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Abstract Background Pulp necrosis is one of the main complications of dental trauma. When it happens on an immature tooth, pulp necrosis implies a lack of root maturation and apical closure. A therapy called apexification is required to induce the formation of a calcified apical barrier allowing a permanent and hermetic root filling. The aim of this prospective randomized clinical trial is to compare Mineral Trioxide Aggregate(MTA)with Calcium Hydroxide(CH)as materials used to induce root-end closure in necrotic permanent immature incisors. Methods/Design This study, promoted by AP-HP, was approved by the ethics committee(CPP Paris Ile de France IV). 34 children aged from 6 to 18 years and presenting a non-vital permanent incisor are selected. Prior to treatment, an appropriate written consent has to be obtained from both parents and from children. Patients are then randomly assigned to either the MTA(experimental)or CH(control)groups. Recalls are performed after 3, 6 and 12 months to determine the presence or absence of a calcified apical barrier through the use of clinical and radiographic exams. Additional criteria such as clinical symptoms, apical radiolucencies, periapical index(PAI)are also noted. Trial registration ClinicalTrials.gov no. NCT00472173 (First inclusion: May 10, 2007; Last inclusion: April 23, 2009; study completed: April 15, 2010)

Background: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms., Aims: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs., Methods: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions., Results: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment., Conclusions: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

This study evaluated the association between dietary patterns, Gas-Related Symptoms (GRS) and their impact on quality of life (QoL) in a representative sample (n=936) of the French adult population. During the 2018-2019 "Comportements et Consommations Alimentaires en France" (CCAF) survey (Behaviors and Food Consumption in France), online evaluation of GRS in adult participants was performed using the validated Intestinal Gas Questionnaire (IGQ), which captures the perception of GRS and their impact on QoL via 6 symptom dimensions scores (range 0-100; 100=worse) and a global score (mean of the sum of the 6 symptom dimensions scores). Socio-demographics, lifestyle parameters and dietary habits (7-day e-food diary) were also collected online. Quality of diet was determined using the NRF9.3 score (range 0-900; 900=best). Univariate and multivariate linear regression models were applied to identify factors associated with IGQ global score. K-means was used to identify clusters of subjects based on their dietary records. Data from 936 adults who completed both the IGQ and the food diary showed a mean (SD) IGQ global score of 11.9 (11.2). Younger age and female gender were associated with a higher IGQ global score. Only 7% of subjects reported no symptom at all and nearly 30% of study participants reported a high impact of GRS on their QoL. Two dietary clusters were identified: cluster1, characterized by a higher consumption of fruits and vegetables, lower sugars intake and higher NRF9.3 score and cluster 2, characterized by higher intake of sugars, lower intake in dietary fibers and lower NRF9.3 score. The IGQ global score was lower in cluster1 and higher in cluster2 vs. the total sample average (p<0.001). Prevalence of GRS in the French adult population is high and is associated with impaired QoL and dietary patterns. A change in food habits towards healthier patterns could help reducing the burden of GRS.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects., (© 2022. The Author(s).)

