• 【印度儿科学会关于新生儿听力筛查的共识声明。】 复制标题 收藏 收藏
    DOI:10.1007/s13312-017-1128-9 复制DOI
    作者列表:
    BACKGROUND & AIMS: JUSTIFICATION:Hearing impairment is one of the most critical sensory impairments with significant social and psychological consequences. Evidence-based, standardized national guidelines are needed for professionals to screen for hearing impairment during the neonatal period. PROCESS:The meeting on formulation of national consensus guidelines on developmental disorders was organized by Indian Academy of Pediatrics in Mumbai, on 18th and 19th December, 2015. The invited experts included Pediatricians, Developmental Pediatricians, Pediatric Neurologists and Clinical Psychologists. The participants framed guidelines after extensive discussions. OBJECTIVE:To provide guidelines on newborn hearing screening in India. RECOMMENDATIONS:The first screening should be conducted before the neonate's discharge from the hospital - if it 'fails', then it should be repeated after four weeks, or at first immunization visit. If it 'fails' again, then Auditory Brainstem Response (ABR) audiometry should be conducted. All babies admitted to intensive care unit should be screened via ABR. All babies with abnormal ABR should undergo detailed evaluation, hearing aid fitting and auditory rehabilitation, before six months of age. The goal is to screen newborn babies before one month of age, diagnose hearing loss before three months of age and start intervention before six months of age.
    背景与目标: 证据:听力障碍是最严重的感觉障碍之一,具有重大的社会和心理后果。专业人员在新生儿期筛查听力障碍时,需要以证据为依据的标准化国家准则。
    过程:2015年12月18日至19日,印度儿科学会在孟买组织了关于发展性疾病的国家共识指南的制定会议。受邀的专家包括儿科医生,发育儿科医生,儿科神经病学家和临床心理学家。参加者在广泛讨论后制定了指导方针。
    目的:为印度新生儿听力筛查提供指导。
    建议:应在新生儿出院前进行第一次筛查-如果“失败”,则应在四个星期后或第一次免疫检查时重复进行。如果再次“失败”,则应进行听性脑干反应(ABR)听力测验。所有进入重症监护室的婴儿都应通过ABR进行筛查。所有ABR异常的婴儿应在6个月大之前进行详细评估,安装助听器和进行听觉康复。目的是对一个月大的婴儿进行筛查,在三个月大的婴儿中诊断听力下降,并在六个月大的婴儿开始干预。
  • 【从苏里南筛选5-HT(1A)配体的药用植物:栗色番荔枝果实的生物活性异喹啉生物碱。】 复制标题 收藏 收藏
    DOI:10.1016/S0944-7113(97)80059-1 复制DOI
    作者列表:Hasrat JA,Pieters L,De Backer JP,Vauquelin G,Vlietinck AJ
    BACKGROUND & AIMS: :Plants from Suriname (South-America) and several Annona species, including A. muricata, A. ckerimolia, A. montana and A. glabra were screened for 5-HT(1A) receptor binding activity by ligand-binding-studies (LBS). Crude extracts of all Annona species and from Hibiscus bifurcatus, Irlbarchia purpurascens and Scoparia dulcis showed high activity. The isoquinoline alkaloids asimilobine (1), nornuciferine (2), and annonaine (3) were isolated as the active principles from the fruit of Annona muricata. These results may partially explain the use of Hibiscus bifurcatus and Annona muricata in traditional medicine in Suriname.
    背景与目标: :通过配体结合研究(LBS)筛选了来自苏里南(南美)和几种番荔枝科植物,包括A. muricata,A。ckerimolia,A。montana和A. glabra的植物的5-HT(1A)受体结合活性。 )。所有番荔枝科植物Annfurus bifurcatus,Irlbarchia purpurascens和Scoparia dulcis的粗提物均显示出高活性。从栗Annona muricata的果实中分离出异喹啉生物碱asimilobine(1),nornuciferine(2)和annonaine(3)作为有效成分。这些结果可能部分解释了芙蓉和芙蓉番荔枝在苏里南的传统医学中的使用。
  • 【通过逆转录-聚合酶链反应筛选捷克共和国啤酒花品种中的苹果花叶病毒。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Petrzik K,Svoboda P
    BACKGROUND & AIMS: Thirteen cultivars of hop (Humulus lupulus L.) were tested by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of apple mosaic virus (ApMV). The virus was detected in various amounts in all tested cultivars. Control hop clones derived from tissue cultures, treated by thermotherapy and maintained in greenhouse were virus-free. The procedure for sample preparation and RT-PCR of ApMV is described in detail.

