• 【少数人群未投保的患者成功治疗丙型肝炎的障碍。】 复制标题 收藏 收藏
    DOI:10.1186/s12967-018-1555-y 复制DOI
    作者列表:DeBose-Scarlett A,Balise R,Kwon D,Vadaparampil S,Chen SX,Schiff ER,Ayala GP,Thomas E
    BACKGROUND & AIMS: BACKGROUND:Hepatitis C virus (HCV) treatment regimens (DAAs) are well tolerated, efficacious but costly. Their high cost and restricted availability, raises concerns about the outcome of treatment in uninsured patients. This study investigated sustained virologic response (SVR) outcomes in a predominately uninsured patient population and completion of four steps along the HCV treatment cascade. METHODS:A retrospective chart review was conducted to characterize the patient population and analyze covariates to determine association with insurance status, attainment of SVR and progression through the HCV treatment cascade. RESULTS:Out of a total of 216 patients, 154 (71%) were uninsured. Approximately 50% of patients (109 of 216 patients) were male and 57% were Hispanic (123 of 216 patients). Sex, race, ethnicity, treatment compliance, and rates of complications were not associated with insurance status. Insured patients were older (median 60 years vs 57 years, p-value < 0.001) and had higher rates of cirrhosis: 32 out of 62 patients (52%) vs 48 out of 154 patients (31%) (p-value = 0.005). Insured patients were tested for SVR at similar rates as uninsured patients: 84% (52 of 62 patients) vs 81% (125 of 154 patients), respectively. Of those tested for SVR, the cure rate for insured patients was 98% (51 out of 52 patients) compared to 97% (121 out of 125 patients) in the uninsured. Out of those who completed treatment, 177 of 189 (94%) were tested for attainment of SVR. Compliance rates were significantly different between tested and untested patients: 88% (156 of 177 patients) vs 0% (0 of 12 patients), respectively (p-value < 0.001). However, insurance status, race ethnicity, cirrhosis, and complications were not associated with being tested for SVR. CONCLUSIONS:These results demonstrate that insured and uninsured patients with chronic HCV infection, with access to patient assistance programs, can be treated and have comparable clinical outcomes. In addition, testing for SVR remains an important obstacle in completion of the HCV treatment cascade. Nevertheless, patient assistance programs remove a significant barrier for treatment access in real-world HCV infected populations.
    背景与目标: 背景:丙型肝炎病毒(HCV)治疗方案(DAA)具有良好的耐受性,有效但昂贵。它们的高成本和有限的可获得性引起了对未投保患者的治疗结果的担忧。这项研究调查了在未保险人群中持续的病毒学应答(SVR)结果,以及沿着HCV治疗级联反应完成的四个步骤。
    方法:进行回顾性图表审查以表征患者人群并分析协变量,以确定与保险状况,SVR的获得程度以及通过HCV治疗级联的进展之间的关联。
    结果:在总共216位患者中,有154位(71%)未投保。大约50%的患者(216名患者中的109名)是男性,而57%是西班牙裔(216名患者中的123名)。性别,种族,种族,治疗依从性和并发症发生率与保险状况无关。受保患者年龄较大(中位年龄为60岁vs 57岁,p值<< 0.001)并且肝硬化发生率更高:62位患者中的32位(52%)与154位患者中的48位(31%)(p值= 0.005 )。受保患者接受SVR的检出率与未受保患者相似:分别为84%(62名患者中的52名)和81%(154名患者中的125名)。在接受SVR测试的患者中,参保患者的治愈率为98%(52例中的51例),而未参保患者的治愈率为97%(125例中的121例)。在完成治疗的患者中,有189名中的177名(94%)接受了SVR的检测。在接受测试和未经测试的患者中,依从率显着不同:分别为88%(177名患者中的156名患者)和0%(12名患者中的0名)(p值<0.001)。但是,保险身份,种族,肝硬化和并发症与接受SVR测试无关。
    结论:这些结果表明,患有慢性HCV感染的被保险人和非被保险人,只要获得患者援助计划,就可以得到治疗,并具有可比的临床结果。此外,对SVR的测试仍然是完成HCV治疗级联的重要障碍。尽管如此,患者援助计划消除了在现实世界中被HCV感染人群获得治疗的重大障碍。
  • 【用于治疗用途的抗菌肽:障碍和现实前景。】 复制标题 收藏 收藏
    DOI:10.1016/j.coph.2006.04.006 复制DOI
    作者列表:Marr AK,Gooderham WJ,Hancock RE
    BACKGROUND & AIMS: :Cationic antimicrobial peptides are produced by almost all species of life as a component of their immediate non-specific defense against infections. The assets of these peptides in clinical application include their potential for broad-spectrum activity, rapid bactericidal activity and low propensity for resistance development, whereas possible disadvantages include their high cost, limited stability (especially when composed of L-amino acids), and unknown toxicology and pharmacokinetics. Initial barriers to their success are being increasingly overcome with the development of stable, more cost-effective and potent broad-spectrum synthetic peptides. Thus, there is hope that they will spawn a new generation of antimicrobials with a broad range of topical and systemic applications against infections.
    背景与目标: :阳离子抗菌肽几乎是生活中所有物种所产生的,它们是针对感染的直接非特异性防御​​的组成部分。这些肽在临床应用中的资产包括它们具有广谱活性,快速杀菌活性和耐药性发展倾向的潜力,而可能的缺点包括它们的成本高,稳定性有限(尤其是由L-氨基酸组成时)和未知的毒理学和药代动力学。随着稳定,更具成本效益和有效的广谱合成肽的开发,克服其成功的最初障碍越来越多。因此,希望它们能够产生新一代的抗菌药,具有广泛的局部和全身应用来抵抗感染。
  • 【筛查牛皮癣患者心血管危险因素的障碍和解决方案。】 复制标题 收藏 收藏
    DOI:10.1111/jdv.12159 复制DOI
    作者列表:Wang EC,Ker KJ,Chuah SY,Pan JY
    BACKGROUND & AIMS: BACKGROUND:Psoriasis has been linked with cardiovascular risk factors (CVRFs), including the metabolic syndrome, yet many patients with psoriasis remain unscreened. OBJECTIVE:To assess the reasons for lack of screening for CVRFs in psoriasis patients, and the impact of an education programme targeting these deficiencies. METHODS:All patients with psoriasis, regardless of severity, and all dermatologists working at the National Skin Centre (NSC) in Singapore were surveyed over a 2-month period on their attitudes and knowledge regarding psoriasis and cardiovascular risk. This was followed by a targeted programme which was implemented over 2 months to address these identified deficiencies. Patients and doctors were surveyed a second time to assess the effects of the intervention. RESULTS:Obstacles to screening included lack of patient knowledge, patients not considering screening important, and lack of time during the clinic consultation. After the intervention, there was a significant increase in the proportion of patients who were aware of increased cardiovascular risk in psoriasis (33.0% to 62%), with more patients attending screening (39.1% to 63.2%). While the level of doctors' knowledge did not significantly increase, there was an increase in the proportion of patients who were screened post-intervention (37.1% to 66.2%), and more doctors reported that they were more likely to screen psoriatic patients from an earlier age (30.2% to 58.1%). CONCLUSIONS:The obstacles in implementing universal screening for CVRFs in psoriasis patients stem from patient, doctor and system factors. A comprehensive programme targeting all aspects of this ecosystem helps to achieve holistic care for patients with psoriasis.
    背景与目标: 背景:牛皮癣已与包括代谢综合征在内的心血管危险因素(CVRFs)相关联,但许多牛皮癣患者仍未接受筛查。
    目的:评估缺乏对银屑病患者进行CVRF筛查的原因,以及针对这些缺陷的教育计划的影响。
    方法:对所有牛皮癣患者(不论严重程度)以及在新加坡国家皮肤中心(NSC)工作的所有皮肤科医生进行了为期2个月的调查,了解他们对牛皮癣和心血管疾病的态度和知识。随后是针对性计划,该计划在两个月内实施,以解决这些已发现的缺陷。对患者和医生进行了第二次调查,以评估干预措施的效果。
    结果:筛查的障碍包括缺乏患者知识,不认为筛查重要的患者以及在临床咨询期间缺乏时间。干预后,意识到牛皮癣的心血管风险增加的患者比例显着增加(33.0%至62%),而接受筛查的患者更多(39.1%至63.2%)。尽管医生的知识水平没有显着提高,但接受干预后筛查的患者比例有所增加(37.1%至66.2%),并且更多的医生报告说他们更有可能从银屑病筛查银屑病患者年龄较早(30.2%至58.1%)。
    结论:在牛皮癣患者中进行CVRFs普查的障碍来自患者,医生和系统因素。针对该生态系统各个方面的综合计划有助于为牛皮癣患者提供整体护理。
  • 【英格兰西南部地区初级保健中的公共卫生技能-培训需求,障碍和解决方案的调查。】 复制标题 收藏 收藏
    DOI:10.1038/sj.ph.1900805 复制DOI
    作者列表:Freudenstein U,Yates B
    BACKGROUND & AIMS: The UK government is moving primary care towards a more health needs led service. This will require a greater awareness of public health skills among primary care staff. We therefore sent a postal questionnaire to the chairmen of primary care groups (general practitioners), the chief officers of primary care groups, directors of public health, nurse advisors of health authorities, directors of community nursing and directors of midwifery in the South West region of England. Respondents were asked about skills in health needs assessment, health service planning and other public health skills among general practitioners, health visitors and midwives. The survey also covered perceived obstacles to the acquisition of such skills and possible solutions. The response rate was 67% (96/143). Eighty percent of primary care groups returned at least one reply. Sixty-four percent had either not considered the problem or considered it but not acted. Fifty percent of directors of public health felt that they could not provide more training to non-specialist staff. Most organisations provided little training in public health skills to non-specialist staff despite a perceived skill shortage particularly in health promotion, advocacy and the evaluation of the effectiveness and efficiency of services. We conclude that primary care groups and public health departments need to agree how to access public health advice. Primary care groups need to identify individuals with an interest in strategic working and service planning, identify their skill deficits and seek appropriate training.

    背景与目标: 英国政府正在将初级保健朝着更健康的需求导向服务的方向发展。这将要求基层医疗人员提高对公共卫生技能的认识。因此,我们向西南地区的初级保健团体(全科医生)主席,初级保健团体的首席官员,公共卫生主管,卫生当局的护士顾问,社区护理主管和助产士主管发送了邮政调查问卷英格兰的。受访者被问及全科医生,健康来访者和助产士中的健康需求评估,健康服务计划和其他公共健康技能。该调查还涵盖了在获得此类技能和可能的解决方案方面的公认障碍。回应率为67%(96/143)。 80%的初级保健团体至少返回了一个答复。 64%的人未考虑或未解决问题,但未采取任何措施。 50%的公共卫生总监认为他们无法为非专业人员提供更多培训。尽管人们感觉到技能短缺,特别是在健康促进,宣传和对服务有效性和效率的评估上,但大多数组织很少向非专业人员提供公共卫生技能方面的培训。我们得出的结论是,初级保健团体和公共卫生部门需要就如何获得公共卫生建议达成共识。初级保健团体需要确定对战略性工作和服务计划感兴趣的人员,确定其技能缺陷并寻求适当的培训。

  • 【克服炎症性肠病的治疗障碍:关于新型药物递送策略的全面综述。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejps.2013.04.031 复制DOI
    作者列表:Talaei F,Atyabi F,Azhdarzadeh M,Dinarvand R,Saadatzadeh A
    BACKGROUND & AIMS: :Inflammatory bowel diseases (IBDs) are a group of debilitating inflammatory complications specially inflicting colonic tissue in which full long term remission with current standardized treatments is yet intangible. Therapeutic side effects and efficacy considerations necessitate the development of more effective systems which lower the required drug doses, reduce systemic adverse effects and deliver the drug specifically to the desired site of action in colon. The large surface area in large intestine is suitable for drug absorption but the primary approaches to treatment depend on the gastrointestinal (GI) condition and its movements. Hereafter, there are novel GI-independent targeted drug delivery systems or therapeutic approaches, including micro- and nanoparticles that have been developed for IBD treatment and have the potential to overcome some of the current drawbacks of conventional IBD therapy. This review provides broad but concise information over the arena of the evolving systems aimed at different targets involved in IBD which are being studied in animal or in vitro models of this complication, while comparing these to conventional treatments. It further discusses important pros and cons of therapeutic approaches against IBD while helping to better understand and evaluate the future impact of novel drug delivery systems on human IBD and assisting in focusing the future research in this topic, on strategies which could provide maximum remission in IBD patients.
    背景与目标: :炎症性肠病(IBDs)是一组使人衰弱的炎症性并发症,特别是结肠组织受累,目前采用标准治疗方法仍无法长期完全缓解。考虑到治疗性副作用和功效,必须开发出更有效的系统,以降低所需的药物剂量,减少全身性不良反应并将药物特异性地递送至结肠中所需的作用部位。大肠中的大表面积适合于药物吸收,但是主要的治疗方法取决于胃肠道(GI)状况及其运动。此后,存在新颖的不依赖于GI的靶向药物递送系统或治疗方法,包括已开发用于IBD治疗的微颗粒和纳米颗粒,并且具有克服常规IBD治疗的一些当前缺点的潜力。这篇综述提供了针对正在涉及该疾病的动物或体外模型正在研究的,涉及IBD的不同靶标的正在发展的系统领域的广泛而简洁的信息,同时将它们与常规治疗进行了比较。它进一步讨论了针对IBD的治疗方法的重要利弊,同时有助于更好地理解和评估新型药物递送系统对人IBD的未来影响,并帮助该主题的未来研究重点关注可最大程度缓解IBD的策略。耐心。
  • 【评估护士在服用复苏药物时的知识和对障碍的理解。】 复制标题 收藏 收藏
    DOI:10.1016/j.nedt.2013.04.011 复制DOI
    作者列表:Chen MJ,Yu S,Chen IJ,Wang KW,Lan YH,Tang FI
    BACKGROUND & AIMS: AIM:The aim of the study was to develop and validate an instrument to evaluate nurses' knowledge and to understand the obstacles that they encounter when administering resuscitation medications. BACKGROUND:Insufficient knowledge is a major factor in nurses' drug administration errors. Resuscitation involves situations in which doctors issue oral orders, and is inherently highly stressful. Sufficient knowledge is vital for nurses if they are to respond quickly and accurately when administering resuscitation medications. METHODS:A cross-sectional study was conducted. A questionnaire (20 true-false questions) developed from literature and expert input, and validated by subject experts and one pilot study, was used to evaluate nurses' knowledge of resuscitation medications. Stratified sampling and descriptive statistics were applied. RESULTS:A total of 188 nurses participated. The overall correct answer rate was 70.5% and the greater the nurse's work experience the higher the score. Only 8% of nurses considered themselves to have sufficient knowledge and 73.9% hoped to gain more training about resuscitation medications. The leading obstacle reported was "interruption of the drug administration procedure on resuscitation" (62.8%). Seventeen out of 20 questions achieved a discriminatory power of over 0.36, indicating good to excellent questions. In the study, a total of 16 resuscitation medication errors were reported by the participants, in which the errors involved atropine (five cases), epinephrine (three cases) and others (eight cases). The errors mainly involved misinterpretation of orders, insufficient knowledge and confusing certain drugs for other look-alike drugs. CONCLUSION:Evidence-based results strongly suggest that nurses have insufficient knowledge and could benefit from longer working experience and additional training about resuscitation medications. Further research to validate the instrument is needed and the education of nurses regarding resuscitation medications is recommended.
