Stage-Specific Timing of the microRNA Regulation of \u3cem\u3elin-28\u3c/em\u3e by the Heterochronic Gene \u3cem\u3elin-14\u3c/em\u3e in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

In normal development, the order and synchrony of diverse developmental events must be explicitly controlled. In the nematode Caenorhabditis elegans, the timing of larval events is regulated by hierarchy of proteins and microRNAs (miRNAs) known as the heterochronic pathway. These regulators are organized in feedforward and feedback interactions to form a robust mechanism for specifying the timing and execution of cell fates at successive stages. One member of this pathway is the RNA binding protein LIN-28, which promotes pluripotency and cell fate decisions in successive stages. Two genetic circuits control LIN-28 abundance: it is negatively regulated by the miRNA lin-4, and positively regulated by the transcription factor LIN-14 through a mechanism that was previously unknown. In this report, we used animals that lack lin-4 to elucidate LIN-14’s activity in this circuit. We demonstrate that three let-7 family miRNAs—miR-48, miR-84, and miR-241—inhibit lin-28 expression. Furthermore, we show genetically that these miRNAs act between lin-14 and lin-28, and that they comprise the pathway by which lin-14 positively regulates lin-28. We also show that the lin-4 family member mir-237, also regulates early cell fates. Finally, we show that the expression of these miRNAs is directly inhibited by lin-14 activity, making them the first known targets of lin-14 that act in the heterochronic pathway

The impact of a post-take ward round pharmacist on the risk score and enactment of medication-related recommendations

There is a scarcity of published research describing the impact of a pharmacist on the post-take ward round (PTWR) in addition to ward-based pharmacy services. The aim of this paper was to evaluate the impact of clinical pharmacists' participation on the PTWR on the risk assessment scores of medication-related recommendations with and without a pharmacist. This includes medication-related recommendations occurring on the PTWR and those recommendations made by the ward-based pharmacist on the inpatient ward. A pre-post intervention study was undertaken that compared the impact of adding a pharmacist to the PTWR compared with ward-based pharmacist services alone. A panel reviewed the risk of not acting on medication recommendations that was made on the PTWR and those recorded by the ward-based pharmacist. The relationship between the risk scores and the number and proportion of recommendations that led to action were compared between study groups. There were more medication-related recommendations on the PTWR in the intervention group when a pharmacist was present. Proportionately fewer were in the 'very high and extreme' risk category. Although there was no difference in the number of ward pharmacist recommendations between groups, there was a significantly higher proportion of ward pharmacist recommendations in the "very high and extreme" category in those patients who had been seen on a PTWR attended by a pharmacist than when a pharmacist was not present. There were a greater proportion of "low and medium" risk actionable medication recommendations actioned on the PTWR in the intervention group; and no difference in the risk scores in ward pharmacist recommendations actioned between groups. Overall, the proportion of recommendations that were actioned was higher for those made on the PTWR compared with the ward. The addition of a pharmacist to the PTWR resulted in an increase in low, medium, and high risk recommendations on the PTWR, more very high and extreme risk recommendations made by the ward-based pharmacist, plus an increased number of recommendations being actioned during the patients' admission

Navigating Educational and Behavioral Services: What Parents of Children With ASD Need to Know

Navigating service systems can be difficult. Parents are often unaware of where educational services end and where behavioral health services begin. This interactive panel will aid in navigating the complex matrix of school, BHRS, STS, outpatient, and psychiatric services for school-aged children with an ASD. It will teach parents how to create a collaborative team which aids in providing consistency in all environments. Additionally, parents will gain information about effective advocacy for services in the school, home, and community. The discussion will provide an overview of considerations family need in order to identify supports and advocate for their children

Game-centered approaches in a PETE program

In this article we will describe the use of Game-Centered Approaches (GCAs) within an undergraduate Physical Education Teacher Education (PETE) program. Specifically, our intent is to show the progression of how GCAs are implemented as well as the GCA experiences pre-service teachers receive within this program. The specific program, at Kent State University (KSU) in Ohio, USA, is a typical four year teacher education licensure program (five years if students choose to also pursue a Health Education teaching license). It includes general education, content-based, and pedagogical courses, culminating with a student teaching field experience. Students are first exposed to, and then increasingly study and implement GCAs as they progress throughout the program. This manuscript is organized chronologically in that first we describe the prior experiences of our undergraduate students and their ability to understand GCAs as an innovation. Second, we outline the practical experiences provided to students early in their program of study. These experiences provide initial exposure to GCAs across all game categories (invasion, net/wall, striking/fielding, target – Almond, 1986) and combine the implementation of GCAs with the Sport Education curriculum model (Siedentop, Hastie & van der Mars, 2011). Third, we describe the latter stages of the PETE program in which the emphasis transitions from GCA content to GCA pedagogy. Teaching methods and content courses include the pedagogy of GCAs at both the elementary and secondary levels, and Ohio’s state assessment procedures during student teaching require a focus on assessment of children’s learning while participating in GCAs.El presente artículo describe un programa de formación en la Enseñanza Comprensiva del Deporte (ECD) dentro de un plan de estudios de profesores de Educación Física. El principal interés de este trabajo es mostrar la progresión en la implementación de la ECD, así como las experiencias durante las prácticas de enseñanza sobre este enfoque. El plan de estudios de la Universidad de Kent State (Ohio, EEUU) es un típico programa de cuatro años de licenciatura de formación de profesores (cinco años si los alumnos eligen continuar el programa en Educación para la Salud). Incluye materias de educación general, de contenido y de didáctica, culminando con prácticas externas en centros educativos. A lo largo del plan de estudios los estudiantes primero experimentan la ECD y posteriormente la estudian e implementan. El presente artículo está organizado cronológicamente, la primera parte consta de lo que describimos como las experiencias previas de nuestros alumnos y su capacidad para comprender la ECD como innovación. Segundo, resumimos las experiencias aportadas a los alumnos en las primeras fases del plan de estudios. Estas experiencias aportan una primera exposición a la ECD en todas las categorías de juegos deportivos (invasión, red y muro, campo y bate, y blanco y diana – Almond, 1986), combinada con el modelo de instrucción de Educación Deportiva (Siedentop, Hastie & van der Mars, 2011). Tercero, describimos la última etapa del plan del programa de formación, en el cual se pone énfasis en la transición del contenido de la ECD a la didáctica de la ECD. Las materias de metodología y de contenido incluyen la didáctica de la ECD a los niveles de Educación Primaria y Educación Secundaria, así como los procedimientos de evaluación establecidos por el estado de Ohio, los cuales requieren centrarse en los aprendizajes de los alumnos durante su participación en la ECD

Inhibitory feedback control of NF-κB signalling in health and disease.

Cells must adapt to changes in their environment to maintain cell, tissue and organismal integrity in the face of mechanical, chemical or microbiological stress. Nuclear factor-κB (NF-κB) is one of the most important transcription factors that controls inducible gene expression as cells attempt to restore homeostasis. It plays critical roles in the immune system, from acute inflammation to the development of secondary lymphoid organs, and also has roles in cell survival, proliferation and differentiation. Given its role in such critical processes, NF-κB signalling must be subject to strict spatiotemporal control to ensure measured and context-specific cellular responses. Indeed, deregulation of NF-κB signalling can result in debilitating and even lethal inflammation and also underpins some forms of cancer. In this review, we describe the homeostatic feedback mechanisms that limit and 're-set' inducible activation of NF-κB. We first describe the key components of the signalling pathways leading to activation of NF-κB, including the prominent role of protein phosphorylation and protein ubiquitylation, before briefly introducing the key features of feedback control mechanisms. We then describe the array of negative feedback loops targeting different components of the NF-κB signalling cascade including controls at the receptor level, post-receptor signalosome complexes, direct regulation of the critical 'inhibitor of κB kinases' (IKKs) and inhibitory feedforward regulation of NF-κB-dependent transcriptional responses. We also review post-transcriptional feedback controls affecting RNA stability and translation. Finally, we describe the deregulation of these feedback controls in human disease and consider how feedback may be a challenge to the efficacy of inhibitors

Losing a Limb, Regaining Independence: A Systematic Review of Occupational Therapy Interventions for Lower Extremity Amputations

