Quality of life: psychological symptoms-effects of a 2-month healthy diet and nutraceutical intervention; a randomized, open-label intervention trial (RISTOMED)

Depression symptoms and lower health-related quality of life (HRQoL) are associated with inflammation. This multicenter dietary intervention was shown to reduce inflammation in older people. This was the main outcome. Here, we describe the effects on HRQoL, anxiety, and depressive symptoms according to inflammation status. Overall, 125 healthy older subjects (65-80 year) were recruited (Italy, France, and Germany) and randomized into four arms (A, Healthy diet (HD); B, HD plus De Simone Formulation probiotic blend; C, HD plus AISA d-Limonene; D, HD plus Argan oil). The HD was weight maintaining, rich in antioxidant vitamins, polyphenols, polyunsaturated fatty acids (n6: n3 ratio = 3:1), and fiber. Data on inflammatory parameters, mental (MCS) and physical (PCS) component summaries of HRQoL (SF-36), anxiety symptoms (STAI state), and depressive symptoms (CES-D) were collected before and after 56 days of intervention. Body fat mass proportion (BFM) was considered a co-variable. A decrease of CES-D score was seen in the four arms (A: -40.0%, p = 0.001; B: -32.5%, p = 0.023; C: -42.8%, p = 0.004; and D: -33.3%, p = 0.21). Within the subgroups of subjects with medium/high inflammation a similar decrease in CES-D score occurred in all groups (A: -44.8%, p = 0.021; B, -46.7%, p = 0.024; C, -52.2%, p = 0.039; D, -43.8%, p = 0.037). The effect of interventions on CES-D was not related to baseline inflammation. MCS-HRQoL improved in A and C. There was no change in anxiety or PCS-HRQoL. In this trial with no control group, a decrease in depressive symptoms in healthy older volunteers was observed after a 2-month healthy diet intervention, independently of inflammation but with possible limitations due to participation

MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression

Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT) cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i) mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB); ii) the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT) or γδ T cells, and is characterized by production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2, but not IL-17A; iii) high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1) participation, is required for MAIT cell activation; iv) MAIT cell responses to SEB can occur in a T cell receptor (TCR) Vβ-specific manner but are largely contributed by IL-12 and IL-18; v) as MAIT cells are primed by SAgs, they also begin to develop a molecular signature consistent with exhaustion and failure to participate in antimicrobial defense. Accordingly, they upregulate lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin-3 (TIM-3), and/or programmed cell death-1 (PD-1), and acquire an anergic phenotype that interferes with their cognate function against Klebsiella pneumoniae and Escherichia coli; vi) MAIT cell hyperactivation and anergy co-utilize a signaling pathway that is governed by p38 and MEK1/2. Collectively, our findings demonstrate a pathogenic, rather than protective, role for MAIT cells during infection. Furthermore, we propose a novel mechanism of SAg-associated immunosuppression in humans. MAIT cells may therefore provide an attractive therapeutic target for the management of both early and late phases of severe SAg-mediated illnesses

Nephrol Ther

Contexte La place de l’évaluation gériatrique dans la prise en charge des patients âgés avec insuffisance rénale chronique avancée reste à définir. Dans cette population, les connaissances manquent sur les propositions de soins faites par les gériatres lors de cette évaluation, et sur le suivi de ces propositions. Objectifs Décrire une population de patients dialysés âgés vus en consultation gériatrique ainsi que les syndromes gériatriques identifiés, et étudier les propositions de soins du gériatre et le suivi de ces propositions. Méthodes Il s’agit d’une étude rétrospective, monocentrique, incluant les patients hémodialysés vus à la consultation gériatrique d’une association d’antenne d’auto-dialyse en Aquitaine, de mars 2014 à octobre 2017. Une analyse séparée a été réalisée par domaines : dépendance, cognition, thymie, locomotion, nutrition, médicaments. Résultats Sur 49 patients, d’âge médian 79 ans, 50 % avaient une perte d’indépendance dans les actes de la vie quotidienne, 32 % présentaient des troubles cognitifs, 24 % des troubles thymiques, 55 % des troubles locomoteurs, et 65 % avaient des médicaments potentiellement inappropriés. Les propositions les plus fréquentes du gériatre étaient la révision d’ordonnance, l’intervention du psychologue, du diététicien ou de l’orthophoniste, l’ajout d’aides à domicile, l’exploration des troubles cognitifs. Respectivement, 46, 33 et 18 % des propositions d’intervention d’autres professionnels, d’optimisation médicamenteuse et d’examens complémentaires étaient suivies. Conclusion En antenne d’auto-dialyse, une consultation gériatrique permet de mettre en évidence des syndromes gériatriques fréquents, souvent multiples, nécessitant des interventions coordonnées. La collaboration entre soignants, incluant le gériatre, devrait être renforcée afin d’améliorer le plan de soins personnalisé des patients âgés avec insuffisance rénale chronique avancée, et son suivi.Context The role of comprehensive geriatric assessment for older patients with advanced chronic kidney disease still needs to be defined. In this population, data is lacking on the care proposals made by geriatricians during comprehensive geriatric assessment and on the follow-up of these proposals. Objectives To describe a population of older outpatients with advanced renal disease seen at a geriatric consultation, and geriatric syndromes identified. To study care suggestions made by the geriatrician, and the follow-up of these suggestions. Methods Retrospective monocentric study, including all outpatients treated with hemodialysis and seen at the geriatric consultation implemented in a dialysis facilities network in Aquitaine region, France, from 2014 to 2017. Six domains were analysed: functional independence, cognition, gait/balance, mood, nutrition and drug prescription. Results Among 49 patients, mean age 79 years, 50% had a loss of independence, 32% cognitive impairment, 24% mood disturbance, 55% gait or balance disturbance, and 65% potentially inappropriate medications. The most frequent care suggestions of the geriatrician were drugs optimisation, intervention of a psychologist, a dietetician or a speech and language therapist, home support service implementation, and the exploration of cognitive impairment. Suggestions of intervention of other healthcare professionals, drug optimisation and biological/imaging tests were followed in respectively 46, 33 and 18% of cases. Conclusion A geriatric outpatient consultation in a nephrology facility allows identification of frequent and multiples geriatric syndromes, requiring coordinated interventions. Collaboration between healthcare professionals, including a geriatrician, should be reinforced to improve design and follow-up of the individualised care plan for older patients with advanced chronic kidney disease

