Saltatory Conduction along Myelinated Axons Involves a Periaxonal Nanocircuit.

The propagation of electrical impulses along axons is highly accelerated by the myelin sheath and produces saltating or "jumping" action potentials across internodes, from one node of Ranvier to the next. The underlying electrical circuit, as well as the existence and role of submyelin conduction in saltatory conduction remain, however, elusive. Here, we made patch-clamp and high-speed voltage-calibrated optical recordings of potentials across the nodal and internodal axolemma of myelinated neocortical pyramidal axons combined with electron microscopy and experimentally constrained cable modeling. Our results reveal a nanoscale yet conductive periaxonal space, incompletely sealed at the paranodes, which separates the potentials across the low-capacitance myelin sheath and internodal axolemma. The emerging double-cable model reproduces the recorded evolution of voltage waveforms across nodes and internodes, including rapid nodal potentials traveling in advance of attenuated waves in the internodal axolemma, revealing a mechanism for saltation across time and space.

Epidemiology and potential risk factors of drug-related problems in Hong Kong paediatric wards.

AIMS: A drug-related problem (DRP) is 'an event or circumstance involving drug therapy that actually or potentially interferes with the desired health outcome'. The extent and characteristics of DRPs in children in Hong Kong are unknown. The aim of this study was to determine the epidemiology of and identify riskf actors for DRPs in hospitalized children in Hong Kong. METHODS: This was a prospective cohort study in children aged 0­18 years who were admitted to a medical ward, paediatric intensive care unit or neonatal intensive care unit of seven Hong Kong hospitals, during a 3 month period. Patients' charts, medical records and laboratory data were reviewed daily to identify DRPs; their preventability and severity were assessed. Logistic regression was used to analyse potential risk factors associated with the incidence of DRPs. RESULTS: Three hundred and twenty-nine children (median age, 2 years; interquartile range, 0 months to 9 years) were included. In total, 82 DRPs were experienced by 69 patients. The overall incidence of DRPs was 21.0% (95% confidence interval, 16.7­25.8%). The incidence was higher in neonatal and paediatric intensive care units than medical wards. Dosing problems were the most frequently reported DRPs (n = 35; 42.7%), followed by drug choice problems (n = 19; 23.2%) and adverse drug reactions (n = 11; 13.4%). Sixty-seven (81.7%) DRP cases were assessed as preventable, 42 (51.2%) as minor and 40 (48.8%) as moderate. The number of prescribed drugs and 'certain infectious and parasitic diseases' were potential risk factors for occurrence of DRPs. CONCLUSIONS: Drug-related problems were common in hospitalized children in this study in Hong Kong; the most frequent were dosing and drug choice problems, and the majority of them were preventable. Polypharmacy and 'certain infectious and parasitic diseases' were potential risk factors.

Arrhythmias in structural heart disease.

The presence of structural heart disease is often associated with the development of electrical abnormalities of the heart, manifesting as atrial and ventricular arrhythmias. These can occur in those with ischemic and nonischemic cardiomyopathies, congenital heart disease, and various acquired and intrinsic structural abnormalities of the myocardium. Treatment of these arrhythmias generally involves treatment of the underlying disorder first, if possible, such as with surgical or catheter-based intervention. Other therapies, including medical therapy with beta-blockers and anti-arrhythmic agents, pacemakers and implantable cardioverter-defibrillators (ICDs), and ablation may be offered both as prophylactic therapy or if arrhythmias have developed. In some instances, therapy is undertaken regardless of whether there are symptoms. ICDs provide support for those patients at risk for malignant, life-threatening arrhythmias, but appropriate patient and device selection are vital to improve mortality and to limit adverse events.

Corrigendum: Rapid Eye Movements in Sleep Furnish a Unique Probe Into Consciousness.

[This corrects the article DOI: 10.3389/fpsyg.2018.02087.].

Rapid Eye Movements in Sleep Furnish a Unique Probe Into Consciousness.

