Baby Business: a randomised controlled trial of a universal parenting program that aims to prevent early infant sleep and cry problems and associated parental depression

<p>Abstract</p> <p>Background</p> <p>Infant crying and sleep problems (e.g. frequent night waking, difficulties settling to sleep) each affect up to 30% of infants and often co-exist. They are costly to manage and associated with adverse outcomes including postnatal depression symptoms, early weaning from breast milk, and later child behaviour problems. Preventing such problems could improve these adverse outcomes and reduce costs to families and the health care system. Anticipatory guidance-i.e. providing parents with information about normal infant sleep and cry patterns, ways to encourage self-settling in infants, and ways to develop feeding and settling routines <it>before </it>the onset of problems-could prevent such problems. This paper outlines the protocol for our study which aims to test an anticipatory guidance approach.</p> <p>Methods/Design</p> <p>750 families from four Local Government Areas in Melbourne, Australia have been randomised to receive the <it>Baby Business </it>program (intervention group) or usual care (control group) offered by health services. The <it>Baby Business </it>program provides parents with information about infant sleep and crying via a DVD and booklet (mailed soon after birth), telephone consultation (at infant age 6-8 weeks) and parent group session (at infant age 12 weeks). All English speaking parents of healthy newborn infants born at > 32 weeks gestation and referred by their maternal and child health nurse at their first post partum home visit (day 7-10 postpartum), are eligible. The primary outcome is parent report of infant night time sleep as a problem at four months of age and secondary outcomes include parent report of infant daytime sleep or crying as a problem, mean duration of infant sleep and crying/24 hours, parental depression symptoms, parent sleep quality and quantity and health service use. Data will be collected at two weeks (baseline), four months and six months of age. An economic evaluation using a cost-consequences approach will, from a societal perspective, compare costs and health outcomes between the intervention and control groups.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of a program which aims to prevent both infant sleeping and crying problems and associated postnatal depression symptoms. If effective, it could offer an important public health prevention approach to these common, distressing problems.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN63834603">ISRCTN63834603</a></p

Synergy between EngE, XynA and ManA from Clostridium cellulovorans on corn stalk, grass and pineapple pulp substrates

The synergistic interaction between various hemi/cellulolytic enzymes has become more important in order to achieve effective and optimal degradation of complex lignocellulose substrates for biofuel production. This study investigated the synergistic effect of three enzymes endoglucanase (EngE), mannanase (ManA) and xylanase (XynA) on the degradation of corn stalk, grass, and pineapple fruit pulp and determined the optimal degree of synergy between combinations of these enzymes. It was established that EngE was essential for degradation of all of the substrates, while the hemicellulases were able to contribute in a synergistic fashion to increase the activity on these substrates. Maximum specific activity and degree of synergy on the corn stalk and grass was found with EngE:XynA in a ratio of 75:25%, with a specific activity of 41.1 U/mg protein and a degree of synergy of 6.3 for corn stalk, and 44.1 U/mg protein and 3.4 for grass, respectively. The pineapple fruit pulp was optimally digested using a ManA:EngE combination in a 50:50% ratio; the specific activity and degree of synergy achieved were 52.4 U/mg protein and 2.7, respectively. This study highlights the importance of hemicellulases for the synergistic degradation of complex lignocellulose. The inclusion of a mannanase in an enzyme consortium for biomass degradation should be examined further as this study suggests that it may play an important, although mostly overlooked, role in the synergistic saccharification of lignocellulose

Interaction between Axons and Specific Populations of Surrounding Cells Is Indispensable for Collateral Formation in the Mammillary System

An essential phenomenon during brain development is the extension of long collateral branches by axons. How the local cellular environment contributes to the initial sprouting of these branches in specific points of an axonal shaft remains unclear.The principal mammillary tract (pm) is a landmark axonal bundle connecting ventral diencephalon to brainstem (through the mammillotegmental tract, mtg). Late in development, the axons of the principal mammillary tract sprout collateral branches at a very specific point forming a large bundle whose target is the thalamus. Inspection of this model showed a number of distinct, identified cell populations originated in the dorsal and the ventral diencephalon and migrating during development to arrange themselves into several discrete groups around the branching point. Further analysis of this system in several mouse lines carrying mutant alleles of genes expressed in defined subpopulations (including Pax6, Foxb1, Lrp6 and Gbx2) together with the use of an unambiguous genetic marker of mammillary axons revealed: 1) a specific group of Pax6-expressing cells in close apposition with the prospective branching point is indispensable to elicit axonal branching in this system; and 2) cooperation of transcription factors Foxb1 and Pax6 to differentially regulate navigation and fasciculation of distinct branches of the principal mammillary tract.Our results define for the first time a model system where interaction of the axonal shaft with a specific group of surrounding cells is essential to promote branching. Additionally, we provide insight on the cooperative transcriptional regulation necessary to promote and organize an intricate axonal tree

Copper binding to the Alzheimer’s disease amyloid precursor protein

Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease

Amyloid Precursor Protein Is Required for Normal Function of the Rod and Cone Pathways in the Mouse Retina

Amyloid precursor protein (APP) is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO) mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT) and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry

Differential Responses of Calcifying and Non-Calcifying Epibionts of a Brown Macroalga to Present-Day and Future Upwelling pCO2

