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991.
《Genetics in medicine》2022,24(9):1857-1866
PurposePenetrance estimates of Birt-Hogg-Dubé syndrome (BHD)-associated cutaneous, pulmonary, and kidney manifestations are based on clinically ascertained families. In a health care system population, we used a genetics-first approach to estimate the prevalence of pathogenic/likely pathogenic (P/LP) truncating variants in FLCN, which cause BHD, and the penetrance of BHD-related phenotypes.MethodsExomes from 135,990 patient-participants in Geisinger’s MyCode cohort were assessed for P/LP truncating FLCN variants. BHD-related phenotypes were evaluated from electronic health records. Association between P/LP FLCN variants and BHD-related phenotypes was assessed using Firth’s logistic regression.ResultsP/LP truncating FLCN variants were identified in 35 individuals (1 in 3234 unrelated individuals), 68.6% of whom had BHD-related phenotype(s), including cystic lung disease (65.7%), pneumothoraces (17.1%), cutaneous manifestations (8.6%), and kidney cancer (2.9%). A total of 4 (11.4%) individuals had prior clinical BHD diagnoses.ConclusionIn this health care population, the frequency of P/LP truncating FLCN variants is 60 times higher than the previously reported prevalence. Although most variant-positive individuals had BHD-related phenotypes, a minority were previously clinically diagnosed, likely because cutaneous manifestations, pneumothoraces, and kidney cancer were observed at lower frequencies than in clinical cohorts. Improved clinical recognition of cystic lung disease and education concerning its association with FLCN variants could prompt evaluation for BHD. 相似文献
992.
Yue Kang Yi Li Fengyan Xu Jing Zhang Kun Wang Yuancheng Chen Jufang Wu Beining Guo Jicheng Yu Yingyuan Zhang 《Clinical therapeutics》2019,41(3):505-517.e0
Purpose
Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone that has been approved for the treatment of community-acquired pneumonia (CAP) in adults. The goals of this study were to evaluate the pharmacokinetic (PK) and population PK parameters of nemonoxacin and to provide the appropriate dose adjustment recommendations for patients with hepatic impairment.Methods
An open-label, single-dose, parallel group (moderate hepatic impairment group and healthy control group) PK study of nemonoxacin was conducted. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) was performed to detect the unchanged nemonoxacin concentration in blood and urine samples. The nonlinear mixed effects modeling tool NONMEN (version 7.3) was used to conduct the population PK analysis. The paired-t test was conducted to compare the PK parameters of the hepatic impairment group and the healthy control group by SPSS (Version 17.0).Findings
Ten subjects for each group were enrolled into the PK study. The PK parameters as well as the plasma concentration-time and logarithmic concentration-time profiles after taking a 500-mg single dose of nemonoxacin showed few differences between the two groups (P > 0.05). The mean areas under the plasma concentration vs. time curve from 0 to 72 h (AUC0-72 h) of the moderate hepatic impairment group and the healthy control group in the nemonoxacin PK study were 58.50 (17.30) mg·h/mL and 49.74 (10.16) mg·h/mL, respectively, giving a mean (SD) AUC0-72 h ratio of 1.15 (0.42) with a 90% CI of 0.91–1.39. A 3- compartment model was considered to be the best model for the data, especially in fitting the plasma point at low drug concentrations. Covariate analysis indicated that weight affected CL/F, V1/F, and V3/F and that eGFR only affected CL/F in the power function model, while gender affected V3/F in the linear model by forward selection and backward deletion.Implications
The population PK parameters of nemonoxacin were evaluated in patients with hepatic impairment. The hepatic function did not have a significant impact on the PK parameters of nemonxacin, but renal function was a meaningful covariate that is consistent with its PK characteristics. In this study, nemonoxacin was well tolerated in the patients with moderate hepatic impairment as well as in the healthy subjects. Based on these data, it is not necessary to consider dose adjustment of nemonoxacin in patients with mild or moderate hepatic impairment. ClinicalTrials.gov identifier: NCT02604498. 相似文献993.