Am J Med

BACKGROUND: The absence of fever in bacteremia in patients who are older is known to delay diagnosis. Our objective was to determine whether atypical presentation was associated to mortality as a result of bacteremia in this patient cohort as well as possible factors associated with this atypical presentation. METHODS: We conducted an observational prospective study in 2 French university hospitals in 2016-2017 including patients ages >/=75 years with bacteremia. Atypical presentation was defined as the absence of a temperature >/=38.3 degrees C or <36 degrees C, chills, or hypotension. Mortality and dependence for activities of daily living (ADL) were recorded at 1 week (D7) and 3 months (D90). RESULTS: Among the 151 patients (mean age 85.4+/-5.8 years) enrolled, atypical presentation prevalence was 21.2%. D7 and D90 mortality rates were 7.9% and 40.0%, respectively. Atypical presentation was independently associated with D7 (odds ratio (OR) 4.46, 95% confidence interval (CI) 1.04-19.24) and D90 mortality (OR 3.76, 95% CI 1.30-10.92) after controlling for other prognostic factors. Patients with diabetes and those infected with Staphylococcus aureus were more likely to have atypical signs of infection. ADL score decreased from 3.6+/-2.0 before bacteremia to 2.8+/-2.1 at D90 (P <0.001). CONCLUSION: Patients who are older with bacteremia have poor vital and functional prognoses in the short and long terms. The absence of typical signs of infection is associated with mortality. Blood culture should be considered for patients who are older, especially with diabetes with acute unexplained clinical manifestations

An arithmetic Zariski pair of line arrangements with non-isomorphic fundamental group

In a previous work, the third named author found a combinatorics of line arrangements whose realizations live in the cyclotomic group of the fifth roots of unity and such that their non-complex-conjugate embedding are not topologically equivalent in the sense that they are not embedded in the same way in the complex projective plane. That work does not imply that the complements of the arrangements are not homeomorphic. In this work we prove that the fundamental groups of the complements are not isomorphic. It provides the first example of a pair of Galois-conjugate plane curves such that the fundamental groups of their complements are not isomorphic (despite the fact that they have isomorphic profinite completions)

J Antimicrob Chemother

BACKGROUND: Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria. OBJECTIVES: To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons. METHODS: Patients >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0-24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386. RESULTS: Ten (mean +/- SD age=87+/-7 years) and 16 (age=88+/-5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12+/-5.9 versus 12+/-7.4 mg/L, P=0.97; C2.5=97+/-42 versus 67+/-41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=184+/-90 versus 51+/-66 mg/L, P=0.001). The mean individual AUCs (1126.92+/-334.99 mg.h/L for IV versus 1005.3+/-266.0 mg.h/L for SC, P=0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted. CONCLUSIONS: SC administration of ertapenem is an alternative to IV administration in older patients

Effect of wall thickness on the ferroelastic domain size of BaTiO₃

Abstract Extremely regular self-organized patterns of 90° ferroelastic domains have been reported in free-standing single crystal thin films of ferroelectric BaTiO3. Lukyanchuk et al. [Phys Rev B 79, 144111 (2009)] have recently shown that the domain size as a function of thickness for such free standing films can be well described assuming that the domains are due to stress caused by a surface tension layer that does not undergo the paraelectric–ferroelectric transition. From the starting point of Lukyanchuk’s model, it is shown here that the “universal” relationship between domain size and domain wall thickness previously observed in ferroelectrics, ferromagnets and multiferroics is also valid for ferroelastic domains. Further analysis of experimental data also shows that the domain wall thickness can vary considerably (an order of magnitude) from sample to sample even for the same material (BaTiO3), in spite of which the domain size scaling model is still valid, provided that the correct, sample dependent, domain wall thickness is used