Non-use of cancer information services among people experiencing cancer in Ireland.

PURPOSE: The purpose of this study was to explore the reasons for non-use of a national cancer society's cancer information services among people experiencing cancer. METHOD: This study used a qualitative design. Semi-structured interviews were conducted with a total of 17 participants who had not previously utilised the Cancer Society's information services. Data were analysed using Thematic Analysis. RESULTS: The key themes to emerge from the date were 'living in the here and now' and 'awareness of the Cancer Society'. For most participants, not utilising cancer information services was a means of coping with the initial diagnosis and the impact of treatment. Those who progressed to being ready to seek information identified the multi-disciplinary team as the primary source of trusted information, with particular mention of cancer nurse specialists. For participants with children, their role as a parent was central in how they managed their diagnosis. The majority of participants lacked awareness of the range of services provided by the Cancer Society. CONCLUSIONS: Reasons for non-use of cancer information services were identified as: readiness to seek information and a lack of knowledge of the Cancer Societies' services. Cancer information services need to continue make a concerted effort to enhance visibility and awareness of its services to optimise patient engagement.

Blocking apoptotic signaling rescues axon guidance in Netrin mutants.

Netrins are guidance cues that form gradients to guide growing axons. We uncover a mechanism for axon guidance by demonstrating that axons can accurately navigate in the absence of a Netrin gradient if apoptotic signaling is blocked. Deletion of the two Drosophila NetA and NetB genes leads to guidance defects and increased apoptosis, and expression of either gene at the midline is sufficient to rescue the connectivity defects and cell death. Surprisingly, pan-neuronal expression of NetB rescues equally well, even though no Netrin gradient has been established. Furthermore, NetB expression blocks apoptosis, suggesting that NetB acts as a neurotrophic factor. In contrast, neuronal expression of NetA increases axon defects. Simply blocking apoptosis in NetAB mutants is sufficient to rescue connectivity, and inhibition of caspase activity in subsets of neurons rescues guidance independently of survival. In contrast to the traditional role of Netrin as simply a guidance cue, our results demonstrate that guidance and survival activities may be functionally related.

Drosophila Vap-33 is required for axonal localization of Dscam isoforms.

Mutations in VAPB have been identified in a familial form of amyotrophic lateral sclerosis (ALS), and reduced VAPB levels have been found in patients with sporadic ALS. Vap protein family members from different species and cell types have been implicated in a number of cellular functions, but how Vap dysfunction in neurons and/or muscles contributes to motor neuron degeneration and death is poorly understood. Using Drosophila as a model organism, we show that Vap physically interacts with and affects the axonal functions of the Down syndrome cell adhesion molecule (Dscam). Dscam is a cell-surface receptor involved in axon and dendritic patterning and neuron self-recognition and avoidance. Alternative splicing of the Dscam transcript leads to the production of Dscam isoforms that contain one of two possible transmembrane (TM) domain and flanking sequences that either restrict the isoform to dendrites and cell bodies (TM1) or target the isoform to axon processes (TM2). We find that Vap specifically interacts with Dscam isoforms that contain the TM2 cytoplasmic juxtamembrane flanking sequences. Using loss-of-function genetics, we further show that Vap is required for localization of Dscam isoforms containing TM2 to axons and that Vap loss suppresses Dscam gain-of-function axon phenotypes. We propose that Vap function is required in neurons to selectively traffic proteins to axons, and disruption of this function may contribute to the pathology of ALS.

Drosophila activated Cdc42 kinase has an anti-apoptotic function.

Activated Cdc42 kinases (Acks) are evolutionarily conserved non-receptor tyrosine kinases. Activating somatic mutations and increased ACK1 protein levels have been found in many types of human cancers and correlate with a poor prognosis. ACK1 is activated by epidermal growth factor (EGF) receptor signaling and functions to regulate EGF receptor turnover. ACK1 has additionally been found to propagate downstream signals through the phosphorylation of cancer relevant substrates. Using Drosophila as a model organism, we have determined that Drosophila Ack possesses potent anti-apoptotic activity that is dependent on Ack kinase activity and is further activated by EGF receptor/Ras signaling. Ack anti-apoptotic signaling does not function through enhancement of EGF stimulated MAP kinase signaling, suggesting that it must function through phosphorylation of some unknown effector. We isolated several putative Drosophila Ack interacting proteins, many being orthologs of previously identified human ACK1 interacting proteins. Two of these interacting proteins, Drk and yorkie, were found to influence Ack signaling. Drk is the Drosophila homolog of GRB2, which is required to couple ACK1 binding to receptor tyrosine kinases. Drk knockdown blocks Ack survival activity, suggesting that Ack localization is important for its pro-survival activity. Yorkie is a transcriptional co-activator that is downstream of the Salvador-Hippo-Warts pathway and promotes transcription of proliferative and anti-apoptotic genes. We find that yorkie and Ack synergistically interact to produce tissue overgrowth and that yorkie loss of function interferes with Ack anti-apoptotic signaling. Our results demonstrate how increased Ack signaling could contribute to cancer when coupled to proliferative signals.

Solving hierarchical helical mesostructures by electron tomography.

A direct method to determine the pitch and chirality of complicated hierarchical helical mesostructures is presented by using the state-of-the-art electron tomography technique.

Evolution of helical mesostructures.

An intriguing evolution from a simple internal helix to a hierarchical helical (HH) mesostructure with both internal and external helices or a complicated screwlike and concentric circular (CC) mesostructure is successfully observed. The complicated helical structures are determined by TEM studies and 3D electron tomography. We demonstrate a topological helix-coil transition between the internal and external helices to reveal the origin of the HH mesostructure and the relationship between the straight helical and HH rods. Moreover, the boundary condition of the helix-coil transition is clarified to explain in detail the formation of complex helical structures, such as the screwlike mesostructure. It is proposed that the final structural characteristics are determined exactly by the balance between the decrease in the surface free energy and the maintenance of the hexagonal packing in one individual rod, which explains the formation of unusual CC, HH, and screwlike morphologies in one pot. Our success has opened new opportunities in the characterization of complex porous architectures, thus paving a way to remarkable advances in the fields of synthesis, understanding, and application of novel porous materials.

An efficient approach to characterize pseudo-merohedral twins by precession electron diffraction: application to the LaGaO(3) perovskite.

Pseudo-merohedral twins are frequently observed in crystals displaying pseudo-symmetry. In these crystals, many [u v w] zone axis electron diffraction patterns are very close and can only be distinguished from intensity considerations. On conventional diffraction patterns (selected-area electron diffraction or microdiffraction), a strong dynamical behaviour averages the diffracted intensities so that only the positions of the reflections on a pattern can be considered. On precession electron diffraction patterns, the diffracted beams display an integrated intensity and a "few-beam" or "systematic row" behaviour prevails which strongly reduces the dynamical interactions. Therefore the diffracted intensity can be taken into account. A procedure based on observation of the weak extra-reflections connected with the pseudo-symmetry is given to identify without ambiguity any zone axis. It is successfully applied to the identification and characterization of {1 2 1} reflection twins present in the LaGaO(3) perovskite.

Contribution of electron precession to the study of perovskites displaying small symmetry departures from the ideal cubic ABO3 perovskite: applications to the LaGaO3 and LSGM perovskites.

Electron microscopy and electron diffraction are well adapted to the study of the fine-grained, faulted pure and doped LaGaO(3) and LSGM perovskites in which the latter is useful for fuel cell components. Because these perovskites display small symmetry departures from an ideal cubic ABO(3) perovskite, many conventional electron diffraction patterns look similar and cannot be indexed without ambiguity. Electron precession can easily overcome this difficulty mainly because the intensity of the diffracted beams on the precession patterns is integrated over a large deviation domain around the exact Bragg condition. This integrated intensity can be trusted and taken into account to identify the 'ideal' symmetry of the precession patterns (the symmetry which takes into account both the position and the intensity of the diffracted beams). In the present case of the LaGaO(3) and LSGM perovskites, the determination of the 'ideal' symmetry of the precession patterns is based on the observation of weak 'superlattice' reflections typical of the symmetry departures. It allows an easy and sure identification of any zone axes as well as the correct attribution of hkl indices to each of the diffracted beams. Examples of applications of this analysis to the characterizations of twins and to the identification of the space groups are given. This contribution of electron precession can be easily extended to any other perovskites or to any crystals displaying small symmetry departures.

Evaluation of lethal and non-lethal sampling methods for the detection of white sturgeon iridovirus infection in white sturgeon, Acipenser transmontanus (Richardson).

