A randomized controlled trial of a parent-centered intervention in preventing substance use and HIV risk behaviors in Hispanic adolescents

The present study evaluated the efficacy of Familias Unidas + Parent-Preadolescent Training for HIV Prevention (PATH), a Hispanic-specific, parent-centered intervention, in preventing adolescent substance use and unsafe sexual behavior. Two hundred sixty-six 8th-grade Hispanic adolescents and their primary caregivers were randomly assigned to 1 of 3 conditions: Familias Unidas + PATH, English for Speakers of Other Languages (ESOL) + PATH, and ESOL + HeartPower! for Hispanics (HEART). Participants were assessed at baseline and at 6, 12, 24, and 36 months postbaseline. Results showed that (a) Familias Unidas + PATH was efficacious in preventing and reducing cigarette use relative to both control conditions; (b) Familias Unidas + PATH was efficacious, relative to ESOL + HEART, in reducing illicit drug use; and (c) Familias Unidas + PATH was efficacious, relative to ESOL + PATH, in reducing unsafe sexual behavior. The effects of Familias Unidas + PATH on these distal outcomes were partially mediated by improvements in family functioning. These findings suggest that strengthening the family system, rather than targeting specific health behaviors, may be most efficacious in preventing and/or reducing cigarette smoking, illicit drug use, and unsafe sex in Hispanic adolescents.     

Pathogenic implication of a fibrinogen-binding protein of Staphylococcus epidermidis in a rat model of intravascular-catheter-associated infection

The involvement of Fbe, a fibrinogen-binding protein of Staphylococcus epidermidis, in the pathogenesis of catheter-associated infection was investigated. An fbe (gene encoding Fbe protein) mutant was constructed by allelic replacement, wherein an erythromycin resistance gene replaced a portion of the A region of fbe. Meanwhile, a rat central venous catheter (CVC) infection model was established to assess the importance of Fbe in the pathogenesis of CVC-associated infection due to S. epidermidis. Fbe-positive S. epidermidis strain HB was significantly more likely to cause a CVC-associated infection resulting in bacteremia and metastatic disease than its isogenic Fbe-deficient mutant (100% versus 20%, P < 0.01). These results confirm the importance of adherence associated with Fbe in the pathogenesis of CVC-associated infection caused by S. epidermidis.     

Systematically generated antibodies against human gene products: high throughput screening on sections from the rat nervous system

Completion of the Human Genome Project and recent developments in proteomics make it possible to systematically generate affinity reagents to a large portion of the proteome. Recently an antibody-based human protein atlas covering many organs including four areas of the brain has been released (www.proteinatlas.org). Due to the heterogeneity, size, and availability of tissue a more thorough analysis of the human brain is associated with considerable difficulties. Here we applied 120 antibodies raised against 112 human gene products to the smaller rat brain, a rodent animal model, where a single section represents a 'superarray' including many brain areas, and consequently allowing analysis of a huge number of cell types and their neurochemicals. Immunoreactive structures were seen in the investigated brain tissue after incubation with 56 antibodies (46.6%), of which 25 (20.8%) showed a clearly discrete staining pattern that was limited to certain areas, or subsets of brain cells. Bioinformatics, pre-adsorption tests and Western blot analysis were applied to identify non-specific antibodies. Eleven antibodies, including such raised against four 'ambiguous' proteins, passed all validation criteria, and the expression pattern and subcellular distribution of these proteins were studied in detail. To further explore the potential of the systematically generated antibodies, all 11 antibodies that passed validation were used to analyze the spinal cord and lumbar dorsal root ganglia after unilateral transection of the sciatic nerve. Discrete staining patterns were observed for four of the proteins, and injury-induced regulation was found for one of them. In conclusion, the study presented here suggests that a significant portion (10%) of the antibodies generated to a human protein can be used to analyze orthologues present in the rodent brain and to produce a protein-based atlas of the rodent brain. It is hoped that this type of antibody-based, high throughput screening of brain tissue from various rodent disease models will provide new information on the brain chemical neuroanatomy and insights in processes underlying neurological pathologies.     

Thiamine deficiency induces endoplasmic reticulum stress in neurons

Thiamine (vitamin B1) deficiency (TD) causes region selective neuronal loss in the brain; it has been used to model neurodegeneration that accompanies mild impairment of oxidative metabolism. The mechanisms for TD-induced neurodegeneration remain incompletely elucidated. Inhibition of protein glycosylation, perturbation of calcium homeostasis and reduction of disulfide bonds provoke the accumulation of unfolded proteins in the endoplasmic reticulum (ER), and cause ER stress. Recently, ER stress has been implicated in a number of neurodegenerative models. We demonstrated here that TD up-regulated several markers of ER stress, such as glucose-regulated protein (GRP) 78, growth arrest and DNA-damage inducible protein or C/EBP-homologus protein (GADD153/Chop), phosphorylation of eIF2alpha and cleavage of caspase-12 in the cerebellum and the thalamus of mice. Furthermore, ultrastructural analysis by electron microscopic study revealed an abnormality in ER structure. To establish an in vitro model of TD in neurons, we treated cultured cerebellar granule neurons (CGNs) with amprolium, a potent inhibitor of thiamine transport. Exposure to amprolium caused apoptosis and the generation of reactive oxygen species in CGNs. Similar to the observation in vivo, TD up-regulated markers for ER stress. Treatment of a selective inhibitor of caspase-12 significantly alleviated amprolium-induced death of CGNs. Thus, ER stress may play a role in TD-induced brain damage.     

