Down Syndrome Cures: Perspectives of People With Down Syndrome and Their Parents.

Down syndrome (DS) research is advancing rapidly, yet efforts have raised ethical questions. This mixed methods study describes views of people with DS (self-advocates) and their parents regarding medical interventions for DS. Responses from 35/171 (20.5%) self-advocates and 430/867 (49.6%) parents showed the majority of self-advocates were glad they have DS (27/35; 77.1%) and liked who they are (33/35; 94.3%), but did want to learn faster (23/35; 65.7%). Parents much more commonly agreed with a willingness to give medications to prevent Alzheimer's disease (427/429; 99.5%) or blood cancer (428/430; 99.5%) as compared with a medicine to cure DS (225/425; 52.9%). Qualitative comments intertwined DS with identity, yet indicated desire for improved quality of life and opportunities. Responses decoupled DS itself from the complications of DS, with treatment of complications being more acceptable.

High Cervical Intrathecal Targeted Drug Delivery: A Case Report of Refractory Oropharyngeal Cancer Pain.

INTRODUCTION: Some patients with head and neck cancers have pain refractory to aggressive multimodal therapies. Herein, we report the use of an intrathecal targeted drug delivery (TDD) system catheter tip placed at C1 for the treatment of recalcitrant oropharyngeal cancer pain. CASE REPORT: A patient with recurrent metastatic squamous cell tongue cancer reported severe pain not controlled despite high-dose opioids and nonopioid adjuvants. It was elected to proceed with an intrathecal TDD system with the catheter tip placed at the C1 level. After pump placement, we were able to decrease her daily oral morphine equivalents (OME) from nearly 1000 mg to 300 mg over the course of two months while titrating her TDD from 0.3 mg/day to 0.7 mg/day of intrathecal hydromorphone. Unfortunately, her improvement was limited secondary to aggressive cancer-directed treatments likely contributing to device infection and explant. CONCLUSIONS: In this patient, high cervical placement of an intrathecal TDD catheter was associated with a decrease in OME. While used in clinical practice on occasion, the use of high cervical TDD placement such as this implantable C1 intrathecal TDD system for cancer-associated pain is underreported in the literature. Further studies on this intervention within this challenging population are warranted.

How do patients describe their disabilities? A coding system for categorizing patients' descriptions.

BACKGROUND: To provide care that meets the values and preferences of patients with disabilities, health care providers need to understand patients' perceptions and understanding of their disability. No studies have explored patients' definitions of disability within the healthcare setting. OBJECTIVE: The aim of the study was to understand how patients' define their disability in the healthcare setting and to develop a coding system for categorizing how they describe their disability. METHODS: In 2000 all new outpatients at Mayo Clinic, Rochester, MN completed a form that inquired if they had a disability and if so, to write in the disability. The research team categorized the responses by disability type (e.g.: visual or physical) and how the patient described his disability or "disability narrative" (e.g.: diagnosis or activity). RESULTS: Within 128,636 patients, 14,908 reported a disability. For adults, lower limb (26%) and chronic conditions (24%) were the most frequent disability type and activity limitations (56%) were the most frequent disability narrative category. For pediatric patients, developmental disabilities (43%) were the most frequently reported disability type and diagnoses (83%) were the most frequent disability narrative category. Patients used different disability narrative categories to describe different disability types. For example, most adults reporting a mental health listed a diagnosis (97%), compared to only 13% of those with lower limb disabilities. CONCLUSIONS: Patients had diverse descriptions of their disabilities. In order for providers and healthcare organizations to provide high-quality care, they should engage patients in developing a consistent, patient-centered language around disability.

Using professional expertise in partnership with families: A new model of capacity building.

The first five years of parenting are critical to children's development. Parents are known to respond best to interventions with a partnership-based approach, yet child and family health nurses (CFHNs) report some tension between employing their expertise and maintaining a partnership relationship. This article identifies ways in which CFHNs skilfully use their professional expertise, underpinned by helping qualities and interpersonal skills, to assist families build confidence and capacity, and thus buffer against threats to parent and child well-being. It reports on an Australian ethnographic study of services for families with young children. Fifty-two interactions were observed between CFHNs and families in day-stay and home visiting services in Sydney. A new model is presented, based on four partnership activities and the fluid movement between them, to show how CFHNs use their expertise to identify strengths and foster resilience in families in the longer term, without undermining the principles of partnership.

Intergenerational Programs May Be Especially Engaging for Aged Care Residents With Cognitive Impairment: Findings From the Avondale Intergenerational Design Challenge.

Intergenerational programs are an authentic way to engage elders in meaningful activity and report benefits to both elders and youth. The Avondale Intergenerational Design Challenge (AVID) randomly assigned small teams of technology students aged 13 to 15 years (total N = 59) to 1 of 24 aged care residents with a range of cognitive impairment. Students met with the resident 4 times over 15 weeks and ultimately crafted a personalized item for them. Students showed no change in self-reported attitudes to elders, empathy, or self-esteem post-AVID or at 3-month follow-up, compared to a 3-month within-subject control period pre-AVID. Compared to usual lifestyle activities, residents showed significant improvements in self-reported positive affect and negative affect after student visits and were observed to be significantly more engaged during visits, especially residents with greater cognitive impairment. The personal and guided nature of intergenerational programs may be especially effective in engaging elders with cognitive impairment in meaningful activity.

Educating Chinese Nurses About Rehabilitation Nursing: Findings From a Single Cohort Quantitative Pilot Project.

PURPOSE: The purpose of this study was to present results of a pilot program to educate nurses in China about rehabilitation nursing. DESIGN: A single cohort, pre- and posttest design with an educational intervention. METHODS: A 3-day basic rehabilitation nursing education program was conducted in Shanghai and Hangzhou by a certified rehabilitation nurse specialist from the United States. The effect of the educational intervention was measured using pre- and posttests for six topic areas. Data were analyzed using descriptive statistics, correlations, and paired samples t tests. FINDINGS: Paired samples t tests showed a significant improvement (p < .01) as a result of the educational intervention on all three tests covering the six basic topics. CONCLUSIONS: The knowledge of the nurses on topics of basic rehabilitation nursing significantly increased as a result of the educational program. CLINICAL RELEVANCE: Rehabilitation nurses interested in international travel and developing professional relationships with nurses in China can provide education to promote our specialty practice overseas.

Introduction to Disability and Health for Preclinical Medical Students: Didactic and Disability Panel Discussion.

INTRODUCTION: Millions of American patients have a disability, and their health care outcomes depend on the attitudes of their health care providers towards persons with disabilities. Overly negative health care provider attitudes lead to significant misunderstandings about what it means to have a disability, inappropriate assumptions, and poor care. However, very few medical schools teach about disability. METHODS: We developed a preclinical medical student curriculum that addresses the complexity of disability, focusing on health care disparities and bias. Our curriculum was designed with significant input from people with disabilities and was constructed from their perspective. In addition to didactic and discussion sessions on disability history, models of disability, and health disparities, we include a discussion panel with community members who have a disability. RESULTS: The curriculum has been effective at promoting discussion and is well received by students. When rating the relevance to future clinical practice, students gave the curriculum an average of 3.9 on a 5-point Likert scale (1 = poor, 5 = excellent). The majority of students commented that the community involvement in the session was the most meaningful aspect. DISCUSSION: It is possible to integrate community-driven discussions on the social context of disability into traditional medical school preclinical curricula, and students find it valuable to their education.

A community-centered disability curriculum for medical students.

Although disabilities are prevalent, many medical professionals lack knowledge about them. Many haven't been trained to care for patients who have them and have negative attitudes about disabilities and those who have them. Their attitudes can affect health care and patient outcomes. Despite recommendations by U.S. surgeons general to include disability curricula in medical education, only a small minority of medical schools have done so. In 2011, Mayo Medical School developed a new disability curriculum for its first-year students. The aim was that they might gain insight into their potential biases and understand how those biases could affect the care they provide to persons with disabilities. Here we describe Mayo Medical School's experience with its disability-awareness curriculum.

Agonist activated PKCßII translocation and modulation of cardiac myocyte contractile function.

