The pH of the skin surface and its impact on the barrier function

The `acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e. g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e. g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases. Copyright (c) 2006 S. Karger AG, Base

A Comprehensive Model of Audiovisual Perception: Both Percept and Temporal Dynamics

The sparse information captured by the sensory systems is used by the brain to apprehend the environment, for example, to spatially locate the source of audiovisual stimuli. This is an ill-posed inverse problem whose inherent uncertainty can be solved by jointly processing the information, as well as introducing constraints during this process, on the way this multisensory information is handled. This process and its result - the percept - depend on the contextual conditions perception takes place in. To date, perception has been investigated and modeled on the basis of either one of two of its dimensions: the percept or the temporal dynamics of the process. Here, we extend our previously proposed audiovisual perception model to predict both these dimensions to capture the phenomenon as a whole. Starting from a behavioral analysis, we use a data-driven approach to elicit a Bayesian network which infers the different percepts and dynamics of the process. Context-specific independence analyses enable us to use the model's structure to directly explore how different contexts affect the way subjects handle the same available information. Hence, we establish that, while the percepts yielded by a unisensory stimulus or by the non-fusion of multisensory stimuli may be similar, they result from different processes, as shown by their differing temporal dynamics. Moreover, our model predicts the impact of bottom-up (stimulus driven) factors as well as of top-down factors (induced by instruction manipulation) on both the perception process and the percept itself

Team-taught versus individually taught undergraduate education: A qualitative study of student experiences and preferences

Team teaching is becoming more common in undergraduate programmes of study although the relative merits to the more traditional individually taught courses have not been determined for best practice. For this study, 15 final year undergraduate students were interviewed to gain insight into their learning experiences. A thematic analysis of the interview data identified the perceived advantages and disadvantages of each mode of teaching. The advantages of individually taught courses included: Consistency of content delivery and advice, Familiarity with the lecturer’s teaching style and better Continuity of the subject content. The disadvantage of individually taught modules included Missing knowledge, compared to a team approach. Advantages of team taught modules included: Greater insight into a topic delivered by multiple team members. Disadvantages included: Content overlap, Conflicting messages relating to assessment, team members not taking Ownership of their roles and responsibilities and a belief that overall Team failure is worse than individual failure to deliver a module well. The results revealed that individually taught modules were generally preferred to team taught modules. A set of best practice recommendations are proposed to address the challenges when delivering team-taught teaching and become more student focused

Efficacy of motor imagery in post-stroke rehabilitation: a systematic review

BACKGROUND: Evaluation of how Motor Imagery and conventional therapy (physiotherapy or occupational therapy) compare to conventional therapy only in their effects on clinically relevant outcomes during rehabilitation of persons with stroke. DESIGN: Systematic review of the literature METHODS: We conducted an electronic database search in seven databases in August 2005 and also hand-searched the bibliographies of studies that we selected for the review.Two reviewers independently screened and selected all randomized controlled trials that compare the effects of conventional therapy plus Motor Imagery to those of only conventional therapy on stroke patients.The outcome measurements were: Fugl-Meyer Stroke Assessment upper extremity score (66 points) and Action Research Arm Test upper extremity score (57 points).Due to the high variability in the outcomes, we could not pool the data statistically. RESULTS: We identified four randomized controlled trials from Asia and North America. The quality of the included studies was poor to moderate. Two different Motor imagery techniques were used (three studies used audiotapes and one study had occupational therapists apply the intervention). Two studies found significant effects of Motor Imagery in the Fugl-Meyer Stroke Assessment: Differences between groups amounted to 11.0 (1.0 to 21.0) and 3.2 (-4 to 10.3) respectively and in the Action Research Arm Test 6.1 (-6.2 to 18.4) and 15.8 (0.5 to 31.0) respectively. One study did not find a significant effect in the Fugl-Meyer Stroke Assessment and Color trail Test (p = 0.28) but in the task-related outcomes (p > 0.001). CONCLUSION: Current evidence suggests that Motor imagery provides additional benefits to conventional physiotherapy or occupational therapy. However, larger and methodologically sounder studies should be conducted to assess the benefits of Motor imagery