    背景与目标: 目的:该研究的目的是开发和验证一种工具,以评估护士的知识并了解他们在服用复苏药物时遇到的障碍。
    背景:知识不足是造成护士用药错误的主要因素。复苏涉及医生发出口头命令的情况,并且固有地压力很大。如果护士要在服用复苏药时迅速而准确地做出反应,那么足够的知识对他们至关重要。
    方法:进行横断面研究。根据文献和专家的意见编制了问卷(20个真假问题),并经过主题专家和一项先导研究的验证,用于评估护士对复苏药物的知识。应用分层抽样和描述性统计。
    结果:共有188名护士参加。总体正确答案率为70.5%,护士的工作经验越多,得分就越高。只有8%的护士认为自己具有足够的知识,而73.9%的护士希望获得更多有关复苏药物的培训。报告的主要障碍是“复苏时中断给药过程”(62.8%)。 20个问题中有17个的歧视能力超过0.36,表明问题的优劣。在该研究中,参与者报告了总共16例复苏用药错误,其中错误涉及阿托品(5例),肾上腺素(3例)和其他(8例)。错误主要包括对命令的误解,知识不足以及将某些药物与其他相似药物混淆。
    结论:基于证据的结果强烈表明护士知识不足,可以从更长的工作经验和有关复苏药物的额外培训中受益。需要进行进一步的研究以验证该仪器,并建议对护士进行复苏药物的教育。
  • 【克服障碍:患有和不患有唐氏综合症的儿童的预期改变。】 复制标题 收藏 收藏
    DOI:10.1007/s00221-004-1971-5 复制DOI
    作者列表:Virji-Babul N,Brown M
    BACKGROUND & AIMS: :The purpose of this study was to explore the mechanism of anticipatory control of gait in relation to the perception of an obstacle. Typically developing (TD) children (4-7 years of age) and children with Down syndrome (5-6 years of age) walked and stepped over obstacles of two different heights-a "subtle" obstacle that was placed at a very low distance from the floor (1% of total body height) and an "obvious" obstacle that was placed at a much higher distance from the floor (15% of total body height). Spatial and temporal measures of the gait cycle were analyzed. TD children showed increased variability in pre-obstacle step lengths only in response to the higher obstacle. Children with DS showed a decrease in variability in response to the higher obstacle and marked qualitative changes in their gait cycle. Both groups of children were able to scale toe clearance with obstacle height. These results show that TD young children can make task-specific anticipatory adjustments by modulating step length and toe clearance. Children with DS show appropriate scaling of toe clearance and are beginning to show the emergence of anticipatory responses under specific environmental conditions.
