UK Breastfeeding Helpline support: An investigation of influences upon satisfaction

Background Incentive or reward schemes are becoming increasingly popular to motivate healthy lifestyle behaviours. In this paper, insights from a qualitative and descriptive study to investigate the uptake, impact and meanings of a breastfeeding incentive intervention integrated into an existing peer support programme (Star Buddies) are reported. The Star Buddies service employs breastfeeding peer supporters to support women across the ante-natal, intra-partum and post-partum period. Methods In a disadvantaged area of North West England, women initiating breastfeeding were recruited by peer supporters on the postnatal ward or soon after hospital discharge to participate in an 8 week incentive (gifts and vouchers) and breastfeeding peer supporter intervention. In-depth interviews were conducted with 26 women participants who engaged with the incentive intervention, and a focus group was held with the 4 community peer supporters who delivered the intervention. Descriptive analysis of routinely collected data for peer supporter contacts and breastfeeding outcomes before and after the incentive intervention triangulated and retrospectively provided the context for the qualitative thematic analysis. Results A global theme emerged of 'incentives as connectors', with two sub-themes of 'facilitating connections' and 'facilitating relationships and wellbeing'. The incentives were linked to discussion themes and gift giving facilitated peer supporter access for proactive weekly home visits to support women. Regular face to face contacts enabled meaningful relationships and new connections within and between the women, families, peer supporters and care providers to be formed and sustained. Participants in the incentive scheme received more home visits and total contact time with peer supporters compared to women before the incentive intervention. Full participation levels and breastfeeding rates at 6-8 weeks were similar for women before and after the incentive intervention. Conclusion The findings suggest that whilst the provision of incentives might not influence women's intentions or motivations to breastfeed, the connections forged provided psycho-social benefits for both programme users and peer supporters

Callers’ attitudes and experiences of UK breastfeeding helpline support

Background: Breastfeeding peer support, is considered to be a key intervention for increasing breastfeeding duration rates. Whilst a number of national organisations provide telephone based breastfeeding peer support, to date there have been no published evaluations into callers’ experiences and attitudes of this support. In this study we report on the descriptive and qualitative insights provided by 908 callers as part of an evaluation of UK-based breastfeeding helpline(s). Methods: A structured telephone interview, incorporating Likert scale responses and open-ended questions was undertaken with 908 callers over May to August, 2011 to explore callers’ experiences of the help and support received via the breastfeeding helpline(s). Results: Overall satisfaction with the helpline was high, with the vast majority of callers’ recalling positive experiences of the help and support received. Thematic analysis was undertaken on all qualitative and descriptive data recorded during the evaluation, contextualised within the main areas addressed within the interview schedule in terms of ‘contact with the helplines’; ‘experiences of the helpline service’, ‘perceived effectiveness of support provision’ and ‘impact on caller wellbeing’. Conclusion: Callers valued the opportunity for accessible, targeted, non-judgmental and convenient support. Whilst the telephone support did not necessarily influence women’s breastfeeding decisions, the support they received left them feeling reassured, confident and more determined to continue breastfeeding. We recommend extending the helpline service to ensure support can be accessed when needed, and ongoing training and support for volunteers. Further advertising and promotion of the service within wider demographic groups is warranted

Combining PPI with qualitative research to engage ‘harder-to-reach’ populations: service user groups as co-applicants on a platform study for a trial

Abstract Background: Patient and public involvement (PPI) in all research studies is recommended from the earliest point and in as many stages as possible. Qualitative research is also recommended in the early stages of designing. complex intervention trials. Combining both together might enable inclusion of ‘harder-to-reach’ perspectives from the target population(s), particularly when the research is intended for their benefit. However, the interface between PPI and qualitative research has received little attention. Methods: In a multi-disciplinary, mixed methods study to inform the design of incentive trials for smoking cessation in pregnancy and breastfeeding, we combined PPI and qualitative research, with some overlap. Mother and baby groups from two geographically separate disadvantaged areas, with diverse experiences of the smoking and breastfeeding, but no training or previous involvement in research, were recruited as PPI research grant co-applicants. An iterative partnership approach facilitated involvement in research conduct and design across all project phases. Group PPI members were also invited to contribute to more formal qualitative data collection, as and when indicated by the research questions, and emerging analysis. Results: We engaged with ‘harder-to-reach’ women in mother and baby group settings, rather than in academic or home environments. These settings were relaxed and informal, which facilitated rapport-building, disclosures of unexpected information and maintained trust. 21 women participated in standard PPI activities: feedback on study protocols and documents; piloting questionnaires and interview schedules. PPI members voiced some different perspectives from those captured within the qualitative dataset. 19 participated in focused qualitative research. Novel aspects were audio recorded PPI discussions, which contributed qualitative data; first, to interpret systematic review findings and construct intervention vignettes for use in the qualitative research; second, to assist with recruitment to improve sample diversity in the formal qualitative dataset; and third, to translate theory and findings presented in a researcher generated logic model into a lay tool. This had face validity for potential trial participants and used the metaphor of a ladder. Conclusions: Combining and overlapping PPI and qualitative research added ‘harder-to-reach’ contributions, sample diversity, trust and engagement in creative approaches beyond what could be achieved through PPI or qualitative research alone. (350/350