    背景与目标: 通过逆转录-聚合酶链反应(RT-PCR)测试了13个酒花(Humulus lupulus L.)的苹果花叶病毒(ApMV)的存在。在所有测试品种中都检测到了各种数量的病毒。来自组织培养物的对照蛇麻草克隆,经热疗处理并保存在温室中,均不含病毒。详细描述了ApMV的样品制备和RT-PCR步骤。

  • 【为遗传性非息肉病性结直肠癌家庭的妇女提供“一站式”妇科筛查诊所是否会对她们的心理发病率和健康感知产生影响?】 复制标题 收藏 收藏
    DOI:10.1111/j.1525-1438.2007.01009.x 复制DOI
    作者列表:Wood NJ,Munot S,Sheridan E,Duffy SR
    BACKGROUND & AIMS: :Screening programs can reduce the burden of disease, however, they can be associated with raised levels of anxiety. The risk of endometrial and ovarian cancer is increased in hereditary nonpolyposis colorectal cancer (HNPCC). There is no prospective evidence to support screening for gynecological disease in HNPCC, however, current recommendations include the use of ultrasound and endometrial biopsy. This study assesses the impact of screening for gynecological cancer on self-reported symptoms of anxiety, depression, and perceptions of health. Women from HNPCC families attending gynecological screening (n = 26) completed the Hospital Anxiety and Depression Scale and the ShortForm36v2 questionnaires prior to screening with transvaginal ultrasound, outpatient/office hysteroscopy, endometrial biopsy, and ovarian tumor marker assessment (CA125). The same questionnaires were completed at 3 and 6 months following screening (15/26). Women in HNPCC families attending for gynecological screening did not have excess symptoms of anxiety or depression at baseline in subjective comparison to other populations. The process of screening and false positive screening results had no significant impact on symptoms of anxiety and depression or perceptions of health. We conclude that within the limitations of analysis in this small study group, screening for gynecological disease in HNPCC does not appear to be associated with any psychological morbidity.
    背景与目标: :筛查程序可以减轻疾病的负担,但是,它们可能与焦虑水平上升有关。遗传性非息肉病性结直肠癌(HNPCC)会增加子宫内膜和卵巢癌的风险。没有前瞻性证据支持筛查HNPCC中的妇科疾病,但是,当前的建议包括使用超声和子宫内膜活检。这项研究评估了筛查妇科癌症对自我报告的焦虑,抑郁和健康观症状的影响。来自HNPCC家庭的妇科妇女(n = 26)在通过阴道超声,门诊/宫腔镜检查,子宫内膜活检和卵巢肿瘤标志物评估(CA125)进行筛查之前,完成了医院焦虑和抑郁量表和ShortForm36v2问卷。筛选后的3个月和6个月完成了相同的问卷调查(15/26)。与其他人群相比,从主观上看,参加妇科筛查的HNPCC家庭中的妇女在基线时没有过多的焦虑或抑郁症状。筛查的过程和假阳性筛查结果对焦虑和抑郁症状或健康感知没有显着影响。我们得出的结论是,在这个小型研究小组的分析范围内,HNPCC妇科疾病筛查似乎与任何心理疾病均不相关。
  • 【比较活化的凝血活酶部分时间与Russell毒蛇毒液时间测试筛查因子V(Leiden)(FVR506Q)的过程。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Sweeney JD,Blair AJ,King TC
    BACKGROUND & AIMS: :Factor V(Leiden) is the most common abnormality detected in patients examined because of hereditary thrombophilia. The most widely used clot-based screening test is based on the activated partial thromboplastin (aPTT) time. This test has a low sensitivity. A comparison of the aPTT-based test with a Russell viper venom time test (RVVT) was performed in matched samples. All samples were analyzed by polymerase chain reaction (PCR) for the factor V(Leiden) defect. We studied 139 samples, of which 109 were PCR-negative; 30 were PCR-positive. Using the manufacturer's suggested threshold ratio of 2, the aPTT test showed a sensitivity of 0.43, a specificity of 0.86, and a positive predictive value (PPV) of 0.97. The RVVT test had a sensitivity of 1.0, a specificity of 0.95, and a PPV of 0.91. Segregation of a subpopulation of this study population into ABO group O vs non-group O showed an effect of ABO group on the aPTT test but not on the RVVT test, consistent with an influence of factor VIII clotting (factor VIII:C) on the aPTT test. The RVVT test seems superior to the unmodified aPTT test as a screening test for factor V(Leiden).
    背景与目标: :因子V(Leiden)是由于遗传性血栓形成而在检查的患者中检测到的最常见异常。最广泛使用的基于凝块的筛选测试是基于活化的部分凝血活酶(aPTT)时间。此测试的灵敏度较低。在匹配的样本中将基于aPTT的测试与Russell毒蛇毒时间测试(RVVT)进行了比较。通过聚合酶链反应(PCR)分析所有样品中的因子V(Leiden)缺陷。我们研究了139个样本,其中109个为PCR阴性。 30个是PCR阳性的。使用制造商建议的阈值比率2,aPTT测试显示灵敏度为0.43,特异性为0.86,阳性预测值(PPV)为0.97。 RVVT测试的灵敏度为1.0,特异性为0.95,PPV为0.91。将该研究人群的亚群分为ABO组O和非O组,显示ABO组对aPTT测试有影响,但对RVVT测试无影响,这与VIII因子凝血(VIII:C因子)对APTT的影响一致。 aPTT测试。 RVVT测试似乎优于未修改的aPTT测试作为因子V(Leiden)的筛选测试。
  • 【受唐氏综合症影响的怀孕中的早孕期无尿β-hCG,β核心和总雌三醇:含环半透明和无血清β-hCG的早孕筛查的意义。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0223(199706)17:6<525::aid-pd105 复制DOI
    作者列表:Spencer K,Noble P,Snijders RJ,Nicolaides KH
    BACKGROUND & AIMS: :We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Down's syndrome) in an attempt to see if any of the analytes have a value in Down's syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Down's syndrome with average multiple of the median levels of 1.81 and 2.91, respectively. Urine total oestriol was reduced (0.83) whilst maternal serum free beta hCG was increased (1.72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Down's group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false-positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first-trimester screening. Optimal first-trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy-associated plasma protein A.
