INFLUENCE OF STEEL FIBRES OF CRIMPED AND HOOKED-END SHAPE ON THE MECHANICAL PROPERTIES OF PORTLAND CEMENT

Cement mortar without fibers might crack due to shrinkage or volume changes. Cracking in cement mortar leads to elastic deformation. The development of these cracks causes elastic deformation of cement mortar. This study examined the influence of two steel fibers' geometrical forms (crimped and hooked with just one end) in different amounts by volume (Volume fraction = 0.25%, 0.5%, and 0.75%) on the cement mortar's mechanical features. Among the characteristics were splitting, compressive as well as flexural strength. The samples were prepared, poured into cubic molds for compressive strength testing cylindrical molds used for splitting strength testing, and prismatic molds for flexural strength testing, and processed at various times 3, 14, and 28 days before the tests. According to the findings, the highest increase was obtained after adding 0.75% of crimped fibers, the compressive strength increased by 13.3 %21.29%, and 44.8%, for 3,14.28 days respectively, and split tensile strength increased by 66.17%,68.9%, and 79.48% for 3.14 and 28 days respectively and flexural strength increased by 72 %,91% and 92% for 3.14 and 28 days, respectively

Effect of Quercetin on Diabetic Rat

Background: Quercetin (QR) is one of the major constituents of the methanolic extract of the leaves of Psidium guajava (Guava leaves). Objectives: The work’s aim is to understand the Quercetin’s mechanism in improving insulin resistance, use the homeostasis model assessment for insulin resistance (HOMA-IR) to determine the influence of quercetin on glycemic control, Look at how quercetin affects diabetes-related lipid metabolism and lipid profile measures. Analyze the impact of QR on oxidative stress in diabetic rats and contrast its antidiabetic effects whether administered as a nutrient or supplement. Materials and methods: Sixty adult male Wister rats that were matched in age and had starting body weights between 150 and 200 g were used in this study. One normoglycemic control group and 3 diabetic control groups (15 rats per group) were used. The diabetic control rats received the vehicle orally as saline daily, the normoglycemic control group received quercetin orally in a dose of 50 mg/kg per day, and the diabetic rats received quercetin orally in a dose of 100 mg/kg per day. Results: After six weeks of therapy, the rats with diabetes receiving isolated quercetin at doses of 50 and 100 mg/kg had reduced blood glucose levels, and their triglyceride, low-density lipoprotein, and total cholesterol profiles all significantly improved. Also, there was significant decrease homeostatic model assessment for insulin resistance, serum transaminases, hepatic malondialdehyde, and HMG CoA expression in liver and a substantial rise in levels of insulin, hepatic GSH, and insulin receptor substrate (IRS2) expression & Phosphoinositide 3-kinases in liver as compared to those of control group, but non- significance changes in high-density lipoprotein, AKT expression in liver were observed. Conclusions: Quercetin could be considered as a potential hypoglycmeic medication with possible mechanisms controlling the hyperglycemic state and cholesterol, triglycerides and LDL levels

Social and Economic Factors that Influence Health Outcomes in Family Medicine

Over the last twenty years, the social determinants of health (SDOH) have gained more and more attention in the public health community. SDOH are non-medical elements that may be significantly impacted by social policies and have an impact on health. The increasing variety that exists within our societies makes it absolutely necessary for us to incorporate into undergraduate medical education social determinants of health such as racial factors, financial instability, partner violence, insufficient accessibility to transportation, and inadequate social supports, as well as the crucial role of health education.  Nonetheless, a growing body of research indicates that a variety of health outcomes are fundamentally caused by socioeconomic variables including wealth, income, and education together. In this review we highlight the influence of socio-economic factors on health outcomes, approaches to incorporate social determinants of health in family medicine practice, and we also talk about challenges and solutions in addressing social determinants in family medicine. The objective of this research was to assess the impact of social determinants of health on family medicine practice in which socioeconomic determinants of health might have an effect on health outcomes and healthcare delivery within the context of a family medicine clinical environment

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

Prevalence and global trends of polypharmacy among people living with HIV: a systematic review and meta-analysis

