Sex and Gender in Medical Education, and proceedings from the 2015 Sex and Gender Education Summit

The Sex and Gender Medical Education Summit: a roadmap for curricular innovation was a collaborative initiative of the American Medical Women\u27s Association, Laura W. Bush Institute for Women’s Health, Mayo Clinic, and Society for Women\u27s Health Research (www.sgbmeducationsummit.com). It was held on October 18–19, 2015 to provide a unique venue for collaboration among nationally and internationally renowned experts in developing a roadmap for the incorporation of sex and gender based concepts into medical education curricula. The Summit engaged 148 in-person attendees for the 1 1/2-day program. Pre- and post-Summit surveys assessed the impact of the Summit, and workshop discussions provided a framework for informal consensus building. Sixty-one percent of attendees indicated that the Summit had increased their awareness of the importance of sex and gender specific medicine. Other comments indicate that the Summit had a significant impact for motivating a call to action among attendees and provided resources to initiate change in curricula within their home institutions. These educational efforts will help to ensure a sex and gender basis for delivery of health care in the future

Constitutive alzheimer\u27s-type tau epitopes in a neuritogenic rat CNS cell line

Paired helical filaments (PHFs) of Alzheimer\u27s disease (AD) largely comprise hyperphosphorylated forms of the cytoskeletal protein tau. AD-type tau phosphoepitopes, detected by various monoclonal antibodies, are absent from normal adult neurons, but recent studies have shown that their expression may contribute to neuritogenesis and axon differentiation in the developing nervous system. Therefore, we have examined a brain nerve cell line that is spontaneously neuritogenic for possible expression of AD-type tau epitopes. The neuritogenic rat brain cell line B103 was found to constitutively produce two AD-related epitopes of tau, detected by cellular immunofluorescence studies with the PHF-1 and Alz-50 monoclonal antibodies. Biochemical studies showed that the antibodies bound to proteins within the molecular weight range expected for phosphorylated tau isoforms. Further verification was established by use of tau antisense oligomers, which eliminated cellular immunofluorescence due to the AD-related monoclonals and polyclonal anti-tau but did not eliminate fluorescence due to anti-tubulin. Cells treated with tau antisense were not neurite-free. Neurites that remained, however, were abnormal, generally short and wavy in appearance. Cellular distribution of the tau epitopes was found to be particularly interesting. Alz-50 recognized only cytoplasmic tau whereas PHF-1 recognized nuclear tau as well as cytoplasmic. Thus, the two epitopes are morphologically segregated within the cell. Because subcellular segregation of tau is compromised in Alzheimer\u27s disease, mechanisms that segregate AD-type phosphotau epitopes in B103 cells may have relevance to this neurodegenerative disorder

Is the association between optimistic cardiovascular risk perceptions and lower rates of cardiovascular disease mortality explained by biomarkers of systemic inflammation or endothelial function? A case-cohort study

<p>Abstract</p> <p>Background</p> <p>More optimistic perceptions of cardiovascular disease risk are associated with substantively lower rates of cardiovascular death among men. It remains unknown whether this association represents causality (i.e. perception leads to actions/conditions that influence cardiovascular disease occurrence) or residual confounding by unmeasured factors that associate with risk perceptions and with physiological processes that promote cardiovascular disease (i.e. inflammation or endothelial dysfunction).</p> <p>Purpose</p> <p>To evaluate whether previously unmeasured biological markers of inflammation or endothelial dysregulation confound the observed association between cardiovascular disease risk perceptions and cardiovascular disease outcomes;</p> <p>Methods</p> <p>We conducted a nested case-cohort study among community-dwelling men from Southeastern New England (USA) who were interviewed between 1989 and 1990 as part of the Pawtucket Heart Health Program. We measured C-reactive protein (CRP) and Vascular Endothelial Growth Factor (VEGF) levels from stored sera for a random sample of the parent cohort (control sample, n = 127) and all cases of cardiovascular death observed through 2005 (case sample, n = 44). We evaluated potential confounding using stratified analyses and logistic regression modeling.</p> <p>Results</p> <p>Optimistic ratings of risk associated with lower odds of dying from cardiovascular causes among men (OR = 0.39, 95% CI = 0.17, 0.91). Neither CRP nor VEGF confounded these findings.</p> <p>Conclusions</p> <p>The strong cardio-protective association between optimistic ratings of cardiovascular disease risk and lower rates of cardiovascular mortality among men is not confounded by baseline biomarkers of systemic inflammation or endothelial dysfunction.</p