Ex vivo expanding hematopoietic stem cells by intracellular delivery of Cdx4 fusion proteins

Hematopoietic stem cells transplantation has been wildly used in clinical settings and has shown exciting results in treating a wide variety of diseases. However, the relative small number of hematopoietic stem cells in bone marrow, even lower in peripheral or umbilical cord blood limits its clinical utility. There are several protocols, which have been developed to expand hematopoietic stem cells to reach clinical goal. With the recent insights into the mechanisms of hematopoietic stem cells self-renewal, we postulate that Cdx4, which is coded by one of the caudal related homeobox genes and regulates the expression of hox genes, could fuse with protein transduction domains, thereby get the ability to cross cellular membrane. And the recombinant fusion proteins could be used in expanding hematopoietic stem cells. Meanwhile, Cdx4 fusion proteins would be more efficient than other methods that had been developed for it can up-regulate a cocktail of hox genes, which has been proved to be capable of amplifying hematopoietic stem cells. It would provide us an alternative protocol to amplify hematopoietic stem cells if the hypothesis proved to be practical.     

Non-invasive method to detect and locate haemorrhagic focus of GI tract

Traditional diagnostic methods do not work well for gastrointestinal bleeding, and location of the haemorrhagic focus is even more difficult. Here a novel method with a microelectronic system is presented effectively to detect and locate the haemorrhagic focus. The outstanding advantage of this method is that it is non-invasive. The composition and working principles of the system are described in detail. Key to this system is the development of a haemoglobin (Hb) sensor. Through MEMS technology a micro haemoglobin sensor is developed and fabricated. The sensor's response performance, pH dependence and temperature dependence are tested experimentally. Initial tests suggest that the device is sufficiently sensitive to Hb concentration and insensitive to pH and temperature changes in the working range. As a result, the system has potential for development of an advanced instrument for detecting, localizing and treating gastrointestinal bleeding.     

The dependence of the modulation transfer function on the blocking layer thickness in amorphous selenium x-ray detectors

Blocking layers are used to reduce leakage current in amorphous selenium detectors. The effect of the thickness of the blocking layer on the presampling modulation transfer function (MTF) and on dark current was experimentally determined in prototype single-line CCD-based amorphous selenium (a-Se) x-ray detectors. The sampling pitch of the detectors evaluated was 25 microm and the blocking layer thicknesses varied from 1 to 51 microm. The blocking layers resided on the signal collection electrodes which, in this configuration, were used to collect electrons. The combined thickness of the blocking layer and a-Se bulk in each detector was approximately 200 microm. As expected, the dark current increased monotonically as the thickness of the blocking layer was decreased. It was found that if the blocking layer thickness was small compared to the sampling pitch, it caused a negligible reduction in MTF. However, the MTF was observed to decrease dramatically at spatial frequencies near the Nyquist frequency as the blocking layer thickness approached or exceeded the electrode sampling pitch. This observed reduction in MTF is shown to be consistent with predictions of an electrostatic model wherein the image charge from the a-Se is trapped at a characteristic depth within the blocking layer, generally near the interface between the blocking layer and the a-Se bulk.     

Two-dimensional multi-level strain estimation for discontinuous tissue

A large number of the strain estimation methods presented in the literature are based on the assumption of tissue continuity that establishes a continuous displacement field. However, in certain locations in the body such as the arteries in vivo scanning may produce displacement fields that are discontinuous between the two walls of the artery. Many of the displacement or strain estimators fail when the displacement fields are discontinuous. In this paper, we present a new 2D multi-level motion or displacement tracking method for accurate estimation of the strain in these situations. The final high-resolution displacement estimate is obtained using two processing steps. The first step involves an estimation of a coarse displacement estimate utilizing B-mode or envelope signals. To reduce computational time, the coarse displacement estimates are obtained starting from down-sampled B-mode pre- and post-compression image pairs using a pyramidal processing approach. The coarse displacement estimate obtained from the B-mode data is used to guide the final 2D cross-correlation computations on radio-frequency (RF) data. Results from finite element simulations and in vivo experimental data demonstrate the feasibility of this approach for imaging tissue with discontinuous displacement fields.     

抗原修复技术研究进展

自从应用抗原修复技术的文章于1991年发表后,抗原修复技术（煮沸石蜡切片于水溶液中）迅速、广泛应用于常规甲醛固定、石蜡包埋组织切片的免疫组织化学染色,从而打开了从传统形态学迈向分子形态学的大门。抗原修复技术被誉为免疫组织化学技术的革命性突破旧。Gown在评价抗原修复技术所取得的成就时,指出“在过去十多年里,抗原修复技术在诊断性免疫组织化学分析方面造成了如此深远的影响,使得这方面的文献分为2个时代：抗原修复技术前与抗原修复技术后时代。20世纪90年代初抗原修复技术的问世就是这两个阶段的分水岭”。