Promoting Neuron Adhesion and Growth

During nervous system development, the extracellular matrix (ECM) plays a pivotal role offering anchorage points to maturing neurons and neurites, as well as a permissive environment for tissue formation. Thus enhancement of cell adhesion is often an important criterion when designing biomaterials for neural tissue engineering. In addition to functionalizing biomaterials with ECM-derived cell adhesive molecules, there is emerging evidence that indicates the surface topography, stiffness, and electrical properties play an important role in neuron adhesion and neurite outgrowth. We describe recent developments in biomaterials modification for simulating the microenvironment in order to promote neuron adhesion and growth, as well as to encourage nerve regeneration after injury or disease. http://dx.doi.org/10.1016/S1369-7021(08)70088-

Peripheral Blood Mitochondrial DNA as a Biomarker of Cerebral Mitochondrial Dysfunction Following Traumatic Brain Injury in a Porcine Model

Background Traumatic brain injury (TBI) has been shown to activate the peripheral innate immune system and systemic inflammatory response, possibly through the central release of damage associated molecular patterns (DAMPs). Our main purpose was to gain an initial understanding of the peripheral mitochondrial response following TBI, and how this response could be utilized to determine cerebral mitochondrial bioenergetics. We hypothesized that TBI would increase peripheral whole blood relative mtDNA copy number, and that these alterations would be associated with cerebral mitochondrial bioenergetics triggered by TBI. Methodology Blood samples were obtained before, 6 h after, and 25 h after focal (controlled cortical impact injury: CCI) and diffuse (rapid non-impact rotational injury: RNR) TBI. PCR primers, unique to mtDNA, were identified by aligning segments of nuclear DNA (nDNA) to mtDNA, normalizing values to nuclear 16S rRNA, for a relative mtDNA copy number. Three unique mtDNA regions were selected, and PCR primers were designed within those regions, limited to 25-30 base pairs to further ensure sequence specificity, and measured utilizing qRT-PCR. Results Mean relative mtDNA copy numbers increased significantly at 6 and 25 hrs after following both focal and diffuse traumatic brain injury. Specifically, the mean relative mtDNA copy number from three mitochondrial-specific regions pre-injury was 0.84 ± 0.05. At 6 and 25 h after diffuse non-impact TBI, mean mtDNA copy number was significantly higher: 2.07 ± 0.19 (P \u3c 0.0001) and 2.37 ± 0.42 (P \u3c 0.001), respectively. Following focal impact TBI, relative mtDNA copy number was also significantly higher, 1.35 ± 0.12 (P \u3c 0.0001) at 25 hours. Alterations in mitochondrial respiration in the hippocampus and cortex post-TBI correlated with changes in the relative mtDNA copy number measured in peripheral blood. Conclusions Alterations in peripheral blood relative mtDNA copy numbers may be a novel biosignature of cerebral mitochondrial bioenergetics with exciting translational potential for non-invasive diagnostic and interventional studies

Capacity self-assessment as a catalyst for improved municipal service delivery

CITATION: Van Baalen, S. M., Schutte, C. S. L. & Von Leipzig, K. 2015. Capacity self-assessment as a catalyst for improved municipal service delivery. Journal of the South African Institution of Civil Engineering, 57(1):2–15, doi:10.17159/2309-8775/2015/v57n1a1.The original publication is available at http://www.scielo.org.zaENGLISH ABSTRACT: This research paper illustrates that accurate and truthful capacity assessments are a fundamental phase of any capacity building process, and that capacity assessments play a fundamental role in reaching the necessary performance efficiency. Service delivery performance enhancements by municipalities are becoming increasingly necessary. At the same time, however, the majority of municipalities in South Africa find themselves under-capacitated. Some municipalities are aware of the lack of capacity within their organisation, but are unable to identify, define and quantify these shortcomings. Many other municipalities are not aware of their capacity shortfalls. In both cases, this is often caused by the lack of necessary systems and procedures to assess the different dimensions of organisational capacity. In this regard, this research paper introduces a proposed Subjective Municipal Capacity Self-Assessment Model (SMCSAM) as an alternative solution to the current practices of the Municipal Demarcation Board. It is intended that this model be used internally by municipalities to sustain internal capacity building and performance enhancement initiatives.AFRIKAANSE OPSOMMING: Geen opsomming beskikbaarhttp://www.scielo.org.za/scielo.php?script=sci_abstract&pid=S1021-20192015000100001&lng=en&nrm=iso&tlng=enPublisher's versio

The rate of hypo-osmotic challenge influences regulatory volume decrease (RVD) and mechanical properties of articular chondrocytes

Zhao Wang is funded on a China Scholarships PhD Studentship. Jerome Irianto was supported on a project grant from The Wellcome Trust (ref no. 084717)

Disparities and guideline adherence in drugs of abuse screening in intracerebral hemorrhage

