Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Systematic analysis of research underfunding in maternal and perinatal health

Background  Little published evidence supports the widely held contention that research in pregnancy is underfunded compared with other disease areas.
Objectives  To assess absolute and relative government and charitable funding for maternal and perinatal research in the UK and internationally.
Search strategy, selection criteria, data collection, and analysis  Major research funding bodies and alliances were identified from an Internet search and discussions with opinion leaders/senior investigators. Websites and annual reports were reviewed for details of strategy, research spend, grants awarded, and allocation to maternal and/or perinatal disease using generic and disease-specific search terms.
Main results  Within the imprecision in the data sets, ≤1% of health research spend in the UK was on maternal/perinatal health. Other countries fared better with 1–4% investment, although nonexclusive categorisation may render this an overestimate. In low-resource settings, government funders focused on infectious disease but not maternal and perinatal health despite high relative disease burden, while global philanthropy concentrated on service provision rather than research. Although research expenditure has been deemed as appropriate for 'reproductive health' disease burden in the UK, there are no data on the equity of maternal/perinatal research spend against disease burden, which globally may justify a manyfold increase.
Author's conclusions  This systematic review of research expenditure and priorities from national and international funding bodies suggests relative underinvestment in maternal/perinatal health. Contributing factors include the low political priority given to women's health, the challenging nature of clinical research in pregnancy, and research capacity dearth as a consequence of chronic underinvestment.     

Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors.     

Problems in standartization of population fluorographic screening

The authors have developed the methodology and techniques for standardizing fluorographic screening by using computed technology. The proposed does not require any manually written registration, the accounting of both patient and fluorogram in-and-outflows, the keeping on-going medical documents and paper archives. At the same time the technique allows one to form computerized lists, the dates of patients' visits, to control radiologists' activities, to supervise control over the use of hospital and mobile equipment, to plan expendable materials, etc. The efficiency and novelty of the technology are based on the computerization to make a diagnosis, and to set up a centralized bank of data on patients. This provides favorable conditions for continuous monitoring of fluographic screening of the population at any level of management and administration.     

The role of acid in the pathogenesis of indomethacin-induced gastric antral ulcers in the rat.

BACKGROUND: The role of acid in the pathogenesis of indomethacin- induced ulcers of the rat gastric antrum was studied by comparing the effects of pretreating animals with both long-acting (loxtidine, AH22216) and short-acting (ranitidine and cimetidine) inhibitors of acid secretion. RESULTS: Ranitidine and cimetidine were much weaker at inhibiting antral damage when compared to their reported potencies as antisecretory agents. In marked contrast, loxtidine and AH22216 inhibited indomethacin-induced antral ulcers at doses similar to their reported potencies as inhibitors of acid secretion. Histological analysis at doses causing near maximal inhibition of macroscopic damage revealed an almost complete absence of ulcers but a large and significant increase in mucosal damage due to superficial erosions. Hourly dosing with hydrochloric acid reversed the protective effect of ranitidine, cimetidine and loxtidine on macroscopic damage and, histologically, this was associated with the widespread appearance of antral ulcers and a reduction in the proportion of mucosal damage caused by superficial erosions. CONCLUSIONS: The results of this study suggest that the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced antral ulcers involves at least two stages: (1) an initial acid-independent formation of mucosal erosions followed by (2) an acid-dependent conversion of erosions to frank ulcers. Clinically, drugs that suppress acid completely for long periods may be very effective in preventing NSAID-induced gastric antral ulcers.     

The Effects of Hormones of the Hypothalamo-Hypophyseal-Adrenal, Renin-Angiotensin, and Thyroid Hormone Systems on the Formation of Dyscirculatory Encephalopathy

Measurements were made of plasma levels of free (f) thyroxine (fT4), triiodothyronine (fT3), thyrotropic hormone (TSH), adrenocorticotrophic hormone (ACTH), aldosterone, and renin in patients with dyscirculatory encephalopathy (DE). Their influences on the development of chronic circulatory insufficiency were assessed. A total of 39 patients were studied (aged 45-73 years) with DE stages I and II, without acute or chronic (in the exacerbation phase) somatic illness. These observations showed that diffuse lesions of brain tissues of different severities were accompanied by the following changes in thyroid homeostasis: 1) significant combined increases in TSH without alteration to the "fT3-TSH" negative feedback regulatory mechanism in patients with stage I DE; 2) significant combined decreases in TSH levels with marked suppression of the conversion of thyroxine into triiodothyronine and an interaction with impairments in the "fT3-hypophysis" system in patients with stage II DE. In addition, there were changes (increases) in cortisol levels with simultaneous decreases in renin levels in patients with stage II DE as compared with patients with stage I DE. Correlation analysis demonstrated the absence of any relationship between the age of the patients, the state of hormonal homeostasis, and the extent of vascular stenosis. These results suggest a role for hormones of the hypothalamo-hypophyseal-adrenal, thyroid, and renin-angiotensin systems in the mechanism by which DE develops as well as the possibility of using tests for these hormones as additional criteria for assessing the severity of diffuse brain lesions.