Women Bound to be Active: Differences in Long-Term Physical Activity Between Completers and Noncompleters of a Book Club Intervention

Background: Ideal approaches to increasing long-term physical activity (PA) adherence in women remain unclear. This study used a longitudinal mixed-methods approach to 1) determine the effectiveness of an 8-month book club intervention for increasing PA participation and self-worth, and reducing barriers at 1-year followup; and 2) identify reasons why completers and noncompleters did or did not maintain PA. Methods: One year after the cessation of Women Bound to be Active (WBA), completers (participated in posttesting; n = 30) and noncompleters (did not participate in posttesting; n = 22) responded to questionnaires and interviews assessing their body mass index (BMI), current PA participation, barriers, and global self-worth. Results: Compared with noncompleters, completers reported decreases in BMI, higher motivation for PA, higher ratio of benefits to barriers, and more consistent PA. Both groups still reported barriers to PA, especially time; however, completers more often reported strategies for overcoming these barriers. Completers more directly discussed the impact of their improved self-worth on their PA participation. Conclusions: In the future, a greater focus on time management and self-regulation strategies should be emphasized in PA interventions, specifically those that focus on women. This may help to prevent program and long-term PA attrition

Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience.

BackgroundActivated PI3K/AKT/mTOR pathway frequently occurs in metastatic or recurrent cervical carcinomas. However, the clinical benefits of matched therapy, a therapeutic approach targeting a specific mutational abnormality, have not yet been established.MethodsWe analyzed the outcomes of patients with metastatic or recurrent cervical carcinomas who had a test for PIK3CA mutation and/or PTEN loss/mutation, and received ≥1 phase I therapeutic regimen between January 2006 and June 2013.ResultsPatients with adenocarcinoma had fewer PIK3CA mutations (14%), and survived longer (median, 14.2 months) than those with squamous cell carcinoma (48% and 7.2 months; p = 0.016, and 0.001, respectively). Matched therapy targeting the activated PI3K/AKT/mTOR pathway led to a favorable rate of SD ≥ 6 months/CR/PR (53%) and significantly longer progression-free survival (median, 6.0 months) than non-matched therapy (11% and 1.5 months; p = 0.08 and 0.026; respectively). In patients with squamous cell carcinoma of the cervix, the presence of PIK3CA mutations was associated with a significantly longer overall survival (median, 9.4 months) than the absence of PIK3CA mutations (median, 4.2 months; p = 0.019).ConclusionsMatched therapy targeting the activated PI3K/AKT/mTOR pathway provided meaningful clinical benefits. Thus, further evaluation of PI3K/AKT/mTOR pathway targeted therapy is warranted, especially in metastatic or recurrent squamous cell carcinoma

Supporting caregivers of veterans with Alzheimer’s disease and traumatic brain injury: study protocol for a randomized controlled trial

Background: Patients with Alzheimer's disease and related dementias (ADRD) and traumatic brain injury (TBI) and their caregivers require cognitive and behavioral symptom management, interdisciplinary care, support for caregivers, and seamless care coordination between providers. Caring for someone with ADRD or TBI is associated with higher rates of psychological morbidity and burden, social isolation, financial hardship, and deterioration of physical health. Tremendous need exists for primary care-based interventions that concurrently address the care needs of dyads and aim to improve care and outcomes for both individuals with ADRD and TBI and their family caregivers. Methods: The Aging Brain Care Acquiring New Skills While Enhancing Remaining Strengths (ABC ANSWERS) study is a randomized controlled trial that tests the effectiveness of an intervention based on two evidence-based programs that have been developed for and previously tested in populations with ADRD, TBI, stroke, and late-life depression and/or who have survived an intensive care unit stay. This study includes 200 dyads comprised of a veteran with a diagnosis of ADRD or TBI and the veteran's primary informal caregiver. Dyads are randomized to receive the ABC ANSWERS intervention or routine Veterans Health Administration (VHA) primary care with a standardized educational and resource information packet. Data collection occurs at baseline and three follow-up time points (3 months, 6 months, and 12 months). The primary outcome is caregiver quality of life (QoL). A secondary measure for the caregiver is caregiver burden. Secondary measures for both the veteran and caregiver include symptoms of depression and anxiety. Discussion: The ABC ANSWERS intervention integrates common features of an evidence-based collaborative care model for brain health while concurrently attending to the implementation barriers of delivering care and skills to dyads. We hypothesize that caregivers in dyads randomized to the ABC ANSWERS program will experience higher levels of QoL and lower levels of depression, anxiety, dyadic strain, and caregiver burden at 12 months than those receiving usual VHA primary care

Acyl-coenzyme A synthetases in metabolic control

The 11 long-chain (ACSL) and very long chain acyl-coenzyme A (acyl-CoA) synthetases [(ACSVL)/fatty acid transport protein] are receiving considerable attention because it has become apparent that their individual functions are not redundant

Vitrified magnesia dissolution and its impact on plutonium residue processing

Aqueous chloride operations at the Los Alamos Plutonium Facility cannot directly dispose of acidic waste solutions because of compatibility problems with existing disposal lines. Consequently, all hydrochloric acid must be neutralized and filtered prior to exiting the facility. From a waste minimization standpoint, the use of spent magnesia pyrochemical crucibles as the acid neutralization agent is attractive since this process would take a stream destined for transuranic waste and use it as a reagent in routine plutonium residue processing. Since Los Alamos National Laboratory has several years of experience using magnesium hydroxide as a neutralizing agent for waste acid from plutonium processing activities, the use of spent magnesia pyrochemical crucibles appeared to be an attractive extension of this activity. In order to be competitive with magnesium hydroxide, however, size reduction of crucible shards had to be performed effectively within the constraints of glovebox operations, and acid neutralization time using crucible shards had to be comparable to neutralization times observed when using reagent-grade magnesium hydroxide. The study utilized non-plutonium-contaminated crucibles for equipment evaluation and selection and used nonradioactive acid solutions for completing the neutralization experiments. This paper discusses experience in defining appropriate size reduction equipment and presents results from using the magnesia crucibles for hydrochloric acid neutralization, a logical precursor to introduction into glovebox enclosures

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner

Effort required to finish shotgun-generated genome sequences differs significantly among vertebrates

<p>Abstract</p> <p>Background</p> <p>The approaches for shotgun-based sequencing of vertebrate genomes are now well-established, and have resulted in the generation of numerous draft whole-genome sequence assemblies. In contrast, the process of refining those assemblies to improve contiguity and increase accuracy (known as 'sequence finishing') remains tedious, labor-intensive, and expensive. As a result, the vast majority of vertebrate genome sequences generated to date remain at a draft stage.</p> <p>Results</p> <p>To date, our genome sequencing efforts have focused on comparative studies of targeted genomic regions, requiring sequence finishing of large blocks of orthologous sequence (average size 0.5-2 Mb) from various subsets of 75 vertebrates. This experience has provided a unique opportunity to compare the relative effort required to finish shotgun-generated genome sequence assemblies from different species, which we report here. Importantly, we found that the sequence assemblies generated for the same orthologous regions from various vertebrates show substantial variation with respect to misassemblies and, in particular, the frequency and characteristics of sequence gaps. As a consequence, the work required to finish different species' sequences varied greatly. Application of the same standardized methods for finishing provided a novel opportunity to "assay" characteristics of genome sequences among many vertebrate species. It is important to note that many of the problems we have encountered during sequence finishing reflect unique architectural features of a particular vertebrate's genome, which in some cases may have important functional and/or evolutionary implications. Finally, based on our analyses, we have been able to improve our procedures to overcome some of these problems and to increase the overall efficiency of the sequence-finishing process, although significant challenges still remain.</p> <p>Conclusion</p> <p>Our findings have important implications for the eventual finishing of the draft whole-genome sequences that have now been generated for a large number of vertebrates.</p