Pectoral fin tissue of white sturgeon was investigated as a potential non-lethal sample source for the detection of white sturgeon iridovirus (WSIV) infection. Histopathology and polymerase chain reaction (PCR) results using fin tissue were compared with the standard lethal histopathology sampling method that utilizes head tissue. Tissues for each of the three sampling methods were collected weekly for 8 weeks from individual sturgeon undergoing an experimental cohabitation challenge with fish infected with the Abernathy isolate of WSIV. Non-lethal fin histopathological evaluation did not reveal infection during the first 3 weeks of sampling, while non-lethal PCR and the lethal method were variable. However, all three sampling methods were equally capable of identifying infection from 4 to 8 weeks post-exposure. Of the survivors tested, all were negative by PCR and the lethal method, and only one fish was identified as being positive by non-lethal fin histopathology. In another experiment, all three sampling methods were applied to asymptomatic WSIV carriers in a case study conducted at the Kootenai Tribal Sturgeon Conservation Hatchery. Results showed that both lethal and non-lethal fin histopathology were equally effective in detecting infection, but PCR was unable to identify this strain of WSIV. Depending on the virus isolate, these results suggest that non-lethal sampling of fin tissue (histopathology or PCR) is comparable with the lethal sampling method at identifying WSIV infection once infection is established, and under certain circumstances may provide an alternative to lethal sampling.

Microstructure of pharyngeal tooth enameloid in the parrotfish Scarus rivulatus (Pisces: Scaridae).

The microstructure of parrotfish pharyngeal teeth was examined using scanning electron microscopy to infer possible mechanical properties of the dentition with respect to their function. Parrotfish tooth enameloid is formed from fluorapatite crystals grouped into bundles. In the upper and lower pharyngeal jaw, the majority of the crystal bundles are orientated either perpendicularly or vertically to the enameloid surface. The only exception is in the trailing apical enameloid in which the majority of bundles are orientated perpendicularly or horizontally to the trailing surface. A distinct transition occurs through the middle of the apex between the leading and trailing enameloid in teeth of the lower pharyngeal jaw. This transition appears less distinct in the teeth of the upper pharyngeal jaw. Enameloid microstructure indicates that shear forces predominate at the apex of the teeth. In the remainder of the enameloid, the microstructure indicates that wear is predominant, and the shear forces are of less importance.

The ethics of the introduction of gene therapy into orthopaedic practice.

Gene therapy has the potential to transform musculoskeletal medicine. Orthopaedists have been ready to incorporate innovations in medicine and engineering into their surgical practice, frequently before having full information. There is no reason to doubt the rapid acceptance of gene therapy by the orthopaedic profession. Caution is needed in incorporating gene therapy into standard practice because of the lack of knowledge and risks that are greater than for previous innovations.

DNA vaccines encoding viral glycoproteins induce nonspecific immunity and Mx protein synthesis in fish.

Protective immunity by vaccination with plasmid DNA encoding a viral glycoprotein (G) has long been assumed to result from the induction of a specific immune response. We report here that the initial protection may be due to the induction of alpha/beta interferon, with long-term protection due to a specific response to the encoded viral G. DNA vaccines encoding the Gs of three serologically unrelated fish rhabdoviruses were used to vaccinate rainbow trout against a lethal challenge with infectious hematopoietic necrosis virus (IHNV). All three vaccines, each encoding the G gene of either IHNV (IHNV-G), snakehead rhabdovirus (SHRV) (SHRV-G), or spring viremia of carp virus (SVCV) (SVCV-G), elicited protective immunity against IHNV. Vaccinated fish were challenged at 30 or 70 days postvaccination with lethal doses of IHNV. At 30 days postvaccination, only 5% of fish that had received any of the G vaccines died, whereas more than 50% of the control fish succumbed to virus challenge. When fish were vaccinated and challenged at 70 days postvaccination, only 12% of the IHNV-G-vaccinated fish died compared to 68% for the SHRV-G- and 76% for the SVCV-G-vaccinated fish. Assays for trout Mx protein, an indicator of alpha/beta interferon induction, showed that only fish vaccinated with a G-containing plasmid produced high levels of Mx protein in the kidneys and liver. Interestingly, at day 7 after virus challenge, all of the fish vaccinated with the IHNV-G plasmid were negative for Mx, but the SHRV-G- and SVCV-G-vaccinated fish still showed detectable levels of Mx. These results suggest that DNA vaccines in fish induce an early, nonspecific antiviral protection mediated by an alpha/beta interferon and, later, a specific immune response.

Evaluation and treatment of swallowing impairments.

Swallowing disorders are common, especially in the elderly, and may cause dehydration, weight loss, aspiration pneumonia and airway obstruction. These disorders may affect the oral preparatory, oral propulsive, pharyngeal and/or esophageal phases of swallowing. Impaired swallowing, or dysphagia, may occur because of a wide variety of structural or functional conditions, including stroke, cancer, neurologic disease and gastroesophageal reflux disease. A thorough history and a careful physical examination are important in the diagnosis and treatment of swallowing disorders. The physical examination should include the neck, mouth, oropharynx and larynx, and a neurologic examination should also be performed. Supplemental studies are usually required. A videofluorographic swallowing study is particularly useful for identifying the pathophysiology of a swallowing disorder and for empirically testing therapeutic and compensatory techniques. Manometry and endoscopy may also be necessary. Disorders of oral and pharyngeal swallowing are usually amenable to rehabilitative measures, which may include dietary modification and training in specific swallowing techniques. Surgery is rarely indicated. In patients with severe disorders, it may be necessary to bypass the oral cavity and pharynx entirely and provide enteral or parenteral nutrition.

An exploratory qualitative study examining the social and psychological processes involved in regular dental attendance.

OBJECTIVE: This study aimed to provide a description of the psychosocial process involved in regular dental attendance. METHODS: The study design was a qualitative cross-sectional study using unstructured and semistructured interviews and observations of regular dental visits. The study participants included 12 men and 18 women attending general dental practices and six men and four women attending an emergency dental service. The data were systematically recorded and subjected to line-by-line grounded theory coding around the main concerns of those attending the dentist. RESULTS: The main concern of those attending for a regular dental visit was checking their oral health. The six-month recall was conceptualized as a checking cycle in six phases: recalling, responding, inducing (i), waiting, inducing (ii), and telling. The possible outcomes of the cycle were maintaining oral health, sustaining oral health, and a further checking cycle. Variations in checking cycles resulted from reordering and normalizing pressures within participants' lifestyles. CONCLUSIONS: The findings of this study suggest that people's patterns of dental attendance are similar to those of other chronic illnesses. An understanding of the dynamic psychosocial processes involved in frequent dental attendance may be achieved when further research into this phenomenon is conducted.

Computed tomographic analysis of pes cavus.

Patterns of muscle degeneration in patients with peripheral neuropathies exhibiting pes cavus deformity were studied by computed tomography (CT). Twenty-six patients attending the muscle disease clinic at Newington Children's Hospital with hereditary sensory motor neuropathies (HSMN) I, II, or III had clinical and radiographic assessment in addition to CT scans of the feet and legs at designated levels. The pattern of muscle degeneration was analyzed with other variables, including age, sex, tibial torsion, cavus, heel varus, and claw toes. Multiple regression/correlation analysis clearly demonstrated earlier and more severe involvement of the intrinsic muscles of the foot as compared with the extrinsic muscles. The most consistent early degeneration occurred in the pedal lumbricals and interossei, which have the most distal innervation. The order of muscle degeneration is a centripetal pattern, with two types of degeneration occurring in the leg muscles: type P patients had earlier degeneration of the leg muscles innervated by the peroneal nerve, and type T patients showed earlier degeneration of those extrinsics innervated by the posterior tibial nerve.

Dihydropyridine calcium antagonists in mice: blood and brain pharmacokinetics and efficacy against pentylenetetrazol seizures.

Dihydropyridine calcium antagonists are candidate anticonvulsants, but little is known of their penetration into brain. Nifedipine (NFD) and nimodipine (NMD) pharmacokinetics were compared in mouse blood and brain, and their activity against pentylenetetrazol (PTZ) was assessed. After intraperitoneal (i.p.) injection, both dihydropyridines achieved peak blood and brain concentrations in 5 min. Estimated blood and brain elimination half-lives (t1/2) of NMD (16.7 and 22.4 min) were slightly longer than those of NFD (11.2 and 14.7 min). Brain and blood concentrations correlated with both NFD (r = 0.701, p less than 0.001) and NMD (r = 0.572, p less than 0.001). Injection of the dihydropyridines as a suspension (Tween 80) did not alter brain penetration, although systemic absorption was more erratic. NFD (p less than 0.001), NMD (p less than 0.02), and carbamazepine (CBZ, p less than 0.001) i.p. inhibited PTZ-induced seizures. Brain concentrations of PTZ were not altered by NFD pretreatment. Combining NFD and CBZ was less effective than giving NFD alone (p less than 0.005). NFD (p less than 0.002) and NMD (p less than 0.001) inhibited PTZ seizures after 2-week oral dosing, but low dosing was more effective than high dosing (p less than 0.002). NFD and NMD cross the blood-brain barrier (BBB) in mice and inhibit PTZ seizures. A possible therapeutic window was identified, and NFD and CBZ were less effective in combination than singly. A pharmacodynamic interaction may exist, inhibiting effective use of dihydropyridines as adjunctive therapy in epileptic patients.