Background: The adoption of health technologies is key to empower research participants and collect quality data. However, the acceptance of health technologies is usually evaluated in patients or healthcare practitioners, but not in clinical research participants., Methods: A 27-item online questionnaire was provided to the 11,695 members of a nutrition clinical research participant database from the Nantes area (France), to assess (1) participants' social and demography parameters, (2) equipment and usage of health apps and devices, (3) expectations in research setting and (4) opinion about the future of clinical research. Each item was described using frequency and percentage overall and by age classes. A global proportion comparison was performed using chi-square or Fisher-exact tests., Results: A total of 1529 respondents (81.0% women, 19.0% men) completed the survey. Main uses of health apps included physical activity tracking (54.7%, age-related group difference, p < 0.001) and food quality assessment (45.7%, unrelated to age groups). Overall, 20.4% of respondents declared owning a connected wristband or watch. Most participants (93.8%) expected the use of connected devices in research. However, protection of personal data (37.5%), reliability (35.5%) and skilled use of devices (28.5%) were perceived as the main barriers. Most participants (93.3%) would agree to track their food intake using a mobile app, and 80.5% would complete it for at least a week while taking part in a clinical study. Only 13.2% would devote more than 10 min per meal to such record. A majority (60.4%) of respondents would accept to share their social media posts in an anonymous way and most (82.2%) of them would accept to interact with a chatbot for research purposes., Conclusions: Our cross-sectional study suggests that clinical study participants are enthusiastic about all forms of digital health technologies and participant-centered studies but remain concerned about the use of personal data. Repeated assessments are suggested to evaluate the research participant's interest in technologies following the increase in use and demand for innovative health services during the pandemic of COVID-19., Competing Interests: FS and LQ are the employees of Danone Nutricia Research. MK was affiliated to Danone Nutricia Research during the survey design and during data collection as an intern from the Faculty of Medicine and Pharmacy of Poitiers. GF received consultation fees from Danone Nutricia Research. Authors affiliated to Danone Nutricia Research were involved in study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schäfer, Quinquis, Klein, Escutnaire, Chavanel, Chevallier and Fagherazzi.)

Helicobacter pylori ( Hp ) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus ( L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower ( p adj = 0.02), some Enterobacteriaceae , including Escherichia-Shigella ( p adj = 0.0082) and Klebsiella ( p adj = 0.013), were less abundant, and concentrations of major SCFA ( p = 0.035) and valerate ( p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.

Many clinical studies have evaluated the effect of probiotics, but only a few have assessed their dose effects on gut microbiota and host. We conducted a randomized, double-blind, controlled intervention clinical trial to assess the safety (primary endpoint) of and gut microbiota response (secondary endpoint) to the daily ingestion for 4 weeks of two doses (1 or 3 bottles/day) of a fermented milk product (Test) in 96 healthy adults. The Test product is a multi-strain fermented milk product, combining yogurt strains and probiotic candidate strains Lactobacillus paracasei subsp. paracasei CNCM I-1518 and CNCM I-3689 and Lactobacillus rhamnosus CNCM I-3690. We assessed the safety of the Test product on the following parameters: adverse events, vital signs, hematological and metabolic profile, hepatic, kidney or thyroid function, inflammatory markers, bowel habits and digestive symptoms. We explored the longitudinal gut microbiota response to product consumption and dose, by 16S rRNA gene sequencing and functional contribution by shotgun metagenomics. Safety results did not show any significant difference between the Test and Control products whatever the parameters assessed, at the two doses ingested daily over a 4-week-period. Probiotic candidate strains were detected only during consumption period, and at a significantly higher level for the three strains in subjects who consumed 3 products bottles/day. The global structure of the gut microbiota as assessed by alpha and beta-diversity, was not altered by consumption of the product for four weeks. A zero-inflated beta regression model with random effects (ZIBR) identified a few bacterial genera with differential responses to test product consumption dose compared to control. Shotgun metagenomics analysis revealed a functional contribution to the gut microbiome of probiotic candidates.

This study assessed the bio-equivalence of high-quality, plant-based protein blends versus Whey Protein Isolate (WPI) in healthy, resistance-trained men. The primary endpoint was incremental area under the curve (iAUC) of blood essential Amino Acids (eAAs) 4 hours after consumption of each product. Maximum concentration (C max ) and time to maximum concentration (T max ) of blood leucine were secondary outcomes. Subjects ( n = 18) consumed three plant-based protein blends and WPI (control). An analysis of Variance model was used to assess for bio-equivalence of total sum of blood eAA concentrations. The total blood eAA iAUC ratios of the three blends were [90% CI]: #1: 0.66 [0.58-0.76]; #2: 0.71 [0.62-0.82]; #3: 0.60 [0.52-0.69], not completely within the pre-defined equivalence range [0.80-1.25], indicative of 30-40% lower iAUC versus WPI. Leucine C max of the three blends was not equivalent to WPI, #1: 0.70 [0.67-0.73]; #2: 0.72 [0.68-0.75]; #3: 0.65 [0.62-0.68], indicative of a 28-35% lower response. Leucine T max for two blends were similar to WPI (#1: 0.94 [0.73-1.18]; #2: 1.56 [1.28-1.92]; #3: 1.19 [0.95-1.48]). The plant-based protein blends were not bio-equivalent. However, blood leucine kinetic data across the blends approximately doubled from fasting concentrations, whereas blood T max data across two blends were similar to WPI. This suggests evidence of rapid hyperleucinemia, which correlates with a protein's anabolic potential.

