A general framework for experiment design in diffusion MRI and its application in measuring direct tissue‐microstructure features

This article introduces a new and general framework for optimizing the experiment design for diffusion MRI of samples with unknown orientation. An illustration then uses the framework to study the feasibility of measuring direct features of brain‐tissue microstructure in vivo. The study investigates the accuracy and precision with which we can estimate potentially important new biomarkers such as axon density and radius in white matter. Simulation experiments use a simple model of white matter based on CHARMED (composite hindered and restricted model of diffusion). The optimization finds acquisition protocols achievable on modern human and animal systems that consist of 120 measurements with fixed maximum gradient strengths. Axon radii in brain tissue are typically in the range 0.25–10 μm. Simulations suggest that estimates of radii in the range 5–10 μm have highest precision and that a maximum gradient strength of 0.07 T m^?1 is sufficient to distinguish radii of 5, 10, and 20 μm. Smaller radii are more difficult to distinguish from one another but are identifiable as small. A maximum gradient strength of 0.2 T m^?1 distinguishes radii of 1 and 2 μm. The simulations also suggest that axon densities and diffusivity parameters in the normal range for white matter are recoverable. The experiment‐design optimization has applications well beyond the current work to optimize the protocol for fitting any model of the diffusion process. Magn Reson Med 60:439–448, 2008. © 2008 Wiley‐Liss, Inc.     

Effect of Hearing Aids on Psychosocial Dysfunctioning

The perception of communication abilities amongest adolescents with moderate and profound hearing loss was correlated with indices of psychosocial adjustment. This was done to determine whether the use of hearing aids could play a role in presence and improvement of psychosocial functioning among acquired hearing loss persons after the use of hearing aids. Amongest the deaf population, it was found that hearing loss did affect the social, the vocational, the personal and subjective well being, after intervention. The control group did not show any corresponding change except that the state anxiety among this group had increased.     

Investigating general practitioner engagement with pharmacists in Home Medicines Review

Abstract

The Home Medicines Review (HMR) involves a home visit from an accredited HMR pharmacist to review a patient’s medicines, and a report to the patient’s general practitioner (GP) with recommendations for improving medicine management. Notwithstanding evidence supporting the benefits of medicines review, broad uptake by GPs in Australia remains low. We developed the 10-item Home Medicines Review Inventory (HMRI) to assess GP attitudes and behaviours regarding the HMR and modelled factors associated with the frequency of GP engagement with HMRs. Four items assessing frequency of behaviours and six items assessing attitudes related to HMR were answered by 180 GPs in a national GP survey. The HMRI’s psychometric properties were examined with exploratory factor analysis (EFA), Rasch analysis, and correlations with related instruments. Structural equation modelling was used to evaluate factors associated with HMR-related behaviours. EFA and Rasch analysis generally supported the current format of the instrument. Attitudes to HMR, gender, previous positive experiences with pharmacists, a system for working together, and participation in joint education activities predicted frequency of HMR-related behaviours. Although GPs’ attitudes to HMR were generally positive, HMR-related behaviours tended to occur with low frequency. This instrument may be used to investigate why HMR uptake has thus far been low and also help identify opportunities for building interprofessional communication and trust between GPs and pharmacists.     

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified.     

Effects of Several Doses of ~(60)Co Gamma Irradiation on Mouse Peritoneal Macrophages

Effects of several doses of~(60)Co gamma irradiation on mouse macrophages were in-vestigated by means of quantitative cytochemistry.It was found that the activities of lysosomalenzymes(acid phosphatase(AcPase)and a-naphthyl acetate esterose(ANAE)),adenosinetriphosphatase(ATPase)and positive substances of periodic acid Schiff's reaction(PAS)inperitoneal macrophages were increased after total-body irradiation (1,3Gy),and decreasedwith the increase of doses of total-body irradiation(5,8Gy).Meanwhile,the phagocytic ca-pacity and the size of peritoneal macrophages of irradiated mice also changed as compared withthe control group.     

Prognostic significance of the number of metastatic lymph nodes in patients with gastric cancer

To confirm the prognostic significance of the number of the metastatic lymph nodes (MLN) in cases of gastric cancer, the results of surgical treatment of 668 patients with primary gastric cancer were analyzed retrospectively. Five-year survival rates were calculated with reference to the number of MLN, namely, none (89.2%), one to three (77.4%), four to six (55.8%), and seven or more (36.2%). Furthermore, even when the cancer had invaded the serosa, 5-year survival was significantly more frequent in patients with one to three MLN (71.7%) than in those with four to six (35.5%) or more than six (31.5%) (P less than 0.01), and the 5-year survival was close to that of patients with no MLN (70.5%). Not only qualitative but also quantitative evaluation of lymph node metastasis is essential for estimating the prognosis of patients with gastric cancer.     

Quality Control Standards for the Roots of Three Plumbago Species

Physicochemical parameters of roots of three Plumbago species, Plumbago capensis, P. rosea and P. zeylanica belonging to Plumbaginaceae were analyzed. Microbial contamination, aflatoxins, pesticide residue and heavy metal content were also determined. Attempt has also been made to estimate the biologically active chemical plumbagin present in them and the data compared. The study ensures that the quality control parameters do help in the proper standardization of the crude drugs in drug development process for global acceptance.     

Quantitative Structure–Activity Relationships (QSARs) of Pyrimidine Nucleosides as HIV-1 Antiviral Agents

The structural requirements for the antiviral activity of pyrimidine nucleosides against HIV-1 virus was evaluated with the Hansch SAR analysis. Antiviral activity is best related to the hydrophobicity and steric (L and B3) properties of the substituent at the C5 of pyrimidine ring. Further, the antiviral activity is related to B4 of the substituent at position 3' of the sugar ring with a positive slope. The activity of both uracil and cytosine derivatives can be related to their structure by the same equations, which indicates that the SARs are similar in these two groups of congeners. These results suggest that compounds with a small substituent at the 5 position of the pyrimidine ring and a flat substituent at the 3' position of the sugar ring will be the most active compounds against HIV-1 virus.     

Controlled Gastric Emptying. II. In Vitro Erosion and Gastric Residence Times of an Erodible Device in Beagle Dogs

An erodible gastric retention device fabricated from various polymeric blends was examined in vitro for its dissolution properties and in vivo in fasting dogs for assessment of its gastric retention potential. Dissolution studies were conducted with extruded rods of polymer blends to assess their potential as candidates for the erodible component of a gastrically retained device. Based on results from dissolution studies, rods of poly(ortho ester)/polyethylene blends (POE/PE) (45% erosion at pH 1.5 and 24 hr) were used to fabricate arms for tetrahedron-shaped devices. Corners for the tetrahedral device were fabricated from Silastic 382 loaded with 15% barium sulfate for X-ray visualization. Beagle dogs were dosed with tetrahedron-shaped test devices administered in gelatin capsules and gastric retention monitored by X ray over a 24-hr period. A comparison of in vitro erosion rates and in vivo performance of various polymer blends indicated a definite trend for increased gastric retention of devices made from the more slowly eroding blends. The results indicate that the blending of erodible and nonerodible polymers is a valid approach for obtaining materials that will provide the necessary structural properties to achieve gastric retention yet lose integrity within a desired time.