Private Interests and the Start of Fluoride-Supplemented High-Carbohydrate Nutritional Guidelines.

Fluoride has no tangible health benefits other than preventing dental caries and there is a small difference between its minimum effective dose and its minimum toxic dose. Leading global organizations currently recommend fluoride supplementation because they recommend high-carbohydrate diets which can cause dental caries. Low-carbohydrate diets prevent dental caries making such fluoride recommendations largely unnecessary. A dental organization was among the first to initiate the public health recommendations which started fluoride-supplemented high-carbohydrate nutritional guidelines. This start required expert panels at this dental organization to reverse on three key scientific points between 1942 and 1949: (1) that topical fluoride had potential harms, (2) that dental caries was a marker for micronutrient deficiencies, and (3) that low-carbohydrate diets are to be recommended for dental caries prevention. Internal documents show that private interests motivated the events which led these expert panels to engage in pivotal scientific reversals. These private interests biased scientific processes and these reversals occurred largely in an absence of supporting evidence. It is concluded that private interests played a significant role in the start of public health endorsements of fluoride-supplemented high-carbohydrate nutritional guidelines.

SPOP-mutant prostate cancer: Translating fundamental biology into patient care.

Comprehensive cancer genome studies have revealed genetically-defined subtypes of prostate cancer with distinct truncal driver mutations. Because prostate cancer has been largely seen as a rather uniform disease, the clinical significance of this discovery remained largely obscure. However, recent findings imply distinct biological features and therapeutic vulnerabilities linked to specific truncal mutations. Here we review our current understanding of prostate cancers harboring recurrent point mutations in the ubiquitin ligase adaptor protein SPOP and discuss opportunities for future clinical translation. More specifically, activation of the androgen receptor (AR) signaling emerges as the key oncogenic pathway. SPOP-mutant prostate cancer patients respond to AR inhibition in various clinical settings. Molecular insights on how mutant SPOP promotes tumorigenesis may open more specific therapeutic avenues which, in combination with conventional AR-targeting agents, could improve the outcome of patients with SPOP-mutant prostate cancer.

How a Nutritional Deficiency Became Treated with Fluoride.

Ignoring evidence on causes of disease such as smoking can harm public health. This report explores how public health experts started to ignore evidence that pediatric vitamin D deficiencies are associated with dental caries. Historical analyses show that an organization of clinical specialists, the American Dental Association (ADA), initiated this view. The ADA was a world-leading organization and its governing bodies worked through political channels to make fluoride a global standard of care for a disease which at the time was viewed as an indicator of vitamin D deficiencies. The ADA scientific council was enlisted in this endeavor and authorized the statement saying that "claims for vitamin D as a factor in tooth decay are not acceptable". This statement was ghost-written, the opposite of what the ADA scientific council had endorsed for 15 years, and the opposite of what the National Academy of Sciences concluded. Internal ADA documents are informative on the origin of this scientific conundrum; the ADA scientific council had ignored their scientific rules and was assisting ADA governing bodies in conflicts with the medical profession on advertising policies. The evidence presented here suggests that professional organizations of clinical specialists have the power to create standards of care which ignore key evidence and consequently can harm public health.

Bleeding tendency and ascorbic acid requirements: systematic review and meta-analysis of clinical trials.

CONTEXT: The World Health Organization set the recommended daily vitamin C intake, henceforth referred to as ascorbic acid (AA), on the basis of scurvy prevention. Double-blind AA depletion-repletion studies suggest that this recommended AA dose may be too low to prevent microvascular fragility. OBJECTIVES: (1) To conduct a systematic review and meta-analysis of controlled clinical trials on whether AA supplementation leads to a reduced gingival bleeding tendency, a manifestation of microvascular fragility; and (2) to relate AA plasma levels to retinal hemorrhaging, another manifestation of microvascular fragility. DATA SOURCES: Data were reviewed from 15 trials conducted in 6 countries with 1140 predominantly healthy participants with measures of gingival bleeding tendency, and from the National Health and Nutrition Examination Survey (NHANES) III of 8210 US residents with measures of retinal hemorrhaging. RESULTS: In clinical trials, AA supplementation reduced gingival bleeding tendency when estimated baseline AA plasma levels were < 28 µmol/L (standardized mean difference [SMD], -0.83; 95%CI, -1.16 to -0.49; P < 0.002). Supplementation with AA did not unequivocally reduce gingival bleeding tendency when baseline estimated AA plasma levels were >48 µmol/L or unknown (respective standardized mean differences: -0.23, 95%CI, -0.45 to -0.01, P < 0.05; and -0.56; 95%CI: -1.19 to 0.06, P < 0.08). In NHANES III, prevalence of both retinal hemorrhaging and gingival bleeding tendency increased when AA plasma levels were within the range that protects against scurvy (11-28 µmol/L; respective prevalence ratios adjusted for age and sex: 1.47; 95%CI: 1.22-1.77; and 1.64; 95%CI: 1.32-2.03; P < 0.001 for both). CONCLUSION: Consistent evidence from controlled clinical trials indicates that setting human AA requirements based on scurvy prevention leads to AA plasma levels that may be too low to prevent an increased gingival bleeding tendency. Gingival bleeding tendency and retinal hemorrhaging coincide with low AA plasma levels and thus may be reflective of a systemic microvascular pathology that is reversible with an increased daily AA intake.

Covid-19 and vit-d: Disease mortality negatively correlates with sunlight exposure.

The novel COVID-19 disease is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a new virus of the coronavirus family, SARS-CoV-2. Alike with other coronaviruses, some studies show a COVID-19 neurotropism, inducing de-myelination lesions as encountered in Guillain-Barré syndrome. In particular, an Italian report concluded that there is a significant vitamin D deficiency in COVID-19 infected patients. In the current study, we applied a Pearson correlation test to public health as well as weather data, in order to assess the linear relationship between COVID-19 mortality rate and the sunlight exposure. For instance in continental metropolitan France, average annual sunlight hours are significantly (for a p-value of 1.532 × 10-32) correlated to the COVID-19 mortality rate, with a Pearson coefficient of -0.636. This correlation hints at a protective effect of sunlight exposure against COVID-19 mortality. This paper is proposed to foster academic discussion and its hypotheses and conclusions need to be confirmed by further research.

Comparison of high-frequency intensive balneotherapy with low-frequency balneotherapy combined with land-based exercise on postural control in symptomatic knee osteoarthritis: a randomized clinical trial.

Knee osteoarthritis (KOA) can generate postural control impairments which can increase fall risk. Land-based exercise (LBE) and balneotherapy are two modalities currently prescribed, but the impact of the latter on balance control has not been studied. This study aimed to compare two programs of balneotherapy with or without LBE to improve postural control, looking at frequency and duration of treatment. A total of 236 KOA patients (mean age = 64 years) were included in this prospective and randomized study: 122 patients went through 3 weeks of standardized continuous balneotherapy (high frequency/short duration) program (Gr1) and 114 went through 3 weeks of discontinuous (low frequency) balneotherapy program followed by 3 weeks of LBE (Gr2). The total number of treatment sessions was the same for both groups. Posturography was carried out before balneotherapy (W0) and at 3 (W3), 6 (W6), and 12 (W12) weeks after the beginning of treatment. Postural control increased in Gr1 from W0 to W3 and from W0 to W12 and in Gr2 from W0 to W6 and from W3 to W6. The improvement was greater in Gr1 from W0 to W3 and from W6 to W12 and in Gr2 from W3 to W6. High-frequency intensive balneotherapy improved posture control at 3 weeks, while low-frequency balneotherapy did not. This improvement persisted over a 12-week assessment period at the same level. LBE generated an improvement that did not persist over time. Sustained improvement of postural control requires high-frequency repetition of consecutive balneotherapy sessions.

Oil removal and effects of spilled oil on active microbial communities in close to salt-saturation brines.

Abiotic and biotic processes associated with the degradation of a light petroleum in brines close to the salt-saturation (~31 %) and the effect of labile organic matter (LOM) supply (casaminoacids/citrate; 0.2 and 0.1 % w/v, respectively) were followed during an incubation of 30 days. After 4-week incubation at 40 °C under light/dark cycles, a 24 % of abiotic degradation was observed in untreated brines. The stimulation of native brines community with LOM addition allowed an additional 12.8 % oil attenuation due to biodegradation processes. Successional changes in the active microbial community structure due to the oil contamination (16S rRNA DGGE approach) showed the selection of one phylotype affiliated to Salinibacter and the disappearance of Haloquadratum walsbyi in untreated brines. In LOM-amended microcosms, phylotypes related to Salinibacter, Haloarcula, Haloterrigena and Halorhabdus were selected. An effect of hydrocarbon contamination was only observed in the bacterial community with the inhibition of two dominant proteobacterial phylotypes. This study further confirms that short-term and moderate oil biodegradation is possible in LOM-stimulated brines. Biodegradation should be much more reduced under in situ conditions. Self-cleaning capacities of close to saturation hypersaline lakes appears, therefore very limited compared to non-extreme haline environments.

The clinical and immunological significance of GAD-specific autoantibody and T-cell responses in type 1 diabetes.

Antigen-specific interventions are desirable approaches in Type 1 Diabetes (T1D) as they can alter islet-specific autoimmunity without systemic side effects. Glutamic acid decarboxylase of 65 kDa (GAD65) is a major autoantigen in type 1 diabetes (T1D) and GAD-specific autoimmunity is a common feature of T1D in humans but also in mouse models of the disease. In humans, administration of the GAD65 protein in an alum formulation has been shown to reduce C-peptide decline in recently diagnosed patients, however, these observations were not confirmed in subsequent phase II/III clinical trials. As GAD-based immune interventions in different formulations have successfully been employed to prevent the establishment of T1D in mouse models of T1D, we sought to analyze the efficacy of GAD-alum treatment and the effects on the GAD-specific immune response in two different mouse models of T1D. Consistent with the latest clinical trials, mice treated with GAD-alum were not protected from diabetes, although GAD-alum induced a GAD-specific Th2-deviated immune response in transgenic rat insulin promoter-glycoprotein (RIP-GP) mice. These observations underline the importance of a thorough, preclinical evaluation of potential drugs before the initiation of clinical trials.

Vitamin D and dental caries in controlled clinical trials: systematic review and meta-analysis.

Vitamin D has been used to prevent and treat dental caries. The objective of this study was to conduct a systematic review of controlled clinical trials (CCTs) assessing the impact of vitamin D on dental caries prevention. Random-effects and meta-regression models were used to evaluate overall and subgroup-specific relative-rate estimates. Twenty-four CCTs encompassing 2,827 children met the inclusion criteria. Twenty-two of the 24 CCTs predated modern clinical trial design, some of which nonetheless reported characteristics such as pseudo-randomization (n = 2), blinding (n = 4), or use of placebos (n = 8). The relative-rate estimates of the 24 CCTs exhibited significant heterogeneity (P < 0.0001), and there was evidence of significant publication bias (P < 0.001). The pooled relative-rate estimate of supplemental vitamin D was 0.53 (95% CI, 0.43-0.65). No robust differences were identified between the caries-preventive effects of vitamin D(2) , vitamin D(3) , and ultraviolet radiation (Prob > F = 0.22). The analysis of CCT data identified vitamin D as a promising caries-preventive agent, leading to a low-certainty conclusion that vitamin D may reduce the incidence of caries.

Cognitive processing and motor skill learning in motor-handicapped teenagers: effects of learning method.

This study aimed to assess the efficiency of a motor skill learning method intended to promote learning course personalization through an increase in cognitive processing deployment in motor-handicapped persons. Thirty-three secondary school students volunteered to participate in an archery motor skill learning session, 11 motor-handicapped (MH(1)) and 11 able-bodied (AB) teenagers following a standard learning method, and 11 motor-handicapped teenagers following a cognitive enriched learning method (MH(2)) based on the use of an individually written and illustrated document. The results showed that MH(1) displayed lower performances than AB, both in terms of the mental representations of the movements expected and performed and of efficiency of the movement. On the other hand, MH(2) performances were higher than MH(1) for all these parameters, and similar to those of AB at the end of the learning session. Personalization of the learning course allowed optimization of the learning potential in motor-handicapped teenagers to resolve the difficulties inherent to their handicap.

Multisensory interactions within human primary cortices revealed by BOLD dynamics.

Whether signals from different sensory modalities converge and interact within primary cortices in humans is unresolved, despite emerging evidence in animals. This is partially because of debates concerning the appropriate analyses of functional magnetic resonance imaging (fMRI) data in response to multisensory phenomena. Using event-related fMRI, we observed that simple auditory stimuli (noise bursts) activated primary visual cortices and that simple visual stimuli (checkerboards) activated primary auditory cortices, indicative of multisensory convergence. Moreover, analyses of blood oxygen level-dependent response dynamics revealed facilitation of hemodynamic response peak latencies and slopes for multisensory auditory-visual stimuli versus either unisensory condition, indicative of multisensory interactions within primary sensory cortices. Neural processing at the lowest cortical levels can be modulated by interactions between the senses. Temporal information in fMRI data can reveal these modulations and overcome analytic and interpretational challenges of more traditional procedures. In addition to providing an essential translational link with animal models, these results suggest that longstanding notions of cortical organization need to be revised to include multisensory interactions as an inherent component of functional brain organization.

Effect of daily versus twice weekly long-term iron supplementation on iron absorption and status in iron-deficient women: a stable isotope study.

OBJECTIVES: This work aims at studying the effect of daily versus twice weekly long-term Fe supplementation on Fe absorption and status in Fe-deficient women. DESIGN AND METHODS: The study design is a randomized controlled open study carried out in the Internal Medicine Department, CHU de Clermont-Ferrand, France. Twenty-four young women participated in this study and were randomized into two groups: Group 1 received 50 mg Fe daily, and group 2 received 50 mg Fe twice weekly for 3 months. On day 10 (D10) and on day 90 (D90) of Fe supplementation, blood samples were obtained, and women received orally about 5 mg of 57Fe, and blood was sampled at different times over 24 h. The 57Fe absorption was evaluated by calculating the areas under the curves (AUC). Fe and oxidative stress status were also assessed. RESULTS: 57Fe absorption was similar in both groups on D10 but was greatly decreased in Group 1 and remained high in Group 2 on D90. Fe status was more improved in Group 1 than in Group 2. Oxidative stress status remained statistically unchanged. CONCLUSIONS: Our study shows that daily Fe supplementation is able to correct an Fe deficiency much more than twice weekly Fe supplementation in young women.

Influence of regular proprioceptive and bioenergetic physical activities on balance control in elderly women.

BACKGROUND: Balance disorders increase considerably with age due to a decrease in posture regulation quality, and are accompanied by a higher risk of falling. Conversely, physical activities have been shown to improve the quality of postural control in elderly individuals and decrease the number of falls. The aim of this study was to evaluate the impact of two types of exercise on the visual afferent and on the different parameters of static balance regulation. METHODS: Static postural control was evaluated in 44 healthy women aged over 60 years. Among them, 15 regularly practiced proprioceptive physical activities (Group I), 12 regularly practiced bioenergetic physical activities (Group II), and 18 controls walked on a regular basis (Group III). RESULTS: Group I participants displayed lower sway path and area values, whereas Group III participants displayed the highest, both in eyes-open and eyes-closed conditions. Group II participants displayed intermediate values, close to those of Group I in the eyes-open condition and those of Group III in the eyes-closed condition. Visual afferent contribution was more pronounced for Group II and III participants than for Group I participants. CONCLUSIONS: Proprioceptive exercise appears to have the best impact on balance regulation and precision. Besides, even if bioenergetic activity improves postural control in simple postural tasks, more difficult postural tasks show that this type of activity does not develop a neurosensorial proprioceptive input threshold as well, probably on account of the higher contribution of visual afferent.

[Causal research epistemology and epidemiology of complex systems]. / Epistémologie de la recherche causale et épidémiologie des systèmes complexes.

Epidemiology now meets with the crisis of its most fundamental paradigm. The biomedical paradigm of the search for individual-level disease risk factors opposes the public-health paradigm of the search for contextual-level disease risk factors. The public-health paradigm exacerbates the causal research of disease risk factors in that it must now count on a hierarchy of scales of observation. This underlines the need to take into account nonlinear relationships among scales and variables as well as the dynamic aspect of the phenomena. It is concluded that the complex conceptualization required by the public-health paradigm will entail epidemiologists to develop new theories and to familiarize themselves with approaches more akin to those used in the study of complex systems.