The neural correlates of rapid eye movements (REMs) in sleep are extraordinarily robust; including REM-locked multisensory-motor integration and accompanying activation in the retrosplenial cortex, the supplementary eye field and areas encompassing cholinergic basal nucleus (Hong et al., 2009). The phenomenology of REMs speaks to the notion that perceptual experience in both sleep and wakefulness is a constructive process - in which we generate predictions of sensory inputs and then test those predictions through actively sampling the sensorium with eye movements. On this view, REMs during sleep may index an internalized active sampling or 'scanning' of self-generated visual constructs that are released from the constraints of visual input. If this view is correct, it renders REMs an ideal probe to study consciousness as "an exclusively internal affair" (Metzinger, 2009). In other words, REMs offer a probe of active inference - in the sense of predictive coding - when the brain is isolated from the sensorium in virtue of the natural blockade of sensory afferents during REM sleep. Crucially, REMs are temporally precise events that enable powerful inferences based on time series analyses. As a natural, task-free probe, (REMs) could be used in non-compliant subjects, including infants and animals. In short, REMs constitute a promising probe to study the ontogenetic and phylogenetic development of consciousness and perhaps the psychopathology of schizophrenia and autism, which have been considered in terms of aberrant predictive coding.

Pip92: a short-lived, growth factor-inducible protein in BALB/c 3T3 and PC12 cells.

pip92 is a cellular immediate-early gene inducible by serum growth factors in fibroblasts. It is also induced in the rat pheochromocytoma cell line PC12 by agents that cause proliferation, neuronal differentiation, and membrane depolarization. We show that the pip92-encoded polypeptide is a proline-rich protein of 221 amino acids, has an extremely short half-life, and is localized in the cytoplasm. We hypothesize that Pip92 plays a role in mediating the cellular responses to a variety of extracellular signals.

Genomic structure, cDNA sequence, and expression of gly96, a growth factor-inducible immediate-early gene encoding a short-lived glycosylated protein.

We report the cDNA sequence and genomic structure of gly96, an immediate early gene inducible by serum growth factors in mouse fibroblasts. It encodes a 153-amino acid protein that does not share significant sequence similarity with any known protein. In the adult mouse, gly96 is expressed predominantly in the lung, testes and the uterus. We have identified the Gly96 protein in Balb/c 3T3 cells using affinity-purified antibodies recognizing the Gly96 polypeptide. We show that Gly96 is glycosylated and has a short half-life in serum stimulated fibroblasts.

cDNA sequence of a growth factor-inducible immediate early gene and characterization of its encoded protein.

We report the cDNA sequence of 3CH134, an immediate early gene whose transcription is rapidly and transiently stimulated by serum growth factors. 3CH134 encodes a 367 amino acid protein that does not share significant sequence similarity with any known protein. 3CH134 is inducible through multiple signal transduction pathways, and in the adult mouse is expressed predominantly in the lung. Using affinity-purified antibodies, we have identified the 3CH134 protein in serum-stimulated Balb/c 3T3 cells and determined that it has a short half-life.

Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction.

OBJECTIVES: Bone marrow stromal cells are capable of differentiating into cardiomyogenic cells. We tested the hypothesis that transcoronary implantation of bone marrow stromal cells may regenerate infarcted myocardium and reduce cardiac dysfunction. METHODS: Isolated bone marrow stromal cells from the isogenic donor rats were transfected with LacZ reporter gene for cell labeling. To induce cardiomyogenic differentiation, the bone marrow stromal cells were treated with 5-azacytidine before implantation. Two weeks after left coronary ligation, these cells (1 x 10(6) in 150 microL) were infused into the briefly distally occluded ascending aorta of the recipient rats (n = 15) to simulate direct coronary infusion clinically. Control animals were infused with cell-free medium (n = 14). Cardiac function was evaluated by echocardiography at preimplantation and 4 and 8 weeks postimplantation. The hearts were then immunohistochemically studied to identify phenotypic changes of implanted bone marrow stromal cells. RESULTS: Immediately after cell infusion, the bone marrow stromal cells were trapped within coronary vessels in both infarcted and noninfarcted areas. However, after 8 weeks, most of the cells were identified in the scar and periscar tissue, expressing sarcomeric myosin heavy chain and cardiomyocyte-specific protein troponin I-C. Some bone marrow stromal cells were found to be connected to the adjacent host cardiomyocytes with gap junction. Two-way repeated-measures analysis of variance revealed significant improvement in fractional shortening and end-diastolic and end-systolic diameter of the left ventricle (P =.0465,.002,.0004, respectively) in the bone marrow stromal cell group. CONCLUSIONS: Although bone marrow stromal cells had been reported to improve cardiac function when injected directly into the myocardial scar, this study demonstrated for the first time that bone marrow stromal cells can be delivered via the coronary artery, as they are capable of targeted migration and differentiation into cardiomyocytes in the scar tissue to improve cardiac function.

Short-term microbiological and clinical effects of subgingival irrigation with an antimicrobial mouthrinse.

Fifty chronic adult periodontitis patients completed a 6-week controlled, double-blind, split mouth clinical study to determine the effects of subgingival irrigation with an antimicrobial mouthrinse on periodontal microflora, supragingival plaque, and gingivitis when used as an adjunct to normal oral hygiene. Qualifying subjects had at least four sites, two on each side of the mouth, with probing depths between 4 and 6 mm, which bled on gentle probing. Following baseline examinations, subjects received a half mouth scaling and prophylaxis and full mouth subgingival irrigation with either the antimicrobial mouthrinse or sterile colored water control professionally delivered. Subjects continued irrigation at home once daily for 42 days with their assigned rinse delivered via a subgingival delivery system. All sites in the mouth were scored at baseline and at day 42 for supragingival plaque, bleeding on probing, and redness. For the four selected periodontitis sites, probing depth and attachment level were measured at baseline and on day 42; additionally, supragingival plaque and gingival redness were scored on days 7 and 21. Subgingival plaque samples for microbiological analysis were harvested from the selected periodontal sites at baseline and on days 7, 21, and 42. Microbiologically, irrigation with the antimicrobial mouthrinse resulted in statistically significant reductions compared to control in putative periodontopathogens, including black pigmenting species, which persisted at 42 days. Clinically, subgingival irrigation with the antimicrobial mouthrinse produced a significant reduction in supragingival plaque (P < 0.001), bleeding on probing (P = 0.019), and redness (P = 0.017) compared to the control, whether or not the area irrigated received a prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of an antimicrobial mouthrinse on early healing of gingival flap surgery wounds.

A randomized double-blind crossover design study using 25 patients requiring bilateral gingival flap surgery was completed. The effect of rinsing postsurgically three times daily with an antimicrobial mouthrinse or physiological saline on dental plaque formation, gingival inflammation, bleeding, wound healing, and patient comfort was evaluated at 7, 14 and 28 days. The antimicrobial rinse was statistically significantly 28.9% more effective than saline at seven days for reducing plaque. It was also significantly more effective for improving wound healing at day 7 as measured by edema (p less than 0.04). There were no significant differences in gingival index scores or bleeding at any time period. Use of an antimicrobial mouthrinse may be an effective aid in early healing of gingival flap surgery wounds.

Computer-based thermal imaging of human gingiva: preliminary investigation.

Computer-based thermal imaging techniques were used to compare the rewarming rates of normal and inflamed human gingiva following cooling. A Modified Gingival Index (MGI) score, gingival crevicular fluid (GCF) measurement, and clinical photograph were obtained from a maxillary or mandibular anterior facial region in 20 subjects, aged 25 to 44. Baseline thermograms of the marginal/papillary (M/P) and adjacent attached gingiva (AG) were recorded following an acclimatization period with the patient seated and chin resting on a positioning apparatus. The tissue was then cooled with a gentle stream of air and thermograms were recorded at 10 second intervals for 3 minutes as the tissue rewarmed. Rewarming slopes were calculated based on these thermograms. Correlation coefficients were calculated for MGI with GCF, as well as for both MGI and GCF with AG and M/P rewarming slopes. Mean baseline (SE) temperatures (degrees F) for AG were 75.9 (0.9), 78.0 (0.6), and 80.3 (1.3) for normal, mildly inflamed, and moderately-severely inflamed gingivae, respectively; corresponding mean (SE) temperature differences (degrees F) between AG and M/P were 0.5 (0.2), 0.9 (0.2), and 1.4 (0.3). Intragroup mean M/P temperatures were less than mean AG temperatures, with the mean regional differences increasing with greater severity of inflammation. Rewarming rates also increased as inflammation became more severe, with the rewarming slopes of both the AG and M/P having statistically significant correlations with the MGI and the GCF. The correlation between MGI and GCF was also statistically significant. This study suggests that computer-based thermal imaging techniques can detect both static and dynamic temperature differences between normal gingiva and gingivae with increasing severities of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlations among gingival indices: a methodology study.

Using an experimental gingivitis model, 99 subjects completed a 3-week study to determine the correlations between a visual index of gingivitis, the Modified Gingival Index (MGI), and the Gingival Index (GI), the Interdental Bleeding Index (IBI), and the Papillary Bleeding Index (PBI). Following a baseline examination consisting of the MGI and either the GI, IBI, or PBI, each subject received a full mouth scaling and rubber cup polishing to render the teeth plaque and calculus free. Subjects then rinsed twice daily for 30 seconds with 20 ml of either an active antimicrobial or control mouthrinse for 3 weeks while abstaining from all other oral hygiene. The MGI correlated significantly with the GI, IBI, and PBI, both at baseline and at 3 weeks for all subjects.

The efficacy of an essential oil antiseptic mouthrinse vs. dental floss in controlling interproximal gingivitis: a comparative study.

BACKGROUND: The use of dental floss has long been considered to be effective in controlling interproximal plaque and gingivitis. The authors compared this method with that of use of a mouthrinse. METHODS: Subjects with mild-to-moderate gingivitis enrolled in a long-term, six-month study. They received a dental prophylaxis and were randomized into one of the three following treatment groups: brushing and rinsing with an essential oil-containing mouthrinse (the BEO group), brushing and flossing (the BF group) and brushing and rinsing with a control rinse (the B group). RESULTS: A total of 326 subjects were evaluated. The BEO and BF had significantly lower (P < .001) mean interproximal Modified Gingival Index, or MGI, scores than did the B group at six months. The BEO group had lower mean interproximal Plaque Index, or PI, scores than the other two groups at both three and six months. The BF group's mean PI score was significantly lower than the B group's mean score at six months only. The magnitude of reductions for the BEO and the BF groups (vs. the B group) in MGI were 11.1 percent and 4.3 percent and for PI were 20.0 percent and 3.4 percent, respectively. CONCLUSIONS: In conjunction with professional care (prophylaxis) and toothbrushing over six months, rinsing twice daily with an essential oil-containing mouthrinse was at least as good as flossing daily in reducing interproximal plaque and gingivitis. Clinical Implications. When weighing recommendations for oral hygiene home care, clinicians should consider that an essential oil-containing mouthrinse may be a useful adjunct in patients with gingival inflammation.

Adjunctive benefit of an essential oil-containing mouthrinse in reducing plaque and gingivitis in patients who brush and floss regularly: a six-month study.

BACKGROUND: Mechanical methods of oral hygiene can be complemented by the use of chemotherapeutic mouthrinses. The authors sought to quantify the additional benefit provided by an essential oil-, or EO-, containing mouthrinse in reducing plaque and gingivitis in patients who brush and floss regularly. METHODS: The authors randomly assigned patients with gingivitis to one of three treatment groups: brushing and rinsing with a control mouthrinse, or BC; brushing, flossing and rinsing with a control mouthrinse, or BFC; or brushing, flossing and rinsing with an EO-containing mouthrinse, or BFEO. Patients received a dental prophylaxis at baseline, and the authors followed them for six months. RESULTS: Of 246 enrolled subjects enrolled in the study, 237 subjects were evaluable at the study's conclusion. After six months, the subjects using the BFEO regimen had statistically and clinically significant lower mean Modified Gingival Index, or MGI, scores and Plaque Index, or PI, scores than did subjects in the BC group (29.9 percent and 56.3 percent, respectively; P < .001). Subjects in the BFC group had statistically significantly lower mean MGI and PI scores than did subjects in the BC group (11.2 percent and 9.3 percent, respectively; P < .001). Subjects in the BFEO group exhibited statistically and clinically significantly lower mean scores for MGI and PI than did subjects in the BFC group (21 percent and 51.9 percent, respectively; P < .001). CONCLUSIONS: This study confirms that for patients with gingivitis who brush and floss routinely, the adjunctive use of an EO-containing mouthrinse provides a clinically significant and meaningful additional benefit in reducing plaque and gingivitis. CLINICAL IMPLICATIONS: An EO-containing mouthrinse is an effective adjunct to regular brushing and flossing. Therefore, the BFEO regimen can be beneficial for patients with gingival inflammation.

Comparative efficacy of an antiseptic mouthrinse and an antiplaque/antigingivitis dentifrice. A six-month clinical trial.

BACKGROUND: The efficacy of an essential oil-containing antiseptic mouthrinse (Listerine Antiseptic, Pfizer) and an antiplaque/antigingivitis dentifrice (Colgate Total, Colgate-Palmolive) has been demonstrated in numerous double-blind clinical studies. This study was conducted to determine their comparative efficacy. METHODS: Three hundred sixteen subjects with mild-to-moderate gingival inflammation and plaque received a dental prophylaxis and began their randomly assigned brushing and rinsing regimen in an unsupervised setting. Subjects brushed for one minute and rinsed with 20 milliliters for 30 seconds twice daily for six months. The three groups were L (control toothpaste/Listerine rinse), T (Colgate Total toothpaste/control rinse) and P (control toothpaste/control rinse). RESULTS: Subjects in the L and T groups demonstrated statistically significantly lower (P < .001) Modified Gingival Index, or MGI; Bleeding Index, or BI; and Plaque Index, or PI, at both three and six months than subjects in the P group. The magnitude of reduction for the L group was 22.9 percent, 70 percent and 56.1 percent, respectively, and for the T group, 20.8 percent, 58 percent and 22.1 percent, respectively. Subjects in the L group were not different from subjects in the T group in regard to visual signs of gingivitis (MGI), but were more effective (P < .001) than subjects in the T group in experiencing reduced BI and PI. No product-related adverse events were reported. CONCLUSION: Although the Listerine Antiseptic and Colgate Total antiplaque/antigingivitis products produced similar, clinically significant reductions in gingivitis (as measured by MGI and BI), Listerine, when used in conjunction with a fluoride dentifrice and usual oral hygiene, provided a greater benefit in reducing plaque. CLINICAL IMPLICATIONS: When considering an antiplaque/antigingivitis product to recommend to patients, clinicians should consider Listerine Antiseptic, in conjunction with usual oral hygiene, if more rigorous plaque control is desired.

Anticalculus efficacy of an antiseptic mouthrinse containing zinc chloride.

BACKGROUND: The authors undertook a controlled clinical study to determine the efficacy of a tartar-control antiseptic mouthrinse in inhibiting the development of supragingival dental calculus. METHODS: After undergoing a dental prophylaxis, 334 subjects with a moderate rate of calculus formation were stratified and randomly assigned to one of three groups: positive control (using a tartar-control toothpaste and an antiseptic rinse), negative control (using a regular toothpaste and an antiseptic mouthrinse) or experimental (using a regular dentifrice and a tartar-control mouthrinse). Subjects brushed and rinsed twice daily, unsupervised, for four months. The researchers assessed subjects' calculus levels using the Volpe-Manhold Index, or VMI, after 16 weeks. RESULTS: Using analysis of covariance, the authors found that both the experimental group (which used a tartar-control rinse containing zinc chloride) and the positive control group (which used a tartar-control dentifrice containing pyrophosphate) demonstrated statistically significantly lower VMI scores (P = .001) than the negative control group (which used a regular dentifrice and an antiseptic rinse). Both anticalculus agents provided a clinically relevant 21 percent reduction in calculus formation. CONCLUSION: An antiseptic mouthrinse containing 0.09 percent zinc chloride as the anticalculus agent provides a clinically relevant reduction in calculus formation in people with a moderate rate of such formation. CLINICAL IMPLICATIONS: A tartar-control mouthrinse with zinc chloride as the tartar-control ingredient is clinically effective in reducing the formation of calculus.

Effect of an essential oil-containing dentifrice on dental plaque microbial composition.

PURPOSE: To determine the effect of 6 months use of an essential oil-containing (EO) antiplaque/antigingivitis fluoride dentifrice on the balance of the oral microbial flora and on the emergence of resistant microbial forms by analysis of dental plaque and saliva. MATERIALS AND METHODS: The dentifrice essential oils consisted of a fixed combination of thymol, menthol, methyl salicylate, and eucalyptol. An identical fluoride-containing dentifrice without the essential oils served as the control. A subgroup of 66 subjects from a clinical trial population of 321 was randomly selected for characterization of their dental plaque microflora. Saliva was also cultured to monitor for the emergence of opportunistic pathogens. Supragingival plaque and saliva were harvested at baseline, after which subjects received a dental prophylaxis. Subjects were sampled again after 3 and 6 months of product use prior to clinical examination. Plaque was characterized for microbial content by phase contrast microscopy for recognizable cellular morphotypes and by cultivation on nonselective and selective culture media. Determination of the minimum inhibitory concentrations of the test agent against selected Actinomyces and Veillonella isolated bacterial species was conducted at all time points to monitor for the potential development of bacterial resistance. RESULTS: There were no statistically significant differences between the microbial flora obtained from subjects using the essential oil-containing dentifrice and the vehicle control for all parameters and time periods except for the percentage of spirochetes at 6 months and for percentage of "other" microorganisms at 3 months. The EO group exhibited a lower adjusted mean for both parameters. Additionally, there was no evidence of the development of bacterial resistance to the antimicrobial activity of the essential oils or the emergence of opportunistic pathogens.

Effect of an antiseptic mouthrinse on salivary microbiota.

PURPOSE: To evaluate the effect of rinsing with original formulation Listerine Antiseptic (LA) on the level of viable salivary bacteria for periods up to 1 hour. MATERIALS AND METHODS: In this double-blind, controlled, cross-over study, unstimulated saliva was collected from 25 subjects, serially diluted, and cultured on selective and non-selective media under aerobic and anaerobic conditions. Streptococci, Veillonella sp., and total aerobic and anaerobic flora were enumerated just prior to and 2, 15, 30, and 60 minutes after rinsing for 30 seconds with either 20 ml of LA or a 5% hydroalcohol control rinse. RESULTS: After the control rinse, total flora cultivated on MM10 agar exhibited a non-significant (P > 0.05) 10%-20% decrease relative to baseline. In contrast, rinsing with LA resulted in a significant (P < 0.05) 60%-65% decrease from baseline in all four microbial groups at 2 minutes; except in the case of Veillonella, the significant decreases were sustained up to 60 minutes. Total Listerine group aerobic, anaerobic and streptococcal counts were significantly lower than placebo (P < 0.05). The significant reduction in salivary bacterial levels seen in the Listerine group for up to 60 minutes suggests that this antiseptic mouthrinse may have use clinically as a pre-procedural rinse to decrease the level of viable microorganisms in aerosols generated during dental procedures.

Long-term effects of Listerine antiseptic on dental plaque and gingivitis.

Chemotherapeutic mouthrinses are useful adjuncts to normal oral hygiene and regular professional care for patients whose mechanical plaque removal is less than optimal. Recognizing this, the American Dental Association Council on Dental Therapeutics published guidelines for evaluating the safety and efficacy of products for the control of gingivitis. Four 6-month or longer controlled clinical trials have shown Listerine to be significantly effective in helping prevent the development of both supragingival plaque and gingivitis. Two microbiology studies have demonstrated that no resistant microorganisms, opportunistic microorganisms, or presumptive oral pathogens emerge as a result of long-term, daily Listerine use. Listerine is the first nonprescription mouthrinse to receive the Council on Dental Therapeutics Seal of Acceptance as safe and effective in helping to prevent and reduce supragingival plaque accumulation and gingivitis when used in a conscientiously applied program of oral hygiene and regular professional care.