A dynamic basal complex modulates mammalian sperm movement

Centrioles are ancient organelles with a conserved architecture and their rigidity is thought to restrict microtubule sliding. Here authors show that, in mammalian sperm, the atypical distal centriole and its surrounding atypical pericentriolar matrix form a dynamic basal complex that facilitates a cascade of internal sliding deformations, coupling tail beating with asymmetric head kinking

Family-Centered Preventive Intervention for Military Families: Implications for Implementation Science

In this paper, we report on the development and dissemination of a preventive intervention, Families OverComing Under Stress (FOCUS), an eight-session family-centered intervention for families facing the impact of wartime deployments. Specific attention is given to the challenges of rapidly deploying a prevention program across diverse sites, as well as to key elements of implementation success. FOCUS, developed by a UCLA-Harvard team, was disseminated through a large-scale demonstration project funded by the United States Bureau of Navy Medicine and Surgery (BUMED) beginning in 2008 at 7 installations and expanding to 14 installations by 2010. Data are presented to describe the range of services offered, as well as initial intervention outcomes. It proved possible to develop the intervention rapidly and to deploy it consistently and effectively

Mechanisms of Risk and Resilience in Military Families: Theoretical and Empirical Basis of a Family-Focused Resilience Enhancement Program

Recent studies have confirmed that repeated wartime deployment of a parent exacts a toll on military children and families and that the quality and functionality of familial relations is linked to force preservation and readiness. As a result, family-centered care has increasingly become a priority across the military health system. FOCUS (Families OverComing Under Stress), a family-centered, resilience-enhancing program developed by a team at UCLA and Harvard Schools of Medicine, is a primary initiative in this movement. In a large-scale implementation project initiated by the Bureau of Navy Medicine, FOCUS has been delivered to thousands of Navy, Marine, Navy Special Warfare, Army, and Air Force families since 2008. This article describes the theoretical and empirical foundation and rationale for FOCUS, which is rooted in a broad conception of family resilience. We review the literature on family resilience, noting that an important next step in building a clinically useful theory of family resilience is to move beyond developing broad “shopping lists” of risk indicators by proposing specific mechanisms of risk and resilience. Based on the literature, we propose five primary risk mechanisms for military families and common negative “chain reaction” pathways through which they undermine the resilience of families contending with wartime deployments and parental injury. In addition, we propose specific mechanisms that mobilize and enhance resilience in military families and that comprise central features of the FOCUS Program. We describe these resilience-enhancing mechanisms in detail, followed by a discussion of the ways in which evaluation data from the program’s first 2 years of operation supports the proposed model and the specified mechanisms of action

Priorities and strategies for improving disabled women's access to maternity services when they are affected by domestic abuse:a multi-method study using concept maps

BACKGROUND: Domestic abuse is a significant public health issue. It occurs more frequently among disabled women than those without a disability and evidence suggests that a great deal of domestic abuse begins or worsens during pregnancy. All women and their infants are entitled to equal access to high quality maternity care. However, research has shown that disabled women who experience domestic abuse face numerous barriers to accessing care. The aim of the study was to identify the priority areas for improving access to maternity services for this group of women; develop strategies for improved access and utilisation; and explore the feasibility of implementing the identified strategies. METHODS: This multi-method study was the third and final part of a larger study conducted in the UK between 2012 and 2014. The study used a modified concept mapping approach and was theoretically underpinned by Andersen’s model of healthcare use. Seven focus group interviews were conducted with a range of maternity care professionals (n = 45), incorporating quantitative and qualitative components. Participants ranked perceived barriers to women’s access and utilisation of maternity services in order of priority using a 5-point Likert scale. Quantitative data exploration used descriptive and non-parametric analyses. In the qualitative component of each focus group, participants discussed the barriers and identified potential improvement strategies (and feasibility of implementing these). Qualitative data were analysed inductively using a framework analysis approach. RESULTS: The three most highly ranked barriers to women’s access and utilisation of maternity services identified in the quantitative component were: 1) staff being unaware and not asking about domestic abuse and disability; 2) the impact of domestic abuse on women; 3) women’s fear of disclosure. The top two priority strategies were: providing information about domestic abuse to all women and promoting non-judgemental staff attitude. These were also considered very feasible. The qualitative analysis identified a range of psychosocial and environmental barriers experienced by this group of women in accessing maternity care. Congruent with the quantitative results, the main themes were lack of awareness and fear of disclosure. Key strategies were identified as demystifying disclosure and creating physical spaces to facilitate disclosure. CONCLUSIONS: The study supports findings of previous research regarding the barriers that women face in accessing and utilising maternity services, particularly regarding the issue of disclosure. But the study provides new evidence on the perceived importance and feasibility of strategies to address such barriers. This is an important step in ensuring practice-based acceptability and ease with which improvement strategies might be implemented in maternity care settings

Seasonal differences of corticosterone metabolite concentrations and parasite burden in northern bald ibis (Geronticus eremita): The role of affiliative interactions

The reproductive season is energetically costly as revealed by elevated glucocorticoid concentrations, constrained immune functions and an increased risk of infections. Social allies and affiliative interactions may buffer physiological stress responses and thereby alleviate associated effects. In the present study, we investigated the seasonal differences of immune reactive corticosterone metabolite concentrations, endoparasite burden (nematode eggs and coccidian oocysts) and affiliative interactions in northern bald ibis (Geronticus eremita), a critically endangered bird. In total, 43 individually marked focal animals from a freeranging colony were investigated. The analyses included a description of initiated and received affiliative interactions, pair bond status as well as seasonal patterns of hormone and endoparasite levels. During the reproductive season, droppings contained parasite eggs more often and corticosterone metabolite levels were higher as compared to the period after reproduction. The excretion rate of endoparasite products was lower in paired individuals than in unpaired ones, but paired animals exhibited higher corticosterone metabolite concentrations than unpaired individuals. Furthermore, paired individuals initiated affiliative behaviour more frequently than unpaired ones. This suggests that the reproductive season influences the excretion patterns of endoparasite products and corticosterone metabolites and that affiliative interactions between pair partners may positively affect endoparasite burden during periods of elevated glucocorticoid levels. Being embedded in a pair bond may have a positive impact on individual immune system and parasite resistance

Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients