Rho-class small GTPases are implicated in basic cellular processes at nearly all brain developmental steps, from neurogenesis and migration to axon guidance and synaptic plasticity. GTPases are key signal transducing enzymes that link extracellular cues to the neuronal responses required for the construction of neuronal networks, as well as for synaptic function and plasticity. Rho GTPases are highly regulated by a complex set of activating (GEFs) and inactivating (GAPs) partners, via protein:protein interactions (PPI). Misregulated RhoA, Rac1/Rac3 and cdc42 activity has been linked with intellectual disability (ID) and other neurodevelopmental conditions that comprise ID. All genetic evidences indicate that in these disorders the RhoA pathway is hyperactive while the Rac1 and cdc42 pathways are consistently hypoactive. Adopting cultured neurons for in vitro testing and specific animal models of ID for in vivo examination, the endophenotypes associated with these conditions are emerging and include altered neuronal networking, unbalanced excitation/inhibition and altered synaptic activity and plasticity. As we approach a clearer definition of these phenotype(s) and the role of hyper- and hypo-active GTPases in the construction of neuronal networks, there is an increasing possibility that selective inhibitors and activators might be designed via PPI, or identified by screening, that counteract the misregulation of small GTPases and result in alleviation of the cognitive condition. Here we review all knowledge in support of this possibility.
The development of vaccines against herpes simplex virus (HSV) is an important global goal for sexual and reproductive health. A key priority to advance development of HSV vaccines is the definition of preferred product characteristics (PPCs), which provide strategic guidance on World Health Organization (WHO) preferences for new vaccines, specifically from a low- and middle-income country (LMIC) perspective. To start the PPC process for HSV vaccines, the WHO convened a global stakeholder consultation in March 2017, to define the priority public health needs that should be addressed by HSV vaccines and discuss the key considerations for HSV vaccine PPCs, particularly for LMICs. Meeting participants outlined an initial set of overarching public health goals for HSV vaccines in LMICs, which are: to reduce the acquisition of HIV associated with HSV-2 infection in high HIV-prevalence populations and to reduce the burden of HSV-associated disease, including mortality and morbidity due to neonatal herpes and impacts on sexual and reproductive health. Participants also considered the role of prophylactic versus therapeutic vaccines, whether both HSV-2 and HSV-1 should be targeted, important target populations, and infection and disease endpoints for clinical trials. This article summarizes the main discussions from the consultation.
Many industrialized countries have implemented routine immunization policies for older adults, but similar strategies have not been widely implemented in low- and middle-income countries (LMICs). In March 2017, the World Health Organization (WHO) convened a meeting to identify policies and activities to promote access to vaccination of older adults, specifically in LMICs. Participants included academic and industry researchers, funders, civil society organizations, implementers of global health interventions, and stakeholders from developing countries with adult immunization needs. These experts reviewed vaccine performance in older adults, the anticipated impact of adult vaccination programs, and the challenges and opportunities of building or strengthening an adult and older adult immunization platforms. Key conclusions of the meeting were that there is a need for discussion of new opportunities for vaccination of all adults as well as for vaccination of older adults, as reflected in the recent shift by WHO to a life-course approach to immunization; that immunization in adults should be viewed in the context of a much broader model based on an individual’s abilities rather than chronological age; and that immunization beyond infancy is a global priority that can be successfully integrated with other interventions to promote healthy ageing. As WHO is looking ahead to a global Decade of Healthy Ageing starting in 2020, it will seek to define a roadmap for interdisciplinary collaborations to integrate immunization with improving access to preventive and other healthcare interventions for adults worldwide.
Background Internal medicine programs are redesigning ambulatory training to improve the resident experience and answer the challenges of conflicting clinical responsibilities. However, little is known about the effect of clinic redesign on residents' satisfaction.
Evidence suggests that teamwork is essential for safe, reliable practice. Creating health care teams able to function effectively in patient-centered medical homes (PCMHs), practices that organize care around the patient and demonstrate achievement of defined quality care standards, remains challenging. Preparing trainees for practice in interprofessional teams is particularly challenging in academic health centers where health professions curricula are largely siloed. Here, the authors review a well-delineated set of teamwork competencies that are important for high-functioning teams and suggest how these competencies might be useful for interprofessional team training and achievement of PCMH standards. The five competencies are (1) team leadership, the ability to coordinate team members' activities, ensure appropriate task distribution, evaluate effectiveness, and inspire high-level performance, (2) mutual performance monitoring, the ability to develop a shared understanding among team members regarding intentions, roles, and responsibilities so as to accurately monitor one another's performance for collective success, (3) backup behavior, the ability to anticipate the needs of other team members and shift responsibilities during times of variable workload, (4) adaptability, the capability of team members to adjust their strategy for completing tasks on the basis of feedback from the work environment, and (5) team orientation, the tendency to prioritize team goals over individual goals, encourage alternative perspectives, and show respect and regard for each team member. Relating each competency to a vignette from an academic primary care clinic, the authors describe potential strategies for improving teamwork learning and applying the teamwork competences to academic PCMH practices.
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