The effects of thyrotropin-releasing hormone and scopolamine in Alzheimer's disease and normal volunteers

Thyrotropin-releasing hormone (TRH), a neuromodulator and possibly a neurotransmitter in the central nervous system, was shown in a prior study of young normal volunteers to attenuate the memory impairment induced by the anticholinergic drug scopolamine. In the present study, the cognitive, behavioral and physiologic effects of high dose TRH (0.5 mg/kg), both alone and following administration of scopolamine, were examined in 10 Alzheimer's disease (AD) patients (mean age±SD=63.5 years) and 12 older normal volunteers (mean age=64.9±8.8 years). On the day AD subjects received TRH alone, modest but statistically significant improvement from baseline performance was documented on some tests of learning and memory, especially in those with mild dementia severity. In comparing cognitive test performance between the scopolamine alone and scopolamine+TRH conditions, only two test scores were significantly higher in the latter condition. In the group of older volunteers, TRH did not attenuate scopolamine-induced cognitive impairment, contrary to prior findings in a group of younger controls. In fact, older subjects performed worse after receiving scopolamine followed by TRH than after receiving scopolamine alone. In addition, no change from baseline cognitive performance was detected after subjects received TRH alone. These findings raise several questions and speculations on possible age-related changes in the cholinergic system, as well as on the mechanism of the interaction of TRH with the cholinergic system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68371/2/10.1177_026988119200600404.pd

Detection of gastrointestinal cancer by elastic scattering and absorption spectroscopies with the Los Alamos Optical Biopsy System

The Los Alamos National Laboratory has continued the development of the Optical Biopsy System (OBS) for noninvasive, real-time in situ diagnosis of tissue pathologies. In proceedings of earlier SPIE conferences we reported on clinical measurements in the bladder, and we report here on recent results of clinical tests in the gastrointestinal tract. With the OBS, tissue pathologies are detected/diagnosed using spectral measurements of the elastic optical transport properties (scattering and absorption) of the tissue over a wide range of wavelengths. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the fact that many tissue pathologies, including a majority of cancer forms, exhibit significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes m an optical signature that is derived from the wavelength-dependence of elastic scattering. Additionally, the optical geometry of the OBS beneficially enhances its sensitivity for measuring absorption bands. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope or catheter, or to direct surface examination, as well as interstitial needle insertion. Data acquistion/display time is <1 second

A preliminary study of the effects of nighttime administration of the serotonin agonist, m-CPP, on sleep architecture and behavior in healthy volunteers

The effects of m-chlorophenylpiperazine (m-CPP) (0.5 mg/kg) on sleep architecture and behavior were examined in six healthy volunteers following a single or oral dose of the drug in a randomized, double-blind, placebo-controlled study, m-CPP reduced total leep time (TST) and sleep efficiency in all subjects. Slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep were decreased and stage 1 sleep was prolonged in a majority of subjects. Prominent behavioral and psychological effects were reported in five out of six subjects following m-CPP (but not following placebo) that interfered with sleep. The sleep disruption and behavioral activation following nighttime administration of m-CPP contrasts with the sedative properties of its parent compound, trazodone, suggesting that the hypnotic effect of trazodone is not related to the agonist profile of its metabolite, m-CPP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29486/1/0000572.pd

Anglican clergy husbands securing middle-class gendered privilege through religion

Traditionally, clergy wives have been obliged to assist the Church in an unpaid capacity; such work has been feminised, associated with the assumed competencies of women (Denton 1962; Finch 1980, 1983; Murphy-Geiss 2011). Clergy husbands are a relatively recent phenomenon in the Church of England, emerging when women started to be ordained as deacons in 1987 and priests in 1994. Based on interviews with men whose wives were ordained as priests in the Church of England, this article will explore the dynamics of class and gender privilege. Most clergy husbands were middle class, defined through educational, occupational and cultural markers (Bourdieu 1984). The narratives highlighted how gender and class privilege was maintained and extended through the clergy spouse role. The interweaving dynamics of class and gender privilege secured preferential outcomes for participants; outcomes that were less evidenced in relation to working-class spouses. Using Bourdieu’s (1984) concepts of habitus, field and capital and Verter’s (2003) conceptualisation of spiritual capital, this article will highlight the complex ways in which gender and class advantage is perpetuated and sustained, using the Anglican parish as the analytical context, thereby emphasising the role religion plays in consolidating privilege

Worker Reallocation Across Occupations in Western Germany

This paper analyzes the determinants of annual worker reallocation across disaggregated occupations in western Germany for the period 1985-2003. Employing data from the German Socio-Economic Panel, the pattern of average occupational mobility is documented. Worker reallocation is found to be strongly procyclical. Its determinants at the individual level are then investigated while controlling for unobserved worker heterogeneity. A dynamic probit fixed effects model is estimated to obtain coefficients and marginal effects. The incidental parameter bias is reduced by the method proposed in Hahn and Kuersteiner (2004). An interesting finding is that workers changing occupation are about 8 to 9 percent less inclined to experience occupational mobility in the subsequent year than workers who do not change. Except for workers with only compulsory education, the impact of age on the probability of occupational change is declining in the level of education. The unemployment rate has a negative effect on the probability of occupational changes, especially for female foreigners

Current practice of trabeculectomy in a cohort of experienced glaucoma surgeons in Australia and New Zealand