The Archaeology of 19th-Century Farmsteads: The Results of a Workshop Held at the 1997 Annual Meeting of the Council for Northeast Historical Archaeology

A workshop was held at the 1997 annual meeting of the Council for Northeast Historical Archaeology (CNEHA) to address the question What do we do with 19th-century farmsteads in the Northeast? The workshop involved several brainstorming sessions in which the participants examined topics and problems associated with current approaches to the archaeological investigation of farmstead sites. These brainstorming sessions examined questions such as: What is a 19th-century farmstead? What are the research and public values of these sites? Which sites should be examined? and How should these sites be investigated? The workshop ended with the development of an action agenda with recommendations on how we as a discipline, and CNEHA as an organization, should proceed with the research, interpretation, and preservation of these types of sites

Ultra-small graphitization reactors for ultra-microscale 14C analysis at the National Ocean Sciences Accelerator Mass Spectrometry (NOSAMS) Facility

© The Arizona Board of Regents on behalf of the University of Arizona, 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Radiocarbon 57, no. 1 (2015): 109–122, doi:10.2458/azu_rc.57.18118.In response to the increasing demand for 14C analysis of samples containing less than 25 µg C, ultra-small graphitization reactors with an internal volume of ~0.8 mL were developed at NOSAMS. For samples containing 6 to 25 µg C, these reactors convert CO2 to graphitic carbon in approximately 30 min. Although we continue to refine reaction conditions to improve yield, the reactors produce graphite targets that are successfully measured by AMS. Graphite targets produced with the ultra-small reactors are measured by using the Cs sputter source on the CFAMS instrument at NOSAMS where beam current was proportional to sample mass. We investigated the contribution of blank carbon from the ultra-small reactors and estimate it to be 0.3 ± 0.1 µg C with an Fm value of 0.43 ± 0.3. We also describe equations for blank correction and propagation of error associated with this correction. With a few exceptions for samples in the range of 6 to 7 µg C, we show that corrected Fm values agree with expected Fm values within uncertainty for samples containing 6–100 µg C.This work was funded by the NSF Cooperative Agreement for the Operation of a National Ocean Sciences Accelerator Mass Spectrometry Facility (OCE-0753487). S R Shah Walter was also partially supported by the WHOI Postdoctoral Scholar Program

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context - Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective - To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design - Cross-sectional, case-control, whole-brain DTI using TBSS. Setting - University research institute. Participants - Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures - Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results - Subjects with BD vs controls had significantly greater FA (t > 3.0, P = .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P = .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions - To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD

Regional-Specific Effects of Ovarian Hormone Loss on Synaptic Plasticity in Adult Human APOE Targeted Replacement Mice

The human apolipoprotein ε4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer’s disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR) mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX) mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD

CCL2 Accelerates Microglia-Mediated Aβ Oligomer Formation and Progression of Neurocognitive Dysfunction

The linkages between neuroinflammation and Alzheimer's disease (AD) pathogenesis are well established. What is not, however, is how specific immune pathways and proteins affect the disease. To this end, we previously demonstrated that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a Swedish beta-amyloid (Abeta) precursor protein mutant.We now report that CCL2 transgene expression accelerates deficits in spatial and working memory and hippocampal synaptic transmission in beta-amyloid precursor protein (APP) mice as early as 2-3 months of age. This is followed by increased numbers of microglia that are seen surrounding Abeta oligomers. CCL2 does not suppress Abeta degradation. Rather, CCL2 and tumor necrosis factor-alpha directly facilitated Abeta uptake, intracellular Abeta oligomerization, and protein secretion.We posit that CCL2 facilitates Abeta oligomer formation in microglia and propose that such events accelerate memory dysfunction by affecting Abeta seeding in the brain

Regulation of Lean Mass, Bone Mass, and Exercise Tolerance by the Central Melanocortin System

Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity