In this Journal in 1972, 100 leaders in obstetrics and gynecology published a compelling statement that recognized the legalization of abortion in several states and anticipated the 1973 Supreme ...Court decision in Roe v Wade. They projected the numbers of legal abortions that likely would be required by women in the United States and described the role of the teaching hospital in meeting that responsibility. They wrote to express their concern for women’s health in a new legal and medical era of reproductive control and to define the responsibilities of academic obstetrician-gynecologists. Forty years later, 100 professors examine the statement of their predecessors in light of medical advances and legal changes and suggest a further course of action for obstetrician gynecologists.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The intrinsic aerobic capacity of an organism is thought to play a role in aging and longevity. Maximal respiratory rate capacity, a metabolic performance measure, is one of the best predictors of ...cardiovascular- and all-cause mortality. Rats selectively bred for high-(HCR) vs. low-(LCR) intrinsic running-endurance capacity have up to 31% longer lifespan. We found that positive changes in indices of mitochondrial health in cardiomyocytes (respiratory reserve, maximal respiratory capacity, resistance to mitochondrial permeability transition, autophagy/mitophagy, and higher lipids-over-glucose utilization) are uniformly associated with the extended longevity in HCR vs. LCR female rats. Cross-sectional heart metabolomics revealed pathways from lipid metabolism in the heart, which were significantly enriched by a select group of strain-dependent metabolites, consistent with enhanced lipids utilization by HCR cardiomyocytes. Heart-liver-serum metabolomics further revealed shunting of lipidic substrates between the liver and heart via serum during aging. Thus, mitochondrial health in cardiomyocytes is associated with extended longevity in rats with higher intrinsic exercise capacity and, probably, these findings can be translated to other populations as predictors of outcomes of health and survival.
Abstract
Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer’s disease or frontotemporal degeneration typically evaluate changes in volume at ...a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration.
Bruffaerts, Gors et al. studied structural brain changes at the asymptomatic stage of monogenic frontotemporal degeneration. They used hierarchical spectral clustering for MRI segmentation to detect changes at different levels of granularity. In asymptomatic c9orf72 expansion carriers additional structural brain changes were observed in comparison to conventional methods.
Graphical Abstract
Graphical abstract
To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified ...by perfusion imaging mismatch.
Pooled cohort of patients with NIHSS<6 and ICA, M1, M2 occlusions from EXTEND-IA, EXTEND-IA-TNK I/II RCTs and prospective data from 15 EVT centers from 10/2010 to 4/2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary endovascular thrombectomy (EVT
) were compared to those who received primary MM (MM
), including those who deteriorated and received rescue EVT, in overall and PS matched cohorts. Patients were stratified by target mismatch (mismatch-ratio≥1.8 and mismatch-volume≥15cc). Primary outcome was functional independence (90-day mRS:0-2); Secondary outcomes included safety (sICH, neurological worsening, and mortality).
Of 540 patients, 286/540(53%) received EVT
and demonstrated larger critically hypoperfused tissue (Tmax>6s) volumes of (6426-96mL vs MM
:4014-76mL, p<0·001) and higher presentation NIHSS (4(2-5) vs MM
:3(2-4), p<0·001). Functional independence was similar (EVT
:77·4% vs MM
:75.6%, aOR:1.29,95%CI:0.82-2.03,p=0.27). EVT had worse safety: sICH (EVT
:8.8% vs MM
:1.3%, p<0.001) and neurological worsening (EVT
:19.6% vs MM
:6.7%, p<0.001). In 414(76.7%) with target mismatch, EVT was associated with improved functional independence (EVT
:77·4% vs MM
:72.7%, aOR:1.68, 95%CI:1.01-2.81,p=0.048), whereas, there was a trend toward less favorable outcomes with primary EVT (EVT
:77·4% vs MM
:83.3%, aOR:0.39,95%CI:0.12-1.34,p=0.13) without target mismatch, (p
=0.06). Similar findings were observed in a PS matched subpopulation.
Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. This article is protected by copyright. All rights reserved.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in the genes encoding the DNA repair proteins CSA or CSB. Csb
m/m
mice were ...given a high fat, caloric restricted or resveratrol supplemented diet. The high fat diet rescued the phenotype of Csb
m/m
mice at the metabolic, transcriptomic and behavioral levels. Additional analysis suggests that the premature aging seen in CS mice, nematodes and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high fat diet; and β-hydroxybutyrate, PARP inhibition, or NAD
+
supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB is able to displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD
+
, through the deacetylase SIRT1 and suggests possible interventions for CS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Previous research suggests that after coronary artery bypass graft (CABG) surgery, women fare worse than men. This study investigates sex differences in depression during recovery from CABG surgery.
