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Ferraris A Rappaport E Santacroce R Pollak E Krantz I Toth S Lysholm F Margaglione M Restagno G Dallapiccola B Surrey S Fortina P 《Human mutation》2002,20(4):312-320
Hereditary hearing loss (HHL) is one of the most common congenital disorders and is highly heterogeneous. Mutations in the connexin 26 (CX26) gene (GJB2) account for about 20% of all cases of childhood deafness, and approach 50% in documented recessive cases of non-syndromic hearing loss. In addition, a single mitochondrial DNA mutation, mt1555A>G, in the 12S rRNA gene (MTRNR1), is associated with familial cases of progressive deafness. Effective screening of populations for HHL necessitates rapid assessment of several of these potential mutation sites. Pyrosequencing links a DNA synthesis protocol for determining sequence to an enzyme cascade that generates light whenever pyrophosphate is released during primer strand elongation. We assessed the ability of Pyrosequencing to detect common mutations causing HHL. Detection of the most common CX26 mutations in individuals of Caucasian (35delG), Ashkenazi (167delT), and Asian (235delC, V37I) descent was confirmed by Pyrosequencing. A total of 41 different mutations in the CX26 gene and the mitochondrial mt1555A>G mutation were confirmed. Genotyping of up to six different adjacent mutations was achieved, including simultaneous detection of 35delG and 167delT. Accurate and reproducible results were achieved taking advantage of assay flexibility and experimental conditions easily optimized for a high degree of standardization and cost-effectiveness. The standardized sample preparation steps, including target amplification by PCR and preparation of single-stranded template combined with automated sequence reaction and automated genotype scoring, positions this approach as a potentially high throughput platform for SNP/mutation genotyping in a clinical laboratory setting. . 相似文献
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Fang Huang Nittaya Marungruang Olha Kostiuchenko Nadiia Kravchenko Stephen Burleigh Olena Prykhodko Frida Fk Hllenius Lovisa Heyman-Lindn 《Nutrients》2022,14(13)
High-fat diets are associated with neuronal and memory dysfunction. Berries may be useful in improving age-related memory deficits in humans, as well as in mice receiving high-fat diets. Emerging research has also demonstrated that brain health and cognitive function may be related to the dynamic changes in the gut microbiota. In this study, the impact of Nordic berries on the brain and the gut microbiota was investigated in middle-aged C57BL/6J mice. The mice were fed high-fat diets (60%E fat) supplemented with freeze-dried powder (6% dwb) of bilberry, lingonberry, cloudberry, blueberry, blackcurrant, and sea buckthorn for 4 months. The results suggest that supplementation with bilberry, blackcurrant, blueberry, lingonberry, and (to some extent) cloudberry has beneficial effects on spatial cognition, as seen by the enhanced performance following the T-maze alternation test, as well as a greater proportion of DCX-expressing cells with prolongation in hippocampus. Furthermore, the proportion of the mucosa-associated symbiotic bacteria Akkermansia muciniphila increased by 4–14 times in the cecal microbiota of mice fed diets supplemented with lingonberry, bilberry, sea buckthorn, and blueberry. These findings demonstrate the potential of Nordic berries to preserve memory and cognitive function, and to induce alterations of the gut microbiota composition. 相似文献
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Scott T. Chiesa Marietta Charakida Georgios Georgiopoulos Frida Dangardt Kaitlin H. Wade Alicja Rapala Devina J. Bhowruth Helen C. Nguyen Vivek Muthurangu Rukshana Shroff George Davey Smith Debbie A. Lawlor Naveed Sattar Nicholas J. Timpson Alun D. Hughes John E. Deanfield 《JACC: Cardiovascular Imaging》2021,14(2):468-478
ObjectivesThis study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years.BackgroundGreater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood.MethodsAssociations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.ResultsFat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: ?0.0032; 95% CI: 0.004 to ?0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor?associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.ConclusionsSubtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood. 相似文献
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Marilia Carabotti Gianfranco Silecchia Francesco Greco Frida Leonetti Luca Piretta Marco Rengo Mario Rizzello John Osborn Enrico Corazziari Carola Severi 《Obesity surgery》2013,23(10):1551-1557
Background
Altered gastric anatomy following laparoscopic sleeve gastrectomy (LSG) is likely to induce upper gastrointestinal (GI) symptoms. Published studies, however, have focused mainly on gastroesophageal reflux disease (GERD). This study aims to evaluate LSG's impact on the prevalence of upper GI symptoms and to assess the effects of time from surgery, weight loss, and proton pump inhibitor (PPI) therapy.Methods
The validated Rome III Criteria symptom questionnaire for upper GI symptoms, including quality of life items, has been self-administered to 97 patients who underwent LSG. Symptoms were analyzed either separately or altogether to classify patients in GERD or dyspepsia, subdivided in epigastric pain (EPS) and post-prandial distress (PDS) syndromes.Results
Before LSG, 52.7 % of the patients were asymptomatic, 27.0 % had GERD, and 8.1 % had dyspepsia (2.7 % EPS, 5.4 % PDS). After a median follow-up of 13 months, 91.9 % of the patients complained of upper GI symptoms, the most prevalent being PDS (59.4 %). GERD prevalence did not differ before and after LSG. The only symptom strongly related to LSG was dysphagia (OR 4.7, 95 % CI 1.3–20.4, p?=?0.015), which was present in 19.7 % of the patients and mainly associated with PDS rather than GERD. GI symptoms, however, did not have a great impact on quality of life. Time from surgery, weight loss after surgery, as well as concomitant PPI, did not influence the symptoms.Conclusions
After a median follow-up of 13 months, PDS-like dyspepsia, rather than GERD, was the main complaint, both poorly responding to PPI therapy. A longer follow-up will be necessary to evaluate their future persistency. 相似文献9.
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Aurélien Fotso Fotso Frida Longo Paul Désiré Dzeufiet Djomeni Siméon Fogue Kouam Michael Spiteller Alain Bertrand Dongmo J. P. Savineau 《Inflammopharmacology》2014,22(2):105-114
Bidens pilosa is an Asteraceae widely used in traditional medicine for the treatment of various ailments including pain and inflammation. The present work was undertaken to assess the analgesic and antiinflammatory properties of the ethyl acetate fraction of methylene chloride/methanol (1:1) extract of leaves of Bidens pilosa at the gradual doses of 50, 100 and 200 mg/kg in mice and rats, respectively. The analgesic properties of Bidens pilosa were investigated using the acetic acid writhing, hot plate, capsaicin and formalin-induced pain models. This was followed by a study of the antiinflammatory properties using carrageenan, dextran, histamine and serotonin to induce acute inflammation in rat hind paw. The extract provided a significant (p < 0.01) reduction in pain induced by all four models of nociception. It also presented significant (p < 0.05) antiinflammatory activity in all four models of acute inflammation. These results show that the ethyl acetate fraction of methylene chloride/methanol (1:1) of Bidens pilosa has both analgesic and antiinflammatory properties. The qualitative analysis of the fraction by the high-performance liquid chromatography (HPLC) fingerprint revealed the presence of two flavonoids, namely quercetin and iso-okanin, known to have antiinflammatory and antinociceptive properties, which could be responsible for the analgesic and antiinflammatory effects observed. 相似文献