Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Estimation of current density distribution under electrodes for external defibrillation

BACKGROUND: Transthoracic defibrillation is the most common life-saving technique for the restoration of the heart rhythm of cardiac arrest victims. The procedure requires adequate application of large electrodes on the patient chest, to ensure low-resistance electrical contact. The current density distribution under the electrodes is non-uniform, leading to muscle contraction and pain, or risks of burning. The recent introduction of automatic external defibrillators and even wearable defibrillators, presents new demanding requirements for the structure of electrodes. METHOD AND RESULTS: Using the pseudo-elliptic differential equation of Laplace type with appropriate boundary conditions and applying finite element method modeling, electrodes of various shapes and structure were studied. The non-uniformity of the current density distribution was shown to be moderately improved by adding a low resistivity layer between the metal and tissue and by a ring around the electrode perimeter. The inclusion of openings in long-term wearable electrodes additionally disturbs the current density profile. However, a number of small-size perforations may result in acceptable current density distribution. CONCLUSION: The current density distribution non-uniformity of circular electrodes is about 30% less than that of square-shaped electrodes. The use of an interface layer of intermediate resistivity, comparable to that of the underlying tissues, and a high-resistivity perimeter ring, can further improve the distribution. The inclusion of skin aeration openings disturbs the current paths, but an appropriate selection of number and size provides a reasonable compromise

Medical student case presentation performance and perception when using mobile learning technology in the emergency department

Hand-held mobile learning technology provides opportunities for clinically relevant self-instructional modules to augment traditional bedside teaching. Using this technology as a teaching tool has not been well studied. We sought to evaluate medical students’ case presentation performance and perception when viewing short, just-in-time mobile learning videos using the iPod touch prior to patient encounters.Twenty-two fourth-year medical students were randomized to receive or not to receive instruction by video, using the iPod Touch, prior to patient encounters. After seeing a patient, they presented the case to their faculty, who completed a standard data collection sheet. Students were surveyed on their perceived confidence and effectiveness after using these videos.Twenty-two students completed a total of 67 patient encounters. There was a statistically significant improvement in presentations when the videos were viewed for the first time (p = 0.032). There was no difference when the presentations were summed for the entire rotation (p = 0.671). The reliable (alpha = 0.97) survey indicated that the videos were a useful teaching tool and gave students more confidence in their presentations.Medical student patient presentations were improved with the use of mobile instructional videos following first time use, suggesting mobile learning videos may be useful in medical student education. If direct bedside teaching is unavailable, just-in-time iPod touch videos can be an alternative instructional strategy to improve first-time patient presentations by medical students

EEG Correlates of Attentional Load during Multiple Object Tracking

While human subjects tracked a subset of ten identical, randomly-moving objects, event-related potentials (ERPs) were evoked at parieto-occipital sites by task-irrelevant flashes that were superimposed on either tracked (Target) or non-tracked (Distractor) objects. With ERPs as markers of attention, we investigated how allocation of attention varied with tracking load, that is, with the number of objects that were tracked. Flashes on Target discs elicited stronger ERPs than did flashes on Distractor discs; ERP amplitude (0–250 ms) decreased monotonically as load increased from two to three to four (of ten) discs. Amplitude decreased more rapidly for Target discs than Distractor discs. As a result, with increasing tracking loads, the difference between ERPs to Targets and Distractors diminished. This change in ERP amplitudes with load accords well with behavioral performance, suggesting that successful tracking depends upon the relationship between the neural signals associated with attended and non-attended objects

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Electrical cardioversion during pregnancy: safe or not?

Two pregnant patients with a sustained symptomatic maternal supraventricular arrhythmia are presented. Both patients were treated with direct-current cardioversion. Electrical cardioversion during pregnancy is a rarely applied but highly effective procedure in the treatment of maternal cardiac arrhythmias and is assumed safe for both mother and child. However, once foetal viability is reached, monitoring of the foetal heart rate is advised and facilities for immediate caesarean section should be available

Risk factors for bone mineral density at the calcaneus in 40–59 year-old male workers: A cross-sectional study in Korea

<p>Abstract</p> <p>Background</p> <p>Few epidemiologic studies have attempted to investigate the prevalence and risk factors for osteopenia and osteoporosis in middle-aged Asian men. We performed this study to determine the prevalence and risk factors of osteopenia and osteoporosis in this population.</p> <p>Methods</p> <p>This cross-sectional study was conducted from March to July, 2004. The subjects were 2,073 males aged from 40 to 59 years in the KHNP (Korea Hydro & Nuclear Power) workplace-based cohort. Bone mineral density (BMD) was measured by peripheral, dual-energy, X-ray absorptiometry (DXA) at the calcaneus. Anthropometric and lifestyle factors were investigated using a standard, self-reported questionnaire.</p> <p>Results</p> <p>BMD was 0.60 ± 0.09 g/cm²(mean ± standard deviation) and was negatively correlated with age (r = -0.18, <it>P </it>< 0.001), but positively correlated with waist-to-hip ratio (WHR; r = 0.15, <it>P </it>< 0.001), body fat (r = 0.10, <it>P </it>< 0.001), BMI (r = 0.35, <it>P </it>< 0.001), height (r = 0.26, <it>P </it>< 0.001), and weight (r = 0.43, <it>P </it>< 0.001).</p> <p>In multiple linear regression analysis, the independent determinants associated with BMD were increasing age (coefficient = -0.002, <it>P </it>< 0.001), physical activity (≤ 2/week vs. ≥ 3/week; coefficient = 0.017, <it>P </it>< 0.001), WHR (coefficient = -0.796, <it>P </it>< 0.001), body mass index (BMI; coefficient = 0.023, <it>P </it>< 0.001) and smoking status (never vs. ever; coefficient = -0.018, <it>P </it>< 0.001).</p> <p>Conclusion</p> <p>We suggest that BMD of the calcaneus is correlated negatively with exposure to smoke and increased WHR, but positively with regular exercise and increased BMI.</p

Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains

BackgroundShortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet.ResultsChronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis.Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5 inverted question mark9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD.ConclusionIn conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern