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Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition 下载免费PDF全文
Maider Ibarrola‐Villava Rajiv Kumar Eduardo Nagore Meriem Benfodda Mickael Guedj Steven Gazal Hui‐Han Hu Jian Guan P. Sivaramakishna Rachkonda Vincent Descamps Nicole Basset‐Seguin Armand Bensussan Martine Bagot Philippe Saiag Dirk Schadendorf Manuel Martin‐Gonzalez Matias Mayor Bernard Grandchamp Gloria Ribas Soufir Nadem 《International journal of cancer. Journal international du cancer》2015,136(9):2109-2119
Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high‐risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta‐analysis (3940 melanoma cases and 3620 controls) with two‐side p values of 0.002, (OR = 0.86) and 4.07 × 10?10 (OR = 0.80), respectively. Exome sequencing revealed a non‐synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma. 相似文献
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ObjectivesNon-communicable diseases have increased in Tunisia after the epidemiological transition. That is why the national strategy to prevent and control obesity was elaborated and implemented. Improving the quality of foods is one axis of this strategy. The purpose of this paper was to estimate and evaluate the nutritional profiles of Tunisian foods sold by fast food restaurants, and explore ways for improvement.Material and methodsNutritional quality of 35 average recipes or items was assessed by 70 recipes of dishes sold by fast food restaurants. The SAIN,LIM French scoring system was used. Foods were classified into the four SAIN,LIM classes, i.e. from the healthiest (class 1) to the least healthy (class 4). The recipes were then reformulated and improved by deleting or reducing some unfavorable ingredients like salt.ResultsBefore reformulation, the items were spread over the 4 SAIN,LIM classes (class 1: 42.9%; class 2: 8.6%; class 3: 20.0% and class 4: 28.6%). After reformulation, the items were spread over class 1 (85.7%) and class 3 (14.3%), showing clear improvement of their nutritional quality.ConclusionIn Tunisia, an important percentage of foods sold by fast food restaurant have a good nutrient profile (43%). After reformulation, most items were in the healthiest class. This study is the first to show that it is possible to improve the nutritional quality of foods sold by fast food restaurants, and that the SAIN,LIM system can help to that end. 相似文献
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S Chouchane C H Chouchane C H Ben Meriem B Seket S Hammami S Nouri K Monastiri M N Guediche 《Archives de pédiatrie》2004,11(11):1319-1325
BACKGROUND: The first problem to face in prolonged fever is its etiologic diagnosis. Its incidence varies between 0,5 to 3% of all paediatric hospital-stay. Precise diagnosis need an extensive questionnary, complete physical examination and an algorithm of complementary exams. PURPOSE: To precise the epidemiologic profile and causes of prolonged fever in a children. POPULATION AND METHODS: Retrospective review of 67 children between two and 15 years old admitted in the general paediatrics department of the Fattouma Bourguiba university hospital in Monastir (Tunisia), for prolonged fever between 1(st) January 1988 and 31 December 1998. RESULTS: The incidence of prolonged fever was 1,02%. The mean age was seven years with female predominance. The mean fever duration was 30 days. Fever was isolated in 23,9% of cases. Fever was associated to rheumatic or respiratory signs in respectively 26,9% and 20,9% of cases. Hospital-stay was of 11 days in 50% of cases. Prominent causes were dominated by infectious diseases (56,7%) with predominance of localized infections, followed by inflammatory diseases (20,9%) with predominance of rheumatic fever and neoplasms (3%). Fever remained of unknown origin was seen in 19,4% of cases. CONCLUSION: Prolonged fever is still dominated by infectious and inflammatory diseases and depend on local epidemiological particularities. In fact we noted in this study the relative high-frequency of visceral leishmaniasis, complicated pulmonary hydatic cyst and rheumatic fever. The diagnosis approach should be based on complementary exams of first and second stage because of their high number and cost. Prognosis of fever of unknown origin is often favorable. 相似文献
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Antonio Valentín Richard P. Selway Meriem Amarouche Nilesh Mundil Ismail Ughratdar Leila Ayoubian David Martín-López Farhana Kazi Talib Dar Diego Jiménez-Jiménez Elaine Hughes Gonzalo Alarcón 《European journal of paediatric neurology》2017,21(1):223-231
Objectives
To evaluate the efficacy of intracranial stimulation to treat refractory epilepsy in children.Methods
This is a retrospective analysis of a pilot study on all 8 children who had intracranial electrical stimulation for the investigation and treatment of refractory epilepsy at King's College Hospital between 2014 and 2015. Five children (one with temporal lobe epilepsy and four with frontal lobe epilepsy) had subacute cortical stimulation (SCS) for a period of 20–161 h during intracranial video-telemetry. Efficacy of stimulation was evaluated by counting interictal discharges and seizures. Two children had thalamic deep brain stimulation (DBS) of the centromedian nucleus (one with idiopathic generalized epilepsy, one with presumed symptomatic generalized epilepsy), and one child on the anterior nucleus (right fronto-temporal epilepsy). The incidence of interictal discharges was evaluated visually and quantified automatically.Results
Among the three children with DBS, two had >60% improvement in seizure frequency and severity and one had no improvement. Among the five children with SCS, four showed improvement in seizure frequency (>50%) and one chid did not show improvement. Procedures were well tolerated by children.Conclusion
Cortical and thalamic stimulation appear to be effective and well tolerated in children with refractory epilepsy. SCS can be used to identify the focus and predict the effects of resective surgery or chronic cortical stimulation. Further larger studies are necessary. 相似文献87.
