The future of genetic research on neurodegeneration

Why, with all the progress in the field of neurodegeneration, do we still lack disease-modifying drugs that tackle the primary defect of severe cell loss? How much progress has been made toward this goal? Have we spent our time and resources wisely? And, most important, is there room for improvement? This commentary highlights several problems faced by researchers in studying the genetic etiology of neurodegenerative diseases and seeks to provide direction in overcoming some of these obstacles.     

Fertility in the cycle predicts women's interest in sexual opportunism

Research over the past decade has documented clear, robust changes in women's sexual preferences and interests across the ovarian cycle. When fertile, women are particularly attracted to a number of masculine male features (e.g., masculine faces, voices, scents and bodies) and other traits, and especially when they evaluate men's “sexiness” rather than their attractiveness as long-term partners. The current research extended this line of research by examining changes in women's self-reported sexual interests across the cycle. We asked 68 normally ovulating women in committed romantic relationships to fill out questionnaires about their sexual preferences and interests (at that time, not in general) twice across their cycles: once when fertile and once during the luteal phase. Relative to during the luteal phase, fertile women expressed (a) greater emphasis on the physical attractiveness of a partner; (b) greater arousal at the sight or thought of attractive male bodily features; (c) greater willingness to engage in and interest in sex with attractive men, even ones who they do not know well (interest in sexual opportunism). These findings importantly extend our understanding of women's fertile-phase sexuality.     

Individual wealth rank, community wealth inequality, and self-reported adult poor health: a test of hypotheses with panel data (2002-2006) from native Amazonians, Bolivia

Growing evidence suggests that economic inequality in a community harms the health of a person. Using panel data from a small-scale, preindustrial rural society, we test whether individual wealth rank and village wealth inequality affects self-reported poor health in a foraging-farming native Amazonian society. A person's wealth rank was negatively but weakly associated with self-reported morbidity. Each step up/year in the village wealth hierarchy reduced total self-reported days ill by 0.4 percent. The Gini coefficient of village wealth inequality bore a positive association with self-reported poor health that was large in size, but not statistically significant. We found small village wealth inequality, and evidence that individual economic rank did not change. The modest effects may have to do with having used subjective rather than objective measures of health, having small village wealth inequality, and with the possibly true modest effect of a person's wealth rank on health in a small-scale, kin-based society. Finally, we also found that an increase in mean individual wealth by village was related to worse self-reported health. As the Tsimane' integrate into the market economy, their possibilities of wealth accumulation rise, which may affect their well-being. Our work contributes to recent efforts in biocultural anthropology to link the study of social inequalities, human biology, and human-environment interactions.     

Stem cell therapy in the inner ear: recent achievements and prospects

Because of its high prevalence and social impact, hearing impairment is a major public health problem. Whatever the cause--heredity, acoustic trauma, aminoglycoside antibiotics, noise exposure or aging--the hearing impairment is often caused by an irreversible loss of sensory hair cells. So far, hearing aids and cochlear implants are the only possibility to "treat" profound deafness. With the advent of regenerative medicine, extensive studies aimed to repair, regenerate or replace lost hair cells have been initiated. Recently, Stefan Heller and colleagues described a guidance protocol to induce mouse embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) to differentiate into mechanosensitive hair cells. The resulting hair cells hold promise as a tool for hair cell molecular physiology and physiopathology, drug discovery, and possibly also hair cell replacement. The next challenges, alternative strategies, their limitations and prospects are also discussed.     

Toward routine,DNA-based detection methods for marine pests

Marine pest incursions can cause significant ongoing damage to aquaculture, biodiversity, fisheries habitat, infrastructure and social amenity. They represent a significant and ongoing economic burden. Marine pests can be introduced by several vectors including aquaculture, aquarium trading, commercial shipping, fishing, floating debris, mining activities and recreational boating. Despite the inherent risks, there is currently relatively little routine surveillance of marine pest species conducted in the majority of countries worldwide. Accurate and rapid identification of marine pest species is central to early detection and management. Traditional techniques (e.g. physical sampling and sorting), have limitations, which has motivated some progress towards the development of molecular diagnostic tools. This review provides a brief account of the techniques traditionally used for detection and describes developments in molecular-based methods for the detection and surveillance of marine pest species. Recent advances provide a platform for the development of practical, specific, sensitive and rapid diagnosis and surveillance tools for marine pests for use in effective prevention and control strategies.     

Characterization of ochratoxin A-induced apoptosis in primary rat hepatocytes

The main target organ of the mycotoxin ochratoxin A (OTA) in mammals is the kidney but OTA has also been shown to be hepatotoxic in rats and to induce tumors in mouse liver. Even at very low concentrations, OTA causes perturbations of cellular signaling pathways as well as enhanced apoptosis. OTA has been extensively studied in kidney cell systems. Since this substance also affects liver health, we focused our work on apoptosis-related events induced by OTA in primary rat hepatocytes. We performed pathway-specific polymerase chain reaction arrays to assess the expression of genes involved in apoptosis. Treatment with 1 μM OTA for 24 h caused marked changes in apoptosis-related gene expression. Genes as apaf1, bad, caspase 7, polb (DNA polymerase beta, performs base excision repair), and p53, which are marker genes for DNA damage, were upregulated. FAS and faslg were also markedly induced by treatment with OTA. Treatment of hepatocytes with OTA led to a concentration-dependent inhibition of protein biosynthesis. Apoptosis-inducing factor was released from mitochondria following OTA treatment; the mycotoxin induced the activity of caspases 8, 9, and 3/7 and caused chromatin condensation and fragmentation. Caspase inhibition led to a significant but not complete reduction of OTA-induced apoptosis. Our data suggest that not only OTA leads to p53-dependent apoptosis in rat hepatocytes but it also hints to other mechanisms, independent of caspase activation or protein biosynthesis, being involved.     

Multicentre prospective validation of use of the Canadian C-Spine Rule by triage nurses in the emergency department

Objectives

The Canadian C-Spine Rule for imaging of the cervical spine was developed for use by physicians. We believe that nurses in the emergency department could use this rule to clinically clear the cervical spine. We prospectively evaluated the accuracy, reliability and acceptability of the Canadian C-Spine Rule when used by nurses.

Methods

We conducted this three-year prospective cohort study in six Canadian emergency departments. The study involved adult trauma patients who were alert and whose condition was stable. We provided two hours of training to 191 triage nurses. The nurses then assessed patients using the Canadian C-Spine Rule, including determination of neck tenderness and range of motion, reapplied immobilization and completed a data form.

Results

Of the 3633 study patients, 42 (1.2%) had clinically important injuries of the cervical spine. The kappa value for interobserver assessments of 498 patients with the Canadian C-Spine Rule was 0.78. We calculated sensitivity of 100.0% (95% confidence interval [CI] 91.0%–100.0%) and specificity of 43.4% (95% CI 42.0%–45.0%) for the Canadian C-Spine Rule as interpreted by the investigators. The nurses classified patients with a sensitivity of 90.2% (95% CI 76.0%–95.0%) and a specificity of 43.9% (95% CI 42.0%–46.0%). Early in the study, nurses failed to identify four cases of injury, despite the presence of clear high-risk factors. None of these patients suffered sequelae, and after retraining there were no further missed cases. We estimated that for 40.7% of patients, the cervical spine could be cleared clinically by nurses. Nurses reported discomfort in applying the Canadian C-Spine Rule in only 4.8% of cases.

Conclusion

Use of the Canadian C-Spine Rule by nurses was accurate, reliable and clinically acceptable. Widespread implementation by nurses throughout Canada and elsewhere would diminish patient discomfort and improve patient flow in overcrowded emergency departments.Each year, Canadian emergency departments treat 1.3 million patients who have suffered blunt trauma from falls or motor vehicle collisions and who are at risk for injury of the cervical spine.¹ Most of these cases involve adults who are alert and in stable condition, and less than 1% involve fracture of the cervical spine.² Most trauma patients who have been transported in ambulances are protected by a backboard, collar and neck supports. Nurses are responsible for initial triage in the emergency department and usually send such patients to high-acuity resuscitation rooms, where they may remain fully immobilized for hours until assessment by a physician and radiography are complete. This prolonged immobilization is often unnecessary and adds considerably to patient discomfort. The delay also adds to the burden of overcrowded Canadian emergency departments in an era when they are under unprecedented pressures.^3–5 These patients occupy valuable space in resuscitation rooms, and repeated efforts to obtain satisfactory radiographs or computed tomography scans of the cervical spine use valuable time on the part of physicians, nurses and technicians.A clinical decision rule is defined as a decision-making tool incorporating three or more variables from the patient’s history, a physical examination or simple tests. Such rules are derived from original research and help clinicians with diagnostic or therapeutic decisions at the bedside. We previously developed a clinical decision rule for evaluation of the cervical spine.^6,7 The Canadian C-Spine Rule comprises simple clinical variables (Figure 1) and was designed to allow clinicians to “clear” immobilization of the cervical spine (i.e., remove neck collar and other devices) without radiography and to decrease immobilization times.⁸ We also validated the accuracy of the rule when used by physicians.⁹ We recently completed an implementation trial at 12 Canadian hospitals to evaluate the impact on patient care and outcomes of the Canadian C-Spine Rule when used by physicians.¹⁰Open in a separate windowFigure 1The Canadian C-Spine Rule to rule out cervical spine injury, adapted for use by nurses. The rule is intended for patients who have experienced trauma, who are alert (score on Glasgow Coma Scale = 15) and whose condition is stable. *The following mechanisms of injury were defined as dangerous: fall from elevation of more than 3 ft (91 cm) or five stairs, axial load to the head (e.g., diving injury), motor vehicle collision at high speed (> 100 km/h), motor vehicle collision involving a rollover or ejection, injury involving a motorized recreational vehicle, bicycle-related injury (rider struck or collision). †Simple rear-end motor vehicle collisions exclude incidents in which the patient was pushed into oncoming traffic or was hit by a bus, large truck or vehicle travelling at high speed, as well as rollovers; all such incidents would be considered high risk. ‡Neck pain with delayed onset is any pain that did not occur immediately following the precipitating incident. Adapted, with permission, from Stiell IG, Wells GA, Vandemheen K, et al. The Canadian Cervical Spine Radiography Rule for alert and stable trauma patients. JAMA 2001;286:1841–8.⁸ Copyright © 2001 American Medical Association. All rights reserved.Nurses in the emergency department usually do not evaluate the cervical spine of trauma patients, and they routinely send all immobilized patients to the emergency department’s resuscitation room. We believe that nurses could safely evaluate alert patients who have arrived by ambulance and whose condition is stable and could “clear” immobilization of the cervical spine of low-risk patients upon arrival at the triage station.¹¹ Patients could then be much more rapidly, comfortably and efficiently managed in other areas of the emergency department. An expanded decision-making role for nurses has the potential to improve the efficiency of trauma care in all Canadian hospitals. Very little research has been done to determine the ability of nurses to clear immobilization of the cervical spine.^12–15 Our objective in this study was to prospectively evaluate the accuracy, reliability and acceptability of the Canadian C-Spine Rule when used by nurses to assess patients’ need for immobilization.