Positive reinforcement targeting abstinence in substance misuse (PRAISe): Study protocol for a Cluster RCT & process evaluation of contingency management.

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.

Testing five social-cognitive models to explain predictors of personal oral health behaviours and intention to improve them.

PURPOSE: To test the ability of several social-cognitive models to explain current behaviour and to predict intentions to engage in three different health behaviours (toothbrushing, flossing and mouthrinsing). MATERIALS AND METHODS: Constructs from the health belief model (HBM), theory of reasoned action (TRA), theory of planned behaviour (TPB) and the motivational process of the health action process approach (HAPA) were measured simultaneously in an undergraduate student sample of 172 first-year medical students. RESULTS: Regarding toothbrushing, the TRA, TPB, HBM (without the inclusion of self-efficacy SE), HBM+SE and HAPA predictor models explained 7.4%, 22.7%, 10%, 10.2% and 10.1%, respectively, of the variance in behaviour and 7.5%, 25.6%, 12.1%, 17.5% and 17.2%, respectively, in intention. Regarding dental flossing, the TRA, TPB, HBM, HBM+SE and HAPA predictor models explained 39%, 50.6, 24.1%, 25.4% and 27.7%, respectively, of the variance in behaviour and 39.4%, 52.7%, 33.7%, 35.9% and 43.2%, respectively, in intention. Regarding mouthrinsing, the TRA, TPB, HBM, HBM+SE and HAPA predictor models explained 43.9%, 45.1%, 20%, 29% and 36%, respectively, of the variance in behaviour and 58%, 59.3%, 49.2%, 59.8% and 66.2%, respectively, in intention. The individual significant predictors for current behaviour were attitudes, barriers and outcome expectancy. CONCLUSION: Our findings revealed that the theory of planned behaviours and the health action process approach were the best predictor of intentions to engage in both behaviours.

Effect of the nutritional supplement ALAnerv® on the serum PON1 activity in post-acute stroke patients.

BACKGROUND: Paraoxonase-1 (PON1) is one of the HDL-associated proteins which contributes to the antioxidant properties of these lipoproteins. The aim of this pilot study was to evaluate the effect of the nutritional supplement ALAnerv® on serum PON1 activity in post-acute stroke patients undergoing rehabilitation. METHODS: We enrolled 28 post-acute stroke patients and randomly divided them into (-) ALA or (+) ALA study groups. All the patients underwent the same rehabilitation program and received comparable standard medications. Moreover, (+) ALA patients received ALAnerv® for two weeks (2 pills/day). The serum PON1 activity was assessed on blood samples taken at the admission and at the discharge moments, respectively. We used paraoxon (paraoxonase activity, PONA), phenyl acetate (arylesterase activity, ARYLA) and dihydrocoumarin (lactonase activity, LACTA) as substrates, the latter activity being regarded as physiologically relevant. A control group of 14 apparently healthy subjects was also created. RESULTS: In the (+) ALA group, LACTA significantly increased during the study period (17.6 ± 3.2 vs. 27.6 ± 3.5, p = 0.002). Moreover, the percentage of LACTA variation between (-) ALA and (+) ALA groups during the study was also statistically different (-11.7 ± 6.9% vs. +95.1 ± 29.7%, p < 0.0001). CONCLUSIONS: These preliminary results suggest that ALA nerv® could contribute to the improvement of the physiologically relevant LACTA of PON1 in post-acute stroke patients, enabling this enzyme to contribute to the redox correction. Also, this study raises the question about the effect of a longer treatment period over the other enzymatic activities of serum PON1.

Adherence with bisphosphonate therapy in US veterans with rheumatoid arthritis.

