Tolerability and safety of novel half milliliter formulation of glatiramer acetate for subcutaneous injection: an open-label, multicenter, randomized comparative study

Daily glatiramer acetate (GA) 20 mg/1.0 mL is a first-line treatment for relapsing-remitting multiple sclerosis (RRMS). To reduce the occurrence of injection pain and local injection site reactions (LISRs), a reduced volume formulation of GA was developed. This study compared pain and LISRs after injecting the marketed and the novel formulations. RRMS patients currently injecting GA participated in this multicenter, randomized, crossover comparative study. All patients administered once-daily subcutaneous injections of GA 20 mg/1.0 mL (marketed formulation) or GA 20 mg/0.5 mL (reduced volume formulation) for 14 days. Patients were crossed-over to the alternate treatment for an additional 14 days. Using a Visual Analog Scale (VAS), patients recorded in daily diaries the severity of injection pain immediately and 5 min post-injection, and the presence and severity of LISRs (swelling, redness, itching, lump) within 5 min and 24 h post-injection. VAS pain scores were ranked significantly lower immediately and 5 min after GA 20 mg/0.5 mL injections (p < 0.0001). Although LISRs were rare for both preparations, the severity of reactions ranked significantly lower and fewer symptoms occurred within 5 min and 24 h of using the reduced volume formulation (p < 0.0001). GA injected subcutaneously in a reduced volume formulation is a more tolerable option

Predicting participation in group parenting education in an Australian sample: The role of attitudes, norms, and control factors

We examined the theory of planned behavior (TPB) in predicting intentions to participate in group parenting education. One hundred and seventy-six parents (138 mothers and 38 fathers) with a child under 12 years completed TPB items assessing attitude, subjective norms, perceived behavioral control (PBC), and two additional social influence variables (self-identity and group norm). Regression analyses supported the TPB predictors of participation intentions with self-identity and group norm also significantly predicting intentions. These findings offer preliminary support for the TPB, along with additional sources of social influence, as a useful predictive model of participation in parenting education

Training Programmes Can Change Behaviour and Encourage the Cultivation of Over-Harvested Plant Species

Cultivation of wild-harvested plant species has been proposed as a way of reducing over-exploitation of wild populations but lack of technical knowledge is thought to be a barrier preventing people from cultivating a new species. Training programmes are therefore used to increase technical knowledge to encourage people to adopt cultivation. We assessed the impact of a training programme aiming to encourage cultivation of xaté (Chamaedorea ernesti-augusti), an over-harvested palm from Central America. Five years after the training programme ended, we surveyed untrained and trained individuals focusing on four potential predictors of behaviour: technical knowledge, attitudes (what individuals think about a behaviour), subjective norms (what individuals perceive others to think of a behaviour) and perceived behavioural control (self assessment of whether individuals can enact the behaviour successfully). Whilst accounting for socioeconomic variables, we investigate the influence of training upon these behavioural predictors and examine the factors that determine whether people adopt cultivation of a novel species. Those who had been trained had higher levels of technical knowledge about xaté cultivation and higher belief in their ability to cultivate it while training was not associated with differences in attitudes or subjective norms. Technical knowledge and perceived behavioural control (along with socio-economic variables such as forest ownership and age) were predictors of whether individuals cultivate xaté. We suggest that training programmes can have a long lasting effect on individuals and can change behaviour. However, in many situations other barriers to cultivation, such as access to seeds or appropriate markets, will need to be addressed

Functional Analysis of a Breast Cancer-Associated FGFR2 Single Nucleotide Polymorphism Using Zinc Finger Mediated Genome Editing

The authors thank Barts Charity for funding and Breast Cancer Campaign for funding the Barts Breast Tissue Bank

Suicide among adults aged 30–49: A psychological autopsy study in Hong Kong

<p>Abstract</p> <p>Background</p> <p>A surge in suicide rates in middle age people in Hong Kong and many Asian countries was recently observed. However, there is a paucity of suicide research on this subgroup of people in Asia.</p> <p>Methods</p> <p>The next-of-kin of 85 suicide cases and 85 community subjects aged 30–49 years were interviewed by a psychological autopsy approach. Information was triangulated by interview notes, coroner's court files, and police investigation reports.</p> <p>Results</p> <p>A multiple logistic regression analysis identified the following risk factors for suicide among the middle age people in Hong Kong: the presence of at least one psychiatric disorder (OR = 37.5, 95% CI 11.5–121.9, p < 0.001), indebtedness (OR = 9.4, 95% CI 2.2–40.8, p < 0.01), unemployment (OR = 4.8, 95% CI 1.3–17.5, p < 0.05), never married (OR = 4.2, 95% CI 1.1–16.3, p < 0.05), and lived alone (OR = 3.9, 95% CI 1.2–13.4, p < 0.05).</p> <p>Conclusion</p> <p>The data show that socio-economical factors had a strong impact on suicide in the target group. Further research is needed to explore any positive qualities that protect the middle-aged from suicide. The prevention of suicide in the middle-aged requires multiple strategies.</p