Background. Minor digestive symptoms are common and dietary approaches such as probiotic administration or fibre and fermentable carbohydrate intake adjustments are often recommended. A Fermented Milk Product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria has been shown to improve digestive symptoms after 4 weeks of consumption, but the speed of onset of this effect and its dependence on fibre intake or physical activity is unknown. To answer these questions, data from two previously published trials on FMP for minor digestive symptoms were combined. Methods. In total, 538 participants provided weekly assessments of bloating, abdominal pain/discomfort, flatulence, borborygmi/rumbling stomach from which a composite score was calculated. At baseline in one study ( n = 336), dietary fibre consumption was recorded and physical activity classified as high, moderate or low. The speed of the FMP's effect was assessed by a repeated measure analysis of variance measuring the change from baseline for the composite score of digestive symptoms. Results. FMP consumption resulted in a significant decrease in the composite score of symptoms after only 2 weeks in both studies and the pooled data at week 1 (-0.35 [-0.69, 0.00]; p = 0.05), week 2 (-0.66 [-1.04, -0.27]; p < 0.001), week 3 (-0.49 [-0.89, -0.10]; p = 0.01) and week 4 (-0.46 [-0.88, -0.04]; p = 0.03). The interactions fibre intake-by-product group, physical activity-by-product group and time-by-product group were not statistically significant. Conclusion. FMP consumption leads to a rapid improvement in symptoms which is likely to encourage adherence to this dietary intervention. This effect is independent of dietary fibre and physical activity.