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Structural basis of PROTAC cooperative recognition for selective protein degradation

Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that recruit a target protein in proximity to an E3 ubiquitin ligase to trigger protein degradation. Structural elucidation of the key ternary ligase-PROTAC-target species and its impact on target degradation selectivity remain elusive. We solved the crystal structure of Brd4 degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4BD2). The ligand folds into itself to allow formation of specific intermolecular interactions in the ternary complex. Isothermal titration calorimetry studies, supported by surface mutagenesis and proximity assays, are consistent with pronounced cooperative formation of ternary complexes with Brd4BD2. Structure-based-designed compound AT1 exhibits highly selective depletion of Brd4 in cells. Our results elucidate how PROTAC-induced de novo contacts dictate preferential recruitment of a target protein into a stable and cooperative complex with an E3 ligase for selective degradation

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial

BACKGROUND: Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans. METHODS/DESIGN: Patients submitted to unilateral, primary, open groin hernia repair will be included in this randomized, placebo-controlled, double-blind, crossover study. The experimental days take place 6–8 weeks after surgery, time-points at which patients are expected to be almost pain- free. Prior to administration of naloxone or placebo, the primary outcome (a summated measure of pain: at rest, during transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed. These assessments will be repeated at each step of the target-controlled infusion of placebo or naloxone at estimated median (95 % CI) plasma concentrations of 344 ng/ml (130;567), 1059 ng/ml (400;1752) and 3196 ng/ml (1205;5276). DISCUSSION: We aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies. TRIAL REGISTRATION NUMBER: EUDRACT: 2015-000793-36 (Registration date: 16 February 2015) Clinicaltrials.gov: NCT01992146 (Registration date: 12 December 2014

Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult mdx Mice

Duchenne muscular dystrophy (DMD) is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myogflox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myogflox/flox mice (mdx), Myogflox/flox mice (wild-type), and mdx:MyogfloxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted). mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function

Do Herbivores Eavesdrop on Ant Chemical Communication to Avoid Predation?

Strong effects of predator chemical cues on prey are common in aquatic and marine ecosystems, but are thought to be rare in terrestrial systems and specifically for arthropods. For ants, herbivores are hypothesized to eavesdrop on ant chemical communication and thereby avoid predation or confrontation. Here I tested the effect of ant chemical cues on herbivore choice and herbivory. Using Margaridisa sp. flea beetles and leaves from the host tree (Conostegia xalapensis), I performed paired-leaf choice feeding experiments. Coating leaves with crushed ant liquids (Azteca instabilis), exposing leaves to ant patrolling prior to choice tests (A. instabilis and Camponotus textor) and comparing leaves from trees with and without A. instabilis nests resulted in more herbivores and herbivory on control (no ant-treatment) relative to ant-treatment leaves. In contrast to A. instabilis and C. textor, leaves previously patrolled by Solenopsis geminata had no difference in beetle number and damage compared to control leaves. Altering the time A. instabilis patrolled treatment leaves prior to choice tests (0-, 5-, 30-, 90-, 180-min.) revealed treatment effects were only statistically significant after 90- and 180-min. of prior leaf exposure. This study suggests, for two ecologically important and taxonomically diverse genera (Azteca and Camponotus), ant chemical cues have important effects on herbivores and that these effects may be widespread across the ant family. It suggests that the effect of chemical cues on herbivores may only appear after substantial previous ant activity has occurred on plant tissues. Furthermore, it supports the hypothesis that herbivores use ant chemical communication to avoid predation or confrontation with ants