Acceptance and perceived barriers of implementing a guideline for managing low back in general practice

Background

There is considerable interest today in shared decision-making (SDM), defined as a decision-making process jointly shared by patients and their health care provider. However, the data show that SDM has not been broadly adopted yet. Consequently, the main goal of this proposal is to bring together the resources and the expertise needed to develop an interdisciplinary and international research team on the implementation of SDM in clinical practice using a theory-based dyadic perspective.

Methods

Participants include researchers from Canada, US, UK, and Netherlands, representing medicine, nursing, psychology, community health and epidemiology. In order to develop a collaborative research network that takes advantage of the expertise of the team members, the following research activities are planned: 1) establish networking and on-going communication through internet-based forum, conference calls, and a bi-weekly e-bulletin; 2) hold a two-day workshop with two key experts (one in theoretical underpinnings of behavioral change, and a second in dyadic data analysis), and invite all investigators to present their views on the challenges related to the implementation of SDM in clinical practices; 3) conduct a secondary analyses of existing dyadic datasets to ensure that discussion among team members is grounded in empirical data; 4) build capacity with involvement of graduate students in the workshop and online forum; and 5) elaborate a position paper and an international multi-site study protocol.

Discussion

This study protocol aims to inform researchers, educators, and clinicians interested in improving their understanding of effective strategies to implement shared decision-making in clinical practice using a theory-based dyadic perspective.     

Development of polyspermic zygote and possible contribution of polyspermy to polyploid formation in angiosperms

Fertilization is a general feature of eukaryotic uni- and multicellular organisms to restore a diploid genome from female and male gamete haploid genomes. In angiosperms, polyploidization is a common phenomenon, and polyploidy would have played a major role in the long-term diversification and evolutionary success of plants. As for the mechanism of formation of autotetraploid plants, the triploid-bridge pathway, crossing between triploid and diploid plants, is considered as a major pathway. For the emergence of triploid plants, fusion of an unreduced gamete with a reduced gamete is generally accepted. In addition, the possibility of polyspermy has been proposed for maize, wheat and some orchids, although it has been regarded as an uncommon mechanism of triploid formation. One of the reasons why polyspermy is regarded as uncommon is because it is difficult to reproduce the polyspermy situation in zygotes and to analyze the developmental profiles of polyspermic triploid zygotes. Recently, polyspermic rice zygotes were successfully produced by electric fusion of an egg cell with two sperm cells, and their developmental profiles were monitored. Two sperm nuclei and an egg nucleus fused into a zygotic nucleus in the polyspermic zygote, and the triploid zygote divided into a two-celled embryo via mitotic division with a typical bipolar microtubule spindle. The two-celled proembryos further developed and regenerated into triploid plants. These suggest that polyspermic plant zygotes have the potential to form triploid embryos, and that polyspermy in angiosperms might be a pathway for the formation of triploid plants.     

Proteasome-cytochrome c interactions: a model system for investigation of proteasome host-guest interactions

Owing to its high thermal stability and structural simplicity, the archaebacterium Thermoplasma Acidophilum 20S proteasome was selected for mechanistic studies in this work. This oligomeric enzyme complex consists of a barrel-shaped 20S core (approximately 700kDa) comprised of four stacked seven-membered rings with a alpha(7)beta(7)beta(7)alpha(7) subunit structure situated around a 7-fold symmetry axis. The hollow interior of the proteasome has three large interconnected chambers with narrow (13 A diameter) entrances from solution located at either end of the barrel. The 14 beta-subunit proteolytic sites are located on the inner surface of the central chamber. Herein, we demonstrate that unfolded horse heart ferricytochrome c (Cyt c) is a novel chromophoric probe for investigation of the mechanism of proteasome action. Under conditions of temperature and denaturant which unfold Cyt c but do not alter the thermophilic proteasome, Cyt c is extensively cleaved by the proteasome. Ten peptides were isolated and sequenced from the proteasome digest. Analysis of the cleavage products established that unfolded Cyt c and its covalently attached heme prosthetic group are translocated to the central chamber where proteolysis occurs. In the presence of site-specific inhibitors of the proteasome, we demonstrate that unfolded cytochrome c can be sequestered inside the proteasome complex. Upon cooling, a quasistable host-guest complex is formed. Analysis of the complex via UV/visible spectroscopy and mass spectrometry gave evidence that the sequestered Cyt c is essentially intact within the inhibited proteasome. High-performance liquid chromatography data show that (1) complexes with an apparent stoichiometry of approximately one Cyt c per proteasome can be formed and (2) when inhibition is removed from the complex, a rapid turnover of the sequestered Cyt c occurs.     

Interaction between human respiratory syncytial virus (RSV) M2-1 and P proteins is required for reconstitution of M2-1-dependent RSV minigenome activity

We have investigated protein-protein interactions among the respiratory syncytial virus (RSV) RNA polymerase subunits using affinity chromatography. Here we demonstrate a novel interaction of P and M2-1 proteins. Phosphorylation of either M2-1 or P appears to be dispensable for this interaction. Internal deletions within P mapped the M2-1-binding domain to a region between residues 100 and 120. Alanine-scanning mutagenesis within this region of P revealed that substitution of any one of the three residues, L101, Y102, and F109, prevented both M2-1 and P binding and expression of an M2-1-dependent luciferase reporter gene. However, these same mutations did not prevent the activity of an M2-1-independent chloramphenicol acetyltransferase minigenome, suggesting that these residues of P specifically affect M2-1-P interaction. On the basis of these observations, it is possible that the interaction between RSV M2-1 and P proteins is important for viral replication.     