More than Mere Numbers: The Impact of Lethal Control on the Social Stability of a Top-Order Predator

Population control of socially complex species may have profound ecological implications that remain largely invisible if only their abundance is considered. Here we discuss the effects of control on a socially complex top-order predator, the dingo (Canis lupus dingo). Since European occupation of Australia, dingoes have been controlled over much of the continent. Our aim was to investigate the effects of control on their abundance and social stability. We hypothesized that dingo abundance and social stability are not linearly related, and proposed a theoretical model in which dingo populations may fluctuate between three main states: (A) below carrying capacity and socially fractured, (B) above carrying capacity and socially fractured, or (C) at carrying capacity and socially stable. We predicted that lethal control would drive dingoes into the unstable states A or B, and that relaxation of control would allow recovery towards C. We tested our predictions by surveying relative abundance (track density) and indicators of social stability (scent-marking and howling) at seven sites in the arid zone subject to differing degrees of control. We also monitored changes in dingo abundance and social stability following relaxation and intensification of control. Sites where dingoes had been controlled within the previous two years were characterized by low scent-marking activity, but abundance was similar at sites with and without control. Signs of social stability steadily increased the longer an area was allowed to recover from control, but change in abundance did not follow a consistent path. Comparison of abundance and stability among all sites and years demonstrated that control severely fractures social groups, but that the effect of control on abundance was neither consistent nor predictable. Management decisions involving large social predators must therefore consider social stability to ensure their conservation and ecological functioning

Endocytic and Recycling Endosomes Modulate Cell Shape Changes and Tissue Behaviour during Morphogenesis in Drosophila

During development tissue deformations are essential for the generation of organs and to provide the final form of an organism. These deformations rely on the coordination of individual cell behaviours which have their origin in the modulation of subcellular activities. Here we explore the role endocytosis and recycling on tissue deformations that occur during dorsal closure of the Drosophila embryo. During this process the AS contracts and the epidermis elongates in a coordinated fashion, leading to the closure of a discontinuity in the dorsal epidermis of the Drosophila embryo. We used dominant negative forms of Rab5 and Rab11 to monitor the impact on tissue morphogenesis of altering endocytosis and recycling at the level of single cells. We found different requirements for endocytosis (Rab5) and recycling (Rab11) in dorsal closure, furthermore we found that the two processes are differentially used in the two tissues. Endocytosis is required in the AS to remove membrane during apical constriction, but is not essential in the epidermis. Recycling is required in the AS at early stages and in the epidermis for cell elongation, suggesting a role in membrane addition during these processes. We propose that the modulation of the balance between endocytosis and recycling can regulate cellular morphology and tissue deformations during morphogenesis

Molecular Evolution of the Neuropeptide S Receptor

The neuropeptide S receptor (NPSR) is a recently deorphanized member of the G protein-coupled receptor (GPCR) superfamily and is activated by the neuropeptide S (NPS). NPSR and NPS are widely expressed in central nervous system and are known to have crucial roles in asthma pathogenesis, locomotor activity, wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought to have first evolved in the tetrapods. Here we examine the origin and the molecular evolution of the NPSR using in-silico comparative analyses and document the molecular basis of divergence of the NPSR from its closest vertebrate paralogs. In this study, NPSR-like sequences have been identified in a hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR-like sequence in the metazoan lineage. Phylogenetic analyses revealed that the NPSR is most closely related to the invertebrate cardioacceleratory peptide receptor (CCAPR) and the group of vasopressin-like receptors. Gene structure features were congruent with the phylogenetic clustering and supported the orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific analysis between the vertebrate NPSR and the well studied paralogous vasopressin-like receptor subtypes revealed several putative amino acid sites that may account for the observed functional divergence between them. The data can facilitate experimental studies aiming at deciphering the common features as well as those related to ligand binding and signal transduction processes specific to the NPSR

Chemogenomic Analysis of G-Protein Coupled Receptors and Their Ligands Deciphers Locks and Keys Governing Diverse Aspects of Signalling

Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs) is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI) is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic) or inhibitory (antagonistic) ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs) 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences