Deep brain stimulation: a review of basic research and clinical studies

Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control.     

Effects of trimethyltin on repeated acquisition (learning) in the radial-arm maze.

Trimethyltin (TMT) was used as a positive control neurotoxicant to evaluate a repeated acquisition procedure for the 8-arm radial maze. Ten male Long-Evans rats were trained to collect a single food pellet at the end of each baited arm on each trial of a daily 12-trial test session. Four of the eight arms were baited on all trials of a given session. The set of four baited arms was changed each day: thus the rats were required to learn a new set of baited arms in each session. In trained rats, error frequencies (entries into unbaited arms) declined from about 4 on Trial 1 to less than 1 on Trials 4-12 in each session: this within-session error reduction thus defined an acquisition baseline which was evaluated for its sensitivity to TMT. Learning was impaired after 7 mg/kg (iv) TMT, as shown by a slower decline in within-session error frequencies in all treated rats. Errors and response times were elevated for 5 weeks after TMT but returned to control levels thereafter. Histological examination of hippocampi showed damage in all treated rats 18 weeks after treatment; however, no significant relationship between degree of damage and behavioral effect was observed. Analysis of errors showed that TMT more strongly impaired the rats' ability to avoid arms in the current unbaited set than those baited arms already entered on a given trial (i.e., working memory). These dissociations between behavior and hippocampal morphology in terms of time course, magnitude of effect across animals, and error type suggest that performance of this task does not depend upon hippocampal integrity, as do other tasks involving spatial working memory. Recovery of function in this kind of task may shed light on processes of neural plasticity after exposure to neurotoxic compounds.     

Survival and outcome after endotracheal intubation for acute stroke

OBJECTIVE: To assess survival and functional outcome in patients endotracheally intubated after ischemic stroke (IS) or spontaneous intracerebral hemorrhage (ICH). BACKGROUND: Endotracheal intubation is both a necessary life support intervention and a measure of severity in IS or ICH. Knowledge of associated clinical variables may improve the estimation of early prognosis and guide management in these patients. METHODS: We reviewed 131 charts of patients with IS or ICH who were admitted to the Neurosciences Intensive Care Unit at Duke University Medical Center between July 1994 and June 1997 and required endotracheal intubation. Stroke risk factors, stroke type (IS or ICH) and location (hemispheric, brainstem, or cerebellum), circumstances surrounding intubation, neurologic assessment (Glasgow Coma Score [GCS] and brainstem reflexes), comorbidities, and disposition at discharge were documented. Survivors were interviewed for Barthel Index (BI) scores. RESULTS: Survival was 51% at 30 days and 39% overall. Variables that significantly correlated with 30-day survival in multivariate analysis included GCS at intubation (p = 0.03) and absent pupillary light response (p = 0.008). Increase in the GCS also correlated with improved functional outcome measured by the BI (p = 0.0003). In patients with IS, age and GCS at intubation predicted survival, and in patients with ICH, absent pupillary light response predicted survival. CONCLUSIONS: Predictors for mortality differ between patients with IS and ICH; however, decreased level of consciousness is the most important determinant of increased mortality and poor functional outcome. Absent pupillary light responses also correspond with a poor prognosis for survival, but further validation of this finding is needed.     

Diffusion of nucleoside triphosphates and role of the entry site to the RNA polymerase II active center

Nucleoside triphosphates (NTPs) diffuse to the active center of RNA polymerase II through a funnel-shaped opening that narrows to a negatively charged pore. Computer simulation shows that the funnel and pore reduce the rate of diffusion by a factor of approximately 2 x 10(-7). The resulting limitation on the rate of RNA synthesis under conditions of low NTP concentration may be overcome by NTP binding to an entry site adjacent to the active center. Binding to the entry site greatly enhances the lifetime of an NTP in the active center region, and it prevents "backtracking" and the consequent occlusion of the active site.     

Measurement of benefits in economic evaluations of nutrition interventions in low‐ and middle‐income countries: A systematic review

Economic evaluation of nutrition interventions that compares the costs to benefits is essential to priority‐setting. However, there are unique challenges to synthesizing the findings of multi‐sectoral nutrition interventions due to the diversity of potential benefits and the methodological differences among sectors in measuring them. This systematic review summarises literature on the interventions, sectors, benefit terminology and benefit types included in cost‐effectiveness, cost‐utility and benefit‐cost analyses (CEA, CUA and BCA, respectively) of nutrition interventions in low‐ and middle‐income countries. A systematic search of five databases published from January 2010 to September 2019 with expert consultation yielded 2794 studies, of which 93 met all inclusion criteria. Eighty‐seven per cent of the included studies included interventions delivered from only one sector, with almost half from the health sector (43%), followed by food/agriculture (27%), water, sanitation and hygiene (WASH) (10%), and social protection (8%). Only 9% of studies assessed programmes involving more than one sector (health, food/agriculture, social protection and/or WASH). Eighty‐one per cent of studies used more than one term to refer to intervention benefits. The included studies calculated 128 economic evaluation ratios (57 CEAs, 39 CUAs and 32 BCAs), and the benefits they included varied by sector. Nearly 60% measured a single benefit category, most frequently nutritional status improvements; other health benefits, cognitive/education gains, dietary diversity, food security, knowledge/attitudes/practices and income were included in less than 10% of all ratios. Additional economic evaluation of non‐health and multi‐sector interventions, and incorporation of benefits beyond nutritional improvements (including cost savings) in future economic evaluations is recommended.     

Unmyelinated tactile afferents signal touch and project to insular cortex

There is dual tactile innervation of the human hairy skin: in addition to fast-conducting myelinated afferent fibers, there is a system of slow-conducting unmyelinated (C) afferents that respond to light touch. In a unique patient lacking large myelinated afferents, we found that activation of C tactile (CT) afferents produced a faint sensation of pleasant touch. Functional magnetic resonance imaging (fMRI) analysis during CT stimulation showed activation of the insular region, but not of somatosensory areas S1 and S2. These findings identify CT as a system for limbic touch that may underlie emotional, hormonal and affiliative responses to caress-like, skin-to-skin contact between individuals.     

Energy balance of human locomotion in water

In this paper a complete energy balance for water locomotion is attempted with the aim of comparing different modes of transport in the aquatic environment (swimming underwater with SCUBA diving equipment, swimming at the surface: leg kicking and front crawl, kayaking and rowing). On the basis of the values of metabolic power (Ė), of the power needed to overcome water resistance (_d) and of propelling efficiency (_P=_d/_tot, where _tot is the total mechanical power) as reported in the literature for each of these forms of locomotion, the energy cost per unit distance (C=Ė/v, where v is the velocity), the drag (performance) efficiency (_d=_d/Ė) and the overall efficiency (_o=_tot/Ė=_d/_P) were calculated. As previously found for human locomotion on land, for a given metabolic power (e.g. 0.5 kW=1.43 l·min^–1 O₂) the decrease in C (from 0.88 kJ·m^–1 in SCUBA diving to 0.22 kJ·m^–1 in rowing) is associated with an increase in the speed of locomotion (from 0.6 m·s^–1 in SCUBA diving to 2.4 m·s^–1 in rowing). At variance with locomotion on land, however, the decrease in C is associated with an increase, rather than a decrease, of the total mechanical work per unit distance (W_tot, kJ·m^–1). This is made possible by the increase of the overall efficiency of locomotion (_o=_tot/Ė=W_tot/C) from the slow speeds (and loads) of swimming to the high speeds (and loads) attainable with hulls and boats (from 0.10 in SCUBA diving to 0.29 in rowing).