Aims: To evaluate the interest of brain natriuretic peptide (BNP) for heart failure (HF) diagnosis in very old patients., Methods and Results: A total of 383 patients aged 80 years or older, hospitalized in geriatrics care for dyspnoea, had a BNP measurement at the acute phase. Independent cardiologists blinded to BNP values classified the patients into cardiac vs. respiratory aetiology according to the European Society of Cardiology guidelines. Mean (SD) age was 88.5 (5.4) years, 66% (n = 254) of patients were women, 62% (n = 238) had cardiac dyspnoea and 38% (n = 145) had respiratory dyspnoea. The BNP levels were significantly higher in the cardiac group (median = 385.5 ng/L, interquartile range = 174.0-842.0) than in the respiratory group (median = 172.0 ng/L, interquartile range = 70.8-428.0; P < 0.001). On its own, BNP showed poor discriminative ability [area under the curve (AUC) = 0.68; 95% confidence interval (CI) 0.62-0.73] for the diagnostic. In multivariate analysis, BNP remained independently associated with the cardiac aetiology after full-adjustment (odds ratio 1 log increase = 1.87; 95% CI 1.28-2.74), but did not improve the discrimination between the cardiac and the respiratory aetiologies (ΔAUC = 0.013, P = 0.16). In addition, although adding BNP to the other predictive covariates yielded a significant continuous NRI of 57.8% (95% CI 31.2-83.5%), the mean changes in individual predicted probabilities were too low (<3%) to be clinically relevant., Conclusion: In this population of very old patients with acute dyspnoea, despite being independently associated with the cardiac aetiology, BNP was not useful for better discriminating cardiac vs. respiratory origin., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Introduction: Presepsin (sCD14-ST) is an emerging biomarker for infection. We hypothesized that presepsin could specifically increase during acute pyelonephritis and correlate with severity., Methods: We compared presepsin values in patients with acute pyelonephritis and controls, and we assessed its capacity to predict bacteraemia and admission in patients., Results: In 312 patients with acute pyelonephritis (median age 33years), presepsin concentrations were higher than in controls (476 vs 200ng/L, p<0.001). ROC curve indicated an AUC at 0.90 [for presepsin (vs. 0.99 and 0.98 for CRP and PCT, respectively; p<0.05) and an optimal threshold at 340ng/L (74% sensitivity, 94% specificity). Presepsin concentrations increased in acute pyelonephritis patients with bacteraemia (614 vs. 461ng/L, p,=0.001) and in those requiring admission (614ng/L vs. 320ng/L, p<0.001). Performance of presepsin to predict bacteraemia [AUC=0.63, 95%CI: 0.55-0.72] was similar to CRP (AUC=0.64, p=0.87) and less accurate than PCT (AUC=0.78, p<0.001). AUC for presepsin to detect the need for admission was 0.67, and comparable to CRP (p=0.26) and PCT (p=0.18)., Conclusion: Presepsin is a valuable biomarker to detect patients with acute pyelonephritis. However, it presents mild performance to predict bacteraemia and the need for admission, and offers no advantage as compared to CRP and PCT., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: The aim of this study was to assess the efficacy and safety of tumor necrosis factor (TNF)-α inhibition with infliximab (IFX) in treating recurrent and disabling chronic sciatica pain associated with post-operative peridural lumbar fibrosis., Method: A double-blind, placebo-controlled study randomized 35 patients presenting with sciatica pain associated with post-operative peridural lumbar fibrosis to two groups: IFX (n = 18), a single intravenous injection of 3 mg/kg IFX; and placebo (n = 17), a single saline serum injection. The primary outcome was a 50 % reduction in sciatica pain on a visual analog scale (VAS) at day 10. Secondary outcomes were radicular and lumbar VAS pain at day 0 and radicular and lumbar VAS pain, Québec disability score, drug-sparing effect and tolerance at days 10, 30, 90, and 180., Results: At day 10, the placebo and IFX groups did not differ in the primary outcome (50 % reduction in sciatica pain observed in three (17.6 %) versus five (27.8 %) patients; p = 0.69). The number of patients reaching the patient acceptable symptom state for radicular pain was significantly higher in the placebo than IFX group after injection (12 (70.6 %) versus five (27.8 %) patients; p = 0.01). The two groups were comparable for all other secondary outcomes., Conclusion: Treatment with a single 3 mg/kg IFX injection for post-operative peridural lumbar fibrosis-associated sciatica pain does not significantly reduce radicular symptoms at day 10 after injection., Trial Registration: ClinicalTrials.gov NCT00385086 ; registered 4 October 2006 (last updated 15 October 2015).

Rationale: The occurrence of ventilator-associated pneumonia (VAP) is linked to the aspiration of contaminated pharyngeal secretions around the endotracheal tube. Tubes with cuffs made of polyurethane rather than polyvinyl chloride or with a conical rather than a cylindrical shape increase tracheal sealing., Objectives: To test whether using polyurethane and/or conical cuffs reduces tracheal colonization and VAP in patients with acute respiratory failure., Methods: We conducted a multicenter, prospective, open-label, randomized study in four parallel groups in four intensive care units between 2010 and 2012. A cohort of 621 patients with expected ventilation longer than 2 days was included at intubation with a cuff composed of cylindrical polyvinyl chloride (n = 148), cylindrical polyurethane (n = 143), conical polyvinyl chloride (n = 150), or conical polyurethane (n = 162). We used Kaplan-Meier estimates and log-rank tests to compare times to events., Measurements and Main Results: After excluding 17 patients who secondarily refused participation or had met an exclusion criterion, 604 were included in the intention-to-treat analysis. Cumulative tracheal colonization greater than 10(3) cfu/ml at Day 2 was as follows (median [interquartile range]): cylindrical polyvinyl chloride, 0.66 (0.58-0.74); cylindrical polyurethane, 0.61 (0.53-0.70); conical polyvinyl chloride, 0.67 (0.60-0.76); and conical polyurethane, 0.62 (0.55-0.70) (P = 0.55). VAP developed in 77 patients (14.4%), and postextubational stridor developed in 28 patients (6.4%) (P = 0.20 and 0.28 between groups, respectively)., Conclusions: Among patients requiring mechanical ventilation, polyurethane and/or conically shaped cuffs were not superior to conventional cuffs in preventing tracheal colonization and VAP. Clinical trial registered with clinicaltrials.gov (NCT01114022).

Background: The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However, ketoconazole is frequently used as a drug to lower circulating cortisol levels. Several pharmacological agents have recently been approved for the treatment of Cushing's disease (CD) despite limited efficacy or significant side effects. Ketoconazole has been used worldwide for more than 30 years in CD, but in the absence of a large-scale study, its efficacy and tolerance are still under debate., Patients and Methods: We conducted a French retrospective multicenter study reviewing data from patients treated by ketoconazole as a single agent for CD, with the aim of clarifying efficacy and tolerance to better determine the benefit/risk balance., Results: Data from 200 patients were included in this study. At the last follow-up, 49.3% of patients had normal urinary free cortisol (UFC) levels, 25.6% had at least a 50% decrease, and 25.4% had unchanged UFC levels. The median final dose of ketoconazole was 600 mg/d. Forty patients (20%) received ketoconazole as a presurgical treatment; 40% to 50% of these patients showed improvement of hypertension, hypokalemia, and diabetes, and 48.7% had normal UFC before surgery. Overall, 41 patients (20.5%) stopped the treatment due to poor tolerance. Mild (<5N, inferior to 5-fold normal values) and major (>5N, superior to 5-fold normal values) increases in liver enzymes were observed in 13.5% and 2.5% of patients, respectively. No fatal hepatitis was observed., Conclusions: Ketoconazole is an effective drug with acceptable side effects. It should be used under close liver enzyme monitoring. Hepatotoxicity is usually mild and resolves after drug withdrawal.

Background: Relationships between smoking and health-related quality of life (HRQoL) in the general population remain unclear., Objectives: To quantify the independent associations between smoking patterns and HRQoL and to identify any threshold or non-linear tendencies in these associations., Methods: A national representative, cross-sectional household survey of the French general non institutionalized population included 7525 men and 8486 women, aged 25-64 year in 2003. Scores on the eight subscales of the Medical Outcomes Study 36-item Short Form were the primary outcomes. Linear regression analyses were used to evaluate the associations between HRQoL and smoking history, quantity of smoking and smoking cessation while controlling for various socio-economic variables, depression, alcohol dependence and pathological conditions. Analyses were conducted in 2013., Results: Independent associations between smoking and HRQoL were found, including small positive associations for occasional or light smoking (up to 5 cigarettes per day), and larger and diffuse negative associations above this threshold. Much weaker associations and higher thresholds for negative HRQoL were found for women than for men. For ex-smokers of both genders, HRQoL was found to be better between 2 and 5 years after quitting., Conclusions: Smoking was independently related to HRQoL, with large differences according to the pattern and quantity of smoking, and to gender. These results may have considerable relevance both for public health action and care of smokers.

Objectives: To investigate whether prophylactic postoperative NIV prevents respiratory complications following lung resection surgery in COPD patients., Methods: In seven thoracic surgery departments, 360 COPD patients undergoing lung resection surgery were randomly assigned to two groups: conventional postoperative treatment without (n = 179) or with (n = 181) prophylactic NIV, applied intermittently during 6 h per day for 48 h following surgery. The primary endpoint was the rate of acute respiratory events (ARE) at 30 days postoperatively (ITT analysis). Secondary endpoints were acute respiratory failure (ARF), intubation rate, mortality rate, infectious and non-infectious complications, and duration of ICU and hospital stay., Measurements and Main Results: ARE rates did not differ between the prophylactic NIV and control groups (57/181, 31.5 vs. 55/179, 30.7%, p = 0.93). ARF rate was 18.8% in the prophylactic NIV group and 24.5% in controls (p = 0.20). Re-intubation rates were similar in the prophylactic NIV and control group [10/181 (5.5%) and 13/179 (7.2%), respectively, p = 0.53]. Mortality rates were 5 and 2.2% in the control and prophylactic NIV groups, respectively (p = 0.16). Infectious and non-infectious complication rates, and duration of ICU and hospital stays were similar between groups., Conclusions: Prophylactic postoperative NIV did not reduce the rate of ARE in COPD patients undergoing lung resection surgery and did not influence other postoperative complications rates, mortality rates, and duration of ICU and hospital stay.

Background: The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer., Methods: The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥ 2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir., Results: Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ≥ 2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders., Conclusion: Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Université Paris Descartes, Ministère de la Recherche et de l'Enseignement Supérieur, and Assistance Publique-Hôpitaux de Paris.

Purpose: Achievement of athletes' performances is related to several factors including physiological, environmental and institutional cycles where physical characteristics are involved. The objective of this study is to analyse the performance achieved in professional sprint and middle-distance running events (100 m to 1500 m) depending on the organization of the annual calendar of track events and their environmental conditions., Methods: From 2002 to 2008, all performances of the Top 50 international athletes in the 100 m to 1500 m races (men and women) are collected. The historical series of world records and the 10 best annual performances in these events, amounted to a total of 26,544 performances, are also included in the study., Results: Two periods with a higher frequency of peak performances are observed. The first peak occurs around the 27.15(th) ±0.21 week (first week of July) and the second peak around 34.75(th) ±0.14 week (fourth week of August). The second peak tends to be the time of major international competitions (Olympic Games, World Championships, and European Championships) and could be characterized as an institutional moment. The first one, however, corresponds to an environmental optimum as measured by the narrowing of the temperature range at the highest performance around 23.25±3.26°C., Conclusions: This is the first study to demonstrate that there are two performance peaks at a specific time of year (27th and 34th weeks) in sprint and middle distance. Both institutional and ecophysiological aspects contribute to performance in the 100 m to 1500 m best performances and define the contours of human possibilities. Sport institutions may take this into account in order to provide ideal conditions to improve the next records.

Background: Health-related quality of life (HRQoL) measures are increasingly used in the general population. However, little is known about patterns and determinants of unanswered or unusable questionnaires and their consequences on estimates of HRQoL., Methods: The 2003 Decennial Health Survey collected socio-demographic and health information, including HRQoL, for 30,782 adults representative of the French population. The pattern, determinants and impact on estimate validity of non, incomplete and inconsistent responses to the SF-36 questionnaire were determined. For this, phi coefficients, polytomous logistic regression models and multiple imputation methods were used., Results: Only 48% of the subjects eligible for the HRQoL measurement provided a complete and consistent SF-36 questionnaire. Three patterns of non-response and five of partial (incomplete or inconsistent) response were identified, sharing largely similar socio-demographic profiles (higher age, lower educational level and economic status, foreign background, and isolated). The consequences of non and partial responses on HRQoL estimates were large in several groups of subjects although these biases ran in opposite directions and partially neutralized each other., Conclusions: When measuring HRQoL in the general population, missing and inconsistent data are frequent, especially in elderly, educationally and socio-economically deprived, foreign and isolated groups. Methods for handling missing data are required to correct for potentially the associated and serious selection and non-differential information biases in studies targeting or investigating these groups.

Context: Few large studies have been conducted to assess the relationship between circulating IGF and late-life cognition., Objective: The aim of the study was to assess the relationship between IGF-I and IGF binding protein-3 (IGFBP-3) serum levels and cognitive impairment, including Alzheimer's disease (AD)., Methods: In this multicentric cross-sectional study, 694 elderly subjects (218 men, 476 women; 78.6 ± 6.7 yr old) were included; 481 had memory complaints and were diagnosed, after comprehensive cognitive assessment, with AD (n = 224) or mild cognitive impairment (MCI) (n = 257). The control group was comprised of 213 subjects without memory complaint and with normal cognition (recruited among patients' caregivers). IGF-I and IGFBP-3 serum levels were determined by ELISA., Results: IGF-I and IGFBP-3 serum levels were significantly associated with cognitive status in men (IGF-I, 137 ± 69 ng/ml for AD vs. 178 ± 88 ng/ml for MCI and 172 ± 91 ng/ml for controls, P = 0.01; IGFBP-3, 3675 ± 1542 ng/ml for AD vs. 4143 ± 1828 ng/ml for MCI and 4488 ± 1893 ng/ml for controls, P = 0.04). In women, IGFBP-3 was significantly associated with cognitive status (3781 ± 1351 ng/ml for AD vs. 4190 ± 1408 ng/ml for MCI and 4390 ± 1552 ng/ml for controls; P < 0.001), but no significant differences between groups for IGF-I occurred. After adjustment for confounding variables (age, educational level, body mass index, diabetes, apolipoprotein E ε4 status), logistic regression indicated that IGF-I [odds ratio (95% confidence interval) = 0.48 (0.26-0.88)] and IGFBP-3 [odds ratio (95% confidence interval) = 0.71 (0.52-0.97)] serum levels were independently associated with AD in men, but not in women., Conclusions: We report a significant association between low IGF-I and IGFBP-3 serum levels and AD in men, but not in women.

The physiological parameters characterizing human capacities (the ability to move, reproduce or perform tasks) evolve with ageing: performance is limited at birth, increases to a maximum and then decreases back to zero at the day of death. Physical and intellectual skills follow such a pattern. Here, we investigate the development of sport and chess performances during the lifetime at two different scales: the individual athletes' careers and the world record by age class in 25 Olympic sports events and in grandmaster chess players. For all data sets, a biphasic development of growth and decline is described by a simple model that accounts for 91.7% of the variance at the individual level and 98.5% of the variance at the species one. The age of performance peak is computed at 26.1 years old for the events studied (26.0 years old for track and field, 21.0 years old for swimming and 31.4 years old for chess). The two processes (growth and decline) are exponential and start at age zero. Both were previously demonstrated to happen in other human and non-human biological functions that evolve with age. They occur at the individual and species levels with a similar pattern, suggesting a scale invariance property.

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) increases with severity in community-acquired pneumonia (CAP). We investigated whether changes of MR-proANP correlated to bacteremia., Methods: 392 adult patients with CAP visiting emergency department from a prospective observational multicenter study., Results: MR-proANP levels increased in patients with positive bacteremia (92.8 pmol/L vs. 84.3 pmol/L, p = 0.04). Performance of MR-proANP to detect bacteremia (0.60) was equivalent to CRP (0.59) but less accurate than PCT (0.69)., Conclusion: MR-ANP poorly predicts bacteremia in CAP patients.

Introduction: The victory percentages for tennis players who entered the top 10 women and men rankings show various evolutions related to age and time since 1968., Methods: The study analyzed the careers of all top 10 players: 97 women (50,933 matches) and 144 men (92,450 matches). For each player, we describe a biphasic performance course. Two generations were compared: the first one (G1), including players who started their professional career before 1985, and the second one (G2), with players starting after 1985., Results: The average career length is 16.1 ± 3.8 yr for the top 10 men and 15.8 ± 4.4 yr for women. Compared with G1 players, G2 players begin earlier (women = 1.3 yr, men = 0.8 yr), but career length remains the same. An exponential model describes the time course of the victory percentage with a great similarity for both genders. Using this equation, the peak victory rate reaches 82.5% at 21.5 yr for number 1 (no. 1) women and 78.5% at 23.7 yr for no. 1 men, showing a greater precocity and earlier decline in women. Finally, the area under the curve shows a potential that is 22.8% (men) to 56.8% (women) larger for the no. 1 players as compared with all other numbers 2-10., Conclusions: Tennis players in the top 10 show a biphasic career. Women reach their highest level earlier than men, consistent with their more precocious biological development. For the current generation, the peak performance tends toward a younger age than the first generation. We show how to precisely quantify and compare tennis performances using indicators that follow the trends of development and aging and demonstrate that precocity does not provide a larger victory potential.

Background: Pulp necrosis is one of the main complications of dental trauma. When it happens on an immature tooth, pulp necrosis implies a lack of root maturation and apical closure. A therapy called apexification is required to induce the formation of a calcified apical barrier allowing a permanent and hermetic root filling. The aim of this prospective randomized clinical trial is to compare Mineral Trioxide Aggregate(MTA)with Calcium Hydroxide(CH)as materials used to induce root-end closure in necrotic permanent immature incisors., Methods/design: This study, promoted by AP-HP, was approved by the ethics committee(CPP Paris Ile de France IV). 34 children aged from 6 to 18 years and presenting a non-vital permanent incisor are selected. Prior to treatment, an appropriate written consent has to be obtained from both parents and from children. Patients are then randomly assigned to either the MTA(experimental)or CH(control)groups. Recalls are performed after 3, 6 and 12 months to determine the presence or absence of a calcified apical barrier through the use of clinical and radiographic exams. Additional criteria such as clinical symptoms, apical radiolucencies, periapical index(PAI)are also noted., Trial Registration: ClinicalTrials.gov no. NCT00472173 (First inclusion: May 10, 2007; Last inclusion: April 23, 2009; study completed: April 15, 2010)., (© 2011 Beslot-Neveu et al; licensee BioMed Central Ltd.)

Introduction: Mid-regional pro-atrial natriuretic peptide (MRproANP) increases during systemic infections and could possibly correlate with bacteremia., Methods: We determined the characteristics of MRproANP for accuracy to detect positive blood culture., Results: Bacteremia was positive in 58 (15%) of 347 patients. MRproANP levels increased in patients with bacteremia (98.4 pmol/L [interquartile range (IQR) 68.2-153.1] vs. 66.4 pmol/L [IQR 51.0-90.3], p <0.01). Performance of MRproANP to predict bacteremia [AUC = 0.69, 95%CI: 0.61-0.77] was equivalent to C-reactive protein (0.66 [95%CI: 0.59-0.74], p = 0.53) but less accurate than procalcitonin (0.78 [95%CI: 0.72-0.84], p <0.001)., Conclusion: Although MRproANP increased in bacteremic patients with acute pyelonephritis, results of likelihood ratios discarded its use at bedside to predict bacteremia.

A previous analysis of World Records (WR) has revealed the potential limits of human physiology through athletes' personal commitment. The impact of political factors on sports has only been studied through Olympic medals and results. Here we studied 2876 WR from 63 nations in four summer disciplines. We propose three new indicators and show the impact of historical, geographical and economical factors on the regional WR evolution. The south-eastward path of weighted annual barycenter (i.e. the average of country coordinates weighting by the WR number) shows the emergence of East Africa and China in WR archives. Home WR ratio decreased from 79.9% before the second World War to 23.3% in 2008, underlining sports globalization. Annual Cumulative Proportions (ACP, i.e. the cumulative sum of the WR annual rate) highlight the regional rates of progression. For all regions, the mean slope of ACP during the Olympic era is 0.0101, with a maximum between 1950 and 1989 (0.0156). For European countries, this indicator reflects major historical events (slowdown for western countries after 1945, slowdown for eastern countries after 1990). Mean North-American ACP slope is 0.0029 over the century with an acceleration between 1950 and 1989 at 0.0046. Russia takes off in 1935 and slows down in 1988 (0.0038). For Eastern Europe, maximal progression is seen between 1970 and 1989 (0.0045). China starts in 1979 with a maximum between 1990 and 2008 (0.0021), while other regions have largely declined (mean ACP slope for all other countries = 0.0011). A similar trend is observed for the evolution of the 10 best performers. The national analysis of WR reveals a precise and quantifiable link between the sport performances of a country, its historical or geopolitical context, and its steps of development.