Progress has been made recently. Notably, FOLFIRINOX or nab-paclitaxel plus gemcitabine provide survival benefit over gemcitabine alone, which was previously the mainstay of therapy for PDAC. Most of the current trials are testing combinations of repurposed drugs rather than addressing key targets in the PDAC pathogenesis. It is clear that to really make an impact on this disease, it will be necessary to address three different problems with targeted therapeutics. First, it is important to eradicate PDAC stem cells that result in recurrence. Second, it is important to reduce the peritumoral stroma that provides the tumors with growth support and provides a barrier to access of therapeutic agents. Finally, it is important to address the marked cachexia and metabolic derangement that contribute to morbidity and mortality and further complicate therapeutic intervention.
Background: We systematically reviewed and chronicled exposures and outcomes measured in the maternal and birth cohort studies in the Gulf Cooperation Council (GCC) countries and quantitatively summarized the weighted effect estimates between maternal obesity and (1) cesarean section (CS) and (2) fetal macrosomia. Methods: We searched MEDLINE-PubMed, Embase, Cochrane Library, Scopus, and Web of Science electronic databases up to 30 June 2019. We considered all maternal and birth cohort studies conducted in the six GCC countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates (UAE)). We categorized cohort studies on the basis of the exposure(s) (anthropometric, environmental, medical, maternal/reproductive, perinatal, or socioeconomic) and outcome(s) (maternal or birth) being measured. Adjusted weighted effect estimates, in the form of relative risks, between maternal obesity and CS and fetal macrosomia were generated using a randomeffects model. Results: Of 3502 citations, 81 published cohort studies were included. One cohort study was in Bahrain, eight in Kuwait, seven in Qatar, six in Oman, 52 in Saudi Arabia, and seven in the UAE. Majority of the exposures studied were maternal/reproductive (65.2%) or medical (39.5%). Birth and maternal outcomes were reported in 82.7% and in 74.1% of the cohort studies, respectively. In Saudi Arabia, babies born to obese women were at a higher risk of macrosomia (adjusted relative risk (aRR), 1.15; 95% confidence interval (CI), 1.10-1.20; I 2 = 50%) or cesarean section (aRR, 1.21; 95% CI, 1.15-1.26; I 2 = 62.0%). Several cohort studies were only descriptive without reporting the magnitude of the effect estimate between the assessed exposures and outcomes. Conclusions: Cohort studies in the GCC have predominantly focused on reproductive and medical exposures. Obese pregnant women are at an increased risk of undergoing CS delivery or macrosomic births. Longer-term studies that explore a wider range of environmental and biological exposures and outcomes relevant to the GCC region are needed. Systematic review registration: PROSPERO CRD42017068910
Zika virus (ZIKV) pandemic and its implication in congenital malformations and severe neurological disorders had created serious threats to global health. ZIKV is a mosquito-borne flavivirus which spread rapidly and infect a large number of people in a shorter time-span. Due to the lack of effective therapeutics, this had become paramount urgency to discover effective drug molecules to encounter the viral infection. Various anti-ZIKV drug discovery efforts during the past several years had been unsuccessful to develop an effective cure. The NS2B-NS3 protein was reported as an attractive therapeutic target for inhibiting viral proliferation, due to its central role in viral replication and maturation of non-structural viral proteins. Therefore, the current in silico drug exploration aimed to identify the novel inhibitors of Zika NS2B-NS3 protease by implementing an e-pharmacophore-based high-throughput virtual screening. A 3D e-pharmacophore model was generated based on the five-featured (ADPRR) pharmacophore hypothesis. Subsequently, the predicted model is further subjected to the high-throughput virtual screening to reveal top hit molecules from the various small molecule databases. Initial hits were examined in terms of binding free energies and ADME properties to identify the candidate hit exhibiting a favourable pharmacokinetic profile. Eventually, molecular dynamic (MD) simulations studies were conducted to evaluate the binding stability of the hit molecule inside the receptor cavity. The findings of the in silico analysis manifested affirmative evidence for three hit molecules with −64.28, −55.15 and −50.16 kcal/mol binding free energies, as potent inhibitors of Zika NS2B-NS3 protease. Hence, these molecules holds the promising potential to serve as a prospective candidates to design effective drugs against ZIKV and related viral infections.
Background Asthma is a significant public health issue that poses a substantial health and economic burden. Despite the availability of effective asthma medications, its management remain suboptimal. Recent asthma guidelines have highlighted the importance of pharmacist unique position and its interventional strategies in positively impacting asthma treatment outcomes. Therefore, this study aimed to assess the degree of Egyptian pharmacists’ knowledge, attitudes, as well as their practices towards asthma management in line with the recent asthma guidelines. Methods This cross-sectional study was conducted among 800 pharmacists working in different private and governmental sectors. The data were collected using a 37-item pre-validated self-administered KAP questionnaire. The data were analyzed using Student’s t-test and analysis of variance to assess the association between each KAP level and the sociodemographic variables at the significance level of 0.05. Results Of the 800 distributed questionnaire, a total of 550 participants (316 Male, and 234 Female) responded, representing a 68.7% response rate. The mean ± SD score of knowledge, attitude, practice, and barrier was 5.49 ± 1.65 (min = 0; max = 8), 23.5 ± 2.84 (min = 15, max = 30), 43.12 ± 8.61 (min = 28, max = 62), and 27.76 ± 3.72 (min = 17, max = 39), respectively. The results showed that poor knowledge, attitude, and practice scores were achieved by 30.54, 0, and 38.72% of participants, respectively. Conclusion Our findings revealed the inconsistencies between poor pharmacists’ knowledge and practices with respect to their positive attitudes. The lack of pharmacists’ knowledge and compliance to recent GINA guidelines in this study highlight the crucial need for effective Educational strategies that should better equip pharmacists for their potential role in asthma care.
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