66 research outputs found
Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan
No full textAging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan
Lonidamine Extends Lifespan of Adult Caenorhabditis elegans by Increasing the Formation of Mitochondrial Reactive Oxygen Species
No full textPreserved parasympathetic cardiac innervation after atrioventricular node modification : evidence from circle maps of respiratory sinus arrhythmia
No full textIntroduction: Respiratory sinus arrhythmia (RSA) and heart rate variability (HRV) are parameters of autonomic cardiac innervation. They decrease with age and after atrioventricular nodal modification (AVNM) suggesting vagal denervation in both situations. We hypothesized, however, that AVNM causes only a transient, functional decline in vagal activity, whereas aging causes permanent vagal denervation. A new method of analyzing RSA phase dynamics based on circle maps (CM) can potentially differentiate between both forms of reduced vagal activity.Methods: In 18 younger and 14 older healthy control subjects 24-hour Holter ECGs were recorded for HRV analysis. Repeated measurements of RSA were acquired during paced breathing (PB). In 16 consecutive patients undergoing AVNM the same measurements were applied before, 1 day and 3 months after the procedure. CM were calculated from consecutive RR intervals and the similarity between different CM quantified by the Kullback information gain (KIG).Results: HRV analysis revealed lower HF bands, LF bands and RSA amplitudes in older vs. younger control subjects. KIG revealed less similarity between younger and older control subjects than within the respective age groups. After AVNM a decrease in HF bands was noted in HRV analysis. Three months after AVNM, HF bands returned to pre-ablation values. CM obtained before and 1 day after AVNM displayed comparable similarity to CM acquired 1 day before and 3 months after ablation.Conclusions: In contrast to conventional HRV parameters, CM of RSA are not altered by ablation in the posteroseptal space but by aging. Thus, this new method appears to differentiate between transient autonomic modification and chronic denervation
Neuronal sympathetic stimulation for selective enhancement of left ventricular inotropy without increasing cardiac afterload. A novel approach for treating postoperative low output syndromes
No full textTransvascular parasympathetic stimulation for ventricular rate control during atrial fibrillation: A bionic approach
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Lack of prolongation of antegrade wenckbach cycle length : but not persistance of 'Jump' or echo beas is prognostic for the recurrence of AVNRT after AV node modification
No full textSingle-step atrial thrombus exclusion and cardioversion of atrial fibrillation via a transesophageal echocardiography probe
No full textA Case Study of Military-Connected Principals' Trauma-Informed Decision-Making
No full textA substantial body of research spanning almost two decades has demonstrated that
widespread trauma from adverse childhood experiences and toxic environments exists within the
American population and is predictive of increased rates of mental illness, chronic diseases, and
premature death (Chafouleas et al., 2019; Larkin et al., 2014; Zarse et al., 2019). These
experiences, which occur cumulatively prior to age eighteen, are also predictive of limitations in
neural development during childhood and adolescence, and both internalizing and externalizing
behaviors contribute to poor academic success and social isolation (Larkin et al et al., 2014;
Zarse et. al., 2019).
From a public health perspective, researchers have examined ways to leverage the public
school system as a delivery method for systemic prevention and intervention under the umbrella
of “trauma-informed” care, focusing their efforts on grades K-8 and leaving a gap in the
literature for grades 9-12 (Chafouleas et al., 2019; Crosby, 2015; DePedro et al., 2018; Gubi et
al., 2019). Military-connected children are a subset of the population identified as having high
risk factors for adverse childhood experiences or traumatic events (DePedro et al., 2018;
Richardson et al., 2016; Boberiene & Hornback, 2014; Brendel et al., 2014; Cole, 2016; Wolf et
al., 2017). While researchers have begun to examine school-based trauma-informed interventions
targeted at other subsets of students, there is lack of research directed toward school-based
trauma-informed interventions for military-connected students.
While many military-connected students attend regular public schools within the
continental United States, dependents of active military and civilian contractors living overseas
often attend American military-connected schools. This collective case study uses a complexity
leadership theory framework to examine the understandings that school principals in these
American military-connected schools have regarding trauma-informed practices, how those
understandings inform their leadership approaches, and the barriers they perceive.
This study sought to provide current information to principal preparation programs and
professional development trainers regarding the needs of principals and staff in schools attended
by military-connected high school students with trauma. Twelve principals of American militaryconnected
high schools outside of the continental U.S. participated in semi-structured interviews
with eight principals participating in abbreviated follow-up interviews. Initial interview data was
analyzed using iterative rounds of in vivo coding. Follow up interviews used a priori coding, and
artifacts were collected for triangulation. The use of all five functions of leadership were
identified using the complexity leadership theory framework, and overlapping concepts with
SAMHSA’s Six Key Principles of Trauma-Informed Practice were highlighted in the discussion.
Key findings include that principals of military-connected high schools have some
understanding of trauma, but they struggle to explain trauma-informed practices; they are
engaged in strategic leadership activities to address trauma in their schools; and they perceive
structural and knowledge barriers for themselves and their staff that impact their leadership
regarding implementation of trauma-informed practices. The findings suggest that further
research is needed targeting the implementation of research-based interventions in high schools
and with military-connected populations. Findings also suggest that military-connected schools
overseas conduct internal reviews of their programs for issues related to student-staffing ratios
and long-term vacancies in student support service areas as well as the need for more training
and support for principals and staff regarding trauma-informed practices
Circle maps of respiratory sinus arrhythmia : a new method to fast and reliably determine autonomic cardiac innervation
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