Miracle-dz/UniFAR-FTUs huggingface dataset:
Geographical variations of inflammatory bowel disease in France: A study based on national health insurance data

Background and Aim: A north‐south gradient in inflammatory bowel disease (IBD) incidence has been found in Europe and the United States. Its existence is inferred from comparisons of registries that cover only small portions of territories. Several studies suggest that IBD incidence in the north has reached a plateau, whereas in the south it has risen sharply. This evolution tends to reduce the north‐south gradient, and it is uncertain whether it still exists. In France, patients with IBD are fully reimbursed for their health expenses by the national health insurance system, which is a potential source of data concerning the incidence of IBD at the national level. The aim of this study was to assess the geographical distribution of Crohn's disease (CD) and ulcerative colitis (UC) in France and to test the north‐south gradient hypothesis. Methods: This study was conducted in metropolitan France and included patients to whom IBD reimbursement was newly attributed between January 1, 2000 and December 31, 2002. Data provided relate to age, sex, postcode area of residence, and IBD type. The mapping of geographical distribution of smoothed relative risks (RR) of CD and UC was carried out using a Bayesian approach, taking into account autocorrelation and population size in each département. Results: In the overall population, incidence rates were 8.2 for CD and 7.2 for UC per 100,000 inhabitants. A clear north‐south gradient was shown for CD. Départements with the highest smoothed RR were located in the northern third of France. By contrast, the geographical distribution of smoothed RR of UC was homogeneous. Conclusions: This study shows a north‐south gradient in France for CD but not for UC.
The SDQ in Italian clinical practice: evaluation between three outpatient groups compared.

AIM The aim of the study is to evaluate the effectiveness of the Strength and Difficulties Questionnaire (SDQ) as a screening tool for emotional and behavioral problems in three different populations at risk. METHODS The SDQ is a brief screening questionnaire that investigates the presence of emotional and behavioural problems in children and adolescents. We have analyzed 497 questionnaires completed by parents of children referred to Child Neuropsychiatry, Pediatric Endocrinology and Pediatric Oncology Units. RESULTS Results indicate a higher presence of psychopathological disorders in Neuropsychiatry patients than Oncology and Endocrinology patients. Furthermore the Oncology patients have more emotional and behavioral problems than Endocrinology patients. DISCUSSION The findings support the use of the SDQ questionnaire in the assessment of emotional and behavioral problems in these populations at risk. So the SDQ could be used by clinicians to detect early psychopathological disorder in children with different kind of chronic organic diseases.
Mammalian oocyte activation by the synergistic action of discrete sperm head components: induction of calcium transients and involvement of proteolysis.

Sperm-borne oocyte-activating factor (SOAF) elicits activation sufficient for full development and originates from sperm head submembrane matrices. SOAF comprises discrete, heat-sensitive and -stable components (referred to here respectively as SOAF-I and -II) which are each necessary but not sufficient to activate oocytes. The heat-sensitive SOAF component, SOAF-I(m), becomes solubilized from the perinuclear matrix under reducing conditions (the SOAF transition) to generate SOAF-I(s). Although calcium transients likely play an important role in oocyte activation at fertilization, the question is open as to whether demembranated heads or SOAF-I(s) and/or SOAF-II can induce calcium transients. We now report that injection of demembranated sperm heads into mouse oocytes efficiently induced Ca(2+) oscillations. When injected independently, SOAF-I(s) and demembranated heads heated to 48 degrees C failed to generate Ca(2+) oscillations. However, co-injection of SOAF-I(s) and 48 degrees C-heated heads induced oscillations, mirroring their synergistic ability to activate oocytes. This suggests that SOAF-mediated activation proceeds via pathways resembling those at fertilization and provides the first direct evidence that multiple sperm components are required to induce Ca(2+) oscillations. We probed the SOAF-I(s) liberation at the center of this activation and show that in vitro it was sensitive to a profile of serine protease inhibitors. These findings support a model in which mammalian oocyte activation, including the induction of calcium transients, involves proteolytic processing of SOAF from sperm head submembrane compartments.
Orexin research: patent news from 2016

ABSTRACT Introduction: The orexin system consists of two G-protein-coupled receptors, orexin 1 and orexin 2 and two endogenous ligands, orexin A and orexin B . It is evolutionarily highly conserved. It is involved in the promotion of wakefulness as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists are successfully used to treat primary insomnia. The major open questions are now related to the clinical validation of Ox1 selective antagonists. A strong rationale exists for orexin agonism in the treatment of narcolepsy with cataplexy. Areas covered: The patent applications from Thomson Reuters Integrity Database added in 2016 are summarized and discussed together with the most important findings published in the scientific literature. Expert opinion: The large number of patents shows the continuing interest in the orexin receptors as targets. The structural scope covered is narrow. Questions about novelty and inventiveness are evident. The additional information published on X-ray structures on both orexin receptors opens new ways of optimizing antagonists. It might also influence the efforts in the identification of orexin receptor agonists. Being potential treatments for narcolepsy with cataplexy.
Restaging and Survival Analysis of 4036 Ovarian Cancer Patients According to the 2013 FIGO Classification for Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Objective With the 2013 International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and primary peritoneal cancer, the number of substages changed from 10 to 14. Any classification of a malignancy should easily assign patients to prognostic groups, refer patients to individualized treatments, and allow benchmarking and comparison of patients and results between centers. The stage should reflect survival in particular. The objective of the study was to validate these requirements of the revised FIGO staging on a high number of ovarian cancer patients. Materials and Methods Demographic, surgical, histological, and survival data from 4036 ovarian cancer patients were used in the analysis. Five-year survival rates (5YSR) and hazard ratios for the old and revised FIGO staging were calculated using Kaplan-Meier curves and Cox regression. Results A total of 1532 patients were assigned to new stages. Stages IA and IC1 had similar survival (5YSR, 87%); and stages IB, IC2, and IC3 had similar survival (5YSR, 75%–80%). Stage IIC was omitted, resulting in similar survival in stages IIA and IIB (5YSR, 61% and 65%). Of 1660 patients in stage IIIC, 79 were restaged: In 16 cases, IIIC was down-staged to IIIA1, as they had only been stage IIIC owing to lymph node metastases; and in 63 cases, IIIC was down-staged to IIIB, as they had lymph node metastases and abdominal tumor of less than 2 cm. The 5YSR in stage IIIC was unchanged (22%). Stage IV (5YSR, 14% ) was restaged as IVA (13%) and IVB (13%). Both were different from IIIC; P < 0.0001. Conclusion With introduction of new substages, staging becomes more demanding. Second, as fewer patients are allocated to each substage, statistical power is diminished, resulting in uncertainty in the results. Despite this, and most importantly, the revised coding adequately reflects survival, as there was a clear graphical and statistical tendency for poorer survival with increasing stage.
Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.

AIMS To develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified. METHODS The pharmacokinetics of lopinavir in combination with ritonavir were described using NONMEM (version V, level 1.1). First, ritonavir data were fitted to a previously developed model to obtain individual Bayesian estimates of pharmacokinetic parameters. Hereafter, an integrated model for the description of the pharmacokinetics of lopinavir with ritonavir was designed. RESULTS From 122 outpatients 748 lopinavir and 748 ritonavir plasma concentrations were available for analysis. The interaction between the drugs was described by a time-independent inverse relationship between the exposure to ritonavir over a dosing-interval and the apparent clearance (CL/F) of lopinavir. The model parameters volume of distribution and absorption rate constant were 61.6 l (95% prediction interval (PI) 22.4, 83.7) and 0.564 h(-1) (95% PI 0.208, 0.947), respectively. The model yielded a theoretical value for the CL/F of lopinavir without ritonavir of 14.8 l h(-1) (95%PI 12.1, 20.1), which translates to a value of 5.73 l h(-1) in the presence of ritonavir. The only factor with significant effect on the pharmacokinetics was concurrent use of non-nucleoside reverse transcriptase inhibitors (NNRTI), which increased the CL/F of lopinavir by 39% (P < 0.001). CONCLUSIONS We have developed a model that has defined a time-independent inverse relationship between the exposure to ritonavir and the CL/F of lopinavir, and provided an adequate description of the pharmacokinetic parameters for the latter. Concomitant use of the NNRTIs efavirenz and nevirapine increased the CL/F of lopinavir.
Phosphorus studies in pigs

Two experiments were conducted (1) to determine the effects of phytase (EC 3.1.3.26) on the digestibility and availability of P in soya-bean meal for growing pigs and (2) to compare growth v. digestibility variables for assessing the availability of P. In the first experiment the effect of phytase on P availability was assessed in a growth assay using a slope–ratio design of treatments. Two different levels of either monosodium phosphate (MSP) or soya-bean meal were added to a basal sugar–soya-bean-meal diet (2·5 g P/kg) to give two levels of P (g/kg): 3·25 and 4·0 for each source. An additional five diets were supplemented with phytase. The ten diets were offered ad lib. for 35 d to female pigs initially weighing 20 kg live weight. In addition, the relative effectiveness of different variables for assessing P availability were compared: bone bending moment, ash in various bones, and ash and P in the empty body. The addition of phytase increased growth rate (g/d) (741 v. 835; P < 0·05), lowered the food conversion ratio (2·37 v. 2·16; P < 0·01), and increased protein deposition (g/d) (108 v. 123; P < 0·05), protein retention (kg/kg) (0·33 v. 0·36; P < 0·05), energy retention (MJ gross energy/MJ digestible energy) (0·36 v. 0·38; P < 0·05) and the availability of P in soya-bean meal from 0·11 to 0·69 when bone bending moment was the criterion of availability. All other criteria for assessing availability were unsuitable. In the second experiment the availability of (P) in soya-bean meal was assessed in a digestibility experiment with grower pigs using diets 1–5 as for Expt 1 arranged in a slope–ratio design of treatments. In addition, the effects of phytase supplementation on the apparent digestibility of P, dry matter, crude protein (N × 6·25) and energy were determined. The diets were offered at three times maintenance energy requirements to male pigs initially weighing approximately 30 kg live weight and total collection of faeces was conducted over a 10 d period. The availability of P in the soya-bean meal was 0·66 using digestible P intake as the criterion of response. The apparent digestibility of P in soya-bean meal was 0·42. Phytase supplementation increased the apparent digestibility of soya-bean meal P to 0·69 (P < 0·01) but had no effect on the faecal digestibility of dry matter or crude protein. Overall these experiments indicate that (1) estimates of P digestibility and availability were unlikely to be interchangeable and (2) phytase was effective in releasing much of the bound P in soya-bean meal.
Serotonin triggers a transient epigenetic mechanism that reinstates adult visual cortex plasticity in rats

Cortical circuitries are highly sensitive to experience during early life but this phase of heightened plasticity decreases with development. We recently demonstrated that fluoxetine reinstates a juvenile‐like form of plasticity in the adult visual system. Here we explored cellular and molecular mechanisms that underlie the occurrence of these plastic phenomena. Adult rats were intracortically treated with serotonin (5‐HT) whereas long‐term fluoxetine‐treated rats were infused with the 5‐HT1A‐receptor antagonist WAY‐100635, brain‐derived neurotrophic factor (BDNF) scavenger trkB‐IgG or the mitogen‐activated protein kinase inhibitor U0126. Plasticity was assessed as variations of visual cortex responsiveness after unilateral eyelid suture and reverse occlusion by using an electrophysiological approach. Real‐time PCR and chromatin immunoprecipitation analysis were then used to explore alterations in gene expression and modifications of chromatin structure associated with the plastic outcome caused by fluoxetine in the visual system. Local infusion of 5‐HT into visual cortex restored susceptibility to monocular deprivation in adulthood whereas infusion of WAY‐100635, trkB‐IgG or U0126 prevented the process of plasticity reactivation in fluoxetine‐treated animals. Long‐term fluoxetine treatment promoted a transient increase of Bdnf expression in the visual cortex, which was paralleled by an increased histone acetylation status at Bdnf promoter regions and by decreased expression of Hdac5. Accordingly, enhancing histone acetylation levels by systemic treatment with Trichostatin‐A reactivated plasticity in the adult while WAY‐100635‐infusion prevented epigenetic modifications in Bdnf promoter areas. The data suggest a key role for 5‐HT1A receptor and BDNF‐trkB signalling in driving a transitory epigenetic remodelling of chromatin structure that underlies the reactivation of plasticity in the visual system.
The M Domain of atToc159 Plays an Essential Role in the Import of Proteins into Chloroplasts and Chloroplast Biogenesis*

Toc159, a protein located in the outer envelope membrane and the cytosol, is an important component of the receptor complex for nuclear-encoded chloroplast proteins. We investigated the molecular mechanism of protein import into chloroplasts by atToc159 using the ppi2 mutant, which has a T-DNA insertion at atToc159, shows an albino phenotype, and does not survive beyond the seedling stage due to a defect in protein import into chloroplasts. First we established that transiently expressing atToc159 in protoplasts obtained from the white leaf tissues of ppi2 plants complements the protein import defect into chloroplasts. Using this transient expression approach and a series of deletion mutants, we demonstrated that the C-terminal membrane-anchored (M) domain is targeted to the chloroplast envelope membrane in ppi2 protoplasts, and is sufficient to complement the defect in protein import. The middle GTPase (G) domain plays an additional critical role in protein import: the atToc159[S/N] and atToc159[D/L] mutants, which have a mutation at the first and second GTP-binding motifs, respectively, do not support protein import into chloroplasts. Leaf cells of transgenic plants expressing the M domain in a ppi2 background contained nearly fully developed chloroplasts with respect to size and density of thylakoid membranes, and displayed about half as much chlorophyll as wild-type cells. In transgenic plants, the isolated M domain localized to the envelope membrane of chloroplasts but not the cytosol. Based on these results, we propose that the M domain is the minimal structure required to support protein import into chloroplasts, while the G domain plays a regulatory role.
Management of nodules with initially nondiagnostic results of thyroid fine-needle aspiration: can we avoid repeat biopsy?

