Physiological responses and adjustments of corals to strong seasonal temperature variations (20-28°C).

Temperature is a key driver of metabolic rates. So far, we know little about potential physiological adjustments of subtropical corals to seasonal temperature changes (>8°C) that substantially exceed temperature fluctuation experienced by their counterparts in the tropics. This study investigated the effect of temperature reductions on Montastraea cavernosa and Porites astreoides in Bermuda (32°N; sea surface temperature ∼19-29°C) over 5 weeks, applying the following treatments: (i) constant control temperature at 28°C, and (ii) temperature reduction (0.5°C day-1) followed by constant temperature (20 days; acclimatization period) at 24°C and (iii) at 20°C. Both species decreased photosynthesis and respiration during temperature reduction as expected, which continued to decrease during the acclimatization period, indicating adjustment to a low energy turnover rather than thermal compensation. Trajectories of physiological adjustments and level of thermal compensation, however, differed between species. Montastraea cavernosa zooxanthellae metrics showed a strong initial response to temperature reduction, followed by a return to close to control values during the acclimatization period, reflecting a high physiological flexibility and low thermal compensation. Porites astreoides zooxanthellae, in contrast, showed no initial response, but an increase in pigment concentration per zooxanthellae and similar photosynthesis rates at 24°C and 20°C at the end of the experiment, indicating low acute thermal sensitivity and the ability for thermal compensation at the lowest temperature. Respiration decreased more strongly than photosynthesis, leading to significant build-up of biomass in both species (energy reserves). Results are important in the light of potential poleward migration of corals and of potential latitudinal and species-specific differences in coral thermal tolerance.

Exploring the influence of service dogs on participation in daily occupations by veterans with PTSD: A pilot study.

INTRODUCTION: Post traumatic stress disorder (PTSD) resulting from military service can seriously impact quality of life. There is support for the use of service dogs amongst people with PTSD in managing symptoms by reducing anxiety and depression. To date, few studies have investigated this phenomenon comprehensively, particularly in relation to enhancing participation in daily occupations. METHODS: We explored the experience of a group of ex-serving members of the Australian military with PTSD, who had partnered with a service dog. We sought to understand the influence of the service dog on PTSD symptom management and participation in meaningful daily occupations. Seven participants who had been paired with a service dog were recruited from a Veterans' support organisation. Two semi-structured focus group sessions were conducted, audio-recorded and transcribed verbatim. The transcripts from the focus group sessions and researcher field notes were analysed independently by two researchers using an inductive approach to generate codes and themes. RESULTS: The themes that emerged from the data were: isolation, safety, lifeline, reconnection and challenges. Veterans in this study reported that partnering with a service dog helped them to feel safe, helped them to manage the symptoms and impact of PTSD, resulting in improved sleep quality, emotional regulation, reduced anxiety, enhanced anger management, and a reduction in the misuse of alcohol and prescription medication and suicidal ideation. These changes led to improved relationships and increased participation in meaningful daily occupations. Ongoing financial support for veterans who have partnered with a service dog needs to be more closely examined. CONCLUSION: These findings are important and highlight that a larger and more comprehensive, research project examining the impact of service dogs on the quality of life.

Usability of a Wrist-Worn Smartwatch in a Direct-to-Participant Randomized Pragmatic Clinical Trial.

BACKGROUND: The availability of a wide range of innovative wearable sensor technologies today allows for the ability to capture and collect potentially important health-related data in ways not previously possible. These sensors can be adopted in digitalized clinical trials, i.e., clinical trials conducted outside the clinic to capture data about study participants in their day-to-day life. However, having participants activate, charge, and wear the digital sensors for long hours may prove to be a significant obstacle to the success of these trials. OBJECTIVE: This study explores a broad question of wrist-wearable sensor effectiveness in terms of data collection as well as data that are analyzable per individual. The individuals who had already consented to be part of an asymptomatic atrial fibrillation screening trial were directly sent a wrist-wearable activity and heart rate tracker device to be activated and used in a home-based setting. METHODS: A total of 230 participants with a median age of 71 years were asked to wear the wristband as frequently as possible, night and day, for at least a 4-month monitoring period, especially to track heart rhythm during sleep. RESULTS: Of the individuals who received the device, 43% never transmitted any data. Those who used the device wore it a median of ∼15 weeks (IQR 2-24) and for 5.3 days (IQR 3.2-6.5) per week. For rhythm detection purposes, only 5.6% of all recorded data from individuals were analyzable (with beat-to-beat intervals reported). CONCLUSIONS: This study provides some important learnings. It showed that in an older population, despite initial enthusiasm to receive a consumer-quality wrist-based fitness device, a large proportion of individuals never activated the device. However, it also found that for a majority of participants it was possible to successfully collect wearable sensor data without clinical oversight inside a home environment, and that once used, ongoing wear time was high. This suggests that a critical barrier to overcome when incorporating a wearable device into clinical research is making its initiation of use as easy as possible for the participant.

Impact of the 340B Pharmacy Program on Services and Supports for Persons Served by Hemophilia Treatment Centers in the United States.

Purpose Hemophilia Treatment Centers (HTCs) provide integrated and comprehensive services to individuals affected with rare bleeding disorders, such as hemophilia and Von Willebrand disease. Through the 340 Drug Pricing Program, HTCs may use pharmacy income to support clinical staff and patient services. The objective of this study was to describe the impact of the 340B program funding on services and support provided by HTCs to persons affected by rare bleeding disorders. Description Federally designated comprehensive HTCs with established 340B programs were invited to participate in a mailed survey in 2014. Participants were requested to report on 340B program-funded staff and services in the calendar year 2013. Assessment The 31 of 37 HTCs responding served over 10,000 individuals, or one-third of the national HTC patient population. The majority of responding HTCs reported that 340B program income supported over 90% of staff such as nurses, social workers, and physical therapists. Conclusion The results from this survey of 31 centers with established programs demonstrates the HTCs' reliance on 340B program support for vital comprehensive services, that are otherwise non-reimbursable, and highlights the importance of the 340B program in sustaining the high quality of care and in increasing access for a geographically dispersed, medically vulnerable population.

Specific acetylation of p53 by HDAC inhibition prevents DNA damage-induced apoptosis in neurons.

Histone deacetylase (HDAC) inhibitors have been used to promote neuronal survival and ameliorate neurological dysfunction in a host of neurodegenerative disease models. The precise molecular mechanisms whereby HDAC inhibitors prevent neuronal death are currently the focus of intensive research. Here we demonstrate that HDAC inhibition prevents DNA damage-induced neurodegeneration by modifying the acetylation pattern of the tumor suppressor p53, which decreases its DNA-binding and transcriptional activation of target genes. Specifically, we identify that acetylation at K382 and K381 prevents p53 from associating with the pro-apoptotic PUMA gene promoter, activating transcription, and inducing apoptosis in mouse primary cortical neurons. Paradoxically, acetylation of p53 at the same lysines in various cancer cell lines leads to the induction of PUMA expression and death. Together, our data provide a molecular understanding of the specific outcomes of HDAC inhibition and suggest that strategies aimed at enhancing p53 acetylation at K381 and K382 might be therapeutically viable for capturing the beneficial effects in the CNS, without compromising tumor suppression.

HDAC6 is a target for protection and regeneration following injury in the nervous system.

Central nervous system (CNS) trauma can result in tissue disruption, neuronal and axonal degeneration, and neurological dysfunction. The limited spontaneous CNS repair in adulthood and aging is often insufficient to overcome disability. Several investigations have demonstrated that targeting HDAC activity can protect neurons and glia and improve outcomes in CNS injury and disease models. However, the enthusiasm for pan-HDAC inhibition in treating neurological conditions is tempered by their toxicity toward a host of CNS cell types -a biological extension of their anticancer properties. Identification of the HDAC isoform, or isoforms, that specifically mediate the beneficial effects of pan-HDAC inhibition could overcome this concern. Here, we show that pan-HDAC inhibition not only promotes neuronal protection against oxidative stress, a common mediator of injury in many neurological conditions, but also promotes neurite growth on myelin-associated glycoprotein and chondroitin sulfate proteoglycan substrates. Real-time PCR revealed a robust and selective increase in HDAC6 expression due to injury in neurons. Accordingly, we have used pharmacological and genetic approaches to demonstrate that inhibition of HDAC6 can promote survival and regeneration of neurons. Consistent with a cytoplasmic localization, the biological effects of HDAC6 inhibition appear transcription-independent. Notably, we find that selective inhibition of HDAC6 avoids cell death associated with pan-HDAC inhibition. Together, these findings define HDAC6 as a potential nontoxic therapeutic target for ameliorating CNS injury characterized by oxidative stress-induced neurodegeneration and insufficient axonal regeneration.

Stereoselective HDAC inhibition from cysteine-derived zinc-binding groups.

A series of small-molecule histone deacetylase (HDAC) inhibitors, which feature zinc binding groups derived from cysteine, were synthesized. These inhibitors were tested against multiple HDAC isoforms, and the most potent, compound 10, was determined to have IC(50) values below 1 microM. The compounds were also tested in a cellular assay of oxidative stress-induced neurodegeneration. Many of the inhibitors gave near-complete protection against cell death at 10 microM without the neurotoxicity seen with hydroxamic acid-based inhibitors, and were far more neuroprotective than HDAC inhibitors currently in clinical trials. Both enantiomers of cysteine were used in the synthesis of a variety of novel zinc-binding groups (ZBGs). Derivatives of L-cysteine were active in the HDAC inhibition assays, while the derivatives of D-cysteine were inactive. Notably, the finding that both the D- and L-cysteine derivatives were active in the neuroprotection assays suggests that multiple mechanisms are working to protect the neurons from cell death. Molecular modeling was employed to investigate the differences in inhibitory activity between the HDAC inhibitors generated from the two enantiomeric forms of cysteine.

Focused stimulation for a child with autism spectrum disorder: a treatment study.

This study explored the use of focused stimulation as an intervention technique for a three-year-old boy diagnosed with autism spectrum disorder (ASD). His parents were trained to use focused stimulation to facilitate comprehension of what is x doing question forms. Responses to question probes were collected at both pre- and post-treatment intervals. At the beginning of the study, the child did not respond correctly to any of the target questions. Following intervention, the child made significant gains towards the target goal, but little change towards a control goal used for comparison. These findings provide preliminary support for the usefulness of focused stimulation as an intervention strategy for at least some children with ASD.