    背景与目标: :我们检查了373例非整倍性(包括22例唐氏综合症患者)的对照妊娠和43例孕妇的孕产妇尿液中的β核心,游离β人绒毛膜促性腺激素(hCG)和总雌三醇的浓度,以查看是否存在以下任何一种:在妊娠的第十至十四周期间,分析物在唐氏综合症筛查中具有价值。我们已将这些分析物的性能与在怀孕同一时期与孕妇血清游离βhCG相结合的颈部半透明测量结果进行了比较。我们的结果表明,唐氏综合症患者的无尿β-hCG和β-核心水平增加,平均中位数分别为1.81和2.91。尿中总雌三醇减少(0.83),而孕妇血清游离β-hCG增加(1.72)。在三体性18中,所有血清分析物的含量都降低了,尽管无血清的βhCG最为明显。对照组和唐氏组中尿β-核心的结果分布是无血清β-hCG的三倍以上,而无尿β-hCG的结果则宽了两倍。结合产妇年龄,尿中总雌三醇的检出率为32%,假阳性率为5%。尿β-核心34%,尿β-hCG36%,孕妇血清β-hCG44%,口腔半透明82%。结合颈部半透明性,尿液中总雌三醇的含量增加了1%,尿液β-核心的含量增加了2%,无尿β-hCG增加了3%,​​无血清β-hCG增加了5%。任何尿液标记物在孕早期筛查中都没有价值的可能性很小。最佳的早孕筛查程序将在可预见的将来依赖于颈部半透明性,无血清βhCG以及可能与妊娠相关的血浆蛋白A。
  • 【在市区内进行子宫颈筛查的初步研究-一项国家计划的课程。】 复制标题 收藏 收藏
    DOI:10.1046/j.1365-2303.1997.4475044.x 复制DOI
    作者列表:Herity B,McDonald P,Johnson Z,Carroll B,Cody M,Duignan N,McGee D,O'Kelly F,Hurley M
    BACKGROUND & AIMS: :The objectives of this study were to examine aspects of organization of a proposed national screening programme based in general practice. The target population of women aged 25-59 years and their general practitioners (GPs), in a defined inner city area, was identified from a population register of persons eligible for free medical services; a computerized system was developed for invitations and record linkage of cytology results. Smears were examined in one laboratory and follow up of women with abnormal smears was undertaken by one gynaecologist. A random sample of non-responders was surveyed by questionnaire. Response following two invitations was only 20%. Practices with male doctors only had significantly lower response rates (P < 0.001) than those with a female doctor/nurse. A survey of non-responders showed that over 20% of addresses were incorrect and 16% of those interviewed were ineligible for smear tests. A preference for a female to undertake smears was expressed by 67%, and 77% believed that the purpose of the cervical smear was to detect cancer. An accurate population register, health promotion, support for GP practices, provision of alternative venues for smear tests, development of computer systems, accurate data entry and fail-safe follow up are aspects of a cervical screening service which must be addressed prior to setting up a national service.
    背景与目标: :这项研究的目的是检查根据一般实践提出的国家筛查计划的组织方面。从有资格获得免费医疗服务的人员的人口登记册中确定了指定市区内25-59岁的妇女及其全科医生的目标人群;开发了用于邀请和记录细胞学结果链接的计算机化系统。在一个实验室对涂片进行了检查,一名妇科医师对涂片异常的妇女进行了随访。通过问卷调查随机抽取未回答者。两次邀请后的回应率仅为20%。男医生的实践仅比女医生/护士的实践有显着降低的响应率(P <0.001)。一项针对无回应者的调查显示,超过20%的地址不正确,而受访者中有16%没有资格进行涂片测试。 67%的女性表示愿意进行涂片检查,而77%的人认为宫颈涂片检查的目的是检测癌症。准确的人口登记,健康促进,对全科医生实践的支持,提供涂片测试的替代场所,计算机系统的开发,准确的数据输入和故障安全的跟进是宫颈筛查服务的各个方面,在建立之前必须解决这些问题一项国民服务。
  • 【在人结肠癌细胞和神经细胞上对苏拉明衍生物的双重筛选提供了毒性降低的新治疗剂。】 复制标题 收藏 收藏
    DOI:10.1016/0304-3835(91)90116-y 复制DOI
    作者列表:Baghdiguian S,Nickel P,Fantini J
    BACKGROUND & AIMS: :Suramin is a polyanionic compound currently used under evaluation for antineoplastic activity. One of the main problems encountered during clinical trials was an adverse neurotoxic effect, probably due to a direct cytotoxic effect on neural cells. Suramin is also known to trigger differentiation of human colon cancer cells, yet a chronic treatment induces a lysosomal storage disorder. The aim of this study was to evaluate suramin analogs for their effect: (i) on the lysosomal system of the human colon cancer cell clone HT29-D4; and (ii) on C6 glioma cell growth and morphology. One of the derivatives tested, NF036, induced terminal differentiation of HT29-D4 cells without any impairment of the lysosomal system. Furthermore, in contrast to suramin, NF036 did not alter C6 cell growth and morphology. We conclude that there is a relationship between the ability of a suramin derivative to induce a lysosomal storage disorder in human colon cancer cells and its neurotoxic effect. A double screening of suramin analogs on HT29-D4 and C6 cells allowed us to identify a new candidate antineoplastic drug: NF036.