...We followed 137 patients (72 men, 65 women) undergoing elective isolated first CABG surgery between July 2003 and April 2004. Patients were interviewed ≤28 days before surgery and between 6 and 12 weeks after surgery. Patients completed a structured diagnostic interview for major depressive disorder (MDD) and the Beck Depression Inventory (BDI). Clinical data were retrieved from patient charts.
Prevalence of MDD before surgery was 28.2%, but decreased to 16.4% after surgery (
P = .038). Women had significantly more depressive symptoms than men pre-CABG, with a mean BDI of 12.5 (95% CI 10.6-14.4) for women versus 8.0 (95% CI 6.3-9.8) for men (
P = .0001), but not post-CABG. There was a significant sex-by-time interaction with depressive symptoms in women improving almost 6-fold more than in men, with BDI change scores of 4.1 (95% CI 2.0-6.1) for women versus 0.7 (95% CI−1.0-2.5) for men (
P = .008). The interaction remained significant after adjusting the model for the predetermined baseline characteristics education, social support, and operative risk.
Women had more depressive symptoms than men pre-CABG, but improved to a level comparable to men post-CABG. Women benefited from CABG as much or more than men in terms of their mental health. Preoperative depressive symptoms should not preclude women from CABG surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND
Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing ...revascularization methods have excluded a number of important high-risk groups.
OBJECTIVES
This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents.
METHODS
Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI.
RESULTS
A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46).
CONCLUSIONS
Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Neutrophils and alveolar macrophages are essential defence mechanisms against bacterial infection of the lung. The purpose of this study was to evaluate the variability of a panel of neutrophil and ...alveolar macrophage function assays in swine, and to determine if the function of these leukocytes differed at various stages of production. Measured neutrophil functions included chemotaxis, phagocytosis, oxidative burst, and degranulation. Phagocytosis and oxidative burst were measured in alveolar macrophages isolated from bronchoalveolar lavage fluid (BALF). Both neutrophil and alveolar macrophage functions were highly variable from day-to-day and between pigs. Individual pigs did not have consistently high or low neutrophil and macrophage responses over time when compared to their cohorts. Older grower–finisher pigs had significantly greater neutrophil oxidative burst responses than younger suckling and weaner pigs (
P<0.001). Similarly, alveolar macrophages from suckling and early weaner pigs less than 40 days of age had significantly lower oxidative burst responses than those from older pigs (
P=0.02). Age-related variation in phagocytosis, chemotaxis, or granule secretion were not detected. These results establish baseline data for individual and age-related variation in swine leukocyte function, and form a basis for further evaluation of the contribution of non-infectious factors to development of the porcine respiratory disease complex.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A novel oncogenetic clinic was established in 2002 at the Royal Marsden NHS Foundation Trust offering advice and specialist follow-up for families with a germline mutation in BRCA1 or BRCA2. The ...remit of this multidisciplinary clinic, staffed by individuals in both oncology and genetics, is to provide individualised screening recommendations, support in decision making, risk reducing strategies, cascade testing, and an extensive research portfolio.
A retrospective analysis was performed to evaluate uptake of genetic testing, risk reducing surgery and cancer prevalence in 346 BRCA1/BRCA2 families seen between January 1996 and December 2006.
661 individuals attended the clinic and 406 mutation carriers were identified; 85.8% mutation carriers have chosen to attend for annual follow-up. 70% of mutation carriers elected for risk reducing bilateral salpingo-oophorectomy (RRBSO). 32% of unaffected women chose risk reducing bilateral mastectomy. 32% of women with breast cancer chose contralateral risk reducing mastectomy at time of diagnosis. Some women took over 8 years to decide to have surgery. 91% of individuals approached agreed to participate in research programmes.
A novel specialist clinic for BRCA1/2 mutation carriers has been successfully established. The number of mutation positive families is increasing. This, and the high demand for RRBSO in women over 40, is inevitably going to place an increasing demand on existing health resources. Our clinic model has subsequently been adopted in other centres and this will greatly facilitate translational studies and provide a healthcare structure for management and follow-up of such people who are at a high cancer risk.
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