Elevated protein kinase C ßII (PKCßII) expression develops during heart failure and yet the role of this isoform in modulating contractile function remains controversial. The present study examines the impact of agonist-induced PKCßII activation on contractile function in adult cardiac myocytes. Diminished contractile function develops in response to low dose phenylephrine (PHE, 100 nM) in controls, while function is preserved in response to PHE in PKCßII-expressing myocytes. PHE also caused PKCßII translocation and a punctate distribution pattern in myocytes expressing this isoform. The preserved contractile function and translocation responses to PHE are blocked by the inhibitor, LY379196 (30 nM) in PKCßII-expressing myocytes. Further analysis showed downstream protein kinase D (PKD) phosphorylation and phosphatase activation are associated with the LY379196-sensitive contractile response. PHE also triggered a complex pattern of end-target phosphorylation in PKCßII-expressing myocytes. These patterns are consistent with bifurcated activation of downstream signaling activity by PKCßII.

Photoinduced electron transfer and fluorophore motion as a probe of the conformational dynamics of membrane proteins: application to the influenza a M2 proton channel.

The structure and function of the influenza A M2 proton channel have been the subject of intensive investigations in recent years because of their critical role in the life cycle of the influenza virus. Using a truncated version of the M2 proton channel (i.e., M2TM) as a model, here we show that fluctuations in the fluorescence intensity of a dye reporter that arise from both fluorescence quenching via the mechanism of photoinduced electron transfer (PET) by an adjacent tryptophan (Trp) residue and local motions of the dye molecule can be used to probe the conformational dynamics of membrane proteins. Specifically, we find that the dynamics of the conformational transition between the N-terminal open and C-terminal open states of the M2TM channel occur on a timescale of about 500 µs and that the binding of either amantadine or rimantadine does not inhibit the pH-induced structural equilibrium of the channel. These results are consistent with the direct occluding mechanism of inhibition which suggests that the antiviral drugs act by sterically occluding the channel pore.

Non-natural amino acid fluorophores for one- and two-step fluorescence resonance energy transfer applications.

Fluorescence resonance energy transfer (FRET) provides a powerful means to study protein conformational changes. However, the incorporation of an exogenous FRET pair into a protein could lead to undesirable structural perturbations of the native fold. One of the viable strategies to minimizing such perturbations is to use non-natural amino acid-based FRET pairs. Previously, we showed that p-cyanophenylalanine (Phe(CN)) and tryptophan (Trp) constitute such a FRET pair, useful for monitoring protein folding-unfolding transitions. Here we further show that 7-azatryptophan (7AW) and 5-hydroxytryptophan (5HW) can also serve as a FRET acceptor to Phe(CN), and the resultant FRET pairs offer certain advantages over Phe(CN)-Trp. For example, the fluorescence spectrum of 7AW is sufficiently separated from that of Phe(CN), making it straightforward to decompose the FRET spectrum into donor and acceptor contributions. Moreover, we show that Phe(CN), Trp, and 7AW can be used together to form a multi-FRET system, allowing more structural information to be extracted from a single FRET experiment. The applicability of these FRET systems is demonstrated in a series of studies where they are employed to monitor the urea-induced unfolding transitions of the villin headpiece subdomain (HP35), a designed betabetaalpha motif (BBA5), and the human Pin1 WW domain.

A previously unrecognized step in pentachlorophenol degradation in Sphingobium chlorophenolicum is catalyzed by tetrachlorobenzoquinone reductase (PcpD).

The first step in the pentachlorophenol (PCP) degradation pathway in Sphingobium chlorophenolicum has been believed for more than a decade to be conversion of PCP to tetrachlorohydroquinone. We show here that PCP is actually converted to tetrachlorobenzoquinone, which is subsequently reduced to tetrachlorohydroquinone by PcpD, a protein that had previously been suggested to be a PCP hydroxylase reductase. pcpD is immediately downstream of pcpB, the gene encoding PCP hydroxylase (PCP monooxygenase). Expression of PcpD is induced in the presence of PCP. A mutant strain lacking functional PcpD has an impaired ability to remove PCP from the medium. In contrast, the mutant strain removes tetrachlorophenol from the medium at the same rate as does the wild-type strain. These data suggest that PcpD catalyzes a step necessary for degradation of PCP, but not for degradation of tetrachlorophenol. Based upon the known mechanisms of flavin monooxygenases such as PCP hydroxylase, hydroxylation of PCP should produce tetrachlorobenzoquinone, while hydroxylation of tetrachlorophenol should produce tetrachlorohydroquinone. Thus, we proposed and verified experimentally that PcpD is a tetrachlorobenzoquinone reductase that catalyzes the NADPH-dependent reduction of tetrachlorobenzoquinone to tetrachlorohydroquinone.