Sex- and age-specific modulation of brain GABA levels in a mouse model of Alzheimer's disease

Solid state NMR/Biophysical Organic Chemistr

Distinct glutaminyl cyclase expression in Edinger–Westphal nucleus, locus coeruleus and nucleus basalis Meynert contributes to pGlu-Aβ pathology in Alzheimer’s disease

Glutaminyl cyclase (QC) was discovered recently as the enzyme catalyzing the pyroglutamate (pGlu or pE) modification of N-terminally truncated Alzheimer’s disease (AD) Aβ peptides in vivo. This modification confers resistance to proteolysis, rapid aggregation and neurotoxicity and can be prevented by QC inhibitors in vitro and in vivo, as shown in transgenic animal models. However, in mouse brain QC is only expressed by a relatively low proportion of neurons in most neocortical and hippocampal subregions. Here, we demonstrate that QC is highly abundant in subcortical brain nuclei severely affected in AD. In particular, QC is expressed by virtually all urocortin-1-positive, but not by cholinergic neurons of the Edinger–Westphal nucleus, by noradrenergic locus coeruleus and by cholinergic nucleus basalis magnocellularis neurons in mouse brain. In human brain, QC is expressed by both, urocortin-1 and cholinergic Edinger–Westphal neurons and by locus coeruleus and nucleus basalis Meynert neurons. In brains from AD patients, these neuronal populations displayed intraneuronal pE-Aβ immunoreactivity and morphological signs of degeneration as well as extracellular pE-Aβ deposits. Adjacent AD brain structures lacking QC expression and brains from control subjects were devoid of such aggregates. This is the first demonstration of QC expression and pE-Aβ formation in subcortical brain regions affected in AD. Our results may explain the high vulnerability of defined subcortical neuronal populations and their central target areas in AD as a consequence of QC expression and pE-Aβ formation

Capacity and Procedural Accounts of Impaired Memory in Depression

Findings of impaired memory in states of dysphoria or depression are summarized and subsumed under different accounts of mood-related memory deficits. Theoretical accounts based on the assumption of a storage system of limited capacity are compared to accounts which emphasize the role of procedures and strategies in attending and remembering. Two reanalyses of a recent experiment in the process-dissociation paradigm are reported. They address issues of dysphoria-related differences in automatic versus controlled uses of memory in a task of word-stem completion. The two reanalyses rest on different assumptions about the relation between automatic and controlled components, but they converge in highlighting the advantages of a procedural rather than capacity-based view of memory deficits. finally. similarities to other research domains and theoretical approaches are outlined

Correlates of women's cancer screening and contraceptive knowledge among female emergency department patients

<p>Abstract</p> <p>Background</p> <p>Lack of knowledge regarding preventive health services for women might impede campaigns to expand these services in the emergency department setting. For 18–55-year-old English-speaking women visiting an urban emergency department, we aimed to: (1) Ascertain their knowledge regarding the applicability, purpose, and recommended intervals of three women's cancer screening and three contraceptive methods; and (2) Determine if patient age, race/ethnicity, medical insurance status, and current or recent usage of these methods are associated with greater or lesser knowledge about them.</p> <p>Methods</p> <p>Emergency department-based survey on recent or current usage and knowledge about Pap smears, breast self-examinations, mammograms, condoms, birth control, and emergency contraception. Analyses included calculation of summary statistics and creation of multivariable logistic regression models.</p> <p>Results</p> <p>Of 1,100 patients eligible for the study, 69.9% agreed to participate. Most of the participants were < age 35, white, single (never married and no partner), Catholic, and had private medical insurance. Participant's recent or current usage of a particular cancer screening or contraceptive method varied by type of method: Pap smear within the past year (69.1%), breast self-exam within the past month (45.5%), mammogram within the past year (65.7% for women age 45–55), condom usage during every episode of sexual intercourse (15.4%), current usage of birth control pills (17.8%), and ever use of emergency contraception (9.3%). The participants correctly answered 87.9% of all survey questions about condoms, 82.5% about birth control pills, 78.5% about breast self-exams, 52.9% about Pap smears, 35.4% about mammograms, and 25.0% about emergency contraception. In multivariable logistic regression models, survey participants who had private medical insurance and those who recently or currently used a given screening or contraceptive method had a greater odds of correctly answering all questions about each cancer screening or contraceptive method.</p> <p>Conclusion</p> <p>Although these female ED patients demonstrated strong knowledge on some women's cancer screening and contraceptive methods, there were several areas of knowledge deficit. Women without private medical insurance and those who have not used a particular cancer screening or contraceptive method demonstrated less knowledge. Reduced knowledge about women's cancer screening and contraceptive methods should be considered during clinical encounters and when instituting or evaluating emergency department-based initiatives that assess the need for these methods.</p

Resisting the mantle of the monstrous feminine : women's construction and experience of premenstrual embodiment

The female reproductive body is positioned as abject, as other, as site of defciency and disease, the epitome of the ‘monstrous feminine.’ Premenstrual change in emotion, behavior or embodied sensation is positioned as a sign of madness within, necessitating restraint and control on the part of the women experiencing it (Ussher 2006). Breakdown in this control through manifestation of ‘symptoms’ is diagnosed as PMS (Premenstrual Syndrome) or PMDD (Premenstrual Dysphoric Disorder), a pathology deserving of ‘treatment.’ In this chapter, we adopt a feminist material-discursive theoretical framework to examine the role of premenstrual embodiment in relation to women’s adoption of the subject position of monstrous feminine, drawing on interviews we have conducted with women who self-diagnose as ‘PMS sufferers.’ We theorize women’s self-positioning as subjectifcation, wherein women take up cultural discourse associated with idealized femininity and the reproductive body, resulting in self-objectifcation, distress, and self-condemnation. However, women can resist negative cultural constructions of premenstrual embodiment and the subsequent self-policing. We describe the impact of women-centered psychological therapy which increases awareness of embodied change, and leads to greater acceptance of the premenstrual body and greater self-care, which serves to reduce premenstrual distress

Quantitative assessment of paravalvular regurgitation following transcatheter aortic valve replacement

Paravalvular aortic regurgitation (PAR) following transcatheter aortic valve implantation (TAVI) is well acknowledged. Despite improvements, echocardiographic measurement of PAR largely remains qualitative. Cardiovascular magnetic resonance (CMR) directly quantifies AR with accuracy and reproducibility. We compared CMR and transthoracic echocardiography (TTE) analysis of pre-operative and post-operative aortic regurgitation in patients undergoing both TAVI and surgical aortic valve replacement (AVR).Gareth Crouch, Phillip J Tully, Jayme Bennetts, Ajay Sinhal, Craig Bradbrook, Amy L Penhall, Carmine G De Pasquale, Robert A Baker, and Joseph B Selvanayaga

Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

<p>Abstract</p> <p>Background</p> <p>Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4-<it>O</it>-methylhonokiol, a constituent of <it>Magnolia officinalis</it>, on memory deficiency caused by LPS, along with the underlying mechanisms.</p> <p>Methods</p> <p>We investigated whether 4-<it>O</it>-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-<it>O</it>-methylhonkiol (0.5, 1 and 2 μM).</p> <p>Results</p> <p>Oral administration of 4-<it>O</it>-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-<it>O</it>-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In <it>in vitro </it>study, we also found that 4-<it>O</it>-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E₂, tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4-<it>O</it>-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4-<it>O</it>-methylhonokiol inhibited LPS-induced Aβ_1-42generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells.</p> <p>Conclusion</p> <p>These results suggest that 4-<it>O</it>-methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4-<it>O</it>-methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.</p