Specific neural substrate linking respiration to locomotion.

When animals move, respiration increases to adapt for increased energy demands; the underlying mechanisms are still not understood. We investigated the neural substrates underlying the respiratory changes in relation to movement in lampreys. We showed that respiration increases following stimulation of the mesencephalic locomotor region (MLR) in an in vitro isolated preparation, an effect that persists in the absence of the spinal cord and caudal brainstem. By using electrophysiological and anatomical techniques, including whole-cell patch recordings, we identified a subset of neurons located in the dorsal MLR that send direct inputs to neurons in the respiratory generator. In semi-intact preparations, blockade of this region with 6-cyano-7-nitroquinoxaline-2,3-dione and (2R)-amino-5-phosphonovaleric acid greatly reduced the respiratory increases without affecting the locomotor movements. These results show that neurons in the respiratory generator receive direct glutamatergic connections from the MLR and that a subpopulation of MLR neurons plays a key role in the respiratory changes linked to movement.

Stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution.

PURPOSE: To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate hydrochloride (HCl) 5 mg/mL intravenous solution for experimental use. METHODS: A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate Hydrochloride, USP, powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/mL solution was sterilized by filtration technique under USP <797>-compliant conditions. Samples were stored refrigerated (2-8°C) and analyzed at approximately days 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability were evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography analysis. RESULTS: Over the 1-year study period, the samples retained 96.76% to 102.04% of the initial methylphenidate concentration. There was no significant change in the visual appearance, pH level, or particulate matter during the study period. The sterility of samples was maintained and endotoxin levels were undetectable throughout the 1-year stability period. CONCLUSION: Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable at 32, 61, 95, 186, and 365 days when stored in amber glass vials at refrigerated temperatures (2-8°C).

Efficient resource use in simplified complete denture fabrication.

PURPOSE: Conventional dentures will remain the only treatment available to most edentulous people for the foreseeable future. In this study, we compared the efficiency of two methods of making complete conventional dentures-the traditional academic standard (T) and a simplified technique (S) used in private practice. We have previously shown that they produce similar levels of patient satisfaction and denture quality. MATERIALS AND METHODS: Data were gathered during a randomized controlled clinical trial of 122 subjects from initial examination until 6-month follow-up. For this report, the direct costs of providing one set of conventional complete dentures by T or S techniques were estimated. All materials used were recorded and their cost was calculated in Canadian dollars (CAN$). The costs of fabrication in an outside laboratory were added. Clinician's labor time was recorded for every procedure. Between-group comparisons for each clinical procedure were carried out with independent t-tests. The number of patients in each group who needed postdelivery treatment was compared with Chi-square tests. The effect of group assignment and of treatment difficulty on outcomes was analyzed with multiple regression analysis. RESULTS: The mean total cost of the T method was significantly greater than S (CAN$166.3; p < 0.001), and clinicians spent 90 minutes longer (p < 0.001) on clinical care. The difficulty of the case had no significant influence on outcomes. CONCLUSIONS: The results indicate that the S method is the more cost-efficient method and that there are no negative consequences that detract from the cost savings.

Implant overdentures for edentulous elders: study of patient preference.

BACKGROUND: Studies show that elders wearing implant overdentures have improved nutrition and quality of life. However, upfront costs of this therapy are high, and the income of elderly edentulous populations is low. OBJECTIVES: This study was designed (i) to measure the preferences of edentulous patients for mandibular two-implant overdentures using Willingness-To-Pay (WTP) and Willingness-To-Accept (WTA), (ii) to assess the effect of long-term financing on WTP and (iii) to assess the desired role of health care plans in financing dental prostheses. METHODS: Edentulous elders (68-79 years; n = 36) wearing maxillary dentures and either a mandibular conventional denture (CD, n = 13) or a two-implant overdenture with ball attachments (IOD, n = 23) participated in this study. All had received their prostheses 2 years previously, as part of a randomised clinical trial. A three-part questionnaire was completed during a 20-min interview with a trained researcher. RESULTS: Forty-six per cent (6/13) of the CD wearers and 70% (16/23) of the IOD wearers were willing to pay three times more than the current cost of conventional dentures for implant prostheses. These percentages were increased to 77% (CD) and 96% (IOD) if participants could pay for implant overdentures in monthly instalments. Eighty-six per cent (31/36) of all participants in both groups (21/23 IOD; 10/13 CD) thought that the government should cover at least some of the cost of implant overdentures. CONCLUSIONS: This study shows that, the majority of elderly edentate individuals who have not experienced mandibular two-implant overdenture therapy are willing to pay the cost, particularly when payment can be made in monthly instalments.

Electrical properties of interneurons found within the trigeminal motor nucleus.

The trigeminal motor nucleus contains the somata of motoneurons innervating the jaw muscles, but also those of interneurons that we have characterized morphologically and immunohistochemically previously. Here we compare their basic physiological characteristics and synaptic inputs from the peri-trigeminal area (PeriV) to those of motoneurons using whole-cell recordings made with pipettes containing biocytin in brainstem slices of rats that had a tracer injected into their masseters. Values for input resistance, spike duration and overall duration of afterhyperpolarization (AHP) were greater for interneurons than for motoneurons. Some interneurons (44%) and motoneurons (33%) had an outward rectification during depolarization. Hyperpolarization-induced inward rectification was seen predominantly in interneurons (85% vs. 31% for motoneurons). Few interneurons (15%) showed depolarization and time-dependent firing frequency accommodation, while half (52%) of the motoneurons did. Rebound excitation at the offset of hyperpolarization was more common in interneurons than in motoneurons (62% vs. 34%). Both populations received synaptic inputs from PeriV. These inputs were predominantly excitatory and were mediated by non-N-methyl-d-aspartate glutamatergic receptors. Response latencies and rise times of the evoked potentials were longer in interneurons than in motoneurons, suggesting that some of the inputs to interneurons could be polysynaptic and/or occurring at distal dendritic locations. Miniature synaptic events could be seen in about half of the neurons in both populations. These results suggest that interneurons can be clearly distinguished from motoneurons on the basis of some electrophysiological properties like the input resistance and spike and AHP durations, and the kinetics of their synaptic inputs from adjacent areas.

Initial Investigation of the relation between extended computer use and temporomandibular joint disorders.

AIM: To determine if temporomandibular joint disorders (TMDs) are associated with extended computer use. MATERIALS AND METHODS: People with chronic pain and extensive computer use were recruited by means of a newspaper advertisement. Those who responded to the ad were asked to complete an online survey, which included questions on computer use, medical history, pain symptoms, lifestyle and mood. RESULTS: Ninety-two people completed the online survey, but none of them responded to all questions in the survey. Of the 88 respondents who reported their sex, 49 (56%) were female. Most of the respondents had used computers for more than 5 hours per day for more than 5 years, and most believed that their pain was linked to computer use. The great majority had pain in the neck (73/89 [82%]) or shoulder (67/89 [75%]), but many (40/91 [44%]) also had symptoms of TMD. About half of the participants reported poor sleep and fatigue, and many linked their pain to negative effects on lifestyle and poor quality of life. Two multiple regressions, with duration of pain as the dependent variable, were carried out, one using the entire sample of respondents who had completed the necessary sections of the survey (n = 91) and the other using the subset of people with symptoms suggestive of TMD (n = 40). Duration of computer use was associated with duration of pain in both analyses, but 6 other independent variables (injury or arthritis, hours of daily computer use, stress, position of computer screen relative to the eyes, sex, and age) were without effect. In these regression analyses, the intercept was close to 0 years, which suggests that the pain began at about the same time as computer use. DISCUSSION: This web-based survey provides the first evidence that chronic pain in jaw muscles and other symptoms of TMD are associated with long-term, heavy use of computers. However, the great majority of people with these symptoms probably also suffer from pain in the shoulder and neck.

Transcriptional profile of aging in C. elegans.

BACKGROUND: Numerous gerontogene mutants leading to dramatic life extensions have been identified in the nematode Caenorhabditis elegans over the last 20 years. Analysis of these mutants has provided a basis for understanding the mechanisms driving the aging process(es). Several distinct mechanisms including an altered rate of aging, increased resistance to stress, decreased metabolic rate, or alterations in a program causing organismic aging and death have been proposed to underlie these mutants. RESULTS: Whole-genome analysis of gene expression during chronological aging of the worm provides a rich database of age-specific changes in gene expression and represents one way to distinguish among these models. Using a rigorous statistical model with multiple replicates, we find that a relatively small number of genes (only 164) show statistically significant changes in transcript levels as aging occurs (<1% of the genome). Expression of heat shock proteins decreases, while expression of certain transposases increases in older worms, and these findings are consistent with a higher mortality risk due to a failure in homeostenosis and destabilization of the genome in older animals. Finally, a specific subset of genes is coordinately altered both during chronological aging and in the transition from the reproductive form to the dauer, demonstrating a mechanistic overlap in aging between these two processes. CONCLUSIONS: We have performed a whole-genome analysis of changes in gene expression during aging in C. elegans that provides a molecular description of C. elegans senescence.

A transcriptional profile of aging in the human kidney.

In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

A review of burst generation by trigeminal main sensory neurons.

In this paper, we present evidence that neurons in the dorsal part of the trigeminal main sensory nucleus participate in the patterning of mastication. These neurons have special membrane properties that allow them to generate rhythmical bursts of action potentials in the frequency range of natural mastication even when cut off from synaptic inputs. These properties mature during the third postnatal week in rats at the same time as mastication begins. Finally, we present evidence that a reduction on extracellular calcium concentration is an important step in the initiation of mastication.

Can general dentists produce successful implant overdentures with minimal training?

OBJECTIVES: This study was carried out to determine whether inexperienced dentists can provide two-implant overdentures that are as satisfactory and of the same cost as those provided by experienced prosthodontists. METHODS: Edentulous elders were enrolled in a randomized controlled clinical trial to compare the effects of mandibular conventional and two-implant overdentures on nutrition. They were randomly assigned to groups that were treated by either an experienced prosthodontist or by a newly-graduated dentist with minimal training in implant treatment. Data for this study were obtained during the treatment of the first 140 subjects enrolled. The change in patient ratings of satisfaction after treatment, laboratory costs and the number of unscheduled visits up to 6 months following prosthesis delivery were compared. RESULTS: Satisfaction was significantly higher with implant overdentures than with conventional dentures, but there were no differences in scores for either prosthesis between the groups treated by experienced specialists or new dentists. Furthermore, six of the seven inexperienced dentists reported that they found the mandibular two-implant overdenture easier to provide than the conventional denture. CONCLUSIONS: The results of this study suggest that general dentists can provide successful mandibular two-implant overdentures with minimal training.

Brainstem circuits that control mastication: do they have anything to say during speech?

UNLABELLED: Mastication results from the interaction of an intrinsic rhythmical neural pattern and sensory feedback from the mouth, muscles and joints. The pattern is matched to the physical characteristics of food, but also varies with age. There are large differences in masticatory movements among subjects. The intrinsic rhythmical pattern is generated by an assembly of neurons called a central pattern generator (CPG) located in the pons and medulla. The CPG receives inputs from higher centers of the brain, especially from the inferio-lateral region of the sensorimotor cortex and from sensory receptors. Mechanoreceptors in the lips and oral mucosa, in muscles, and in the periodontal ligaments around the roots of the teeth have particularly powerful effects on movement parameters. The central pattern generator includes a core group of neurons with intrinsic bursting properties, as well as a variety of other neurons that receive inputs from oral and muscle spindle afferents. Reorganization of subpopulations of neurons within the CPG underlies changes in movement pattern. In addition to controlling motoneurons supplying the jaw, tongue, and facial muscles, the CPG also modulates reflex circuits. It is proposed that these brainstem circuits also participate in the control of human speech. LEARNING OUTCOMES: Readers will be able to: (1) describe the general location and function of the central pattern generator for mastication, (2) identify the primary nuclei involved in the central pattern generator for mastication, (3) describe the general interactions among the central pattern generators of speech, mastication, respiration, and locomotion, and (4) compare/relate the brainstem systems controlling mastication and speech.

GABAergic control of action potential propagation along axonal branches of mammalian sensory neurons.

The main axons of mammalian sensory neurons are usually viewed as passive transmitters of sensory information. However, the spindle afferents of jaw-closing muscles behave as if action potential traffic along their central axons is phasically regulated during rhythmic jaw movements. In this paper, we used brainstem slices containing the cell bodies, stem axons, and central axons of these sensory afferents to show that GABA applied to the descending central (caudal) axon often abolished antidromic action potentials that were elicited by electrical stimulation of the tract containing the caudal axons of the recorded cells. This effect of GABA was most often not associated with a change in membrane potential of the soma and was still present in a calcium-free medium. It was mimicked by local applications of muscimol on the axons and was blocked by bath applications of picrotoxin, suggesting activation of GABA(A) receptors located on the descending axon. Antidromic action potentials could also be blocked by electrical stimulation of local interneurons, and this effect was prevented by bath application of picrotoxin, suggesting that it results from the activation of GABA(A) receptors after the release of endogenous GABA. We suggest that blockage is caused mainly by shunting within the caudal axon and that motor command circuits use this mechanism to disconnect the rostral and caudal compartments of the central axon, which allows the two parts of the neuron to perform different functions during movement.

The impact of conventional and implant supported prostheses on social and sexual activities in edentulous adults Results from a randomized trial 2 months after treatment.

OBJECTIVES: To determine the impact of mandibular two-implant overdentures or conventional complete dentures on leisure and sexual activities. METHODS: One hundred and two subjects, aged 35-65 years, received either mandibular overdentures retained by two implants (IOD; n=54) or new mandibular conventional complete dentures (CD; n=48) in a randomized controlled clinical trial. A Social Impact Questionnaire was used to assess the impact on social and sexual activity including avoiding conversation, refusing invitations, avoiding sport and feeling uneasy when kissing and in sexual relationships, and the looseness of the prostheses during such activities. Ratings were recorded on categorical scales at baseline and 2 months after treatment. Oral health related quality of life was measured with the Oral Health Impact Profile (OHIP). Between and within group comparisons were carried out using regression models. The correlation between post-treatment OHIP scores and the leisure and sexual impact items was assessed. RESULTS: Two months after delivery of the prosthesis there was significant improvements in the IOD group for looseness when eating, speaking, kissing and yawning. The IOD group reported significantly less post treatment looseness than the CD group for all parameters investigated (p<0.0001). IOD subjects felt less uneasy kissing and less uneasy during sexual activity than CD subjects. Correlations between the two sexual activity items (uneasiness when kissing and during sexual relations) and the OHIP scales were weak. CONCLUSIONS: Edentulism has a negative impact on social and sexual life. Mandibular overdentures provide greater improvement in of unease in intimate activities than new conventional mandibular dentures.

Do traditional techniques produce better conventional complete dentures than simplified techniques?

OBJECTIVES: To compare the quality of conventional complete dentures fabricated with two different techniques. A randomized controlled clinical trial was conducted to compare traditional (T) and simplified (S) methods of making complete conventional dentures on patients' ratings of satisfaction, comfort and function at 3 and 6 months following delivery. The quality of the prostheses was rated by prosthodontists at 6 months. MATERIALS AND METHODS: One hundred twenty-two male and female edentulous individuals, aged 45-75 years, were randomly allocated into groups that received dentures made with either T or S methods. Following delivery, patients' ratings of several denture-related factors were measured using 100mm visual analogue scales, and denture quality was assessed by blinded prosthodontists using ratings on a validated quantitative scale. RESULTS: There were no significant differences between the two groups in patient ratings for overall satisfaction (3 months: mean T = 83 mm, mean S = 83 mm, P = 0.97; 6 months: mean T = 79 mm, mean S = 79 mm, P = 0.96) or in prosthodontists' ratings of denture quality (T = 66, S = 63; P = 0.38). CONCLUSION: These results show that the quality of complete dentures does not suffer when manufacturing techniques are simplified to save time and materials. Dental educators should consider these findings when re-designing prosthodontic training programs.

Persistence of respiratory-swallowing coordination after laryngectomy.

The present study was designed to provide additional insights into the neural mechanisms underlying respiratory-swallowing coupling by studying potential alterations in movement coordination when upper airway protection is no longer necessary. Twelve laryngectomized participants, all at least 3 years postsurgery, were compared to age- and sex-matched controls. Respiration and swallowing were monitored before, during, and after mastication. No significant differences were found between the laryngectomized and normal control participants in the distribution of the respiratory phase in which swallowing occurs, our primary measure of respiratory-swallowing stability. Data suggest that the coupling between the swallowing and respiratory pattern generators is highly stable. Pronounced masticatory-related apnea was observed in 3 of the laryngectomized participants but in none of the controls, suggesting that masticatory/respiratory interactions may become abnormal in these patients.

Immunohistochemical distribution of tachykinins in the CNS of the lamprey Petromyzon marinus.

The presence of tachykinins in the CNS of vertebrates has been known for many decades, and numerous studies have described their distribution in mammals. Tachykinins were also reported in the CNS of lampreys using immunohistochemistry, chromatography, and radioimmunoassay methods, but the use of substance P (SP)-specific antibodies to reveal those tachykinins could have led to an underestimation of their number in this genus. Therefore, we carried out a new immunohistochemical study on Petromyzon marinus using a commercial polyclonal antibody that binds not only to mammalian SP, but also to other neurokinins. This antibody labeled all previously described lamprey tachykinin-containing neuronal populations, but more important, labeled new populations in several parts of the brain. These include the dorsal gray of the rostral spinal cord, the dorsal column nuclei, the octavolateral area, the nucleus of the solitary tract, the medial rhombencephalic reticular formation, the lateral tegmentum of the rostral rhombencephalon, the torus semicircularis, the optic tectum, the habenula, the mammillary area, the dorsal thalamic area, the lateral hypothalamus, and the septum area. Preabsorption experiments confirmed the binding of the antibody to neurokinins and allowed us to propose that the CNS of P. marinus contains at least two different tachykinins.

Muscle pain inhibits cutaneous touch perception.

The processing of noxious and non-noxious sensations differs between chronic pain syndromes, and we believe that studies of sensory processing in the presence of pain will help to clarify the aetiology of the conditions. Here we measured in humans the threshold-level mechanosensitivity in tonic experimental muscle pain. We found (1) that muscle pain induced by hypertonic saline reduced cutaneous threshold-level mechanosensitivity at the site of pain and at the mirror site in the contralateral face, (2) that this effect outlasted the sensation of pain, (3) that it was more pronounced when the painful area was reported to be large, and (4) that the loss of mechanosensitivity was greater in males than females. Comparing our findings to results obtained with other pain models, all classes of nociceptors do not seem to have the same effect on cutaneous mechanosensitivity. The observed threshold-level hypoesthesia is consistent with the hypothesis that the increased mechanical thresholds found in clinic cases of temporomandibular disorders and cervicobrachialgia are a direct result of the activation of muscle nociceptors.

Is myofascial pain of the temporal muscles relieved by oral sumatriptan? A cross-over pilot study.

There is evidence that serotonin may be implicated in the pathophysiology of myofascial pain (MFP). Because of this, we used oral sumatriptan (Imitrex, Glaxo), a peripherally acting agonist of 5-HT1D receptors, in a double-blind, randomized, placebo-controlled double crossover pilot study of 7 patients with episodic MFP of the temporalis muscles. The results showed that there was a significant reduction in pain intensity and increase in pain relief over time with both the active medication and the placebo, but no significant difference between treatments. All but 1 patient reported that they are not interested in retaking the same medication. These data suggest that oral sumatriptan may not be the drug of choice in the control of episodic MFP.

Memories of chronic pain and perceptions of relief.

Clinicians and researchers often ask patients to remember their past pain. They also use patient's reports of relief from pain as evidence of treatment efficacy, assuming that relief represents the difference between pretreatment pain and present pain. We have estimated the accuracy of remembering pain and described the relationship between remembered pain, changes in pain levels and reports of relief during treatment. During a 10-week randomized controlled clinical trial on the effectiveness of oral appliances for the management of chronic myalgia of the jaw muscles, subjects recalled their pretreatment pain and rated their present pain and perceived relief. Multiple regression analysis and repeated measures analyses of variance (ANOVA) were used for data analysis. Memory of the pretreatment pain was inaccurate and the errors in recall got significantly worse with the passage of time (P < 0.001). Accuracy of recall for pretreatment pain depended on the level of pain before treatment (P < 0.001): subjects with low pretreatment pain exaggerated its intensity afterwards, while it was underestimated by those with the highest pretreatment pain. Memory of pretreatment pain was also dependent on the level of pain at the moment of recall (P < 0.001). Ratings of relief increased over time (P < 0.001), and were dependent on both present and remembered pain (Ps < 0.001). However, true changes in pain were not significantly related to relief scores (P = 0.41). Finally, almost all patients reported relief, even those whose pain had increased. These results suggest that reports of perceived relief do not necessarily reflect true changes in pain.

The efficacy of oral splints in the treatment of myofascial pain of the jaw muscles: a controlled clinical trial.

Oral splints are widely used in the treatment of myofascial pain of masticatory muscles, even though their mechanism of action is unknown. The present study evaluated the therapeutic efficacy of splints using a parallel, randomized, controlled and blind design. Following a sample size estimation, 63 subjects were recruited and assigned to 3 groups: (1) passive control: full occlusal splint worn only 30 min at each appointment; (2) active control: palatal splint worn 24 h/day; and (3) treatment: full occlusal splint worn 24 h/day. On each of 7 visits over 10 weeks, subjects rated on 100 mm visual analogue scales their pain intensity and unpleasantness at rest and after experimental mastication. The effect of pain on the quality of life was also rated on category scales. All pain ratings decreased significantly with time, and quality of life improved for all 3 groups. However, there were no significant differences between groups in any of the variables. These data suggest that the gradual reduction in the intensity and unpleasantness of myofascial pain, as well as the improvement of quality of life during the trial, was non-specific and not related to the type of treatment.