Does Amelogenin Nanosphere Assembly Proceed through Intermediary-sized Structures?

Previous studies have demonstrated the presence of supra-molecular assemblages of amelogenin protein (“Nanospheres”) to be present in both in vivo and in vitro situations. We have proposed that these nanosphere structures are functionally involved in the organization and control of initial enamel biomineralization at the ultrastructural level. Based on the observed nanosphere hydrodynamic radii (18–20nm diameter) computation suggests these structures to be compounded of some 100 amelogenin monomers, raising the question as to the possible molecular mechanism for the assembly of such structures? Based on recent dynamic light scattering experiments using the recombinant murine amelogenin M179, and employing a newer size distribution algorithm we now report that the size distribution data for M179 are better described by a bimodal distribution model, than the monomodal distribution as previously described. We suggest that amelogenin nanosphere assembly proceeds through intermediate structures (perhaps represented in vivo by “stippled material”) of some 4–5 nm hydrodynamic radius, and computed to comprise 4–6 amelogenin monomers. We suggest that such intermediary, sub-unit structures, assemble through inter-molecular hydrophobic interactions to generate the 20nm diameter nanospheres observed by TEM in the secretory stage enamel matrix.     

Does problem-solving treatment work through resolving problems?

BACKGROUND: A randomized controlled trial of problem-solving treatment, antidepressant medication and the combination of the two treatments found no difference in treatment efficacy for major depressive disorders in primary care. In addition to treatment outcome, the trial sought to determine possible mechanisms of action of the problem-solving intervention. METHOD: Two potential mechanisms of action of problem-solving treatment were evaluated by comparison with drug treatment. First, did problem-solving treatment work by achieving problem resolution and secondly, did problem-solving treatment work by increasing the patients' sense of mastery and self-control? RESULTS: Problem-solving treatment did not achieve a greater resolution in the patients' perception of their problem severity by comparison with drug treatment, neither did problem-solving treatment result in a greater sense of mastery or self-control. CONCLUSIONS: The results from this study did not support the hypotheses that for patients with major depression, by comparison with antidepressant medication: problem-solving treatment would result in better problem resolution; or that problem-solving treatment would increase the patients' sense of mastery and self-control.     

Does amelogenin nanosphere assembly proceed through intermediary-sized structures?

We have proposed that these nanosphere structures are functionally involved in the organization and control of initial enamel biomineralization at the ultrastructural level. Based on the observed nanosphere hydrodynamic radii (18-20 nm diameter) computation suggests these structures to be compounded of some 100 amelogenin monomers, raising the question as to the possible molecular mechanism for the assembly of such structures? Based on recent dynamic light scattering experiments using the recombinant murine amelogenin M179, and employing a newer size distribution algorithm we now report that the size distribution data for M179 are better described by a bimodal distribution model, than the monomodal distribution as previously described. We suggest that amelogenin nanosphere assembly proceeds through intermediate structures (perhaps represented in vivo by "stippled material") of some 4-5 nm hydrodynamic radius, and computed to comprise 4-6 amelogenin monomers. We suggest that such intermediary, sub-unit structures, assemble through inter-molecular hydrophobic interactions to generate the 20 nm diameter nanospheres observed by TEM in the secretory stage enamel matrix.     

Does exercise induce hypoalgesia through conditioned pain modulation?

Pain sensitivity decreases with exercise. The mechanisms that underlie this exercise‐induced hypoalgesia (EIH) are unclear. Our purpose was to investigate conditioned pain modulation (CPM) as a potential mechanism of EIH. Sixteen women completed pain testing during three sessions: painful exercise, nonpainful exercise, and quiet rest. Intensity and unpleasantness ratings to noxious heat stimuli were assessed at baseline and during and following each session. Results showed that pain sensitivity decreased significantly during both exercise sessions (p < .05), but not during quiet rest. Effect size calculations showed that the size of the hypoalgesic response was greater following painful exercise than nonpainful exercise. Our results suggest that exercise‐induced muscle pain may contribute to the magnitude of EIH. However, as pain sensitivity also decreased following nonpainful exercise, CPM is not likely the primary mechanism of EIH.     