    背景与目标: :Suramin是目前正在评估抗肿瘤活性的聚阴离子化合物。临床试验期间遇到的主要问题之一是不良的神经毒性作用,这可能是由于对神经细胞的直接细胞毒性作用所致。还已知苏拉明会触发人结肠癌细胞的分化,然而长期治疗会引起溶酶体贮积症。这项研究的目的是评估苏拉明类似物的作用:(i)对人结肠癌细胞克隆HT29-D4的溶酶体系统; (ii)C6胶质瘤细胞的生长和形态。测试的衍生物之一NF036诱导了HT29-D4细胞的终末分化,而对溶酶体系统没有任何损害。此外,与苏拉明相反,NF036不会改变C6细胞的生长和形态。我们得出结论,苏拉明衍生物在人结肠癌细胞中诱导溶酶体贮积病的能力与其神经毒性作用之间存在关联。在HT29-D4和C6细胞上对苏拉明类似物的双重筛选使我们能够鉴定出新的候选抗肿瘤药NF036。
  • 【针对50岁以上女性的指南不一致的乳腺癌筛查:一项基于小插图的调查。】 复制标题 收藏 收藏
    DOI:10.1007/s11606-013-2567-1 复制DOI
    作者列表:Kadivar H,Goff BA,Phillips WR,Andrilla CH,Berg AO,Baldwin LM
    BACKGROUND & AIMS: BACKGROUND:Professional organizations have issued guidelines recommending breast cancer screening for women 50 years of age. OBJECTIVE:This study examines the percent of U.S. primary care physicians who report breast cancer screening practices that are not consistent with guidelines, and the characteristics of physicians who reported offering extra test modalities. DESIGN:We analyzed a subset of a 2008 cross-sectional Women's Health Care survey sent to primary care physicians randomly selected from the national American Medical Association (AMA) Physician Masterfile. A subset of physicians received a survey that presented a vignette of a health maintenance visit for an asymptomatic 51-year-old woman who was not at high risk for breast cancer. Responses were weighted to represent physicians nationally. PARTICIPANTS:1,654 U.S. family physicians, general internists, and obstetrician-gynecologists under age 65, who practiced in office or hospital based settings (62.8 % response rate). After exclusions, 553 study physicians remained for analysis. MAIN MEASURE:Physician self-report of breast cancer screening practices that are not consistent with the recommendations of the U.S. Preventive Services Task Force (USPSTF), the American College of Obstetrics and Gynecology (ACOG), and the American Cancer Society (ACS), defined as almost always offering mammography. KEY RESULTS:36.0 % (95 % CI: 31.8 %-40.5 %) of physicians reported offering breast cancer screening tests inconsistent with national guidelines, with most offering extra tests (magnetic resonance imaging [MRI] and/or ultrasound) (33.2 %, 95 % CI 29.1 %-37.6 %). In adjusted analysis, risk-averse physicians and those who believed in the clinical effectiveness of MRI were more likely to offer extra breast cancer screening tests. CONCLUSIONS:Physicians often report offering breast cancer screening test modalities beyond those recommended for a 51-year-old woman. Strategies, such as academic detailing regarding appropriate use of technology and provision of clinical decision support for breast cancer screening, could decrease overuse of resources.
