American Bar Association Criminal Justice Section Report to the House of Delegates

The proposed amendments to the Federal Rules of Evidence, Rules 413-15 regarding the admission of character testimony in cases of sexual abuse and child molestation, have been roundly criticized by the legal community on both substantive and procedural grounds. The ABA has resolved to oppose the substance of these rules, and fear that in addition to the direct concerns regarding the result of the rules, they raise troubling policy issues going forward

Low-flow mediated constriction as a marker of endothelial function in healthy pregnancy and preeclampsia: A pilot study

OBJECTIVES: Overwhelming clinical evidence exists on disturbed vascular and endothelial function in the pathophysiology of preeclampsia (PE). In a non-pregnant (NP) population, L-FMC (low-flow mediated constriction) provides insight in the 'resting' endothelial capacity in contrast to the gold standard of flow mediated dilatation (FMD), reflecting endothelial nitric oxide bioavailability. STUDY DESIGN: Longitudinal follow-up of 100 healthy pregnant (HP) women, 33 PE women and 16 NP controls with non-invasive vascular assessments. HP women were evaluated at 12 and 35 weeks of gestation and at 6 months postpartum. PE patients were assessed at diagnosis (mean 30 weeks) and 6 months postpartum. MAIN OUTCOME MEASURES: Endothelial function (L-FMC, FMD, peripheral arterial tonometry (PAT)) and arterial stiffness (pulse wave velocity (PWV) and analysis (PWA)) were measured at the different visits and compared between groups. RESULTS: Overall endothelial dysfunction is present in PE (FMD HP 9.09 ± 4.20 vs PE 5.21 ± 4.47, p = 0.0004; L-FMC HP -1.90 ± 2.66 vs PE -0.40 ± 2.09, p = 0.03). L-FMC gradually elevates during the course of a HP (1st trim -0.31 ± 1.75 vs 3rd trim -1.97 ± 3.02, p  0.05). CONCLUSION: PE is characterized by dysfunction of both resting and recruitable endothelial capacity. This study offers new insights in different aspects of endothelial function in pregnancy, since L-FMC reflects an adaptation in HP that is absent in PE

Circulating reactive oxygen species in adults with congenital heart disease

Oxidative stress is an important pathophysiological mechanism in the development of numerous cardiovascular disorders, but few studies have examined the levels of oxidative stress in adults with congenital heart disease (CHD). The objective of this study was to investigate oxidative stress levels in adults with CHD and the association with inflammation, exercise capacity and endothelial function. To this end, 36 adults with different types of CHD and 36 age- and gender-matched healthy controls were enrolled. Blood cell counts, hs-CRP, NT-proBNP, fasting glucose, cholesterol levels, iron saturation and folic acid concentrations were determined in venous blood samples. Levels of superoxide anion radical in whole blood were determined using electron paramagnetic resonance spectroscopy in combination with the spin probe CMH. Physical activity was assessed with the IPAQ-SF questionnaire. Vascular function assessment (EndoPAT) and cardiopulmonary exercise testing were performed in the patient group. Superoxide anion radical levels were not statistically significantly different between adults with CHD and the matched controls. Moreover, oxidative stress did not correlate with inflammation, or with endothelial function or cardiorespiratory fitness in CHD; however, a significant negative correlation with iron saturation was observed. Overall, whole blood superoxide anion radical levels in adults with CHD were not elevated, but iron levels seem to play a more important role in oxidative stress mechanisms in CHD than in healthy controls. More research will be needed to improve our understanding of the underlying pathophysiology of CHD