OBJECTIVE: Pharmacy Benefits Management program data for patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were linked with clinical data to determine bisphosphonate adherence and persistence among US veterans with rheumatoid arthritis (RA) and to determine factors associated with adherence. METHODS: The primary outcome measures were the duration of bisphosphonate therapy and the medication possession ratio (MPR). Patients with an MPR <0.80 were classified as nonadherent. Potential covariates considered in the analysis included patient demographics, RA disease activity and severity parameters, and factors associated with osteoporosis risk. Associations of patient factors with duration of therapy and adherence were examined using multivariable regression modeling. RESULTS: Bisphosphonates were prescribed to 573 (41.5%) of 1,382 VARA subjects. The mean ± SD duration of therapy for bisphosphonates was 39.2 ± 31.4 months. A longer duration of therapy correlated with older age, more years of education, and dual x-ray absorptiometry testing. The mean ± SD MPR of VARA subjects for bisphosphonate therapy was 0.69 ± 0.28; 302 (52.7%) were nonadherent. In multivariate analyses, nonadherence with bisphosphonate therapy was associated with a longer duration of RA disease (odds ratio [OR] 1.02, 95% confidence interval [95% CI] 1.00-1.04) and duration of bisphosphonate therapy >32 months (OR 1.63, 95% CI 1.04-2.57). Whites were less likely to have a low MPR compared with nonwhites (OR 0.52, 95% CI 0.30-0.88). CONCLUSION: Nonadherence with bisphosphonates was common in this cohort of RA patients and was associated with nonwhite ethnicity, a longer duration of RA disease, and a greater duration of bisphosphonate therapy.

Deep tissue bio-imaging using two-photon excited CdTe fluorescent quantum dots working within the biological window.

A new approach to deep tissue imaging is presented based on 8 nm CdTe semiconductor quantum dots (QDs). The characteristic 800 nm emission was found to be efficiently excited via two-photon absorption of 900 nm photons. The fact that both excitation and emission wavelengths lie within the "biological window" allows for high resolution fluorescence imaging at depths close to 2 mm. These penetration depths have been used to obtain the first deep tissue multiphoton excited fluorescence image based on CdTe-QDs. Due to the large thermal sensitivity of CdTe-QDs, one may envisage, in the near future, their use in high resolution deep-tissue thermal imaging.

[Effect of afobazole on the psychophysiological state of healthy volunteers].

The influence of the selective anxiolytic drug afobazole in a single dose of 10 mg on the psychophysiological functions of healthy volunteers was studied in laboratory experiments. It is established that afobazole optimizes some psychophysiological characteristics of stress-labile individuals and has no negative influenceon the parameters of attention, psychomotor reaction a nd speed of decision making.

Homocysteine and vitamin therapy in stroke prevention and treatment: a review.

Homocysteine (Hcy), a sulfur amino acid, is the only direct precursor for L-methionine synthesis through a reaction that requires vitamin B12, representing a connection with "one-carbon" units metabolism. Hcy catabolism requires vitamin B6 and as a consequence, alteration in folic acid and B vitamins status impairs Hcy biotransformation. Numerous studies have indicated that Hcy is an independent risk factor for cardio- and cerebrovascular diseases. In the last decade, several clinical trials have investigated the possible correlation between the use of folic acid and vitamins B6 and B12 for lowering Hcy plasma concentration and the reduced risk of stroke or its recurrence. This review is aimed to present some aspects of Hcy biochemistry, as well as the mechanisms through which it exerts the toxic effects on the vascular endothelium. We also discuss the results of some of the clinical trials developed to investigate the beneficial effects of vitamin therapy in the prevention and management of stroke.

[Effect of ladasten on the psychophysiological parameters of healthy volunteers].

The ability of the antiasthenic drug ladasten (single dose, 100 mg) to influence psychophysiological functions was evaluated in laboratory experiments with participation of healthy volunteers. It was established that ladasten does not exhibit behavioral toxicity and improves psychophysiological parameters in the state of mental fatigue. The drug effects were more pronounced in stress-labile individuals.

Imaging of avascular necrosis of femoral head: familiar methods and newer trends.