    背景与目标: 背景:专业组织已发布指南,建议对50岁以下的女性进行乳腺癌筛查。
    目的:本研究调查了报告乳腺癌筛查实践与指南不一致的美国基层医疗医生的百分比,以及报告提供额外测试方式的医生的特征。
    设计:我们分析了2008年横断面的妇女健康护理调查的一部分,该调查发送给从美国国家医学会(AMA)医师主文件中随机选择的初级保健医生。一部分医生接受了一项调查,该调查显示了对没有高乳腺癌风险的无症状51岁女性进行健康维持就诊的情况。回答权重代表全国范围内的医师。
    参与者:1,654位65岁以下的美国家庭医生,普通内科医师和妇产科医师,他们在办公室或医院工作(应答率为62.8%)。排除后,有553名研究医师留待分析。
    主要测量:医师对乳腺癌筛查实践的自我报告与美国预防服务工作队(USPSTF),美国妇产科学院(ACOG)和美国癌症协会(ACS)的建议不一致,被定义为几乎总是提供乳房X光检查。
    关键结果:36.0%(95%CI:31.8%-40.5%)的医生报告说提供的乳腺癌筛查检查与国家指南不一致,大多数提供额外的检查(磁共振成像[MRI]和/或超声检查)(33.2%, 95%CI 29.1%-37.6%)。在调整后的分析中,规避风险的医生和那些相信MRI的临床有效性的医生更有可能提供额外的乳腺癌筛查测试。
    结论:医师通常报告提供了超出推荐给51岁女性的乳腺癌筛查检查方法。策略,例如关于适当使用技术的学术细节以及为乳腺癌筛查提供临床决策支持,可以减少资源的过度使用。
  • 【在计算机和体外筛选与Tenofovir,Darunavir和Dapivirine的P-糖蛋白相互作用:局部预防结直肠HIV传播的抗逆转录病毒药物组合。】 复制标题 收藏 收藏
    DOI:10.1021/acs.molpharmaceut.7b00133 复制DOI
    作者列表:Swedrowska M,Jamshidi S,Kumar A,Kelly C,Rahman KM,Forbes B
    BACKGROUND & AIMS: :The aim of the study was to use in silico and in vitro techniques to evaluate whether a triple formulation of antiretroviral drugs (tenofovir, darunavir, and dapivirine) interacted with P-glycoprotein (P-gp) or exhibited any other permeability-altering drug-drug interactions in the colorectal mucosa. Potential drug interactions with P-gp were screened initially using molecular docking, followed by molecular dynamics simulations to analyze the identified drug-transporter interaction more mechanistically. The transport of tenofovir, darunavir, and dapivirine was investigated in the Caco-2 cell models and colorectal tissue, and their apparent permeability coefficient (Papp), efflux ratio (ER), and the effect of transporter inhibitors were evaluated. In silico, dapivirine and darunavir showed strong affinity for P-gp with similar free energy of binding; dapivirine exhibiting a ΔGPB value -38.24 kcal/mol, darunavir a ΔGPB value -36.84 kcal/mol. The rank order of permeability of the compounds in vitro was tenofovir < darunavir < dapivirine. The Papp for tenofovir in Caco-2 cell monolayers was 0.10 ± 0.02 × 10-6 cm/s, ER = 1. For dapivirine, Papp was 32.2 ± 3.7 × 10-6 cm/s, but the ER = 1.3 was lower than anticipated based on the in silico findings. Neither tenofovir nor dapivirine transport was influenced by P-gp inhibitors. The absorptive permeability of darunavir (Papp = 6.4 ± 0.9 × 10-6 cm/s) was concentration dependent with ER = 6.3, which was reduced by verapamil to 1.2. Administration of the drugs in combination did not alter their permeability compared to administration as single agents. In conclusion, in silico modeling, cell culture, and tissue-based assays showed that tenofovir does not interact with P-gp and is poorly permeable, consistent with a paracellular transport mechanism. In silico modeling predicted that darunavir and dapivirine were P-gp substrates, but only darunavir showed P-gp-dependent permeability in the biological models, illustrating that in silico modeling requires experimental validation. When administered in combination, the disposition of the proposed triple-therapy antiretroviral drugs in the colorectal mucosa will depend on their distinctly different permeability, but was not interdependent.
    背景与目标: :该研究的目的是使用计算机模拟和体外技术评估抗逆转录病毒药物(替诺福韦,达那那韦和达匹韦林)的三重制剂是否与P-糖蛋白(P-gp)相互作用或表现出其他改变通透性的药物药物在大肠黏膜中的相互作用。最初使用分子对接筛选与P-gp的潜在药物相互作用,然后进行分子动力学模拟,以更机械地分析已识别的药物-转运蛋白相互作用。在Caco-2细胞模型和结直肠组织中研究了Tenofovir,darunavir和dapivirine的转运,并评估了它们的表观通透性系数(Papp),流出比(ER)和转运蛋白抑制剂的作用。在计算机模拟中,达匹韦林和达那韦韦对P-gp具有很强的亲和力,具有类似的结合自由能。达匹韦林的ΔGPB值为-38.24 kcal / mol,达拉韦韦的ΔGPB值为-36.84 kcal / mol。化合物在体外的通透性等级为替诺福韦<达鲁那韦<达匹韦林。 Caco-2细胞单层中替诺福韦的Papp为0.10±0.02×10-6 cm / s,ER =1。对于达匹韦林,Papp为32.2±3.7×10-6 cm / s,但ER = 1.3低于根据计算机分析结果预期。替诺福韦和达匹韦林的转运均不受P-gp抑制剂的影响。达那那韦的吸收渗透率(Papp = 6.4±0.9×10-6 cm / s)与浓度有关,ER = 6.3,维拉帕米将其降至1.2。与作为单一药剂给药相比,组合给药与改变通透性没有关系。总之,计算机模拟,细胞培养和基于组织的分析表明,替诺福韦不与P-gp相互作用且渗透性差,与细胞旁运输机制一致。计算机模拟预测,darunavir和dapivirine是P-gp底物,但只有darunavir在生物学模型中显示P-gp依赖性渗透性,这说明计算机模拟需要实验验证。当联合给药时,拟议的三联疗法抗逆转录病毒药物在结直肠粘膜中的分布将取决于它们明显不同的渗透性,但不是相互依赖的。
  • 【多发性精神分裂症患者功能能力的认知筛查和行为观察:一项探索性研究。】 复制标题 收藏 收藏
    DOI:10.1136/bmjopen-2016-014783 复制DOI
    作者列表:Norlin Bagge E,Esbjörnsson E,Sunnerhagen KS
