Studies measuring psychological distress in individuals with cystic fibrosis (CF) have found high rates of both depression and anxiety. Psychological symptoms in both individuals with CF and parent caregivers have been associated with decreased lung function, lower body mass index, worse adherence, worse health-related quality of life, more frequent hospitalisations and increased healthcare costs. To identify and treat depression and anxiety in CF, the CF Foundation and the European CF Society invited a panel of experts, including physicians, psychologists, psychiatrists, nurses, social workers, a pharmacist, parents and an individual with CF, to develop consensus recommendations for clinical care. Over 18 months, this 22-member committee was divided into four workgroups: Screening; Psychological Interventions; Pharmacological Treatments and Implementation and Future Research, and used the Population, Intervention, Comparison, Outcome methodology to develop questions for literature search and review. Searches were conducted in PubMed, PsychINFO, ScienceDirect, Google Scholar, Psychiatry online and ABDATA by a methodologist at Dartmouth. The committee reviewed 344 articles, drafted statements and set an 80% acceptance for each recommendation statement as a consensus threshold prior to an anonymous voting process. Fifteen guideline recommendation statements for screening and treatment of depression and anxiety in individuals with CF and parent caregivers were finalised by vote. As these recommendations are implemented in CF centres internationally, the process of dissemination, implementation and resource provision should be closely monitored to assess barriers and concerns, validity and use.

A large percentage of youth with CF and their parents reported elevated symptoms of depression. Children scoring in the depressed range on a standardized screening measure and those with less secure parent-child relationships were at greatest risk for poor adherence. Thus, depressive symptoms and family relationships are appropriate targets for adherence promotion interventions, which may ultimately improve health outcomes.

The uncontrolled manifold (UCM) approach allows us to address issues concerning the nature of variability. In this study we applied the UCM analysis to gait and to a population known for exhibiting high levels of performance variability, Down syndrome (DS). We wanted to determine if preadolescents (ages between 8 and 10) with DS partition goal-equivalent variability (UCM( ||)) and non-goal equivalent variability differently than peers with typical development (TD) and whether treadmill practice would result in utilizing greater amounts of functional, task-specific variability to accomplish the task goal. We also wanted to determine how variance is structured with respect to two important performance variables: center of mass (COM) and head trajectory at one specific event (i.e., heel contact) for both groups during gait. Preadolescents with and without DS walked on a treadmill below, at, and above their preferred overground speed. We tested both groups before and after four visits of treadmill practice. We found that children with DS partition more UCM( ||) variance than children with TD across all speeds and both pre and post practice. The results also suggest that more segmental configuration variance was structured such that less motion of COM than head position was exhibited at heel contact. Overall, we believe children with DS are employing a different control strategy to compensate for their inherent limitations by exploiting that variability that corresponds to successfully performing the task.

Prostate cancer is the second leading cause of cancer deaths in American males, resulting in an estimated 37,000 deaths annually, typically the result of metastatic disease. A consequence of the unsuccessful androgen ablation therapy used initially to treat metastatic disease is the emergence of androgen-insensitive prostate cancer, for which there is currently no prescribed therapy. Here, three related human prostate cancer cell lines that serve as a model for this dominant form of prostate cancer metastasis were studied to determine the correlation between voltage-gated sodium channel expression/function and prostate cancer metastatic (invasive) potential: the non-metastatic, androgen-dependent LNCaP LC cell line and two increasingly tumorogenic, androgen-independent daughter cell lines, C4 and C4-2. Fluorometric in vitro invasion assays indicated that C4 and C4-2 cells are more invasive than LC cells. Immunoblot analysis showed that voltage-gated sodium channel expression increases with the invasive potential of the cell line, and this increased invasive potential can be blocked by treatment with the specific voltage-gated sodium channel inhibitor, tetrodotoxin (TTX). These data indicate that increased voltage-gated sodium channel expression and function are necessary for the increased invasive potential of these human prostate cancer cells. When the human adult skeletal muscle sodium channel Na(v1.4) was expressed transiently in each cell line, there was a highly significant increase in the numbers of invading LC, C4, and C4-2 cells. This increased invasive potential was reduced to control levels by treatment with TTX. These data are the first to indicate that the expression of voltage-gated sodium channels alone is sufficient to increase the invasive potential of non-metastatic (LC cells) as well as more aggressive cells (i.e., C4 and C4-2 cells). Together, the data suggest that increased voltage-gated sodium channel expression alone is necessary and sufficient to increase the invasive potential of a set of human prostate cancer cell lines that serve as a model for prostate cancer metastasis.