors of endothelial dysfunction, the initiating step of cardiovascular abnormalities. Among these EVs, microparticles (MPs) are vesicles directly released from the cytoplasmic membrane of activated cells. MPs were shown to induce endothelial dysfunction through the activation of endoplasmic reticulum (ER) stress. However, it is not known whether ER stress can lead to MPs release from endothelial cells and what biological messages are carried by these MPs. Therefore, we aimed to assess the impact of ER stress on MPs shedding from endothelial cells, and to investigate their effects on endothelial cell function. EA.hy926 endothelial cells or human umbilical vein endothelial cells (HUVECs) were treated for 24 h with ER stress inducers, thapsigargin or dithiothreitol (DTT), in the presence or absence of 4-Phenylbutyric acid (PBA), a chemical chaperone to inhibit ER stress. Then, MPs were isolated and used to treat cells (10–20 μg/mL) for 24–48 h before assessing ER stress response, angiogenic capacity, nitric oxide (NO) release, autophagy and apoptosis. ER stress (thapsigargin or DDT)-generated MPs did not differ quantitatively from controls; however, they carried deleterious messages for endothelial function. Exposure of endothelial cells to ER stress-generated MPs increased mRNA and protein expression of key ER stress markers, indicating a vicious circle activation of ER stress. ER stress (thapsigargin)-generated MPs impaired the angiogenic capacity of HUVECs and reduced NO release, indicating an impaired endothelial function. While ER stress (thapsigargin)-generated MPs altered the release of inflammatory cytokines, they did not, however, affect autophagy or apoptosis in HUVECs. This work enhances the general understanding of the deleterious effects carried out by MPs in medical conditions where ER stress is sustainably activated such as diabetes and metabolic syndrome.

Objective Cisplatin is a standard treatment approach against lung adenocarcinoma. Resistance to cisplatin and the toxic side effects of cisplatin continue to remain a challenge. Combining drugs with different mechanisms is being investigated as a means to overcome these challenges. In ovarian cancer cells, the knockdown of RSK2 increased the sensitivity of cisplatin. RSK is a downstream mediator of the MAPK pathway that is responsible for cell survival, proliferation and migration. Methods Our study examined the effect of cisplatin, BI-D1870 (RSK inhibitor) or their combination on cell migration, apoptosis, autophagy and cell cycle in A549 human lung adenocarcinoma cells. Key findings The combination of cisplatin and BI-D1870 potentiated the antimigration rate, the activation of caspases-3 and was associated with a significant decrease in RSK1 and ERK expression when compared to cisplatin alone. The combination of cisplatin and BI-D1870 also resulted in the inhibition of LC3 II to LC3 I expression when compared to BI-D1870. The combination of cisplatin and BI-D1870 increased the number of cells in the G2/M-phase when compared to cisplatin alone. Conclusions These findings suggest that combining cisplatin with agents that target the RSK mediated cell survival pathway, may potentiate the cisplatin effect in lung adenocarcinoma.

Upon increased demand for protein synthesis, accumulation of misfolded and/or unfolded proteins within the endoplasmic reticulum (ER), a pro-survival response is activated termed unfolded protein response (UPR), aiming at restoring the proper function of the ER. Prolonged activation of the UPR leads, however, to ER stress, a cellular state that contributes to the pathogenesis of various chronic diseases including obesity and diabetes. ER stress response by itself can result in endothelial dysfunction, a hallmark of cardiovascular disease, through various cellular mechanisms including apoptosis, insulin resistance, inflammation and oxidative stress. Extracellular vesicles (EVs), particularly large EVs (lEVs) commonly referred to as microparticles (MPs), are membrane vesicles. They are considered as a fingerprint of their originating cells, carrying a variety of molecular components of their parent cells. lEVs are emerging as major contributors to endothelial cell dysfunction in various metabolic disease conditions. However, the mechanisms underpinning the role of lEVs in endothelial dysfunction are not fully elucidated. Recently, ER stress emerged as a bridging molecular link between lEVs and endothelial cell dysfunction. Therefore, in the current review, we summarized the roles of lEVs and ER stress in endothelial dysfunction and discussed the molecular crosstalk and relationship between ER stress and lEVs in endothelial dysfunction.