David Moulin Arnaud Bianchi Sandrine Boyault Sylvie Sebillaud Meriem Koufany Mathias Francois Patrick Netter Jean‐Yves Jouzeau Bernard Terlain 《Arthritis \u0026amp; Rheumatology》2005,52(3):759-769
Objective
To study the potency of 2 peroxisome proliferator–activated receptor γ (PPARγ) agonists, 15‐deoxy‐Δ12,14‐prostaglandin J2 (15‐deoxy‐PGJ2) and rosiglitazone, to modulate the expression of interleukin‐1 receptor antagonist (IL‐1Ra) in rat synovial fibroblasts.Methods
Levels of messenger RNA for IL‐1Ra and PPAR isotypes (α, β/δ, γ) were assessed by real‐time polymerase chain reaction in rat synovial fibroblasts exposed to 10 ng/ml of IL‐1β. PPAR levels were assessed by Western blotting and secreted IL‐1Ra levels by immunoassay. The potency of PPARγ agonists and the PPARβ/δ agonist GW‐501516 on IL‐1Ra levels was tested in the range of 1–10 μM and at 100 pM, respectively. The contribution of PPARγ to the effects of rosiglitazone on IL‐1Ra secretion was examined either by its overexpression or by inhibition using wild‐type or dominant‐negative constructs and the antagonist GW‐9662 (10 μM), respectively. The dominant‐negative strategy was also performed to investigate the possible contribution of PPARβ/δ and NF‐κB activation.Results
IL‐1β–induced IL‐1Ra production was increased by 10 μM rosiglitazone but was reduced dose‐dependently by 15‐deoxy‐PGJ2. Both agonists lowered IL‐1β secretion, but rosiglitazone alone reduced the imbalance of IL‐1β/IL‐1Ra toward basal levels. Enhancement of IL‐1β–induced IL‐1Ra production by rosiglitazone was not affected by PPARγ overexpression or by its inhibition with dominant‐negative PPARγ or GW‐9662. Inhibition of NF‐κB was also ineffective against rosiglitazone but abolished the stimulating effect of IL‐1β on IL‐1Ra. All PPAR isotypes were expressed constitutively in rat synoviocytes, but PPARγ decreased dramatically upon IL‐1β exposure, whereas PPARβ/δ remained stable. Dominant‐negative PPARβ/δ abolished the enhancement of IL‐1Ra by rosiglitazone, whereas GW‐501516 reproduced the effect of rosiglitazone on IL‐1Ra secretion.Conclusion
Rosiglitazone stimulates IL‐1Ra production by a PPARβ/δ mechanism in activated rat synovial fibroblasts, further contributing to its potential antiarthritic properties and opening new perspectives for the modulation of inflammatory genes by specific PPAR agonists in articular cells.88.
Mohammed Benzagmout Sa?d Boujraf Badreeddine Alami Hassane Ali Amadou Halima El Hamdaoui Amine Bennani Mounir Jaafari Ismail Rammouz Mustapha Maaroufi Rabia Magoul Driss Boussaoud 《中国神经再生研究》2019,(4)
Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease. 相似文献
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