Avascular necrosis of the femoral head (AVN) is an increasingly common cause of musculoskeletal disability, and it poses a major diagnostic and therapeutic challenge. Although patients are initially asymptomatic, AVN usually progresses to joint destruction, requiring total hip replacement, usually before the fifth decade. Avascular necrosis is characterized by osseous cell death due to vascular compromise. Avascular necrosis of bone results generally from corticosteroid use, trauma, pancreatitis, alcoholism, radiation, sickle cell disease, infiltrative diseases (e.g. Gaucher's disease), and Caisson disease. The most commonly affected site is the femoral head and patients usually present with hip and referred knee pain. The aim of diagnostic imaging procedures in avascular femoral head necrosis is to provide the patient with a stage-adapted therapy. Therefore, a differentiated diagnostic work-up is needed. Native radiography of the hip in two planes is still the first step. Over the past years, the diagnosis of femoral head necrosis has experienced tremendous improvement due to the use of MRI and CT scans. Because of these improvements the correct stage can be diagnosed early and the appropriate therapy can be initiated immediately. Today, MRI is the most sensitive diagnostic imaging procedure. CT scans can be particularly useful to exclude subchondral fractures. The use of bone scintigraphy is restricted to exceptional cases. In Europe, the ARCO classification of avascular femoral head necrosis has been widely accepted. In this overview, we describe the specific characteristics of the different diagnostic imaging procedures and illustrate them with appropriate imaging material.

Picture recognition without picture identification: a method for assessing the role of perceptual information in familiarity-based picture recognition.

The present study examined the claim that unidentifiable test-pictures are processed and recognized on a perceptual, as opposed to a conceptual, level. Using an extension of the recognition without identification paradigm (e.g., Cleary, A. M. & Greene, R. L. (2000). Recognition without identification. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1063-1069; Peynircioglu, Z. F. (1990). A feeling-of-recognition without identification. Journal of Memory and Language, 29, 493-500), it was observed that when test-pictures were unidentifiable during a masked perceptual identification task, old-new discrimination occurred when the study-list consisted of pictures (Experiments 1-3), but not when the study-list consisted of picture names (Experiment 2) or when picture exemplars served as test-cues (Experiment 3). Results provide converging evidence that a study-test perceptual match is needed for the episodic recognition of unidentified test-pictures. Implications for the present paradigm as a tool for examining the role of perceptual information in recognition-familiarity are discussed.

On the use of wireless response systems in experimental psychology: implications for the behavioral researcher.

A method of data collection is presented that unites the efficiency of mass testing with the ease of instant electronic data collection that is typical of computer-based experiments run on individual participants. A wireless response system (WRS), originally designed as a teaching tool, is used to replicate three classic and robust effects from the memory literature (effects of false memory, levels of processing, and word frequency). It is shown that for these types of experimental designs, data can be collected more efficiently (in both time and effort) with the WRS method than through traditional mass- and individual-testing methods alone. The advantages and limitations of WRSs for use in mass electronic data collection are discussed.

A distinct strategy to generate high-affinity peptide binders to receptor tyrosine kinases.

We describe a novel and general way of generating high affinity peptide (HAP) binders to receptor tyrosine kinases (RTKs), using a multi-step process comprising phage-display selection, identification of peptide pairs suitable for hetero-dimerization (non-competitive and synergistic) and chemical synthesis of heterodimers. Using this strategy, we generated HAPs with K(D)s below 1 nM for VEGF receptor-2 (VEGFR-2) and c-Met. VEGFR-2 HAPs bound significantly better (6- to 500-fold) than either of the individual peptides that were used for heterodimer synthesis. Most significantly, HAPs were much better (150- to 800-fold) competitors than monomers of the natural ligand (VEGF) in various competitive binding and functional assays. In addition, we also found the binding of HAPs to be less sensitive to serum than their component peptides. We believe that this method may be applied to any protein for generating high affinity peptide (HAP) binders.

Rolling circle amplification: a new approach to increase sensitivity for immunohistochemistry and flow cytometry.

Immunohistochemistry is a method that can provide complementary diagnostic and prognostic information to morphological observations and soluble assays. Sensitivity, specificity, or requirements for arduous sample preparation or signal amplification procedures often limit the application of this approach to routine clinical specimens. Rolling circle amplification (RCA) generates a localized signal via an isothermal amplification of an oligonucleotide circle. The application of this approach to immunohistochemistry could extend the utility of these methods to include a more complete set of immunological and molecular probes. RCA-mediated signal amplification was successfully applied to the sensitive and specific detection of a variety of cell surface antigens (CD3, CD20, and epithelial membrane antigen) and intracellular molecules (vimentin and prostate-specific antigen) within a variety of routinely fixed specimens, as well as samples prepared for flow cytometry. RCA technology, which has an intrinsically wide dynamic range, is a robust and simple procedure that can provide a universal platform for the localization of a wide variety of molecules as a function of either antigenicity or nucleic acid sequence. The use of RCA in this way could enhance the use of markers of current interest as well as permit the integration of emerging information from genomics and proteomics into cell- and tissue-based analyses.

Effect of topical retinoic acids on the levels of collagen mRNA during the repair of UVB-induced dermal damage in the hairless mouse and the possible role of TGF-beta as a mediator.

Topically applied retinoic acids have been found to enhance the gene expression for collagen types I and III in the skin of UVB-irradiated hairless mice. Prior damage is required because the effect is not observed in the skin of age-matched, non-irradiated control animals. Immunochemical methods have shown an increase in TGF-beta 1 and, to a lesser extent, of TGF-beta 2 in the epidermis following retinoic acid treatment. There were no changes in mRNA levels for any of the isotypes of TGF-beta induced by retinoic acid treatment. This study suggests that TGF-beta may mediate the effect of retinoic acids on dermal repair through the stimulation of collagen gene expression.

[Use of immobilized lysozyme in the treatment of suppurative wounds of the soft tissues]. / Primenenie immobilizovannogo lizotsima v lechenii gnoinykh ran miagkikh tkanei.

The use for local treatment in 45 patients with abscesses and phlegmons of lysozyme immobilized in polymethylsiloxane contributed to acceleration in wound cleaning of necrotic masses, active granulation and epithelization, reduction in duration of patients' treatment by 3-5 days.

Retinoic acids promote the repair of the dermal damage and the effacement of wrinkles in the UVB-irradiated hairless mouse.

Chronic irradiation of hairless mice with UVB leads to elastosis as evidenced by both histologic means and an increase in skin desmosine content. Treatment with topical all-trans- or 13-cis-retinoic acid causes dose-dependent increments in the area of the dermal "repair zone"; skin desmosine content increases during irradiation but does not change significantly after irradiation is discontinued and retinoic acid treatment commenced. During the course of the irradiation the animals develop permanent wrinkles on the exposed dorsal surface, which can be recorded in plastic impressions. The extent of wrinkling can be quantitated and it has been demonstrated that topically applied retinoic acids lead to the complete effacement of these surface features and that the process appears to be permanent.

[Importance of the radioimmune method of determining renin activity in the blood plasma for the differential therapy of hypertension]. / Znachenie radioimmunnogo metoda opredeleniia aktivnosti renina v plazme krovi dlia differentsirovannoi terapii gipertonicheskoi bolezni.

The results of differentiated treatment of patients with hypertensive disease depending on blood plasma renin activity are analyzed. Sixty-seven patients with hypertensive disease and 14 healthy individuals (controls) were examined. Sets of the JCN firm (USA) were used. Persons with high, moderate and low renin activity were distinguished among patients with hypertensive disease. Differentiated therapy was applied depending on the activity of renin: in high renin activity obsidan was given, in low activity drugs of the saluretic group were used. Treatment proved effective in 60 patients (89%). High renin activity is a prognostically unfavourable sign.