Primary Focus: Rehab, Disability & Participation Learning Objectives: Describe lower extremity residual limb care interventions within the scope of occupational therapy Explain the prevalence of individuals who sustain a lower extremity amputation and understand the impact on the U.S. health-care system Identify lower extremity residual limb care interventions to maximize occupational performance Abstract: The purpose of this presentation is to report findings of a systematic review regarding residual limb care interventions supporting increased occupational performance in adults post lower extremity amputation. A systematic review was completed utilizing PubMed, CINHAL, and OTseeker. Inclusion criteria included articles with a sample of adults (mean age of 18-64 years old) with all levels of lower extremity amputations resulting from various etiologies. In addition, these articles were published within the past 10 years and in the English language. Exclusion criteria included articles that contained interventions outside of the scope of occupational therapy practice, systematic reviews, and meta-analyses. Two million people in the U.S. are currently living with limb loss. Hospital costs associated with amputees in 2009 totaled 8.3 billion dollars. Approximately half of individuals with amputations due to vascular disease will require an additional amputation within 2-3 years (Amputee Coalition, 2016). Although there is evidence on surgical techniques and physical therapy’s role in rehabilitation of lower extremity amputations, there is limited evidence to support occupational therapy’s unique role (Robinson, Sansam, Hirst, & Neumann, 2010). However, occupational therapists can provide valuable interventions to improve participation in all activities of daily living (Klarich & Brueckner, 2014). Critical appraisals of eligible articles were performed to identify themes and clinical implications utilizing quantitative and qualitative critical review forms. Four themes concluded from the literature associated with residual limb care interventions and their impact on occupational performance included education, health-care costs, pain, and skin integrity. These findings present implications for occupational therapy research, education, and practice in regards to advocating for occupational therapy’s role in the continuum of care for individuals with lower extremity amputation, and the implementation of interventions to increase occupational performance and decrease health-care costs. This presentation material is of intermediate level and targeted for an audience of occupational therapists and occupational therapy assistants with experience working with individuals with lower limb amputations. References: Amputee Coalition. (2016). Limb loss statistics. Retrieved from http://www.amputee-coalition/limb-loss-resource-center/resources-by-topic/limb-loss-statistics/limb-loss-statistics/ Robinson, V., Sansam, K., Hirst, L., & Neumann, V. (2010). Major lower limb amputation -- what, why and how to achieve the best results. Orthopaedics & Trauma, 24(4), 276-285 10p. doi:10.1016/j.mporth.2010.03.017 Klarich, J., & Brueckner, I. (2014). Amputee rehabilitation and preprosthetic care. Physical Medicine and Rehabilitation Clinics of North America, 25(1), 75-91. doi:10.1016/j.pmr.2013.09.005 Presentation: 31:5

Medical abortion with mifepristone and vaginal misoprostol between 64 and 70 days' gestation.

ObjectiveTo evaluate outcomes with mifepristone 200 mg orally followed 24-48 h later by misoprostol 800 mcg vaginally for medical abortion at 64-70 days of gestation.Study designWe reviewed electronic databases and medical records for medical abortion cases at 64-70 days' gestation at British Pregnancy Advisory Service clinics in England and Wales from May 2015 through October 2016. Women selected in-office follow-up or self-evaluation of abortion outcome using a checklist along with low-sensitivity urine pregnancy testing. We excluded cases in which we could not locate records and when women did not proceed with medical abortion, did not use misoprostol following mifepristone if abortion had not occurred and did not attend a scheduled follow-up assessment. We analyzed demographic characteristics, treatment outcomes and significant adverse events. We defined treatment success as complete abortion without surgical evacuation and without continuing pregnancy.ResultsOf 2743 cases identified, we could not locate 40 charts and excluded 30 cases, leaving a final sample of 2673. Overall, 2538 (94.9%, 95% CI 94.1-95.8) women had a successful medical abortion. Reasons for failure included continuing pregnancy (n=90, 3.4%, 95% CI 2.7-4.1), retained nonviable pregnancy (n=2, 0.1%, 95% CI 0-0.2) and incomplete abortion (n=43, 1.6%, 95% CI 1.1-2.1). Of those with continuing pregnancies, 81 underwent a uterine aspiration and 9 opted to continue the pregnancy. Thirty-five (1.3%, 95% CI 0.9-1.7) women had significant adverse events; 16 (0.6%, 95% CI 0.3-0.9) underwent an in-hospital aspiration. Pelvic infection (n=4, 0.2%) and transfusion (n=1, 0.03%) occurred rarely.ConclusionMedical abortion from 64 to 70 days with mifepristone and vaginal misoprostol is effective with a low rate of serious adverse events.ImplicationsMedical abortion between 64 and 70 days of gestation may be offered on an outpatient basis using mifepristone and vaginal misoprostol. Service provision without an in-person follow-up is feasible. Not all women with a continuing pregnancy after medical abortion treatment opt to have an aspiration procedure

IMP Dehydrogenase Inhibitors as Immunomodulators

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74880/1/j.1749-6632.1993.tb35869.x.pd