Background: There has been a rising prevalence of polypharmacy among people living with HIV (PLWH). Uncertainty however remains regarding the exact estimates of polypharmacy among these cohorts of patients. Methods: We conducted a systematic search of PubMed; EMBASE, CROI, Cochrane Database of Systematic Reviews; Science Citation Index and Database of Abstracts of Reviews of Effects for studies between 1 January 2000 and 30 June 2021 that reported on the prevalence of polypharmacy (ingestion of > 5 non-ART medications) among PLWH on antiretroviral therapy regimen (ART). Prevalence of polypharmacy among HIV-positive patients on ART with Clopper–Pearson 95% confidence intervals were presented. The heterogeneity between studies was evaluated using (Formula presented.) and (Formula presented.) statistics. Results: One hundred ninety-seven studies were initially identified, 23 met the inclusion criteria enrolling 55,988 PLWH, of which 76.7% [95% confidence interval (CI): 76.4–77.1] were male. The overall pooled prevalence of polypharmacy among PLWH was 33% (95% CI: 25–42%) (I2 = 100%, τ2 = 0.9170, p < 0.0001). Prevalence of polypharmacy is higher in the Americas (44%, 95% CI: 27–63%) (I2 = 100%, τ2 = 1.0886, p < 0.01) than Europe (29%, 95% CI: 20–40%) (I2 = 100%, τ2 = 0.7944, p < 0.01). Conclusion: The pooled prevalence estimates from this synthesis established that polypharmacy is a significant and rising problem among PLWH. The exact interventions that are likely to significantly mitigate its effect remain uncertain and will need exploration by future prospective and systematic studies. Registration: PROSPERO: CRD42020170071 Plain Language Summary: Background: In people living with HIV (PLWH), what is the prevalence of polypharmacy and is this influenced by sociodemographic factors? Methods and Results: In this systematic review and meta-analysis of 23 studies comprising 55,988 participants, we have for the first time found an estimated polypharmacy pooled prevalence of 33% among PLWH. There was a relatively higher pooled prevalence of polypharmacy among the America’s compared with European cohorts of PLWH. Conclusion: Polypharmacy among PLWH is a rising morbidity that needs urgent intervention both at policy and patient levels of care.This research was supported by the Qatar National Library

The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial.

Tebotelimab, a bispecific PD-1×LAG-3 DART molecule that blocks both PD-1 and LAG-3, was investigated for clinical safety and activity in a phase 1 dose-escalation and cohort-expansion clinical trial in patients with solid tumors or hematologic malignancies and disease progression on previous treatment. Primary endpoints were safety and maximum tolerated dose of tebotelimab when administered as a single agent (n = 269) or in combination with the anti-HER2 antibody margetuximab (n = 84). Secondary endpoints included anti-tumor activity. In patients with advanced cancer treated with tebotelimab monotherapy, 68% (184/269) experienced treatment-related adverse events (TRAEs; 22% were grade ≥3). No maximum tolerated dose was defined; the recommended phase 2 dose (RP2D) was 600 mg once every 2 weeks. There were tumor decreases in 34% (59/172) of response-evaluable patients in the dose-escalation cohorts, with objective responses in multiple solid tumor types, including PD-1-refractory disease, and in LAG-3+ non-Hodgkin lymphomas, including CAR-T refractory disease. To enhance potential anti-tumor responses, we tested margetuximab plus tebotelimab. In patients with HER2+ tumors treated with tebotelimab plus margetuximab, 74% (62/84) had TRAEs (17% were grade ≥3). The RP2D was 600 mg once every 3 weeks. The confirmed objective response rate in these patients was 19% (14/72), including responses in patients typically not responsive to anti-HER2/anti-PD-1 combination therapy. ClinicalTrials.gov identifier: NCT03219268

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

Death from mantle cell lymphoma limits sequential therapy, particularly after first relapse: Patterns of care and outcomes in a series from Australia and the United Kingdom

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Patients can often receive sequential treatments, yet these typically yield diminishing periods of disease control, raising questions about optimal therapy sequencing. Novel agents, such as chimeric antigen receptor T-cell therapies and bispecific antibodies, show promise in relapsed MCL, but are often reserved for later treatment lines, which may underserve patients with aggressive disease phenotypes who die early in the treatment journey. To assess the problem of patient attrition from lymphoma-related death limiting sequential treatment, we performed a multicentre retrospective cohort analysis of 389 patients treated at Australian and UK centres over a 10-year period. Deaths from MCL increased after each treatment line, with 7%, 23% and 26% of patients dying from uncontrolled MCL after first, second and third lines respectively. Patients with older age at diagnosis and early relapse after induction therapy were at particular risk of death after second-line treatment. This limitation of sequential treatment by lymphoma-related death provides support for the trial of novel therapies in earlier treatment lines, particularly in high-risk patient populations

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (Fludarabine/busulfan=166, Fludarabine/melphalan=327) and 379 using MAC (Fludarabine/busulfan=247, Busulfan/cyclophosphamide=132). In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91, p=0.01) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade III-IV HR 2.21, 95%CI 1.28-3.83, p=0.004) compared to Fludarabine/busulfan. In the MAC setting, Busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25, p\u3c0.001; grade III-IV HR 2.31, 95% CI 1.52-3.52, p\u3c0.001) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53, p\u3c0.001) as compared to Fludarabine/busulfan. Hence, our study suggests that Fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GVHD) and MAC (lower acute GVHD and better GRFS) in myelofibrosis