Background/Objectives: To evaluate current routine trabeculectomy technique preferences among Australian and New Zealand Glaucoma Society surgeons regularly performing trabeculectomy surgery. Subjects/Methods: Survey of experienced surgeons who perform trabeculectomy. Results: Forty-nine surgeons (33 male:16 female) participated in the survey. Trabeculectomy was performed as day surgery (39/47, 83.0%) under local anesthesia (44/47, 93.6%). The surgical techniques most commonly used were a corneal traction suture (44/47, 93.6%), fornix-based conjunctival flap (43/47, 91.5%) and half-thickness scleral flap (38/47, 81.0%). Mitomycin C antifibrotic agent was used in routine cases by 45/46 (97.8%) surgeons. Surgeons applied the antifibrotic agent under the Tenon layer with a pledget (36/46, 78.2%) with a concentration of 0.02% (37/46, 80.4%) for 2 (11/46, 23.9%) or 3 min (30/46, 65.2%). The Kelly (26/46, 56.5%) and the Khaw Descemet (19/46, 41.3%) punches were used to perform the sclerostomy. Most surgeons performed a peripheral iridectomy in all phakic patients (46/47, 97.9%), but less commonly in pseudophakic patients (34/47, 72.3%). Techniques for closure of the limbal conjunctival edge were quite varied with a combination of suturing including purse string (21/47, 57.4%), wing (20/47, 42.6%) and horizontal mattress sutures (33/47, 70.2%). Surgeons reviewed their routine patients four times in the first month (29/47, 61.7%) and continued the postoperative topical steroids for 3–4 months (28/47, 59.6%). Conclusions: Although a wide range of techniques for trabeculectomy exists among surgeons, there are consistent procedures currently in use to optimize patient outcomes. This report will assist surgeons in choosing which surgical techniques fit their best practice

Expression of a protease-resistant insulin-like growth factor-binding protein-4 inhibits tumour growth in a murine model of breast cancer

BACKGROUND: Insulin-like growth factor 1 (IGF1) promotes breast cancer and disease progression. Bioavailability of IGF1 is modulated by IGF-binding proteins (IGFBPs). IGFBP4 inhibits IGF1 activity but cleavage by pregnancy-associated plasma protein-A (PAPP-A) protease releases active IGF1. METHODS: Expression of IGF pathway components and PAPP-A was assessed by western blot or RT-PCR. IGFBP4 (dBP4) resistant to PAPP-A cleavage, but retaining IGF-binding capacity, was used to block IGF activity in vivo. 4T1.2 mouse mammary adenocarcinoma cells transfected with empty vector, vector expressing wild-type IGFBP4 or vector expressing dBP4 were implanted in the mammary fat pad of BALB/c mice and tumour growth was assessed. Tumour angiogenesis and endothelial cell apoptosis were assessed by immunohistochemistry. RESULTS: 4T1.2 cells expressed the IGF1R receptor and IGFBP4. PAPP-A was expressed within mammary tumours but not by 4T1.2 cells. Proliferation and vascular endothelial growth factor (VEGF) production by 4T1.2 cells was increased by IGF1(E3R) (recombinant IGF1 resistant to binding by IGFBPs) but not by wild-type IGF1. IGF1-stimulated microvascular endothelial cell proliferation was blocked by recombinant IGFBP4. 4T1.2 tumours expressing dBP4 grew significantly more slowly than controls or tumours expressing wild-type IGFBP4. Inhibition of tumour growth by dBP4 was accompanied by the increased endothelial cell apoptosis. CONCLUSION: Protease-resistant IGFBP4 blocks IGF activity, tumour growth and angiogenesis

Characterising activity and diet compositions for dementia prevention: protocol for the ACTIVate prospective longitudinal cohort study

Introduction Approximately 40% of late-life dementia may be prevented by addressing modifiable risk factors, including physical activity and diet. Yet, it is currently unknown how multiple lifestyle factors interact to influence cognition. The ACTIVate Study aims to (1) explore associations between 24-hour time-use and diet compositions with changes in cognition and brain function; and (2) identify duration of time-use behaviours and the dietary compositions to optimise cognition and brain function.Methods and analysis This 3-year prospective longitudinal cohort study will recruit 448 adults aged 60-70 years across Adelaide and Newcastle, Australia. Time-use data will be collected through wrist-worn activity monitors and the Multimedia Activity Recall for Children and Adults. Dietary intake will be assessed using the Australian Eating Survey food frequency questionnaire. The primary outcome will be cognitive function, assessed using the Addenbrooke's Cognitive Examination-III. Secondary outcomes include structural and functional brain measures using MRI, cerebral arterial pulse measured with diffuse optical tomography, neuroplasticity using simultaneous transcranial magnetic stimulation and electroencephalography, and electrophysiological markers of cognitive control using event-related potential and time frequency analyses. Compositional data analysis, testing for interactions between time point and compositions, will assess longitudinal associations between dependent (cognition, brain function) and independent (time-use and diet compositions) variables. Conclusions The ACTIVate Study will be the first to examine associations between time-use and diet compositions, cognition and brain function. Our findings will inform new avenues for multidomain interventions that may more effectively account for the co-dependence between activity and diet behaviours for dementia prevention. Ethics and dissemination Ethics approval has been obtained from the University of South Australia's Human Research Ethics committee (202639). Findings will be disseminated through peer-reviewed manuscripts, conference presentations, targeted media releases and community engagement events. Trial registration number >Australia New Zealand Clinical Trials Registry (ACTRN12619001659190).Ashleigh E Smith, Alexandra T Wade, Timothy Olds, Dorothea Dumuid, Michael J Breakspear, Kate Laver ... et al