A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson's disease.

More than 80 years after iron accumulation was initially described in the substantia nigra (SN) of Parkinson's disease (PD) patients, the mechanisms responsible for this phenomenon are still unknown. Similarly, how iron is delivered to its major recipients in the cell - mitochondria and the respiratory complexes - has yet to be elucidated. Here, we report a novel transferrin/transferrin receptor 2 (Tf/TfR2)-mediated iron transport pathway in mitochondria of SN dopamine neurons. We found that TfR2 has a previously uncharacterized mitochondrial targeting sequence that is sufficient to import the protein into these organelles. Importantly, the Tf/TfR2 pathway can deliver Tf bound iron to mitochondria and to the respiratory complex I as well. The pathway is redox-sensitive and oxidation of Tf thiols to disulfides induces release from Tf of highly reactive ferrous iron, which contributes to free radical production. In the rotenone model of PD, Tf accumulates in dopamine neurons, with much of it accumulating in the mitochondria. This is associated with iron deposition in SN, similar to what occurs in PD. In the human SN, TfR2 is also found in mitochondria of dopamine neurons, and in PD there is a dramatic increase of oxidized Tf in SN. Thus, we have discovered a novel mitochondrial iron transport system that goes awry in PD, and which may provide a new target for therapeutic intervention.

High frequency deep brain stimulation: what are the therapeutic mechanisms?

High frequency deep brain stimulation (HFS) used to treat the symptoms of Parkinson's disease (PD) was first assumed to act by reducing an excessive tonic GABAergic inhibitory output from the internal globus pallidus (GPi). Stimulation in GPi might produce this directly by mechanisms such as depolarization block or activation of presynaptic inhibitory fibers, and the same mechanisms evoked by HFS in the subthalamic nucleus (STN) could reduce the excitatory action of STN on GPi neurons. Although somatic recordings from neurons near the stimulation site may appear to support this potential mechanism, the action downstream from the site of stimulation often is not consistent with this interpretation. A more parsimonious explanation for the similar effects of HFS in STN or GPi and a lesion of either of these structures is that both HFS and pallidotomy interrupt an abnormal pattern of firing in cortico-basal ganglia-thalamocortical loops that is responsible for the symptoms of PD.

Undergraduate nursing students' knowledge of and attitudes toward aging: comparison of context-based learning and a traditional program.

The purpose of this study was to investigate nursing students' knowledge of and attitudes toward older adults in the first and fourth years of a baccalaureate program, following the introduction of a context-based learning (CBL) curriculum, and to compare the fourth-year CBL student findings to those of fourth-year students in the final year of the traditional, lecture-based baccalaureate program. The Facts on Aging Questionnaire was used to assess knowledge, and the Aging Semantic Differential was used to assess attitudes toward aging related to societal influences. Although there were differences in knowledge and attitudes between fourth-year CBL and fourth-year traditional students, the differences were not significant. These findings support earlier work that an integrated curriculum may not significantly improve knowledge of age-related changes nor positively influence attitudes that are already positive. The Reactions to Ageing Questionnaire was used to examine students' attitudes toward personal aging. There was a significant positive increase in CBL students' attitudes toward personal aging from the first to fourth years of the program. This suggests that CBL learning fosters an inner maturity toward personal aging.

Context-dependent modulation of movement-related discharge in the primate globus pallidus.

A selective contribution of the basal ganglia (BG) to memory-contingent motor control has long been hypothesized. The importance of memory context remains an open question, however, for the BG skeletomotor circuit. To investigate this question, we studied the perimovement discharge of a carefully selected group of 74 "arm-related" pallidal cells in two rhesus monkeys. The animals performed three tasks designed to dissociate multiple independent aspects of memory-contingent reaching while controlling movement kinematics. The activity of most neurons (88%) was influenced strongly by the memory demands of a task (remembering "where" or "when" to move), but the population as a whole showed no systematic preference for memory- or sensory-contingent conditions. The effects of memory context were primarily additive with those of movement kinematics (particularly movement direction). Considered separately, decreases and increases in firing had very different context preferences: decreases were nearly always larger for sensory-triggered movements, whereas increases were enhanced most often under memory-contingent conditions (i.e., self-initiated or self-guided movements). A similar pattern of preferences was found for both pallidal segments. The distinct context-specific enhancements of decreases and increases could not be explained as simple sensory responses or as interactions with preparatory or anticipatory processes present before movement initiation. Rather, they appear related to movement execution under specific contexts. Our results lead to the conclusion that movement facilitatory decreases in internal pallidal (GPi) activity are primarily greater under sensory-triggered conditions. GPi increases and their suppressive effects, perhaps on competing activity in pallidal-recipient centers, have increased prevalence under memory-contingent conditions.

An inventory of nursing education research.

PURPOSE: To describe nursing education research literature in terms of quality, content areas under investigation, geographic location of the research, research designs utilized, sample sizes, instruments used to collect data, and funding sources. DESIGN AND METHODS: Quantitative and qualitative research literature published between January 1991 and December 2000 were identified and classified using an author-generated Relevance Tool. FINDINGS: 1286 articles were accepted and entered into the inventory, and an additional 22 were retained as references as they were either literature reviews or meta-analyses. Not surprisingly, 90% of nursing education research was generated in North America and Europe, the industrialised parts of the world. Of the total number of articles accepted into the inventory, 61% were quantitative research based. The bulk of the research was conducted within the confines of a course or within a program, with more than half based in educational settings. Sample sizes of the research conducted were diverse, with a bare majority using a sample between 50 and 99 participants. More than half of the studies used questionnaires to obtain data. Surprising, 80% of the research represented in these articles was not funded. The number of publications of nursing education research generated yearly stabilised at approximately 120 per year. CONCLUSION: Research programs on teaching and learning environments and practice in nursing education need to be developed. Lobbying is needed to increase funding for this type of research at national and international levels.

The prevalence of pressure ulcers in a tertiary care pediatric and adult hospital.

OBJECTIVE: To describe the pressure ulcer prevalence, stage and body location, and demographic characteristics of patients with pressure ulcers at a tertiary care adult hospital and a tertiary care pediatric hospital. DESIGN: Prevalence survey. SETTING AND SUBJECTS: A total of 513 inpatients, including 416 adults admitted to a tertiary care hospital and 97 children admitted to a tertiary care pediatric hospital. Only inpatients with mental health-related diagnoses were excluded. INSTRUMENTS: The Kinetics Concepts International's Prevalence and Incidence Study Collection Form was used to assess variables, including demographic information; presence, location, and stage of pressure ulcers; and presence of special support surfaces. METHODS: All patients had head-to-toe skin assessments performed during an 8-hour period by teams of 3 multidisciplinary staff members. Kinetics Concepts International's Prevalence and Incidence Program software and Microsoft Excel were used for data entry and analysis. RESULTS: Combined pressure ulcer prevalence was 26.3%, with 29.2% in adult patients and 13.1% in pediatric patients. The most common body locations for pressure ulcers were the sacrum (22.1%), heels (14.8%), ears (12.9%), elbows (10.6%), and the buttocks (6.8%). Forty-eight percent of the ulcers were stage I, 36% Stage II, 6% Stage III-IV, and 10% unable to stage. CONCLUSIONS: Overall combined pressure ulcer prevalence and common body locations were consistent with findings from comparable hospitals. Patients at the extreme ends of the age spectrum had an increased risk of pressure ulcers. Stage I and II ulcers occurred most frequently. Potential prevention and early management strategies may be effective in decreasing the prevalence of these ulcers.

Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey.

The reduction in symptoms of Parkinson's disease produced by high-frequency stimulation (HFS) in the internal globus pallidus (GPi) has been proposed to be due to stimulus-induced inactivation of pallidal neurons and resulting disinhibition of thalamic neurons. We tested this in awake Macaca fascicularis by stimulating between pairs of electrodes inserted into GPi under electrophysiological control and recording the responses evoked in thalamic neurons. HFS produced a reduction, not an increase, in discharge frequency during the stimulus train in 77% of the responsive thalamic neurons. Only 16% of the responsive cells showed an increase in discharge during stimulation and, for some of these, stimulation at a similar intensity produced contralateral muscle contraction, a probable sign of current spread to the internal capsule. The few thalamic neurons studied during bursting had a reduction in burst frequency and duration during HFS. We conclude that high-frequency stimulation within GPi does not necessarily facilitate thalamic discharge, and it may act, instead, to interrupt abnormal patterns of thalamic discharge associated with parkinsonian symptoms.

Twentieth-century social and health-care influences on location of death in Canada.

Providing the right care, in the right place, to dying persons is hampered by a lack of understanding of where death and dying normally take place and ignorance about what influences location of death. This paper reports the findings of a multidisciplinary historical investigation of 20th-century influences on location of death in Canada. It builds on a study that found a hospitalization-of-death trend in Canada over much of the 20th century but a reduction in hospital deaths beginning in 1994. This study found 2 key influences on location of death: (1) health-care and health-system developments that consolidated care in hospitals while also raising and sustaining public expectations of beneficial if not curative hospital care--the rising hospital-death rate throughout the 20th century can thus be considered an outcome of the shift of illness care from the home to the hospital; and (2) reduced availability of home-based caregivers. A number of developments limited the availability of home care for chronically ill and terminally ill persons, including the increased participation of women in the workforce and the shift in nursing from private home duty to hospitals. Although some health and social support for home care has developed recently, this support clearly does not match that for hospital care. These findings indicate that location of death is an important focal point for studying and planning improvements in end-of-life care.

Toward a model for effectiveness. What Alberta occupational health nurses think.

Effectiveness is difficult to define or measure, but is frequently associated with cost. A two phase study conducted with occupational health nurses in Alberta, Canada resulted in a beginning model for effectiveness. In 1997, Phase One of an exploratory descriptive study focused on physical assessment by occupational health nurses (N = 137) and perceptions of effectiveness in practice (n = 104). In 2001, Phase Two used focus groups (n = 7) to determine occupational health nurses' reactions to the preliminary analysis of questionnaire responses on effectiveness. The focus groups confirmed and expanded categories, and reconfigured the developing model. The model makes explicit the foundations, functions, relationships, and goals for effectiveness in occupational health nursing practice. The foundation includes registered nurse (RN) experience and baseline competence comprising occupational health nursing education, RN and occupational health nurse experience, and multidisciplinary knowledge. Ten specific functions and nine relationships describe the occupational health nursing specialty practice and promote achievement of five goals: balance, communication, continuing competence, leadership, and trust. The goal of balance needs articulation in the nursing literature.

Consecuencias del reflujo gastroesofágico en la esfera O. R. L. y los síntomas laríngeos: revisión clínica / Consequence of the gastroesophageal reflux in the sphere O. R. L. and of the symptoms larygeal: clinical review

La presente revisión evidencia la asociación entre el reflujo gastroesofágico (RG) y los síntomas laríngeos de tipo persistente, entre ellos disfonía, tos, globus hystericus, carraspera, etc, así como también la correspondencia clínica patológica de estos síntomas. En las últimas tres décadas, se sugirió la idea de que el RG podía ser un factor predisponente en el desarrollo de las patologías relacionadas al espectro de la laringitis posterior ácida, tales como úlceras de contacto, granulomas, eritema interaritenoide. Fue cuando a partir de entonces, en múltiples estudios clínicos realizados a pequeñas escala se ha intentado establecer la causalidad de esa relación. La hipótesis encuentra uno de sus más sólidos argumentos, en la consistente remisión de los síntomas laríngeos observados en pacientes que han recibido tratamiento antirreflujo. De ser comprobada la relación de causalidad, se pondría de manifiesto la necesidad de realizar despistaje de RG en todo paciente que se presente con síntomas laríngeos, en especial a predominio nocturno.