Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications

The evaluation of disability and its related factors among the elderly population in Kashan, Iran

<p>Abstract</p> <p>Background</p> <p>Recent literature indicates that developing countries in Asia are aging faster than other countries in the world and disability has become one of the greater public health concern in these countries. Pausity of published data on the elderly disability in Iran signifies the importance of this study designed to evaluate the disability and its related factors among the elderly population in Kashan, Iran during 2006–2007.</p> <p>Methods/Design</p> <p>A cross-sectional study is conducting on a multy-stage random sample of elderly people in Kashan ages 65 years and older. Volunteer participants were included by age 65 and older and excluded if they had the medical diagnosis of Alzhimer disease. The WHO DAS II was used as the generic disability measure in this survey. The original version of WHO DAS II was translated into Farsi according to the standardized guidelines for cross-cultural adaptation of health-related measures. Upon completion of data collection the descriptive statistics will compute all the variables. Chi-square, t-test analysis and ANOVA will be used to examine significant differences between the subgroups.</p> <p>Discussion</p> <p>This is the first research protocol to study disability among the Iranian elderly population. Presently, 80% of eligible subjects have been selected. The results of this study will help to develop more effective protocols to assist Iranian elderly population with disabilities.</p

Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies

Temozolomide, an oral cytotoxic agent with approximately 100% bioavailability after one administration, has demonstrated schedule-dependent clinical activity against highly resistant cancers. Thirty patients with minimal prior chemotherapy were enrolled in this phase I trial to characterize the drug's safety, pharmacokinetics and anti-tumour activity, as well as to assess how food affects oral bioavailability. To determine dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD), temozolomide 100–250 mg m−2 was administered once daily for 5 days every 28 days. The DLT was thrombocytopenia, and the MTD was 200 mg m−2 day−1. Subsequently, patients received the MTD to study how food affects the oral bioavailability of temozolomide. When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression. The most common non-haematological toxicities were mild to moderate nausea and vomiting. Clinical activity was observed against several advanced cancers, including malignant glioma and metastatic melanoma. Temozolomide demonstrated linear and reproducible pharmacokinetics and was rapidly absorbed (mean Tmax ~1 h) and eliminated (mean t1/2 = 1.8 h). Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide 200 mg m−2 day−1 for 5 days, every 28 days, is recommended for phase II studies. © 1999 Cancer Research Campaig

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Breast imaging technology: Probing physiology and molecular function using optical imaging - applications to breast cancer

The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring

Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database

A comparison of data held by the U.S. Food and Drug Administration (FDA) against data from journal reports of clinical trials enables estimation of the extent of publication bias for antipsychotics

Identification of novel Coxiella burnetii genotypes from Ethiopian ticks

Background: Coxiella burnetii , the etiologic agent of Q fever, is a highly infectious zoonotic bacterium. Genetic information about the strains of this worldwide distributed agent circulating on the African continent is limited. The aim of the present study was the genetic characterization of C. burnetii DNA samples detected in ticks collected from Ethiopian cattle and their comparison with other genotypes found previously in other parts of the world. Methodology/Principal Findings: A total of 296 tick samples were screened by real-time PCR targeting the IS 1111 region of C. burnetii genome and from the 32 positive samples, 8 cases with sufficient C. burnetii DNA load ( Amblyomma cohaerens ,n 5 6; A. variegatum ,n 5 2) were characterized by multispacer sequence typing (MST) and multiple-locus variable-number tandem repeat analysis (MLVA). One novel sequence type (ST), the proposed ST52, was identified by MST. The MLVA-6 discriminated the proposed ST52 into two newly identified MLVA genotypes: type 24 or AH was detected in both Amblyomma species while type 26 or AI was found only in A. cohaerens . Conclusions/Significance: Both the MST and MLVA genotypes of the present work are closely related to previously described genotypes found primarily in cattle samples from different parts of the globe. This finding is congruent with the source hosts of the analyzed Ethiopian ticks, as these were also collected from cattle. The present study provides genotype information of C. burnetii from this seldom studied East-African region as well as further evidence for the presumed host-specific adaptation of this agent

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants

Activated forms of jasmonic acid (JA) are central signals coordinating plant responses to stresses, yet tools to analyse their spatial and temporal distribution are lacking. Here we describe a JA perception biosensor termed Jas9-VENUS that allows the quantification of dynamic changes in JA distribution in response to stress with high spatiotemporal sensitivity. We show that Jas9-VENUS abundance is dependent on bioactive JA isoforms, the COI1 co-receptor, a functional Jas motif and proteasome activity. We demonstrate the utility of Jas9-VENUS to analyse responses to JA in planta at a cellular scale, both quantitatively and dynamically. This included using Jas9-VENUS to determine the cotyledon-to-root JA signal velocities on wounding, revealing two distinct phases of JA activity in the root. Our results demonstrate the value of developing quantitative sensors such as Jas9-VENUS to provide high-resolution spatiotemporal data about hormone distribution in response to plant abiotic and biotic stresses