Gene expression profile of circulating tumor cells in breast cancer by RT-qPCR

<p>Abstract</p> <p>Background</p> <p>Circulating tumor cells (CTCs) have been associated with prognosis especially in breast cancer and have been proposed as a liquid biopsy for repeated follow up examinations. Molecular characterization of CTCs is difficult to address since they are very rare and the amount of available sample is very limited.</p> <p>Methods</p> <p>We quantified by RT-qPCR <it>CK-19, MAGE-A3, HER-2, TWIST1, hTERT α+β+</it>, and <it>mammaglobin </it>gene transcripts in immunomagnetically positively selected CTCs from 92 breast cancer patients, and 28 healthy individuals. We also compared our results with the CellSearch system in 33 of these patients with early breast cancer.</p> <p>Results</p> <p>RT-qPCR is highly sensitive and specific and can detect the expression of each individual gene at the one cell level. None of the genes tested was detected in the group of healthy donors. In 66 operable breast cancer patients, <it>CK-19 </it>was detected in 42.4%, <it>HER-2 </it>in 13.6%, <it>MAGE-A3 </it>in 21.2%, <it>hMAM </it>in 13.6%, <it>TWIST-1 </it>in 42.4%, and <it>hTERT α+β+ </it>in 10.2%. In 26 patients with verified metastasis, <it>CK-19 </it>was detected in 53.8%, <it>HER-2 </it>in 19.2%, <it>MAGE-A3 </it>in 15.4%, <it>hMAM </it>in 30.8%, <it>TWIST-1 </it>in 38.5% and <it>hTERT </it>α⁺β⁺in 19.2%. Our preliminary data on the comparison between RT-qPCR and CellSearch in 33 early breast cancer patients showed that RT-qPCR gives more positive results in respect to CellSearch.</p> <p>Conclusions</p> <p>Molecular characterization of CTCs has revealed a remarkable heterogeneity of gene expression between breast cancer patients. In a small percentage of patients, CTCs were positive for all six genes tested, while in some patients only one of these genes was expressed. The clinical significance of these findings in early breast cancer remains to be elucidated when the clinical outcome for these patients is known.</p

How does the general public view posthumous organ donation? A meta-synthesis of the qualitative literature

<p>Abstract</p> <p>Background</p> <p>Many individuals are unwilling to become posthumous organ donors, resulting in a disparity between the supply and demand for organ transplants. A meta-synthesis of the qualitative literature was therefore conducted to determine how the general public views posthumous organ donation.</p> <p>Methods</p> <p>Three online databases (PubMed, PsycINFO, Scopus) were searched for articles published between January 1990 and May 2008 using the following search terms: organ donation, qualitative, interview. Eligibility criteria were: examination of beliefs about posthumous organ donation; utilization of a qualitative research design; and publication in an English peer-reviewed journal. Exclusion criteria were examining how health professionals or family members of organ donors viewed posthumous organ donation. Grounded theory was used to identify the beliefs emerging from this literature. Thematically-related beliefs were then grouped to form themes.</p> <p>Results</p> <p>27 articles from 24 studies met the inclusion criteria and were reviewed. The major themes identified were: religion, death, altruism, personal relevance, the body, the family, medical professionals, and transplant recipients. An altruistic motivation to help others emerged as the most commonly identified motivator for becoming an organ donor, although feeling a sense of solidarity with the broader community and believing that donated organs are put to good use may be important preconditions for the emergence of this motivation. The two most commonly identified barriers were the need to maintain bodily integrity to safeguard progression into the afterlife and the unethical recovery of organs by medical professionals. The influence of stakeholder groups on willingness to become an organ donor was also found to vary by the level of control that each stakeholder group exerted over the donation recovery process and their perceived conflict of interest in wanting organ donation to proceed.</p> <p>Conclusions</p> <p>These findings afford insights into how individuals perceive posthumous organ donation.</p

How well do second-year students learn physical diagnosis? Observational study of an objective structured clinical examination (OSCE)