Recreational boats as a vector of secondary spread for aquatic invasive species and native crustacean zooplankton

Recreational boats in tow between lakes are a known vector of the spread of aquatic invading species (AIS), but we have no test of the hypothesis that recreational boats are also a vector of secondary spread of AIS among freshwater ecosystems via in-water transport i.e., while boating between interconnected waterways. In this study, we surveyed recreational boaters travelling into Lake Simcoe (44°25′N, 79°20′W), Ontario, Canada, on their recreational activities, boat maintenance, and travel destinations, measured the degree of vessel fouling, and sampled all standing water and attached macrophytes associated with their vessels. A total of 321 zooplankton individuals comprising 15 different species were collected from the standing water in vessels, including veligers of the invasive zebra mussel Dreissena. The volume of water collected within the vessels significantly increased the number of zooplankton transported. Zooplankton species from pelagic habitats or with planktonic life stages were collected more frequently than species that occupy littoral or benthic habitats, likely reflecting the recreational activities of boaters. Patterns of boater activities, movements and hygiene habits, suggest recreational boating in the Lake Simcoe region is contributing to the spread of native and invasive species into nearby waterways. Our study validates the widespread assumption that recreational boats are an important in-water vector for the secondary spread of both native and invasive zooplankton species. Future management strategies to reduce the spread of AIS should be aimed at increasing awareness of boater hygiene practices, particularly the frequent draining of standing water.     

The Effects of NPY and Insulin on Food Intake Regulation in Fish

Recent abundant studies report that in rodents starvation inducesincreased neuropeptide Y (NPY) mRNA expression and peptide secretionin the hypothalamus which reduces autonomic nervous activityand promotes food intake, and intracerebroventricular (ICV)injection of NPY has potent orexigenic effects. Conversely,the effect of insulin in the central nervous system is to inhibitfood intake and NPY biosynthesis and secretion. In mammals bodyfatness is regulated and insulin acts as one intake inhibitorysignal related to fatness. In salmon (Oncorhynchus sp.) we havedemonstrated a rise in NPY-like mRNA expression and a coincidentdecrease in plasma insulin levels during 2 to 3 weeks of starvation.Additionally, experimentally manipulating body fatness withhigh and low fat diets has demonstrated that body fatness affectsfood intake in teleost fishes, raising the possibility thatNPY and insulin act to regulate their food intake. Therefore,we hypothesized that as in rodents, ICV treatment with NPY wouldstimulate food intake while ICV insulin would reduce food intake.Preliminary results suggest that ICV NPY administration doesstimulate food intake in channel catfish (Ictalurus punctatus),but central injection of insulin has no effect. Results of treatmentswith the sulfated octapeptide of cholecystokinin and the recombinantfragment of rat leptin 22–56 are also discussed.     

Sex matters during adolescence: testosterone-related cortical thickness maturation differs between boys and girls

Age-related changes in cortical thickness have been observed during adolescence, including thinning in frontal and parietal cortices, and thickening in the lateral temporal lobes. Studies have shown sex differences in hormone-related brain maturation when boys and girls are age-matched, however, because girls mature 1-2 years earlier than boys, these sex differences could be confounded by pubertal maturation. To address puberty effects directly, this study assessed sex differences in testosterone-related cortical maturation by studying 85 boys and girls in a narrow age range and matched on sexual maturity. We expected that testosterone-by-sex interactions on cortical thickness would be observed in brain regions known from the animal literature to be high in androgen receptors. We found sex differences in associations between circulating testosterone and thickness in left inferior parietal lobule, middle temporal gyrus, calcarine sulcus, and right lingual gyrus, all regions known to be high in androgen receptors. Visual areas increased with testosterone in boys, but decreased in girls. All other regions were more impacted by testosterone levels in girls than boys. The regional pattern of sex-by-testosterone interactions may have implications for understanding sex differences in behavior and adolescent-onset neuropsychiatric disorders.     

Genetic Variants and Early Cigarette Smoking and Nicotine Dependence Phenotypes in Adolescents

Background

While the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes.

Methods

In a prospective study of 1294 adolescents aged 12–13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7–8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator).

Results

The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076.

Conclusions

Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3).

Impact

Dopaminergic pathways may be salient during early smoking and the development of ND.     

Microfilariae infection in wild birds from the Brazilian cerrado

We report the occurrence of microfilariae in wild birds of a cerrado area in northern Brazil (Tocantins State). Analyses of 166 passerine birds belonging to 46 species and 17 families captured between 2006 and 2008 revealed that 11 individuals (6.6%) were hosts for microfilariae. Two bird species, Formicivora grisea and Formicivora rufa (Thamnophilidae), were identified as hosts for microfilariae for the first time, and had high intensities of microfilaremia (65 and 107 in 100 microscopic fields, respectively). The prevalence and intensity of microfilariae described in the present study are among the highest reported for wild bird communities in the neotropics.     

Prefrontal Response and Frontostriatal Functional Connectivity to Monetary Reward in Abstinent Alcohol-Dependent Young Adults

Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence.