The slow force response to stretch: Controversy and contradictions

When exposed to an abrupt stretch, cardiac muscle exhibits biphasic active force enhancement. The initial, instantaneous, force enhancement is well explained by the Frank‐Starling mechanism. However, the cellular mechanisms associated with the second, slower phase remain contentious. This review explores hypotheses regarding this “slow force response” with the intention of clarifying some apparent contradictions in the literature. The review is partitioned into three sections. The first section considers pathways that modify the intracellular calcium handling to address the role of the sarcoplasmic reticulum in the mechanism underlying the slow force response. The second section focuses on extracellular calcium fluxes and explores the identity and contribution of the stretch‐activated, non‐specific, cation channels as well as signalling cascades associated with G‐protein coupled receptors. The final section introduces promising candidates for the mechanosensor(s) responsible for detecting the stretch perturbation.     

Reward‐related distracters and working memory filtering

Reward‐related stimuli capture attention, even when they are task irrelevant. A consequence of attentional prioritization of reward‐related stimuli is that they may also have preferential access to working memory like other forms of emotional information. However, whether reward‐related distracters leak into working memory remains unknown. Here, using a well‐validated change detection task of visual working memory capacity and filtering, we conducted two studies to directly assess the impact of reward‐related distracters on working memory. In both studies, the distracters consisted of colored bars or circles that were previously associated with monetary reward. In Experiment 1, results indicated that previously rewarded distracters did not impact behavioral measures of working memory filtering efficiency compared to neutral distracters. In Experiment 2, using ERPs, we measured the contralateral delay activity (CDA), a psychophysiological index of the number of items retained in working memory, to further assess filtering efficiency. We observed that the CDA for high reward distracters was similar to low reward and neutral distracters. However, in early trials, behavioral measures revealed that previously rewarded stimuli negatively impacted working memory capacity, an effect not observed with neutral distracters. This effect, though, was not found for the CDA in early trials. In summary, our findings across two studies suggest that attentional capture by task‐irrelevant reward may have minimal impact on visual working memory—findings that have important implications for delineating the boundaries of reward‐cognition interactions.     

Lisdexamfetamine: chemistry,pharmacodynamics, pharmacokinetics,and clinical efficacy,safety, and tolerability in the treatment of binge eating disorder

Introduction: The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED).

Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED.

Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.     

The effect of calcium fluoride (CaF(2)) on the chemical solubility of an apatite-mullite glass-ceramic material.

OBJECTIVE: To assess the effect of varying CaF(2) on the chemical solubility of apatite-mullite glass-ceramic (G-C) materials in both the glassy and crystallized states. METHODS: Apatite-mullite forming glasses used in this study are ionomer cement derivatives based on the general formula (4.5SiO(2)-3Al(2)O(3)-1.5P(2)O(5)-3CaO-XCaF(2)). Six glass formulations were produced where X=0.5, 1, 1.5, 2, 2.5 and 3, and called HG1-6, respectively. Batches were melted in covered silliminite crucibles in a furnace overnight at 1050 degrees C, then at 1450 degrees C for 2h, before quenching in water. The six glass compositions were analyzed using differential thermal analysis (DTA), X-ray diffraction (XRD) and X-ray fluorescence spectrometry (XRF). Thirty discs (2mm thick and 12 mm diameter) were produced per glass using the lost wax casting technique. Ten were left as cast and 10 heat treated to either apatite or apatite-mullite. Solubility testing was carried out according to International Standard BS EN ISO 6872 1999 and the mass difference in solubility calculated as mug/cm(2). A lithium disilicate G-C system was used as a control material. RESULTS: All compositions formed glasses and on heat treatment could form apatite and apatite-mullite. The as-cast glass samples were the most soluble followed by the apatite samples. The apatite-mullite G-C was significantly less soluble than the other two phases (p<0.05) for all six compositions. The control material was significantly less soluble than all the HG glass-ceramic compositions for every phase (p<0.05). Decreasing the CaF(2) content (3-0.5 mol%) led to a decrease in solubility, without affecting the ability of the material to form apatite and apatite-mullite phases. SIGNIFICANCE: Increasing the CaF(2) content increases the chemical solubility for the glass, apatite G-C and apatite-mullite G-C phases. The solubility values obtained show that all the compositions, as cast and heat treated would be suitable for use as core ceramics.     

Clinical evaluation of a novel dental whitening lamp and light-catalyzed peroxide gel

OBJECTIVE: This study examined whether an ultraviolet light enhanced the whitening efficacy of a peroxide gel containing a photo-Fenton activator. METHODOLOGY: Fifty subjects were enrolled into the trial at two geographically separate sites. As directed by the randomization keys, teeth of half of the study subjects were concurrently exposed to the whitening lamp, while the gel was on their teeth, for a total light exposure of 45 minutes. The other half of the subjects received no light treatment. At each examination, clinical data were collected on the gingival index, shade score, and self-assessed dentinal hypersensitivity. RESULTS: Changes in tooth shade were significantly better (approximately 26% improvement; p < 0.05) for subjects exposed to the gel and dental whitening lamp (average = 7.7 shade changes) compared to subjects exposed to the gel only (average 6.1 shades) immediately after treatment. No reports of erythema, desquamation, ulceration of soft tissues, gross changes in teeth, gingiva, or restorations were documented. The relative changes in mean sensitivity scores were similar for both groups, with no significant differences between the Light and No-light groups at any interval. CONCLUSION: The whitening effect was improved by approximately 26% when the Zoom2 dental whitening lamp was used. It was demonstrated that the a photo-Fenton activator used with a bleaching light and 20% hydrogen peroxide gel is safe and effective for whitening teeth rapidly.     

In-vivo incorporation of [3H]-proline into rabbit dental pulp collagen.

Collagen metabolism of rabbit dental pulp was studied by following the incorporation of [³H]-proline into pulp collagen. The specific activity of hydroxyproline was studied in various collagen fractions in rabbit incisor and molar teeth of different ages. The specific activity of the collagen fractions was consistently higher in incisor than in molar pulps at all ages, except for the pepsin-resistant fraction. In the molar at most ages, the pepsin-resistant fraction had a specific activity equal to, or greater than, that in the fractions solubilized by either acid or pepsin. The results demonstrate the high metabolic activity of dental pulp, and rapid incorporation of new collagen into the insoluble fibre network.     

Replacing a broken facing on a removable partial denture.

A technique for using a denture tooth to replace a broken facing on an RPD is described. The technique is simple, inexpensive, and easily accomplished in the dental office with minimum time.     

Measuring dental drift and orthodontic tooth movement in response to various initial forces in adult rats

A method for the quantification of orthodontic tooth movement in the rat is presented. Reliability, sensitivity, and validity were assessed and tooth movement kinetics were determined for initial forces of 20, 40, and 60 gm. The appliance consisted of a 9 mm length of closed coil spring suspended between a cleat and bonded to the occlusal surface of the maxillary first molars and the maxillary incisors. Initial tipping forces were placed by suspending known weights from the anterior end of these coils before fixation to the incisors. Tooth movement was quantified from enlarged cephalograms by measuring the position of a reproducible landmark on the molar cleat with respect to either zygomatic amalgam implants or a barbed broach placed submucosally on the palate. All measurements were made along the molar-incisor vector by projecting at 90 degrees to this line. Validity and sensitivity were assessed by quantifying molar distal drift and comparing these results with reports of bone turnover rates adjacent to distally drifting adult rat molars. Reliability was obtained by estimating the error of a single measurement in a longitudinal study of 12 adult male Sprague-Dawley rats (180 to 200 days) receiving both amalgam and broach implants and a cross-sectional study of 72 animals divided equally into six groups to be killed at 1, 3, 5, 7, 10, and 14 days. No orthodontic forces were used in this portion of the study. Implant stability within the craniofacial complex was assessed by measuring bilateral broaches as a function of time with respect to each other. There were no systematic errors between replicate films for either the amalgam or the broach method. The 95% confidence limit for a single determination of molar position was 62 microns using the amalgams and 47 microns for the broach (p less than 0.001). The latter could be reduced to 23 microns when the average of four independent determinations was used. Homologous implants did not differ with respect to each other in the sagittal plane but did in the transverse plane (p less than 0.01), migrating laterally 9 microns/day. Linear regression analysis of molar distal movement over time predicted 7.7 microns/day distal drift (p less than 0.01), which compared favorably with reports of 6.7 microns/day of alveolar bone turnover during this drifting process. Characteristic three-part cumulative tooth movement kinetics were obtained for the 40 and 60 gm initial force groups. No individual time point at 60 gm differed from its counterpart at 40 gm.(ABSTRACT TRUNCATED AT 400 WORDS)