    BACKGROUND & AIMS: OBJECTIVES:To evaluate the usability of a neuropsychological screening instrument and two observation scales of everyday behaviour to describe cognitive and functional capacity of patients with multiepisode schizophrenia and considerable care needs, who frequently refuse to participate in cognitive testing or performance-based functional measurement. SETTING:One psychiatric unit specialised in severe mental illness at the Sahlgrenska University Hospital, Gothenburg, Sweden. PARTICIPANTS:Patients were included consecutively from date of admission to the unit. INCLUSION CRITERIA:age 18-65 years, International Classification of Diseases 10 diagnoses F20.0-F20.9 (schizophrenia) or F25.0-F25.9 (schizoaffective disorder) since at least 5 years. EXCLUSION CRITERIA:acute serious psychotic episodes or physical illness, alcohol or drug abuse during the year before the study, diagnosed cerebral disorder at admission to the unit, and insufficient ability to speak Swedish. 64 patients filled the criteria and 19 accepted participation: 14 males, 5 females, median age 56 years. OUTCOME MEASURES:Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) scores, measured by a psychologist; Frontal Systems Behaviour Scale (FrSBe) Family Version and Functional Independence Measure (FIM) V.4.0 scores, measured by nursing staff. Non-parametric statistics were consistently applied to process the data. RESULTS:Failure analysis showed differences regarding gender and subdiagnoses between participants and non-participants. All participants had BNIS scores indicating cognitive dysfunction. FrSBe group medians showed apathy and executive problems, indicating possible frontal lobe disturbance. FIM showed dependency on others for linguistic and social communication, everyday problem solving, and remembering persons and daily routines. Correlations between FrSBe and FIM (p≤0.01) suggested executive dysfunction being crucial to explain difficulties in performing activities of daily functioning. CONCLUSIONS:Indications of considerable cognitive and functional difficulties found among the participants suggestedthat the instruments are clinically applicable for tentative assessment of cognitive and functional ability among patients with multiepisode schizophrenia and considerable care needs.
    背景与目标: 目的:评估神经心理筛查仪器的可用性和两种日常行为观察量表,以描述多发性精神分裂症患者和需要大量护理的患者的认知和功能能力,这些患者经常拒绝参加认知测试或基于性能的功能测量。
    地点:瑞典哥德堡萨尔格伦斯卡大学医院的一个专门治疗严重精神疾病的精神病科。
    参加者:自入院之日起连续纳入患者。
    纳入标准:年龄18-65岁,国际疾病分类10至少从5年开始诊断为F20.0-F20.9(精神分裂症)或F25.0-F25.9(精神分裂症)。
    排除标准:在研究前的一年中发生了严重的精神病发作或身体疾病,酗酒或滥用药物,入院时被诊断出脑部疾病以及瑞典语说能力不足。符合标准的64位患者和19位接受研究的患者:男14例,女5例,中位年龄56岁。
    观察指标:巴罗神经病学研究所筛查的较高脑功能(BNIS)分数,由心理学家进行测量;额叶系统行为量表(FrSBe)家庭版本和功能独立性量度(FIM)V.4.0分数,由护理人员衡量。非参数统计被一致地应用于处理数据。
    结果:故障分析显示,参与者和非参与者之间在性别和亚诊断方面存在差异。所有参与者的BNIS评分均表明认知功能障碍。 FrSBe组中位数显示冷漠和执行问题,表明可能存在额叶紊乱。 FIM在语言和社交沟通,日常问题解决以及对人和日常活动的记忆方面表现出对他人的依赖。 FrSBe与FIM之间的相关性(p≤0.01)表明执行功能障碍对于解释日常工作活动中的困难至关重要。
    结论:在参与者中发现的相当多的认知和功能困难的指征表明,该仪器在临床上可用于多发性精神分裂症和相当大的护理需求的患者的认知和功能能力的初步评估。
  • 【对计划进行心脏手术的患者的营养筛查工具的评估。】 复制标题 收藏 收藏
    DOI:10.1016/j.nut.2012.08.006 复制DOI
    作者列表:Lomivorotov VV,Efremov SM,Boboshko VA,Nikolaev DA,Vedernikov PE,Lomivorotov VN,Karaskov AM
    BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to assess the prognostic value of different nutritional screening tools in patients undergoing cardiopulmonary bypass with regard to an adverse clinical course. METHODS:This prospective cohort study analyzed 894 adult patients who underwent cardiopulmonary bypass. Patients were screened using four nutritional screening tools: Nutritional Risk Screening 2002 (NRS-2002), the Malnutrition Universal Screening Tool (MUST), the Mini-Nutritional Assessment (MNA), and the Short Nutritional Assessment Questionnaire (SNAQ). Nutritional status was assessed using the Subjective Global Assessment. In-hospital mortality, postoperative complications, length of stay in the intensive care unit, and length of hospitalization were analyzed. RESULTS:The sensitivities of the SNAQ, MUST, and NRS-2002 to detect the malnutrition confirmed by the Subjective Global Assessment were 91.5%, 97.9%, and 38.3%, respectively, and the MNA showed a sensitivity of 81.8% for the elderly. Malnutrition detected by the SNAQ, MUST, and NRS-2002 was associated with postoperative complications (odds ratios [ORs] 1.75, 1.98, and 1.82, respectively) and a stay in the intensive care unit longer than 2 d (ORs 1.46, 1.56, and 2.8). Malnutrition as detected by the SNAQ and MUST was also associated with prolonged hospitalization (ORs 1.49 and 1.59). According to multivariate logistic regression analysis, postoperative complications were independently predicted by the European System for Cardiac Operative Risk Evaluation (OR 1.1, P < 0.0001), cardiopulmonary bypass time (OR 1.01, P < 0.0001), and malnutrition identified by the MUST (OR 1.2, P = 0.01). CONCLUSION:The MUST independently predicts postoperative complications. The SNAQ and MUST have comparable accuracy in detecting malnutrition. Whether preoperative nutritional therapy would improve the outcome in malnourished patients needs to be studied.
    背景与目标: 目的:本研究旨在评估不同营养筛查工具对体外循环不良患者的不良临床病程的预后价值。
    方法:这项前瞻性队列研究分析了894例接受了体外循环的成年患者。使用四种营养筛查工具对患者进行筛查:2002年营养风险筛查(NRS-2002),营养不良通用筛查工具(MUST),微量营养评估(MNA)和短期营养评估问卷(SNAQ)。营养状况使用主观全球评估进行评估。分析了院内死亡率,术后并发症,重症监护病房的住院时间和住院时间。
    结果:SNAQ,MUST和NRS-2002对主观全球评估确认的营养不良的敏感度分别为91.5%,97.9%和38.3%,而MNA对老年人的敏感度为81.8%。 SNAQ,MUST和NRS-2002发现的营养不良与术后并发症(赔率[OR]分别为1.75、1.98和1.82)和在重症监护病房停留超过2 d(OR为1.46、1.56,和2.8)。 SNAQ和MUST发现营养不良还与住院时间延长有关(OR 1.49和1.59)。根据多因素logistic回归分析,欧洲心脏手术风险评估系统(OR 1.1,P <0.0001),体外循环时间(OR 1.01,P <0.0001)和MUST(OR)确定的营养不良是独立预测术后并发症的1.2,P = 0.01)。
    结论:必须独立预测术后并发症。 SNAQ和MUST在检测营养不良方面具有相当的准确性。术前营养治疗是否可以改善营养不良患者的预后,需要研究。
  • 【在匈牙利Cerambycinae(Coleoptera:Cerambycidae)亚科中长角甲虫已知信息素成分的现场筛选。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Imrei Z,Millar JG,Janik G,Tóth M
    BACKGROUND & AIMS: :Five compounds known to be pheromone components of longhorned beetles (Coleoptera: Cerambycidae) in the subfamily Cerambycinae were field-tested as attractants and possible pheromones for the cerambycid fauna of Hungary. Nine cerambycid species were caught in baited traps. Large numbers of both sexes of the cerambycine species Molorchus umbellatarum Schreb. were caught in traps baited with (2R*,3S*)-octanediol, while the diastereomeric (2R*,3R*)-octanediol was to some extent attractive as well. This is the first report on an aggregation attractant and a likely pheromone for a species in the cerambycine tribe Molorchini. The results of our study support the hypothesis that the diol/hydroxyketone pheromone motif is characteristic of and highly conserved within the subfamily Cerambycinae. Intraspecific chemical communication is summarized for the subfamily Cerambycinae, and possible links between taxonomy, insect behaviour, and pheromone structures are described.