PURPOSE To identify demographic and ultrasonographic (US) features associated with malignancy after initially nondiagnostic results of fine-needle aspiration (FNA) to help clarify the role of repeat FNA, surgical excision, or serial US in these nodules. MATERIALS AND METHODS This study was HIPAA compliant and institutional review board approved; informed consent was waived. Thyroid nodules (n = 5349) that underwent US-guided FNA in 2004-2012 were identified; 393 were single nodules with nondiagnostic FNA results but adequate cytologic, surgical, or US follow-up. Demographic information and diameters and volume at US at first biopsy were modeled with malignancy as outcome through medical record review. Exact logistic regression was used to model malignancy outcomes, demographic comparisons with age were made (Student t test, Satterthwaite test), and proportion confidence intervals (CIs) were estimated (Clopper-Pearson method). RESULTS Of 393 nodules with initially nondiagnostic results, nine malignancies (2.3%) were subsequently diagnosed with repeat FNA (n = 2, 0.5%) or surgical pathologic examination (n = 7, 1.8%), 330 (84.0%) were benign, and 54 (13.7%) were stable or decreased in size at serial US (mean follow-up, 3.0 years; median, 2.5 years; range, 1.0-7.8 years). Patients with malignancies were significantly older (mean age, 62.7 years; median, 64 years; range, 47-77 years) than those without (mean age, 55.4 years; median, 57 years; range, 12-94 years; P = .0392). Odds of malignancy were 4.2 times higher for men versus women (P = .045) and increased significantly for each 1-cm increase in anteroposterior, minimum, and mean nodule diameter (1.78, 2.10, and 1.96, respectively). In 393 nodules, no malignancies were detected in cystic or spongiform nodules (both, n = 11, 2.8%; 95% CI: 1.4%, 5.0%), nodules with eggshell calcifications (n = 9, 2.3%; 95% CI: 1.1%, 4.3%), or indeterminate echogenic foci (n = 39, 9.9%; 95% CI: 7.2%, 13.3%). CONCLUSION Very few malignancies were diagnosed with repeat FNA following nondiagnostic FNA results (two of 336, 0.6%); therefore, clinical and US follow-up may be more appropriate than repeat FNA following nondiagnostic biopsy results.
Levels of Sentence Constraint and Lexical Decision in the Two Hemispheres

This study used a lexical decision-priming paradigm to investigate the relative sensitivity of the two cerebral hemispheres to linguistic constraint. Level of constraint of syntactically and semantically correct priming sentences was determined by the Cloze procedure and constraint was manipulated by means of these sentences. High-, medium-, and low-constraining as well as neutral incomplete sentences were presented centrally prior to the appearance of a target word or nonword either to the left or to the right visual field of sixteen righthanded subjects. The hypothesis tested was that the left hemisphere benefits more from linguistic constraint than the right hemisphere. Although reaction time data generally supported this hypothesis, the right hemisphere also seemed to benefit from the constraint produced by high-constraint sentences. The relevance of these findings to the manner in which the two hemispheres process different kinds of linguistic material is discussed.
Heart Rate Turbulence After Short Runs of Nonsustained Ventricular Tachycardia in Chronic Heart Failure

Background: Heart rate turbulence (HRT) following isolated premature complexes is a baroreceptor‐mediated prognostic marker. Short runs of spontaneous, nonsustained ventricular tachycardia (nsVT) exert a greater hemodynamic effect than extrasystoles and may trigger a more potent turbulence‐like response (HRTVT), possibly related to other risk‐related markers, such as heart rate variability (HRV), left ventricular ejection fraction (EF), and original HRT parameters (turbulence slope [TS] and turbulence onset [TO]).
Modulatory effect of spice extracts on iron‐induced lipid peroxidation in rat liver

The antioxidants in foods play an important role in preventing the generation of reactive oxygen species (ROS). Some of the dietary constituents, commonly used in Indian foods such as cloves (Syzygium aromaticum), licorice (Glycyrrhiza glabra), mace (aril of Myristica fragrans) and greater cardamom (Amomum subulatum), were selected as the test samples to find their effect on the inhibition of lipid peroxidation (LPO) in rat liver homogenate. Three different oxidant systems were used to induce LPO. The results show that all the spices have antioxidant activities at various concentrations. None of the spices showed prooxidant properties. The effect of spices on the inhibition of LPO was concentration dependent. Cloves, mace and cardamom inhibited the initiation as well as propagation phases of FeCl3 induced LPO, while licorice inhibited the initiation phase only. The reducing power and the superoxide scavenging activity of spices was also measured in vitro. The reducing power of various spices increased with concentration. The percentage inhibition of superoxide radical generation by the spices was also observed to be concentration dependent. The results show that spices used in the present study have significant ability to inhibit LPO due to their polyphenol content, strong reducing power and superoxide radical scavenging activity. Cloves showed the highest antioxidant activity probably due to the higher polyphenol content as compared to other spices.