Seaweeds are key species of the Baltic Sea benthic ecosystems. They are the substratum of numerous fouling epibionts like bryozoans and tubeworms. Several of these epibionts bear calcified structures and could be impacted by the high pCO2 events of the late summer upwellings in the Baltic nearshores. Those events are expected to increase in strength and duration with global change and ocean acidification. If calcifying epibionts are impacted by transient acidification as driven by upwelling events, their increasing prevalence could cause a shift of the fouling communities toward fleshy species. The aim of the present study was to test the sensitivity of selected seaweed macrofoulers to transient elevation of pCO2 in their natural microenvironment, i.e. the boundary layer covering the thallus surface of brown seaweeds. Fragments of the macroalga Fucus serratus bearing an epibiotic community composed of the calcifiers Spirorbis spirorbis (Annelida) and Electra pilosa (Bryozoa) and the non-calcifier Alcyonidium hirsutum (Bryozoa) were maintained for 30 days under three pCO2 conditions: natural 460±59 µatm, present-day upwelling1193±166 µatm and future upwelling 3150±446 µatm. Only the highest pCO2 caused a significant reduction of growth rates and settlement of S. spirorbis individuals. Additionally, S. spirorbis settled juveniles exhibited enhanced calcification of 40% during daylight hours compared to dark hours, possibly reflecting a day-night alternation of an acidification-modulating effect by algal photosynthesis as opposed to an acidification-enhancing effect of algal respiration. E. pilosa colonies showed significantly increased growth rates at intermediate pCO2 (1193 µatm) but no response to higher pCO2. No effect of acidification on A. hirsutum colonies growth rates was observed. The results suggest a remarkable resistance of the algal macro-epibionts to levels of acidification occurring at present day upwellings in the Baltic. Only extreme future upwelling conditions impacted the tubeworm S. spirorbis, but not the bryozoans

Androgen receptor expresion in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors

<p>Abstract</p> <p>Background</p> <p>In the present study we analyze, in patients with breast cancer, the tumor expression of androgen receptors (AR), its relationship with clinicopathological characteristics and with the expression of several matrix metalloproteases (MMPs) and their inhibitors (TIMPs), as well as with prognosis.</p> <p>Methods</p> <p>An immunohistochemical study was performed using tissue microarrays and specific antibodies against AR, MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 2,800 determinations on tumor specimens from 111 patients with primary invasive ductal carcinoma of the breast (52 with axillary lymph node metastases and 59 without them) and controls were performed. Staining results were categorized using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically.</p> <p>Results</p> <p>A total of 83 cases (74.8%) showed a positive immunostaining for AR, but with a wide variation in the staining score values. There were no significant associations between the total immunostaining scores for AR and any clinicopathological parameters. However, score values for MMP-1, -7 and -13, were significantly higher in AR-positive tumors than in AR-negative tumors. Likewise, when we considered the cellular type expressing each factor, we found that AR-positive tumors had a higher percentage of cases positive for MMP-1, -7, -11, and TIMP-2 in their malignant cells, as well as for MMP-1 in intratumoral fibroblasts. On the other hand, multivariate analysis demonstrated that patients with AR-positive tumors have a significant longer overall survival than those with AR-negative breast carcinomas (<it>p </it>= 0.03).</p> <p>Conclusion</p> <p>Our results confirm that AR are commonly expressed in breast cancer, and are correlated with the expression of some MMPs and TIMP-2. Although we found a specific value of AR expression to be a prognostic indicator in breast cancer, the functional role of AR in these neoplasms is still unclear and further data are needed in order to clarify their biological signification in breast cancer.</p

What is psychiatry? Co-producing complexity in mental health

What is psychiatry? Such a question is increasingly important to engage with in light of the development of new diagnostic frameworks that have wide-ranging and international clinical and societal implications. I suggest in this reflective essay that ‘psychiatry' is not a singular entity that enjoins consistent forms of critique along familiar axes; rather, it is a heterogeneous assemblage of interacting material and symbolic elements (some of which endure, and some of which are subject to innovation). In underscoring the diversity of psychiatry, I seek to move towards further sociological purchase on what remains a contested and influential set of discourses and practices. This approach foregrounds the relationships between scientific knowledge, biomedical institutions, social action and subjective experience; these articulations co-produce both psychiatry and each other. One corollary of this emphasis on multiplicity and incoherence within psychiatric theory, research and practice, is that critiques which elide this complexity are rendered problematic. Engagements with psychiatry are, I argue, best furthered by recognising its multifaceted nature

Bacteriophage-encoded depolymerases: their diversity and biotechnological applications

Bacteriophages (phages), natural enemies of bacteria, can encode enzymes able to degrade polymeric substances. These substances can be found in the bacterial cell surface, such as polysaccharides, or are produced by bacteria when they are living in biofilm communities, the most common bacterial lifestyle. Consequently, phages with depolymerase activity have a facilitated access to the host receptors, by degrading the capsular polysaccharides, and are believed to have a better performance against bacterial biofilms, since the degradation of extracellular polymeric substances by depolymerases might facilitate the access of phages to the cells within different biofilm layers. Since the diversity of phage depolymerases is not yet fully explored, this is the first review gathering information about all the depolymerases encoded by fully sequenced phages. Overall, in this study, 160 putative depolymerases, including sialidases, levanases, xylosidases, dextranases, hyaluronidases, peptidases as well as pectate/pectin lyases, were found in 143 phages (43 Myoviridae, 47 Siphoviridae, 37 Podoviridae, and 16 unclassified) infecting 24 genera of bacteria. We further provide information about the main applications of phage depolymerases, which can comprise areas as diverse as medical, chemical, or food-processing industry.DPP acknowledges the financial support from the Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BD/76440/2011. SS is an FCT investigator (IF/01413/2013). The authors also thank FCT for the Strategic Project of the UID/BIO/04469/2013 unit, FCT and European Union funds (FEDER/COMPETE) for the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER027462)