TRPM7 Is Required for Breast Tumor Cell Metastasis

TRPM7 encodes a Ca(2+)-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation. Cancer Res; 72(16); 4250-61. ?2012 AACR.     

Adherence to Child Feeding Practices and Child Growth: A Retrospective Cohort Analysis in Cambodia

Appropriate feeding in the first 1000 days of a child’s life is critical for their health and growth. We determined associations between adherence to age-appropriate feeding practices and child growth in Cambodia. Children (n = 1079) were included in the first follow-up (FU) data analyses and followed for 30 months (six FUs). Data were analyzed by generalized linear mixed-effect models. Children who adhered to feeding practices on at least three FUs, with an adequate minimal dietary diversity (MDD), a minimal acceptable diet (MAD), and age-appropriate daily feeding (ADF) were less stunted (14.8%, 12.3%, and 6.4%, respectively) than children who never adhered to these indicators (25.2%, 30.1%, and 24.8%, respectively). A higher adherence to MDD and ADF was associated with a higher height-for-age Z-score (HAZ) (β: 0.13, 95% CI: 0.01–0.25 and β: 0.36, 95% CI: 0.22–0.50), while a higher adherence to the MDD and MAD was associated with a higher weight-for-height Z-score (WHZ) (β: 0.19, 95% CI: 0.08–0.30; and β: 0.16, 95% CI: 0.05–0.27). A higher adherence to a minimum meal frequency (MMF) was associated with a lower HAZ (β: −0.99, 95% CI: −1.28–−0.70). Our findings showed that to reduce wasting and stunting in Cambodia, interventions should focus on improving both the quality and quantity of food intake of children under two while targeting the whole complementary feeding period.     

Fundic accommodation assessed by SPECT scanning: comparison with the gastric barostat

BACKGROUND: Recently, single photon emission computed tomography (SPECT) scanning was described as a non-invasive technique to assess fundic accommodation. However, in contrast with the barostat, no intragastric distending force is applied during SPECT scanning. We hypothesised that in the absence of a barostat balloon, SPECT scanning largely detects the volume effect of the ingested meal and is a rather insensitive tool to detect fundic relaxation. METHODS: After an overnight fast, healthy volunteers underwent a barostat study and SPECT scanning on two separate days to assess: (1) meal induced fundic accommodation (Nutridrink, 200 ml, 300 kcal); and (2) gastric relaxation to 1 mg intravenous glucagon. RESULTS: Fasting fundic volumes (145 (8) v 280 (32) ml; p=0.001) and average postprandial volume (329 (10) v 571 (53) ml; p=0.001) were significantly lower measured with SPECT compared with the barostat study. Meal induced fundic relaxation (183 (10) v 289 (46) ml; p=0.050) and the postprandial/fasting volume ratio (2.32 (0.10) v 2.27 (0.29); p=0.892) did not differ significantly between SPECT scanning and the barostat. However, no correlation could be determined between accommodation volumes measured by both techniques. In contrast with meal induced relaxation, the glucagon induced increase in fundic volume (19 (5) v 406 (56) ml; p=0.007) and post/pre glucagon ratio (1.16 (0.03) v 3.02 (0.54); p=0.046) were significantly lower when measured by SPECT scanning compared with the barostat. CONCLUSION: SPECT scanning detects changes in postprandial volume but is less suitable than the gastric barostat in detecting changes in gastric tone. Our study therefore questions its role as a tool to detect impaired accommodation and warrants further validation of this technique.     

Chronic Metformin Treatment is Associated with Reduced Myocardial Infarct Size in Diabetic Patients with ST-segment Elevation Myocardial Infarction

Purpose

Increased myocardial infarct (MI) size is associated with higher risk of developing left ventricular dysfunction, heart failure and mortality. Experimental studies have suggested that metformin treatment reduces MI size after induced ischaemia but human data is lacking. We aimed to investigate the effect of metformin on MI size in patients presenting with an acute MI.

Methods

All consecutive patients (n?=?3,288) presenting to our hospital with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI between January 2004 and December 2010 were included in this retrospective analysis. Patients with diabetes were divided according to metformin versus non-metformin based pharmacotherapy. MI size was estimated using peak values of serum creatine kinase (CK), myocardial band of CK (CK-MB), and troponin-T.