    背景与目标: :对五个​​已知为长角甲虫科中长角甲虫(鞘翅目:天蛾科)的信息素成分的化合物进行了田间试验,作为匈牙利的陶瓷动物的引诱剂和可能的信息素。在诱饵诱捕器中捕获了9种陶器种。 cerambycine物种Molorchus umbellatarum Schreb的许多性别。在(2R *,3S *)-辛二醇诱饵中捕获了诱捕剂,而(2R *,3R *)-辛二醇的非对映异构体在某种程度上也很有吸引力。这是关于cerambycine部落Molorchini中某个物种的聚集引诱剂和可能的信息素的首次报道。我们的研究结果支持以下假设:二醇/羟基酮信息素基序是Cerambycinae亚科的特征,并且在其内部高度保守。概述了唇形科亚科的种内化学通讯,并描述了分类学,昆虫行为和信息素结构之间的可能联系。
  • 【咖啡和茶与大肠癌风险之间关系的前瞻性研究:PLCO癌症筛查试验。】 复制标题 收藏 收藏
    DOI:10.1038/bjc.2013.434 复制DOI
    作者列表:Dominianni C,Huang WY,Berndt S,Hayes RB,Ahn J
    BACKGROUND & AIMS: BACKGROUND:Coffee and tea are commonly consumed and carry potential anticancer components that could reduce the risk of colorectal cancer; however, their relationships with colorectal cancer risk remain inconsistent. METHODS:A prospective analysis was carried out to examine the relationships of coffee and tea intake with colorectal cancer risk in 57,398 men and women in the intervention arm of the National Cancer Institute-Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, a national screening study that limits differential detection biases. Coffee and tea intakes were assessed by food frequency questionnaire. RESULTS:Six hundred and eighty-one incident colorectal cancer cases were ascertained during a median follow-up of 11.4 years. Greater coffee intake was not associated with risk of colorectal cancer (relative risk (RR)=1.08, 95% confidence interval (CI)=0.79-1.48, Ptrend=0.23). Stratifying by cancer site (Pheterogeneity=0.48) or stage (Pheterogeneity=0.83) did not alter the relationship. Associations remained unchanged in subsets of participants for either caffeinated or decaffeinated coffee or when stratifying by several colorectal cancer risk factors. Similarly, greater tea intake was not associated with colorectal cancer risk overall (RR=0.77, 95% CI=0.55-1.09, Ptrend=0.17) or by cancer site (Pheterogeneity=0.14) or stage (Pheterogeneity=0.60). These associations were not modified by several colorectal cancer risk factors. CONCLUSION:The findings of this study do not provide evidence to suggest that drinking coffee or tea is beneficial in protecting against colorectal cancer.
    背景与目标: 背景:咖啡和茶是经常食用的食物,并带有潜在的抗癌成分,可降低结直肠癌的风险。然而,它们与大肠癌风险的关系仍然不一致。
    方法:在美国国家癌症研究所-前列腺癌,肺癌,结肠直肠癌和卵巢癌筛查试验(一项全国筛查)的干预部门中,对57,398名男女中的咖啡和茶摄入量与大肠癌风险之间的关系进行了前瞻性分析。限制差分检测偏差的研究。通过食物频率问卷评估咖啡和茶的摄入量。
    结果:在中位随访11。4年中,确定了481例大肠癌事件。摄入更多咖啡与大肠癌风险无关(相对风险(RR)= 1.08,95%置信区间(CI)= 0.79-1.48,Ptrend = 0.23)。按癌症部位(致癌性= 0.48)或分期(致癌性= 0.83)进行分层并没有改变这种关系。对于咖啡因或脱咖啡因的咖啡,或按几种结直肠癌危险因素进行分层时,参与者的关联性保持不变。同样,摄入更多茶与总体结肠直肠癌风险(RR = 0.77,95%CI = 0.55-1.09,Ptrend = 0.17),癌症部位(致癌性= 0.14)或分期(致癌性= 0.60)也不相关。这些关联并未因几种结直肠癌的危险因素而改变。
    结论:这项研究的结果没有提供证据表明喝咖啡或茶对预防结直肠癌有益。
  • 【用于靶标特异性筛选的CAS9转录激活因子和用于协作基因组工程的配对切口酶。】 复制标题 收藏 收藏
    DOI:10.1038/nbt.2675 复制DOI
    作者列表:Mali P,Aach J,Stranges PB,Esvelt KM,Moosburner M,Kosuri S,Yang L,Church GM
    BACKGROUND & AIMS: :Prokaryotic type II CRISPR-Cas systems can be adapted to enable targeted genome modifications across a range of eukaryotes. Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA). Using this functionality we developed a transcriptional activation-based assay to determine the landscape of off-target binding of sgRNA:Cas9 complexes and compared it with the off-target activity of transcription activator-like (TALs) effectors. Our results reveal that specificity profiles are sgRNA dependent, and that sgRNA:Cas9 complexes and 18-mer TAL effectors can potentially tolerate 1-3 and 1-2 target mismatches, respectively. By engineering a requirement for cooperativity through offset nicking for genome editing or through multiple synergistic sgRNAs for robust transcriptional activation, we suggest methods to mitigate off-target phenomena. Our results expand the versatility of the sgRNA:Cas9 tool and highlight the critical need to engineer improved specificity.
    背景与目标: :原核II型CRISPR-Cas系统可进行改造,以实现跨一系列真核生物的靶向基因组修饰。在这里,我们设计了这个系统,通过将转录激活域直接与核酸酶无效的Cas9蛋白或适体修饰的单向导RNA(sgRNA)绑定在一起,从而实现人细胞中RNA指导的基因组调控。使用此功能,我们开发了一种基于转录激活的测定法来确定sgRNA:Cas9复合物脱靶结合的情况,并将其与转录激活剂样(TALs)效应子的脱靶活性进行比较。我们的结果表明,特异性谱是sgRNA依赖性的,并且sgRNA:Cas9复合物和18-mer TAL效应子可以分别耐受1-3和1-2个靶错配。通过设计用于基因组编辑的偏移切口或通过多个协同sgRNA进行鲁棒的转录激活来设计对协同性的要求,我们提出了减轻脱靶现象的方法。我们的结果扩展了sgRNA:Cas9工具的多功能性,并强调了工程改造更高特异性的关键需求。

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