A longitudinal implementation evaluation of a physical activity program for cancer survivors: LIVESTRONG(R) at the YMCA

Purpose: Increased physical activity (PA) levels in cancer survivors are associated with decreased risk of recurrence and mortality as well as additional positive health outcomes. PA interventions have shown to be efficacious, though many lack translation to and sustainability in community settings. We used dimensions of the RE-AIM framework to evaluate LIVESTRONG(R) at the YMCA, a nation-wide community-based PA program for cancer survivors delivered at Ys. Methods: This was a longitudinal study design using national LIVESTRONG at the YMCA data compiled between 2010 and 2018. Data is from all YMCAs who deliver LIVESTRONG at the YMCA, submitted by Program Directors to the YMCA-USA. We assessed reach (number of participants), adoption (associations offering the program), implementation (conducting 3 fidelity checks), and organizational level maintenance (associations recently offering program). We also examined relationships between organizational characteristics (years of program existence and association area household income) and program implementation factors with member conversion rates. Results: As of 2018, LIVESTRONG at the YMCA has reached 62,044 survivors and 245 of the 840 (29.2%) of Y associations have adopted the program. Among the adopters, 91% were aware of fidelity checks; implementation of observational (62.3%), goal setting (49.9%), and functional (64.6%) checklists varied. Most (95.1%) adopters reported offering \u3e /= 1 LIVESTRONG session per year (organizational-level maintenance) and a facility-level mean membership conversion percentage of 46.9 +/- 31.2%. Fewer years implementing the program and higher association area household income were significantly associated with a greater membership conversion rate vs their comparison. In a multiple regression model controlling for organizational characteristics, conducting the fidelity checks independently (observational, beta = 8.41; goal-setting, beta = 9.70; and functional, beta = 9.61) and collectively (beta = 10.82; 95% CI 5.90-16.80) was positively associated with higher membership conversion rates. Conclusions: LIVESTRONG at the YMCA, in its early years, has shown promise for high reach, while adoption at more associations could be facilitated. Implementing fidelity checks along with organizational characteristics were associated with membership conversion rate. Identification of association-level strategies to increase reach, adoption, implementation, and maintenance may increase the impact of this community-based PA program

Galactosemia produces ARI-preventable nodal changes similar to those of diabetic neuropathy

The present study was designed to examine the development of structural changes, characteristic of diabetic neuropathy, in chronic galactosemia and their responsiveness to inhibition of the polyol-pathway. Sprague-Dawley rats weighing 70-90 g were given a 50% galactose diet continued for 4 or 8 months. Half of these animals were simultaneously given the aldose reductase inhibitor (ARI) WAY 121-509. ARI-treatment normalized galactitol and myoinositol levels in the sciatic nerve. At 4 months, sciatic nerve conduction velocity (NCV) in galactosemic rats was reduced by 30% which was prevented in ARI-treated rats. At 8 months galactosemia reduced NCV to 58% of control values, while ARI-treatment for 8 months improved NCV to 71% of control values. ARI-treatment prevented in galactosemic rats nodal structural changes characteristic of diabetic neuropathy, whereas axonal atrophy was not affected by ARI-treatment, which may in part account for the only partial prevention of the NCV slowing at 8 months. Nerve fiber regeneration was increased 4-fold in ARI-treated rats compared with untreated galactosemic rats. These data suggest that chronic galactosemia produces a neuropathy structurally similar to diabetic neuropathy. The lack of an ARI-treatment effect on axonal atrophy suggests that this defect is not polyol related in galactosemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31346/1/0000256.pd

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Exchange Reactions between Alkanethiolates and Alkaneselenols on Au{111}

When alkanethiolate self-assembled monolayers on Au{111} are exchanged with alkaneselenols from solution, replacement of thiolates by selenols is rapid and complete, and is well described by perimeter-dependent island growth kinetics. The monolayer structures change as selenolate coverage increases, from being epitaxial and consistent with the initial thiolate structure to being characteristic of selenolate monolayer structures. At room temperature and at positive sample bias in scanning tunneling microscopy, the selenolate-gold attachment is labile, and molecules exchange positions with neighboring thiolates. The scanning tunneling microscope probe can be used to induce these place-exchange reactions

Impairment of Afferent Arteriolar Myogenic Responsiveness in the Galactose-Fed Rat

Abstract Previous studies from our laboratory have demonstrated impaired afferent arteriolar responsiveness to pressure in rats 4-6 weeks after the induction of diabetes mellitus. Although the responsible mechanisms mediating this renal autoregulatory defect have not been fully defined, increased polyol metabolism has been implicated as a possible factor involved in the pathogenesis of diabetic complications. We therefore investigated the possible role of this metabolic disturbance in renal autoregulation using the galactose-fed rat, a model characterized by increased polyol pathway activity independent of hyperglycemia or insulin deficiency. Hydronephrosis was induced to permit direct visualization of renal microvessels. Pressure-induced vasoconstriction of afferent arterioles was assessed by quantitating vessel diameter following stepwise increments of renal perfusion pressure (RAP; from 80 to 180 mm Hg) in the hydronephrotic kidneys from control rats and rats fed a 50% galactose diet for 2 or 4 weeks. Vessel diameters were measured from video images by computer-assisted image processing. Control rats exhibited progressive afferent arteriolar vasoconstriction when RAP was increased from 80 to 180 mm Hg (-17.3% ± 1.0%; P < 0.001). In contrast, myogenic responses to increases in pressure were absent in the afferent arterioles of rats fed a 50% galactose diet for either 2 (-4.1% ± 1.9%; not significant) or 4 weeks (-2.9 ± 3.4%; not significant). Our demonstration that the impairment of afferent arteriolar responsiveness to increasing RAP in the normoglycemic galactose-fed rat was identical to that observed in the STZ-diabetic rat suggests that increased polyol accumulation may contribute to the impairment of renal auto-regulation in the diabetic rat

Exchange reactions between alkanethiolates and alkaneselenols on Au{111}.

When alkanethiolate self-assembled monolayers on Au{111} are exchanged with alkaneselenols from solution, replacement of thiolates by selenols is rapid and complete, and is well described by perimeter-dependent island growth kinetics. The monolayer structures change as selenolate coverage increases, from being epitaxial and consistent with the initial thiolate structure to being characteristic of selenolate monolayer structures. At room temperature and at positive sample bias in scanning tunneling microscopy, the selenolate-gold attachment is labile, and molecules exchange positions with neighboring thiolates. The scanning tunneling microscope probe can be used to induce these place-exchange reactions