    背景与目标: :本研究的目的是探讨与障碍物感知有关的预期步态控制机制。通常发育中的(TD)儿童(4-7岁)和患有唐氏综合症的儿童(5-6岁)走路并跨过两个不同高度的障碍物-距离很近的“微妙”障碍物距离地板(占车身总高度的1%)和“明显的”障碍物放置在距离地板更高的距离(占车身总高度的15%)的位置。分析了步态周期的时空测量。 TD儿童仅在对较高障碍物有反应的情况下,障碍物前步长的变异性增加。 DS儿童表现出对较高障碍物的反应的可变性降低,并且步态周期有明显的质性变化。两组儿童都能够根据障碍物的高度确定脚趾的间隙。这些结果表明,TD幼儿可以通过调节步长和脚趾间隙来进行任务特定的预期性调整。患有DS的儿童表现出适当的脚趾清除比例,并且开始显示在特​​定环境条件下预期反应的出现。
  • 【全国性的候选人调查:II:对精神分析培训越来越感兴趣的动机,障碍和想法。】 复制标题 收藏 收藏
    DOI:10.1177/0003065112460090 复制DOI
    作者列表:Katz DA,Kaplan M,Stromberg SE
    BACKGROUND & AIMS: :A national survey of candidates was conducted to identify motivations for pursuing psychoanalytic training, obstacles that prevent progression or completion, and candidates' ideas on how best to increase interest among potential trainees. In 2009-2010, 40 percent of candidates on the affiliate member e-mail list completed an anonymous web-based survey. Candidates strongly endorsed contact with a personal psychotherapist, psychoanalyst, or supervisor as the most important influence in discovering psychoanalysis and deciding to pursue training. They identified the total cost of analytic training as the greatest obstacle. This was followed by the cost of personal analysis, loss of income for low-fee cases, time away from family, and difficulty finding cases. To enhance training, local institutes should work to improve institute atmosphere and provide assistance with finding cases; national organizations should increase outreach activities and publicize psychoanalysis. Psychoanalytic institutes could recruit future candidates by working to increase personal contact with psychoanalysts, reducing the cost of training, improving institute atmosphere, assisting with case-finding, enhancing outreach activities, and widely publicizing psychoanalysis. Narrative comments from candidates and the implications of these findings regarding engagement of future trainees are discussed.
    背景与目标: :对候选人进行了全国性调查,以确定从事心理分析培训的动机,阻碍进步或完成的障碍,以及候选人如何最大程度地提高潜在学员的兴趣的想法。在2009-2010年,会员会员电子邮件列表中40%的候选人完成了一项基于网络的匿名调查。候选人强烈支持与个人心理治疗师,心理分析员或主管的联系,这是发现心理分析和决定接受培训的最重要影响力。他们认为分析培训的总成本是最大的障碍。其次是个人分析的成本,低收费案件的收入损失,与家人在一起的时间以及难以找到案件的费用。为了加强培训,地方机构应努力改善机构氛围,并为查案提供帮助;国家组织应增加宣传活动并宣传心理分析。精神分析机构可以通过增加与精神分析人员的私人联系,减少培训成本,改善研究所的氛围,协助案例查找,加强推广活动以及广泛宣传精神分析来招募未来的候选人。讨论了候选人的叙述性评论以及这些发现对未来学员培训的影响。
  • 【发展中国家和发达国家之间在职业卫生领域进行合作的机会和障碍。】 复制标题 收藏 收藏
    DOI:10.1016/j.tox.2004.01.038 复制DOI
    作者列表:Rantanen J,Lehtinen S,Savolainen K
    BACKGROUND & AIMS: :The 2.4 billion working people in the developing countries often have to endure employment conditions, which do not meet even basic occupational safety and health (OSH) standards. The lack of work safety, excessive work loads, and occupational physical, chemical and biological exposures result in occupational diseases, injuries and as many as 1.2 million fatalities each year. Furthermore, as little as 15% of workers in the developing countries have access to occupational health and safety services. Some collaboration between the industrialized and developing countries in the field of OSH has been practiced for 30 years but its volume has been modest compared to other sectors of development assistance. The lessons learned from 30 years of experience are that the most important OSH improving factors in developing countries include legal and policy instruments, national OSH programs, infrastructure for OSH implementation, and OSH services. The establishment of OSH expert human resources, centers serving as engines for research, training, as well as information and registration systems can also be considered as key factors in any such collaboration. A convincing government OSH policy, and close cooperation between social partners and the government are also critical factors that guarantee sustainable OSH programs in a developing country over a long-term basis.