目的探讨广西地区人群中LncRNA GAS5基因启动子区1个功能性插入/缺失位点(rs145204276I/D)多态性的分布特点,并分析广西地区人群与其他地区人群rs145204276I/D位点多态性的分布差异。方法采用SNPscan技术对289例广西地区人群GAS5基因rs145204276I/D位点进行基因分型检测,统计其基因型和等位基因在广西地区人群不同性别间的分布,并分析其多态性与国际千人基因组计划(1000 genome project)数据库公布的欧洲人群(European,EUR)、日本人群(Japanese in Tokyo;JPT,)、西亚人群(South Asian,SAS)、美国人群(Ad Mixed American,AMR)、非洲人群(African,AFR)、北京人群(Han Chinese in Beijing,CHB)以及文献报道的南京、吉林、重庆和昆明人群的分布差异。结果广西地区人群GAS5基因rs145204276I/D位点I/I、I/D和D/D基因型频率分别为48.4%、43.6%和8.0%,I和D等位基因频率分别为70.2%和29.8%。rs145204276I/D基因型和等位基因频率在广西地区人群不同性别间比较差异无统计学意义(P0.05)。广西地区人群GAS5基因rs145204276I/D位点的基因型和等位基因频率与EUR、AFR、AMR和JPT人群比较差异均有统计学意义(P均0.05),而与CHB、南京、吉林、重庆和昆明人群比较差异均无统计学意义(P0.05)。结论广西地区人群LncRNA GAS5基因rs145204276I/D位点基因多态性在男性和女性人群中分布无差异,而其多态性与其他地区人群间比较存在不同程度的差异。 相似文献
994.
Marta Krenz-Niedbała Sylwia Łukasik Jakub Macudziński Szymon Chowański 《Anatomical record (Hoboken, N.J. : 2007)》2022,305(8):1947-1961
Human auditory ossicles, the malleus, the incus, and the stapes, are located in the tympanic cavity in the temporal bone and through forming a chain for the sound transmission from the tympanic membrane to the cochlea, they play an important role in the hearing process. Despite their clinical, phylogenetic, and evolutionary significance, the morphometry of the human ear bones has not been examined systematically. The ear ossicles are the smallest bones of the human skeleton, attaining their final size and morphology already at birth. Initially, they have been found to exhibit minimal morphometric variation, but further studies brought the opposite results. The aim of this study was to examine the morphometric variation of human auditory ossicles recovered from medieval and postmedieval subadult skeletons from Poland, Central Europe. The analysis involved in a total of 166 ear bones. Their measurements were performed on microscopic images using CorelDraw x4, according to a protocol of Quam and Rak with modification of Flohr et al. and Wadhwa et al. Our study showed a significant metric variation in the measurements taken at areas of the greatest morphological variability of the ossicles. We found that greater linear dimensions were associated with lower values of angular measurements. These results reveal the inherent variation found in these supposed functionally constrained structures. Representation of even greater number of populations, time periods, and developmental stages are needed. Further study will expand our understanding of the global scope of variation found in ear ossicular morphology and its functional implications for paleoanthropology. 相似文献
995.
Mandana Rafeey Reza Ghotaslou Solmaz Nikvash Asghar Ashrafy Hafez 《Journal of infection and chemotherapy》2007,13(5):291-295
Helicobacter pylori-associated infection is extre-mely common in Iran, as in other developing countries, but few data exist on the susceptibility
of H. pylori to antimicrobials commonly used in the eradication schedules in this country. This study was performed to determine the resistance
rate to six antimicrobial agents used in the treatment of H. pylori infection in dyspeptic Iranian children and to recommend an updated anti-H. pylori treatment regimen to use in children. All H. pylori isolated from children who were undergoing gastroscopy were prospectively collected and subcultured to yield their susceptibility
to six antimicrobial agents, by E test and disk diffusion methods. Demographic data and presenting symptoms were also collected.
A prospective study was carried out from January 2003 to January 2005 with 100 strains of H. pylori isolated from children (40 girls and 60 boys; age range, 1.5 to 16 years [mean, 9.22 ± 3.25 years]); the strains had been
successfully subcultured to yield antimicrobial sensitivity. Overall the H. pylori resistance rate was 95% to metronidazole, 59% to amoxicillin, 16% to clarithromycin, 9% to furazolidone, 7% to ciprofloxacin,
and 5% to tetracycline. The most common presenting symptom was abdominal pain. There were no statistically significant differences
in antimicrobial resistance rates related to age, sex, or clinical presentation. In the Iranian children, the prevalence of
H. pylori resistance was very high to metronidazole and amoxicillin, moderate to clarithromycin, and low to ciprofloxacin and tetracycline. 相似文献
996.
Fukuda T Yukawa E Kondo G Maeda T Shin-o T Kondo Y Imamura T Irikura M Irie T 《Journal of clinical pharmacy and therapeutics》2005,30(6):591-596
OBJECTIVE: To estimate the population pharmacokinetics of theophylline in very premature infants using the non-linear mixed effects modelling. METHOD: A total of 167 serum concentration measurements obtained from routine theophylline monitoring of 107 very premature Japanese infants were collected. RESULTS: The final pharmacokinetic parameters were CL (mL/h) = [6.98 . body weight (BW) (kg)(2.17) + 0.244 . post-conceptional age (weeks)] . 1.24(oxygen support), Vd (L) = 0.492 . BW (kg) and F = 0.660, respectively. Clearance was increased by 24% for patients receiving oxygen support. The inter-individual variabilities in clearance and apparent volume of distribution were 15.6% and 80.4%, respectively, and the residual variability was 34.2% as a coefficient of variation. CONCLUSION: Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target theophylline concentrations, thus enabling the clinician to achieve the desired therapeutic effect in very premature Japanese infants. 相似文献
997.