Results

We identified 677 (20.6 %) patients with diabetes, of whom 189 (27.9 %) were treated with metformin. Chronic metformin treatment was associated with lower peak levels of CK (1,101 vs. 1,422 U/L, P?=?0.005), CK-MB (152 vs. 182 U/L, P?=?0.018) and troponin-T (2.5 vs. 4.0 ng/L, P?=?0.021) compared to non-metformin using diabetics. After adjustment for age, sex, TIMI flow post PCI, and previous MI, the use of metformin treatment remained an independent predictor of smaller MI size. Patient with diabetes treated with metformin had even smaller MI size than patients without diabetes.

Conclusions

Chronic metformin treatment is associated with reduced MI size compared to non-metformin based strategies in diabetic patients presenting with STEMI. Metformin might have additional beneficial effects beyond glucose lowering efficacy.     

Evaluation of the Mediseus epidural simulator

The demand for increased patient safety has led to greater use of simulation training of health professionals performing medical procedures. The study aim was to evaluate the usefulness of the Mediseus? Epidural Simulator in teaching basic epidural needle-handling skills. Three groups of 15 anaesthetists (Novice=zero to two year anaesthesia trainees; Intermediate=three- to five-year anaesthesia trainees; Expert=consultants and regional-specialist anaesthetists) from three different medical centres participated. Each participant performed 20 simulated epidural needle insertions and was scored on several parameters (e.g. time, success of the insertion, bone collisions). Following familiarisation with the simulator and the needle insertions, participants answered seven questions on the applicability of the simulator to the teaching of basic epidural needle-handling skills. There was a clear learning effect with regard to the simulation procedure time, this decreasing throughout the experiment (P=0.037). There was no significant influence of either group or experience with the simulator in the study on the number or type of errors made. The quality of the simulation was scored 2.3 out of 5.0 (for bone simulation) and 4.7 (for loss-of-resistance simulation). All groups considered that the simulator was best suited for training prospective anaesthetists. Each group rated the usefulness of the simulator for training novices at greater than 3.0 out of 5.0. The Mediseus? Epidural Simulator seems to be an appropriate training device for an introduction to epidural needle insertion. For medical professionals with procedural knowledge, the simulation is not realistic enough and the simulator did not distinguish between the groups based on the errors made.     

Mutational scanning of large genes by extensive PCR multiplexing and two-dimensional electrophoresis: application to the RB1 gene

With the rapid increase in the number of identified human disease genes, the development of accurate and cost-efficient mutation tests has become opportune. Here we present a combination of extensive PCR multiplexing and two-dimensional (2-D) DNA electrophoresis to screen for mutations in 26 exons of the retinoblastoma (RB1) tumor suppressor gene. In 2-D electrophoresis, fragments are separated according to size and base pair sequence in non-denaturing and denaturing gradient gels, respectively. All target fragments, designed to have optimal melting characteristics, were prepared in a two-step PCR (a 6-plex long-PCR pre- amplification and a subsequent 25-plex short-PCR) followed by heteroduplexing. The mixture of PCR amplicons was then subjected to 2-D electrophoresis under a single set of experimental conditions. With this design, 35 previously identified mutations in 18 different exons were detected in 33 bilateral retinoblastoma patients. These results suggest that 2-D electrophoresis in this format provides a generally applicable, practical and fast way to diagnose with high accuracy large genes for a broad spectrum of possible disease-causing mutations.      

Relationship between image quality and ultrasound exposure level in diagnostic US devices

Ultrasonographic B-mode images were obtained at various exposure levels with three real-time diagnostic scanners. Adult human and tissue-equivalent phantom images were compared in terms of diagnostic content and depth of penetration. For the exposure level settings used, spatial-peak pulse-average intensities ranged from approximately 10 to 500 W/cm2. At the 3.50-3.75-MHz nominal frequencies used in the study, images of the human abdomen showed little discernible change in quality with varying exposure levels. However, phantom tests confirmed that depth of penetration is a function of exposure level. The results suggest that a judicious use of exposure level and receiver gain controls can be a practical means for minimizing patient exposure to ultrasound without sacrifice of diagnostic effectiveness.     

Deletion of the DXS165 locus in patients with classical Choroideremia

Using various probes from the Xq21 region which is known to carry the choroideremia (tapetochoroideal dystrophy, TCD) locus, we have screened the DNAs from eight unrelated male choroidermia patients for microdeletions. In two of these patients, but not in any of 45 males tested as controls, lack of hybridization signals with probe plbD5 suggested a deletion encompassing the DXS165 locus and (part of) the TCD gene. Absence of additional clinical features in these patients and the fact that two closely linked, and probably flanking, TCD markers (DXYS1 and DXS72) are not deleted may indicate that the physical distance between the DXS165 locus and the TCD gene is small.