Stress shielding of the proximal humerus following total shoulder arthroplasty (TSA) can promote unfavorable bone remodeling, especially for osteoporotic patients. The objective of this finite element (FE) study was to determine if a hollow, rather than solid, titanium stem can mitigate this effect for healthy, osteopenic, and osteoporotic bone. Using a population-based model of the humerus, representative average healthy, osteopenic, and osteoporotic humerus FE models were created. For each model, changes in bone and implant stresses following TSA were evaluated for different loading scenarios and compared between solid versus hollow-stemmed implants. Selleck ISA-2011B For cortical bone, using an implant decreased von Mises stress with respect to intact values up to 34.4%, with a more pronounced effect at more proximal slices. In the most proximal slice, based on changes in strain energy density, hollow-stemmed implants outperformed solid-stemmed ones through reducing cortical bone volume with resorption potential by 11.7% ± 2.1% (p = .01). For cortical bone in this slice, the percentage of bone with resorption potential for the osteoporotic bone was greater than the healthy bone by 8.0% ± 1.4% using the hollow-stemmed implant (p = .04). These results suggest a small improvement in bone-implant mechanics using hollow-stemmed humeral implants and indicate osteoporosis could exacerbate stress shielding to some extent. The hollow stems maintained adequate strength and using even thinner walls may further reduce stress shielding. After further developing these models, future studies could yield optimized implant designs tuned for varying bone qualities. Aim of this study is to evaluate the capacity of a pharmacist-delivered screening model for type 2 diabetes and cardiovascular disease (CVD) in identifying and referring individuals at risk. A screening programme was implemented in 12 community pharmacies in three cities in the United Arab Emirates. Trained pharmacists screened adults (≥40years) without a previous diagnosis of diabetes or CVD. Most participants were recruited during their visits to the pharmacies; pharmacy-based advertising and social media were also used. The screening included medical history, anthropometric measurements, point-of-care glycated haemoglobin (HbA ) levels, and a lipid panel. High-risk individuals (HbA ≥5.7% [39mmol/mol], a high diabetes risk score, or a 10-year CVD risk ≥7.5%) were given a referral letter and advised to visit their physician. Risk factors for elevated HbA were identified by logistic regression. Of the 568 screened participants, 332/568 (58%) were identified to be at risk HbA levels were consistent with diabetes 67/560 (12%) or prediabetes 148/560 (26%), high diabetes risk score 243/566 (43%), CVD risk score>7.5% 79/541 (15%). Obese people were more likely to have prediabetes or diabetes OR (95% CI) 3.2 (1.3, 7.5), as were those who spent more than 11h/day sitting 5.7 (1.8, 17.6). Of the 332 at-risk participants, 206 (62%) responded to a telephone follow-up at six weeks; one-third had discussed screening results with their physician. Community pharmacists detected and referred individuals at risk for diabetes or CVD, although participant follow-up with their physician could be improved. Pharmacy screening is feasible and will potentially improve outcomes.Community pharmacists detected and referred individuals at risk for diabetes or CVD, although participant follow-up with their physician could be improved. Pharmacy screening is feasible and will potentially improve outcomes.Thiazolidinediones are well-known anti-diabetic drugs. However, they are not widely used due to their cardiotoxic effects. Therefore, in this study, we aimed to determine the molecular toxicological alterations induced in the mouse hearts after thiazolidinedione administration. Balb/c mice received doses clinically equivalent to those given to humans of the most commonly used thiazolidinediones, pioglitazone, and rosiglitazone for 30 days. After that, RNA samples were isolated from the hearts. The mRNA expression of cytochrome (cyp) p450 genes that synthesize the cardiotoxic 20-hydroxyeicosatetraenoic acid (20-HETE) in addition to 92 cardiotoxicity biomarker genes were analyzed using quantitative polymerase chain reaction array technique. The analysis demonstrated that thiazolidinediones caused a significant upregulation (p 0.05) by rosiglitazone administration. In conclusion, this study showed that thiazolidinediones induce toxicological molecular alterations in the mouse hearts, such as the induction of cyp450s that synthesize 20-HETE, chemokine activation, inflammatory responses, blood clotting, and oxidative stress. These findings may help us understand the mechanism of cardiotoxicity involved in thiazolidinedione administration.To obtain new anti-inflammatory agents, recent studies have aimed to replace the carboxylate functionality of nonsteroidal anti-inflammatory drugs with less acidic heterocyclic bioisosteres like 1,3,4-oxadiazole to protect the gastric mucosa from free carboxylate moieties. In view of these observations, we designed and synthesized a series of 3,5-disubstituted-1,3,4-oxadiazole derivatives as inhibitors of prostaglandin E2 (PGE2 ) and NO production with an improved activity profile. As initial screening, and to examine the anti-inflammatory activities of the compounds, the inhibitions of the productions of lipopolysaccharide-induced NO and PGE2 in RAW 264.7 macrophages were evaluated. The biological assays showed that, compared with indomethacin, compounds 5a, 5g, and 5h significantly inhibited NO production with 12.61 ± 1.16, 12.61 ± 1.16, and 18.95 ± 3.57 µM, respectively. Consequently, the three compounds were evaluated for their in vivo anti-inflammatory activities. Compounds 5a, 5g, and 5h showed a potent anti-inflammatory activity profile almost equivalent to indomethacin at the same dose in the carrageenan-induced paw edema test. Moreover, the treatment with 40 mg/kg of 5h produced significant anti-inflammatory activity data. Furthermore, docking studies were performed to reveal possible interactions with the inducible nitric oxide synthase enzyme. Docking results were able to rationalize the biological activity data of the studied inhibitors. In summary, our data suggest that compound 5h is identified as a promising candidate for further anti-inflammatory drug development with an extended safety profile.