An-Jing Kuo Jwu-Ching Shu Tsui-Ping Liu Jang-Jih Lu Ming-Hsun Lee Ting-Shu Wu Lin-Hui Su Tsu-Lan Wu 《Journal of microbiology, immunology, and infection》2018,51(6):821-828
Background/purposes
Vancomycin resistance increased significantly to 31.3% among Enterococcus faecium in 2006 and remained high thereafter at a university hospital in Taiwan. A longitudinal study was retrospectively conducted to characterize these vancomycin-resistant E. faecium (VRE-fm).Methods
A total of 378 non-repetitive VRE-fm blood isolates collected during 2002–2015 were studied. Multilocus sequence typing, pulsed-field gel electrophoresis, analysis of van genes and the Tn1546 structure, and conjugation experiments were performed.Results
The majority (78.0%) of the isolates were associated with hospital-acquired infections. Molecular typing revealed nine major pulsotypes and five predominant sequence types (STs): ST17 (33.9%), ST78 (18.3%), ST414 (14.6%), ST18 (10.6%), and ST203 (7.4%). Fluctuation of these prevailing STs among the study years in association with some major pulsotypes was noted. All isolates carried vanA genes, except that in four isolates vanB genes were found. Among the vanA-carrying Tn1546-like elements, one predominant structure type (Type I, 55.9%) was noted throughout the study years. Since 2009, another predominant structure type (Type II, 40.1%) has emerged firstly in ST414 and gradually spread to other 11 STs in subsequent years. Isolates carrying these Type II Tn1546-like elements have become the most predominant population since 2014, majorly found in ST78 and ST17. Preliminary experiments indicated that plasmids carrying the Type II Tn1546-like elements demonstrated ten-fold higher efficiency than those carrying the Type I Tn1546-like elements.Conclusion
Dissemination of some major STs and horizontal transfer of plasmids carrying two major structure types of Tn1546-like elements may have together contributed to the increase of VRE-fm infection. 相似文献998.
中国南方汉族人群MICA-TM基因座等位基因分布 总被引:4,自引:0,他引:4
目的调查中国南方汉族人群MICA基因穿膜区(TM)基因座多态性分布。方法应用聚合酶链反应和荧光(6-FAM)自动化技术,对中国南方地区106例无亲缘关系汉族人群样本检测MICA—TM,计算基因频率、基因型频率、个体鉴别力、期望杂合性、多态性信息含量和非父排除率。结果MICA—TM基因型分布符合Hardy—Weinberg平衡,共检出MI—CA—TM 5个等位基因,即A4、A5、A5.1、A6和A9;MICA—TM A5基因频率(O.2877)最高,A4基因频率(0.1321)最低;A5—5.1和A5—5基因型分布频率分别为14.15%和10.38%。结论MICA—TM基因座适合作为中国人群的遗传标志,可用于人类学、遗传病的基因连锁分析、法医学亲子鉴定和个体识别等研究领域。 相似文献
999.
Mari Sasaki Jennifer J. Koplin Shyamali C. Dharmage Michael J. Field Susan M. Sawyer Vicki McWilliam Rachel L. Peters Lyle C. Gurrin Peter J. Vuillermin Jo Douglass Angela Pezic Maia Brewerton Mimi L.K. Tang George C. Patton Katrina J. Allen 《The Journal of allergy and clinical immunology》2018,141(1):391-398.e4
1000.
为了解温州市外来流动人口HIV感染情况及其分布特征。对1988-2001年由确诊实验室确诊的流动人口HIV感染者进行统计分析。结果表明,至2001年底温州市共检出102例HIV感染者,其中流动人口82例,占82.39%,死亡10例。82例HIV感染者中外省54例(65.85%),外籍华人华侨28例(34.15%)。外省流动人口HIV感染者以新疆籍为主。男性多于女性。年龄以20-40岁之间为多。感染途径以经血传播为主,占总流动人口感染者的64.63%。1998年前感染者以华侨华人为主,而1999年后则以新疆籍的流动人口为主。调查表明,目前温州市HIV感染者仍以流动人口为主,采取切实可行的措施对控制和预防流动人口艾滋病的流行非常必要和迫切。 相似文献