OBJECTIVE: To characterize the pattern of urine drug screening in a cohort of intracerebral hemorrhage (ICH) patients at our academic centers. METHODS: We identified cases of primary ICH occurring from 2009 to 2011 in our academic centers. Demographic data, imaging characteristics, processes of care, and short-term outcomes were ascertained. We performed logistic regression to identify predictors for screening and evaluated preguideline and postguideline reiteration screening patterns. RESULTS: We identified 610 patients with primary ICH in 2009-2011; 379 (62.1%) were initially evaluated at an outside hospital. Overall, 142/610 (23.3%) patients were screened, with 21 positive for cocaine and 3 for amphetamine. Of patients <55 years of age, only 65/140 (46.4%) were screened. Black patients <55 years of age were screened more than nonblack patients <55 years of age (38/61 [62.3%] vs 27/79 [34.2%]; p = 0.0009). In the best multivariable model, age group (p = 0.0001), black race (p = 0.4529), first Glasgow Coma Scale score (p = 0.0492), current smoking (p < 0.0001), and age group × black race (p = 0.0097) were associated with screening. Guideline reiteration in 2010 did not improve the proportion <55 years of age who were screened: 42/74 (56.8%) were screened before and 23/66 (34.9%) after (p = 0.01). CONCLUSIONS: We found disparities in drugs of abuse (DOA) screening and suboptimal guideline adherence. Systematic efforts to improve screening for DOA are warranted. Improved identification of sympathomimetic exposure may improve etiologic classification and influence decision-making and prognosis counseling

Cooperative learning in the first year of undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Despite extensive research data indicating that cooperative learning promotes higher achievement, the creation of positive relationships, and greater psychological health for students at all levels in their education, cooperative learning as a teaching strategy is still underutilized in undergraduate medical education.</p> <p>Methods</p> <p>A cooperative learning task was introduced as part of the mandatory first Year undergraduate Pathology course. The task was to create an 8.5" × 11" poster summary of pre-assigned content in self-chosen groups of four or five students. On the designated "Poster Day," the posters were displayed and evaluated by the students using a group product evaluation. Students also completed an individual group process reflection survey. An objective evaluation of their understanding was gauged at the midterm examination by specific content-related questions.</p> <p>Results</p> <p>Majority (91–96%) of students judged the group products to be relevant, effective, easy-to-understand, and clearly communicated. The majority of the students (90–100%) agreed that their group process skills of time management, task collaboration, decision-making and task execution were effective in completing this exercise. This activity created a dynamic learning environment as was reflected in the students' positive, professional discussion, and evaluation of their posters. The content-related questions on the midterm examination were answered correctly by 70–92% of the students. This was a mutually enriching experience for the instructor and students.</p> <p>Conclusion</p> <p>These findings demonstrate that cooperative learning as a teaching strategy can be effectively incorporated to address both content <it>and </it>interpersonal skill development in the early years of undergraduate medical education.</p

The Pine River Statement: Human Health Consequences of DDT Use

Objectives: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction: We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDThttp://dx.doi.org/10.1289/ehp.1174

Potential drug interactions and duplicate prescriptions among ambulatory cancer patients: a prevalence study using an advanced screening method

<p>Abstract</p> <p>Background</p> <p>The pharmacotherapeutic treatment of patients with cancer is generally associated with multiple side-effects. Drug interactions and duplicate prescriptions between anti-cancer drugs or interactions with medication to treat comorbidity can reinforce or intensify side-effects.</p> <p>The aim of the present study is to gain more insight into the prevalence of drug interactions and duplicate prescriptions among patients being treated in the outpatient day care departments for oncology and hematological illnesses. For the first time the prevalence of drug interactions with OTC-drugs in cancer patients will be studied. Possible risk factors for the occurrence of these drug-related problems will also be studied.</p> <p>Methods/Design</p> <p>A multicenter cross-sectional observational study of the epidemiology of drug interactions and duplicate prescriptions is performed among all oncology and hemato-oncology patients treated with systemic anti-cancer drugs at the oncology and hematology outpatient day care department of the VU University medical center and the Zaans Medical Center.</p> <p>Discussion</p> <p>In this article the prevalence of potential drug interactions in outpatient day-care patients treated with anti-cancer agents is studied using a novel more extensive screening method. If this study shows a high prevalence of drug interactions clinical pharmacists and oncologists must collaborate to develop a pharmaceutical screening programme, including an automated electronic warning system, to support drug prescribing for ambulatory cancer patient. This programme could minimize the occurrence of drug related problems such as drug interactions and duplicate prescriptions, thereby increasing quality of life.</p> <p>Trial registration</p> <p>This study is registered, number NTR2238.</p

Retroviral DNA Integration: Viral and Cellular Determinants of Target-Site Selection

Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates preferentially within active transcription units, whereas murine leukemia virus (MLV) integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN) coding region into HIV (to make HIVmIN) caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN) further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag) displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I–hypersensitive sites (i.e., +/− 1 kb), and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins