Premature vascular damage in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease associated with a striking increase in the risk of premature cardiovascular (CV) complications due to accelerated atherosclerosis. Traditional CV risk factors seem to be less important predictors of CV events than the presence of active SLE. Immune dysregulation characteristic of lupus appears to play the dominant role in atherogenesis. While both SLE-specific and non-specific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. We have proposed that an imbalance between vascular damage and repair likely induced by Interferon-α could play a prominent role in the induction of accelerated atherosclerosis in SLE. This review summarizes some of the proposed mechanisms that may promote accelerated vascular damage in lupus and explores potential targets for CV risk prevention in this patient population.     

Stress distribution of different implant connections associated with multiple implant-supported prostheses

Abstract

In some clinical situations, the clinician may encounter previously installed implants that should be associated with other implants for a proper rehabilitation. The aim of this study was to evaluate the biomechanical behaviour of a multiple prosthesis joined by different implant connections using photoelasticity. Photoelastic models with a screwed fixed prosthesis supported by implants with different connection systems (Morse taper, external hexagon, internal hexagon, and Flexcone), and different combinations among them, were fabricated. Each assembly was placed in a circular polariscope, and axial and oblique (45°) loads of 100 N were applied on the occlusal surface of the crowns. The fringe patterns were photographed and the analysis was performed by counting the number of high-intensity fringes and also according to the stress distribution region where they appeared. Among implants of the same connection, the external connections obtained a greater number of high intensity fringes when compared to the internal connections. From the biomechanical point of view, the association between different types of connections obtained positive results.     

Exploring caregiver understanding of medications immediately after a pediatric primary care visit

Objective

Assess accuracy of caregiver understanding of children's prescribed medications and examine factors associated with accurate recall.

Methods

Cross-sectional, observational study of English- or Spanish-speaking caregivers of primary care patients aged 0–7 years. Child and visit characteristics and caregiver health literacy (Short Test of Health Literacy in Adults) were assessed. Post-visit, caregivers completed questionnaires on medications prescribed. Caregiver and medical record agreement on medication name and administration (dose and frequency) were examined using chi square and logistic regression.

Results

Analyses included 68 caregivers (28% low health literacy); 96% of children had public insurance. Caregivers indicated that the doctor provided clear medication information (100%) and they could follow instructions (98%). 101 medicines were prescribed; 6 were recalled by caregiver only. 71% of medications were accurately named; 37% of administration instructions were accurately recalled. Accurate naming was more often found for patients 3–7 years, without conditions requiring repeat visits, and new medications. Accurate administration responses were associated with having only 1 child at the visit.

Conclusion

Unperceived medication instruction understanding gaps exist at physician visits for caregivers of all literacy levels. Communication and care delivery practices need further evaluation.

Practice implications

Clinicians should be aware of the frequency of caregiver medication misunderstanding.     

Health effects of exposure to chlorination by-products in swimming pools

Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since some have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming pools (water ingestion, skin absorption, and inhalation) contribute to the individual exposome. Some CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated pools as customers, particularly children, may also be affected has been a matter of debate. In this article, we discuss the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports, and recreational attendance) and identify the main recommendations and unmet needs for research in this area.     

Hypersensitivity reactions and anaphylaxis to checkpoint inhibitor–monoclonal antibodies and desensitization

ObjectiveTo review type 1 hypersensitivity reactions and anaphylaxis to checkpoint inhibitor–monoclonal antibodies and its management with drug desensitization.Data SourcesEnglish-language literature on MEDLINE regarding hypersensitivity, anaphylaxis, and checkpoint inhibitor–monoclonal antibodies.Study SelectionsReferences were selected based on relevance, novelty, robustness, and applicability.ResultsThere are well-known tissue toxicities associated to checkpoint inhibitors, but hypersensitivity reactions and anaphylaxis have been underreported. The presentation of these reactions is based on clinical phenotypes with underlying endotypes identified by specific biomarkers. Drug desensitizations have been successfully applied to checkpoint inhibitor drugs to allow patients with cancer to receive first-line therapies. This review provides current best practices for the recognition and diagnosis of hypersensitivity reactions and anaphylaxis to checkpoint inhibitors and their management using drug desensitization.ConclusionHypersensitivity reactions and anaphylaxis have been identified as potential adverse effects induced by checkpoint inhibitor–monoclonal antibodies. Drug desensitization is a safe and effective treatment option for patients who experience hypersensitivity reactions in need of these monoclonal antibodies to improve cancer outcomes.     

Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR−/−)

BackgroundAtherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors.MethodsAnimals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses.ResultsNo changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly.ConclusionsThe results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis.