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The aim of this study is to evaluate the efficacy of taking a daily supplement based on active compounds (AUDISTIM ® Day Night: A D/N) in alleviating tinnitus-related disability, as suggested by previous real-life studies. This double-blind randomized placebo-controlled study was conducted in adults with mild to severe tinnitus receiving a 3-month supplementation with A D/N (magnesium, vitamins, phytochemicals) or placebo (excipients without active ingredients). Tinnitus-related handicap (THI), psychological stress (MSP-9), and sleep quality (PSQI) were assessed at baseline and during intervention, perceived impression of tinnitus improvement at the end of the follow-up. The full set analysis included 114 patients (59 A D/N, 55 placebo) aged 53.8 ± 11.4 years, 58% women, with fluctuating (45%) or permanent (55%) tinnitus from 9.3 ± 9.4 years. A D/N supplementation led to greater changes in THI (-13.2 ± 16.0 vs. -6.2 ± 14.4, p = 0.0158,Cohen's d =0.44) at 3 months (primary outcome), especially with continuous tinnitus (-15.0 ± 16.3 vs. -4.6 ± 12.8, p = 0.0065), and, to a lesser extent, at 1 month (-9.8 ± 13.1 for A vs. -4.3 ± 12.1, p = 0.0213). PSQI significantly improved over time in both groups, but MSP-9 only with A D/N. In lines with previous observational studies, both clinical (THI score > 7 pts) and statistical (vs. placebo) improvement, more pronounced in permanent tinnitus, demonstrate the effectiveness of the combination of active compounds and support its use in the management of mild to severe tinnitus., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups treated with RE at two different doses determined by its content of rhein (supplementation of 12.5 mg and 25 mg per day) vs. placebo (maltodextrin) for 30 days. We demonstrated that daily oral supplementation of RE for 30 days was safe even at the higher dose. Stool frequency and consistency, and perceived change in transit problem, transit speed and difficulty in evacuating, investigated by validated questionnaires, were improved in both groups of RE-treated volunteers compared to placebo. Higher abundance of Lachnospiraceae (mainly Roseburia and Agathobacter ) only occurred after RE treatment when present at low levels at baseline, whereas an opposite shift in short-chain fatty acid (SCFA) levels was observed in both RE-treated groups (increase) and placebo (decrease). Fecal Lachnospiraceae and SCFA were positively correlated with stool consistency. This study demonstrates that RE supplementation promotes butyrate-producing bacteria and SCFA, an effect that could contribute to relieving chronic constipation in middle-aged persons.

Dietary fibres are important in the human diet with multiple health benefits. This study aimed to determine the gastrointestinal tolerance of short-chain fructo-oligosaccharides (scFOS), well-known prebiotic fibres, at doses up to 40 g/d. An observational, connected, dose-ranging trial was conducted in 116 healthy volunteers. During the first week, the participants were instructed to consume their usual diet. During the second week, half of the subjects consumed 15 g scFOS per day, and the other half consumed 20 g scFOS per day. For the third week, the scFOS dose was doubled for all subjects. Gastrointestinal symptom severity was reported daily, as well as stool consistency and frequency. The results show that scFOS are well tolerated up to 40 g/d; all reported symptoms remained very mild from a clinical perspective. Stool consistency stayed normal, between 3 and 5 on the Bristol stool scale, confirming that no diarrhoea appeared after scFOS intake. Stool frequency also remained within the normal range. In conclusion, scFOS intake is well tolerated up to 40 g/d in healthy subjects. Thanks to their short chains and unique composition, scFOS prebiotic fibres are much better tolerated than other types of inulin-type fructans with longer chains. The digestive tolerance of fibres should be considered when added to foods and beverages.

The implementation of REGULATION (EC) No 1924/2006 has led to the formation of a list of health claims that can be used in food supplements (EU 432/2012). However, such supplements are often composed of plant preparations with claims omitted from this list. The peculiarity of plants is related to their long history of use, that could allow claims based on traditionally recognized health effects. In addition, the scientific literature has been enriched over the years through clinical studies that have assessed the bioavailability and efficacy of bioactive components, and investigated their mechanisms of action. Based on existing recognized models which aim to classify research according to the level of scientific evidence, Synadiet developed a three-grade model (A, B or C) for assessing plants health claims. In this paper, the applicability of the model is illustrated through an example for which a Grade B health claim attesting the possible contribution of red clover isoflavones to the improvement of blood lipid levels in postmenopausal women has been attributed. The model appears able to be easily extrapolated to claims pertaining to other plants. If adopted by consensus at European level, this model could initiate the implementation of a positive list of health claims on plant preparations.

Several studies suggest that microbial alterations (dysbiosis) are intimately linked to chronic inflammation occurring upon aging. The aim of this study was to investigate the potential interest of a synbiotic approach (co-administration of a probiotic bacteria and a prebiotic dietary fibre) to improve gastrointestinal wellness and inflammatory markers in middle-aged people. Middle-aged subjects were randomized to take synbiotic (Bifidobacterium animalis lactis and fructo-oligosaccharides (FOS)) or placebo for 30 days. Stool frequency and consistency were improved in both placebo and synbiotic-treated volunteers while the synbiotic treatment significantly decreased the number of days with abdominal discomfort. Synbiotic treatment had no impact on mood dimensions, quality of life scores or the overall composition of the gut microbiota (16S rRNA gene sequencing of DNA extracted from stool). Importantly, plasma proinflammatory cytokines (interleukin (IL)-6, IL-8, IL-17a and interferon-gamma (IFNγ)) were significantly lower after 30 days of synbiotic supplementation. This effect appears to be independent of the gut barrier function. This study demonstrates that a combination of B. animalis lactis and the well-known prebiotic FOS could be a promising synbiotic strategy to decrease inflammatory status with improvement of gut disorders in middle-aged people.

Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe). We infer that the same physics shapes both AGB winds and PNe; additionally, the morphology and AGB mass-loss rate are correlated. These characteristics can be explained by binary interaction. We propose an evolutionary scenario for AGB morphologies that is consistent with observed phenomena in AGB stars and PNe., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In the European Regulation 1924/2006 and especially its first recital, the evaluation of health claims (HC) by European Food Safety Agency (EFSA) was introduced so as "to ensure a high level of consumer protection, [and] give the consumer the necessary information to make choices in full knowledge of the facts…". Now, with 10 years of hindsight since the Regulation was adopted, it can be asked whether EFSA HC process of evaluation that led to a marginal number of accepted claims is consistent with this objective, not just for protecting consumers but for allowing them to decide freely and make informed choices. The aim of this paper was to demonstrate that the inclusion of a ranking of the weight of evidence in the assessment of EFSA's scientific substantiation of HC would allow consumers to benefit from the very high standard of scientific evaluation performed by EFSA. The definition of standards of proof is a generalized practice and rests on the principle that evaluations of health practices should be understood in terms of descriptions ranging from formal proof from high-power double-blind placebo-controlled studies to rankings based on the consensus views of experts or even agreement among professionals. Grading of weight of evidence - not of scientific expertise - is pervasive in all the recommendations or consensus meetings of health authorities or learned societies. This approach would stimulate research and product innovation as industrials would see a positive return on investment.

Aims: We aim to investigate the physical and chemical properties of the molecular envelope of the oxygen-rich AGB star IK Tau., Methods: We carried out a millimeter wavelength line survey between ~79 and 356 GHz with the IRAM-30 m telescope. We analysed the molecular lines detected in IK Tau using the population diagram technique to derive rotational temperatures and column densities. We conducted a radiative transfer analysis of the SO 2 lines, which also helped us to verify the validity of the approximated method of the population diagram for the rest of the molecules., Results: For the first time in this source we detected rotational lines in the ground vibrational state of HCO + , NS, NO, and H 2 CO, as well as several isotopologues of molecules previously identified, namely, C 18 O, Si 17 O, Si 18 O, 29 SiS, 30 SiS, Si 34 S, H 13 CN, 13 CS, C 34 S, H 2 34 S, 34 SO, and 34 SO 2 . We also detected several rotational lines in vibrationally excited states of SiS and SiO isotopologues, as well as rotational lines of H 2 O in the vibrationally excited state ν 2 =2. We have also increased the number of rotational lines detected of molecules that were previously identified toward IK Tau, including vibrationally excited states, enabling a detailed study of the molecular abundances and excitation temperatures. In particular, we highlight the detection of NS and H 2 CO with fractional abundances of f (NS)~10 -8 and f (H 2 CO)~[10 -7 -10 -8 ]. Most of the molecules display rotational temperatures between 15 and 40 K. NaCl and SiS isotopologues display rotational temperatures higher than the average (~65 K). In the case of SO 2 a warm component with T rot ~290 K is also detected., Conclusions: With a total of ~350 lines detected of 34 different molecular species (including different isotopologues), IK Tau displays a rich chemistry for an oxygen-rich circumstellar envelope. The detection of carbon bearing molecules like H 2 CO, as well as the discrepancies found between our derived abundances and the predictions from chemical models for some molecules, highlight the need for a revision of standard chemical models. We were able to identify at least two different emission components in terms of rotational temperatures. The warm component, which is mainly traced out by SO 2 , is probably arising from the inner regions of the envelope (at ≲8 R ∗ ) where SO 2 has a fractional abundance of f (SO 2 )~10 -6 . This result should be considered for future investigation of the main formation channels of this, and other, parent species in the inner winds of O-rich AGB stars, which at present are not well reproduced by current chemistry models.

Knowledge about the outermost portions of galaxies is limited owing to the small amount of light coming from them. It is known that in many cases atomic hydrogen (H I) extends well beyond the optical radius. In the centres of galaxies, however, molecular hydrogen (H2) usually dominates by a large factor, raising the question of whether H2 is also abundant in the outer regions. Here we report the detection of emission from carbon monoxide (CO), the most abundant tracer of H2, beyond the optical radius of the nearby galaxy NGC 4414. The host molecular clouds probably formed in the regions of relatively high H i column density and in the absence of spiral density waves. The relative strength of the lines from the two lowest rotational levels indicates that both the temperature and density of the H2 are quite low compared to conditions closer to the centre. The inferred surface density of the molecular material continues the monotonic decrease from the inner regions. We conclude that although molecular clouds can form in the outer region of this galaxy, there is little mass associated with them.

We present Infrared Space Observatory long-wavelength spectrometer observations of the proto-planetary nebula CRL 618, a star evolving very fast toward the planetary nebula stage. In addition to the lines of 12CO, 13CO, HCN, and HNC, we report on the detection of H2O and OH emission together with the fine-structure lines of [O i] at 63 and 145 µm. The abundance of the latter three species relative to 12CO are 4x10-2, 8x10-4, and 4.5 (approximate value) in the regions where they are produced. We suggest that O-bearing species other than CO are produced in the innermost region of the circumstellar envelope. The UV photons from the central star photodissociate most of the molecular species produced in the asymptotic giant branch (AGB) phase and allow a chemistry dominated by standard ion-neutral reactions. They not only allow these reactions for the formation of O-bearing species but also modify the abundances of C-rich molecules like HCN and HNC for which we found an abundance ratio of approximately 1, which is much lower than in AGB stars. The molecular abundances in the different regions of the circumstellar envelope have been derived from radiative transfer models and from our knowledge of its physical structure.

In a large study of chromosome rearrangements occurring in human lymphocytes from normal subjects, inv (14)(q12qter) or (q11.2q32.3) is found to be the most frequent, affecting 0.15% of mitoses. The same inversion is observed in the lymphocytes of the chimpanzee, indicating the ancestry of this inversion. It is not induced by ionizing radiations, and its frequency may be increased in Fanconi anemia, but not in ataxia telangiectasia. It may represent one of the steps of the process of leukemogenesis.