BACKGROUND: Little is known about using the Objective Structured Clinical Examination (OSCE) in physical diagnosis courses. The purpose of this study was to describe student performance on an OSCE in a physical diagnosis course. METHODS: Cross-sectional study at Harvard Medical School, 1997–1999, for 489 second-year students. RESULTS: Average total OSCE score was 57% (range 39–75%). Among clinical skills, students scored highest on patient interaction (72%), followed by examination technique (65%), abnormality identification (62%), history-taking (60%), patient presentation (60%), physical examination knowledge (47%), and differential diagnosis (40%) (p < .0001). Among 16 OSCE stations, scores ranged from 70% for arthritis to 29% for calf pain (p < .0001). Teaching sites accounted for larger adjusted differences in station scores, up to 28%, than in skill scores (9%) (p < .0001). CONCLUSIONS: Students scored higher on interpersonal and technical skills than on interpretive or integrative skills. Station scores identified specific content that needs improved teaching

Identification of a Kinase Profile that Predicts Chromosome Damage Induced by Small Molecule Kinase Inhibitors

Kinases are heavily pursued pharmaceutical targets because of their mechanistic role in many diseases. Small molecule kinase inhibitors (SMKIs) are a compound class that includes marketed drugs and compounds in various stages of drug development. While effective, many SMKIs have been associated with toxicity including chromosomal damage. Screening for kinase-mediated toxicity as early as possible is crucial, as is a better understanding of how off-target kinase inhibition may give rise to chromosomal damage. To that end, we employed a competitive binding assay and an analytical method to predict the toxicity of SMKIs. Specifically, we developed a model based on the binding affinity of SMKIs to a panel of kinases to predict whether a compound tests positive for chromosome damage. As training data, we used the binding affinity of 113 SMKIs against a representative subset of all kinases (290 kinases), yielding a 113×290 data matrix. Additionally, these 113 SMKIs were tested for genotoxicity in an in vitro micronucleus test (MNT). Among a variety of models from our analytical toolbox, we selected using cross-validation a combination of feature selection and pattern recognition techniques: Kolmogorov-Smirnov/T-test hybrid as a univariate filter, followed by Random Forests for feature selection and Support Vector Machines (SVM) for pattern recognition. Feature selection identified 21 kinases predictive of MNT. Using the corresponding binding affinities, the SVM could accurately predict MNT results with 85% accuracy (68% sensitivity, 91% specificity). This indicates that kinase inhibition profiles are predictive of SMKI genotoxicity. While in vitro testing is required for regulatory review, our analysis identified a fast and cost-efficient method for screening out compounds earlier in drug development. Equally important, by identifying a panel of kinases predictive of genotoxicity, we provide medicinal chemists a set of kinases to avoid when designing compounds, thereby providing a basis for rational drug design away from genotoxicity

Sperm Chromatin-Induced Ectopic Polar Body Extrusion in Mouse Eggs after ICSI and Delayed Egg Activation

Meiotic chromosomes in an oocyte are not only a maternal genome carrier but also provide a positional signal to induce cortical polarization and define asymmetric meiotic division of the oocyte, resulting in polar body extrusion and haploidization of the maternal genome. The meiotic chromosomes play dual function in determination of meiosis: 1) organizing a bipolar spindle formation and 2) inducing cortical polarization and assembly of a distinct cortical cytoskeleton structure in the overlying cortex for polar body extrusion. At fertilization, a sperm brings exogenous paternal chromatin into the egg, which induces ectopic cortical polarization at the sperm entry site and leads to a cone formation, known as fertilization cone. Here we show that the sperm chromatin-induced fertilization cone formation is an abortive polar body extrusion due to lack of spindle induction by the sperm chromatin during fertilization. If experimentally manipulating the fertilization process to allow sperm chromatin to induce both cortical polarization and spindle formation, the fertilization cone can be converted into polar body extrusion. This suggests that sperm chromatin is also able to induce polar body extrusion, like its maternal counterpart. The usually observed cone formation instead of ectopic polar body extrusion induced by sperm chromatin during fertilization is due to special sperm chromatin compaction which restrains it from rapid spindle induction and therefore provides a protective mechanism to prevent a possible paternal genome loss during ectopic polar body extrusion

MIRTFnet: Analysis of miRNA Regulated Transcription Factors

Several expression datasets of miRNA transfection experiments are available to analyze the regulatory mechanisms downstream of miRNA effects. The miRNA induced regulatory effects can be propagated via transcription factors (TFs). We propose the method MIRTFnet to identify miRNA controlled TFs as active regulators if their downstream target genes are differentially expressed