Circulating Reactive Oxygen Species in Adults with Congenital Heart Disease

Oxidative stress is an important pathophysiological mechanism in the development of numerous cardiovascular disorders, but few studies have examined the levels of oxidative stress in adults with congenital heart disease (CHD). The objective of this study was to investigate oxidative stress levels in adults with CHD and the association with inflammation, exercise capacity and endothelial function. To this end, 36 adults with different types of CHD and 36 age- and gender-matched healthy controls were enrolled. Blood cell counts, hs-CRP, NT-proBNP, fasting glucose, cholesterol levels, iron saturation and folic acid concentrations were determined in venous blood samples. Levels of superoxide anion radical in whole blood were determined using electron paramagnetic resonance spectroscopy in combination with the spin probe CMH. Physical activity was assessed with the IPAQ-SF questionnaire. Vascular function assessment (EndoPAT) and cardiopulmonary exercise testing were performed in the patient group. Superoxide anion radical levels were not statistically significantly different between adults with CHD and the matched controls. Moreover, oxidative stress did not correlate with inflammation, or with endothelial function or cardiorespiratory fitness in CHD; however, a significant negative correlation with iron saturation was observed. Overall, whole blood superoxide anion radical levels in adults with CHD were not elevated, but iron levels seem to play a more important role in oxidative stress mechanisms in CHD than in healthy controls. More research will be needed to improve our understanding of the underlying pathophysiology of CHD

Effect of training on vascular function and repair in heart\ua0failure with preserved ejection fraction

Abstract: BACKGROUND Exercise training improves peak oxygen uptake (_VO2peak) in heart failure with preserved ejection fraction (HFpEF). Multiple adaptations have been addressed, but the role of circulating endothelium-repairing cells and vascular function have not been well defined. OBJECTIVES The authors investigated effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on vascular function and repair in HFpEF. METHODS This study is a subanalysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure) study randomizing patients with HFpEF (n 1/4 180) to HIIT, MICT, or guideline control. At baseline, 3, and 12 months, the authors measured peripheral arterial tonometry (valid baseline measurement in n 1/4 109), flow -mediated dilation (n 1/4 59), augmentation index (n 1/4 94), and flow cytometry (n 1/4 136) for endothelial progenitor cells and angiogenic T cells. Abnormal values were defined as outside 90% of published sex-specific reference values. RESULTS At baseline, abnormal values (%) were observed for augmentation index in 66%, peripheral arterial tonometry in 17%, flow-mediated dilation in 25%, endothelial progenitor cells in 42%, and angiogenic T cells in 18%. These parameters did not change significantly after 3 or 12 months of HIIT or MICT. Results remained unchanged when confining analysis to patients with high adherence to training. CONCLUSIONS In patients with HFpEF, high augmentation index was common, but endothelial function and levels of endothelium-repairing cells were normal in most patients. Aerobic exercise training did not change vascular function or cellular endothelial repair. Improved vascular function did not significantly contribute to the _VO2peak improvement after different training intensities in HFpEF, contrary to previous studies in heart failure with reduced ejection fraction and coronary artery disease. (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure [OptimEx-Clin]; NCT02078947) (J Am Coll Cardiol HF 2023;11:454-464) (c) 2023 by the American College of Cardiology Foundation

CD44-specific antibody treatment and CD44 deficiency exert distinct effects on leukocyte recruitment in experimental arthritis

CD44, the leukocyte adhesion receptor for hyaluronan, has been considered a therapeutic target on the basis of the robust anti-inflammatory effect of CD44-specific antibodies in animal models of immune-mediated diseases. However, CD44 deficiency does not provide substantial protection against inflammation. Using intravital video microscopy in a murine model of rheumatoid arthritis, we show that CD44 deficiency and anti-CD44 antibody treatment exert disparate effects on leukocyte recruitment in inflamed joints. Leukocyte rolling, which is increased in CD44-deficient mice, is promptly abrogated in anti–CD44-treated wild-type mice. CD44-specific antibodies also trigger platelet deposition on granulocytes and subsequent depletion of this leukocyte subset in the circulation. These in vivo effects require CD44 cross-linking and are reproducible with an antibody against Gr-1, a molecule that, like CD44, is highly expressed on granulocytes. Anticoagulant pretreatment, which prevents platelet deposition, mitigates both granulocyte depletion and the suppressive effect of CD44-specific antibody on joint swelling. Our observations suggest that cross-linking of prominent cell surface molecules, such as CD44 or Gr-1, can initiate a rapid self-elimination program in granulocytes through engagement of the coagulation system. We conclude that the robust anti-inflammatory effect of CD44-specific antibodies in arthritis is primarily the result of their ability to trigger granulocyte depletion