Does unconventional medicine work through conventional modes of action?

It is often maintained that although conventional medicine works by means of pharmacotherapy with predominantly proved effects, unconventional therapies are more or less spiritual therapeutic approaches without a scientific basis. We hypothesize that both conventional and unconventional medicine might be effective because of similar modes of action. Certainly, this does not imply that every unconventional method has any effect. Conventional and effective unconventional medicine might both work by means of pharmacology (eg, substances in medical herbs), including pharmacologic interactions between the 2 treatment options (eg, herbs and drugs with coagulation effects). Both conventional and unconventional treatments involve a considerable risk of side effects, which are sometimes even severe. In general, the pattern of side effects of alternative treatments is similar to that observed with the use of conventional medicine. The placebo effect and suggestive aspects are also apparent in both treatments. Furthermore, mind-body medicine (eg, use of relaxation techniques) might be explained by pathophysiologic mechanisms. Overall, many aspects seem to contribute to the mosaic of joint modes of action involved in both conventional and unconventional medicine. This might demystify the aura of some of the complementary and alternative approaches and might help to bring both conventional and unconventional approaches together on a scientific basis.     

Does yawning increase arousal through mechanical stimulation of the carotid body?

Yawning is a stereotyped event that occurs in humans and animals from fish to mammals, but neither its mechanisms nor its functions are entirely known. Its widespread nature suggests that it has important physiological functions. It is associated with stretching of muscles in a large area, but the function of this stretching is understood far from completely. It has been proposed that yawning increases arousal and that it is an arousal defense reflex, whose aim is to reverse brain hypoxia. Whilst yawning has been speculated to have an important role in reversing hypoxia, there is a structure in the neck that is known to be intimately involved in the regulation of oxygen homeostasis, namely the carotid body. It senses acute changes in oxygen levels. In spite of this, a connection has never been proposed either between the carotid body and arousal, or between yawning and the carotid body. We propose that yawning stimulates mechanically the carotid body (and possibly other structures in the neck). We further propose that this stimulation gives rise to increased arousal, alertness and wakefulness and that one important physiological function of yawning is increase of arousal through this stimulation. We also propose that mechanical effects on the shunt system of the carotid body may be involved in this stimulation. Our hypothesis is supported by several facts. For example, yawning causes movements and compressions that may affect the carotid body that is situated strategically at the bifurcation of the common carotid artery. Thus, yawning may stimulate the carotid body. The carotid body is highly vascular and compressions may affect its shunt system and blood flow and for example give rise to release of hormones or other substances. Also several facts related to situations where people yawn or do not yawn support our hypothesis and are discussed. Further support comes from facts related to somnogenic substances, hormones and transmitters, and from facts related to the interconnection of homeostatic mechanisms, sleep, arousal and ventilation.     

Does insomnia kill?

STUDY OBJECTIVES: We investigated the prevalence and hazard ratios for insomnia complaints in a large cohort of middle-aged men and women. DESIGN: The Atherosclerosis Risk in Communities Study is a prospective study of cardiovascular disease. Using multivariate regression analysis, we predicted the likelihood of endorsing the insomnia complaints by age, sex, alcohol intake, smoking, diabetes, heart disease, menopausal status, use of hypnotics, hypertension, depressive symptoms, education level, body mass index, respiratory symptoms, and pulmonary function status. We predicted the hazard ratios (HR) of death at 6.3 +/- 1.1 year by endorsement of insomnia complaints and by hypnotic use controlling for covariates. SETTING: North American communities. PARTICIPANTS: 13563 participants aged 45 to 69 years at baseline INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The prevalence of insomnia complaints in this cohort was 23%. Predictors of insomnia complaints were female sex (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.45-0.70 for men), annual family income below 50,000 dollars (OR 1.23, CI 1.09-1.40), age 40 to 49 years (OR 1.29, CI 1.11-1.50), depressive symptoms (OR 5.05, CI 4.60-5.55), heart disease (OR 1.89, CI 1.67-2.14), severe airflow obstruction (OR 1.61, CI 1.17-2.22), pulmonary symptoms (OR 1.71, CI 1.5-1.95), and restrictive lung disease (OR 1.27, CI 1.10-1.47). After controlling for covariates, insomnia complaints were not associated with an increased risk for death (OR 1.01, CI 0.85-1.21), nor was the use of hypnotics (OR 1.38, CI 0.90-2.13). CONCLUSIONS: In this cohort, the prevalence of insomnia complaints was 23%. After controlling for confounders, neither insomnia complaints nor hypnotic use predicted increased mortality over 6.3 years.     

Does thiamin dehydrogenase exist?

Summary The results of experiments on the study of the reaction between thiamine and certain forms of adrenalin leading to formation of thiochromine are presented. Contrary to the views of A. A. Titaev this reaction is not catalysed by a specific enzyme thiamindehydrase. The quantity of thiochrome formed in control tests is always greater than that in the test with the extracts or homogenates of various tissues. The tissue extracts and homogenates do not activate, but on the contrary depress the reaction. This depression is found to be considerably decreased after preliminary thermal denaturation of the preparations.Presented by Active Member of the AMN SSSR S. E. Severin     

Does allergen avoidance work?

Allergic rhinitis affects a large portion of the population. Patients are frequently sensitized to indoor allergens. The most important contributors are house dust mites, pets, and fungi. In very controlled environments where allergen exposure is significantly reduced, individuals have been shown to have clinical improvement in allergic rhinitis and/or asthma symptoms. Achieving sufficient exposure reduction in the home has proven difficult. Nonetheless, evidence exists that demonstrates exposure avoidance can be useful as an adjunct to other therapies, such as pharmacotherapy and immunotherapy, for the treatment of allergic rhinitis.     

Does osteopenia warrant treatment?

The progressive loss of bone mass that leads to osteoporosis in postmenopausal women is known to result in substantial morbidity and mortality. Underdiagnosed and undertreated, osteoporosis jeopardizes the health of an estimated 8 million American women 50 years of age or older who are at high risk for hip, vertebral, and other fractures. Because osteopenia is generally a subclinical condition that results in a lower fracture rate than osteoporosis, its potential impact is more difficult to recognize, although it is nearly three times more prevalent than osteoporosis. The question arises as to whether osteopenia should be diagnosed and treated before it transitions into osteoporosis. Because the number of postmenopausal women is projected to increase substantially in the near future and the number of postmenopausal women who will or who have discontinued their use of hormone therapy has increased sharply, the consequences of failing to identify and treat women at increased fracture risk are considerable. Moreover, the rate of bone loss in the first year after discontinuation of hormone therapy is especially rapid and similar to the rate that occurs early after menopause. Accordingly, fracture risk is substantially increased at this time in relation to the magnitude of bone loss. The goal of nonpharmacologic and pharmacologic therapy is to prevent the first fracture in any woman at risk for fracture. Initiation of antiresorptive therapy known to provide rapid efficacy can be particularly important in achieving the treatment goal in appropriate osteopenic women.     

Does limb proprioception drift?

Summary The hypothesis that proprioceptively perceived limb position drifts during visual occlusion was re-examined by combining some of the protocols used in previous experiments. Sixteen adult subjects made judgements of static limb position during visual occlusion lasting up to 2 min. In addition, the effect of brief 250 ms glimpses of the limb, occasional proprioceptive stimulation and directed attention were examined. Despite, conflicting evidence from earlier experiments, there was clear evidence of a drift in perceived limb position, towards the body, during visual occlusion. This drift was halted if brief glimpses of the limb were provided, or minor re-positioning (without vision) was allowed. In neither case, however, did the supplementary cues reset limb position to its originally perceived position. Drift was amplified when subjects attempted to attend to limb position rather than perform a secondary tracking task. The results are not easily accounted for if drift is considered purely as an effect of peripheral sensor adaptation. A notion of central-drift between visual and proprioceptive maps is suggested as an alternative hypothesis.