    背景与目标: :发展中国家的24亿劳动人口常常不得不忍受甚至不符合基本职业安全与卫生(OSH)标准的就业条件。缺乏工作安全,工作量过多以及职业的物理,化学和生物暴露会导致职业病,伤害和每年多达120万人的死亡。此外,发展中国家只有15%的工人可以获得职业健康和安全服务。工业化国家和发展中国家之间在职业安全与卫生领域进行了一些合作,这种合作已经进行了30年,但与其他发展援助部门相比,其合作规模并不大。从30年的经验中吸取的教训是,发展中国家最重要的职业安全与卫生改善因素包括法律和政策工具,国家职业安全与卫生计划,实施职业安全与卫生的基础设施以及职业安全与卫生服务。建立职业安全与卫生专家人力资源,充当研究,培训引擎以及信息和注册系统的中心也可以被视为任何此类合作的关键因素。令人信服的政府职业安全与卫生政策以及社会伙伴与政府之间的紧密合作也是确保发展中国家长期可持续的职业安全与卫生计划的关键因素。
  • 10 Modeling root system growth around obstacles. 复制标题 收藏 收藏

    【围绕障碍物对根系生长进行建模。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-020-72557-8 复制DOI
    作者列表:Jin W,Aufrecht J,Patino-Ramirez F,Cabral H,Arson C,Retterer ST
    BACKGROUND & AIMS: :State-of-the-Art models of Root System Architecture (RSA) do not allow simulating root growth around rigid obstacles. Yet, the presence of obstacles can be highly disruptive to the root system. We grew wheat seedlings in sealed petri dishes without obstacle and in custom 3D-printed rhizoboxes containing obstacles. Time-lapse photography was used to reconstruct the wheat root morphology network. We used the reconstructed wheat root network without obstacle to calibrate an RSA model implemented in the R-SWMS software. The root network with obstacles allowed calibrating the parameters of a new function that models the influence of rigid obstacles on wheat root growth. Experimental results show that the presence of a rigid obstacle does not affect the growth rate of the wheat root axes, but that it does influence the root trajectory after the main axis has passed the obstacle. The growth recovery time, i.e. the time for the main root axis to recover its geotropism-driven growth, is proportional to the time during which the main axis grows along the obstacle. Qualitative and quantitative comparisons between experimental and numerical results show that the proposed model successfully simulates wheat RSA growth around obstacles. Our results suggest that wheat roots follow patterns that could inspire the design of adaptive engineering flow networks.
    背景与目标: :根系统架构(RSA)的最新模型不允许模拟刚性障碍物周围的根生长。但是,障碍物的存在可能会严重破坏根系。我们在没有障碍的密封培养皿中以及在带有障碍物的定制3D打印根瘤菌中种植了小麦幼苗。延时摄影被用于重建小麦根的形态网络。我们使用无障碍的重建小麦根网络来校准在R-SWMS软件中实现的RSA模型。带有障碍物的根系网络可以校准新功能的参数,该功能可以模拟刚性障碍物对小麦根系生长的影响。实验结果表明,刚性障碍物的存在不会影响小麦根轴的生长速率,但是会影响主轴经过障碍物后的根轨迹。生长恢复时间,即主轴根部恢复其由地向性驱动的生长的时间,与主轴沿障碍物生长的时间成正比。实验和数值结果之间的定性和定量比较表明,该模型成功模拟了障碍物周围小麦RSA的生长。我们的结果表明,小麦根系遵循的模式可能会启发自适应工程流网络的设计。
  • 【持续干扰:使用小分子干扰RNA作为小分子药物的前景和障碍。】 复制标题 收藏 收藏
    DOI:10.1146/annurev.bioeng.8.061505.095848 复制DOI
    作者列表:Dykxhoorn DM,Lieberman J
    BACKGROUND & AIMS: :RNA interference (RNAi) is a well-conserved, ubiquitous, endogenous mechanism that uses small noncoding RNAs to silence gene expression. The endogenous small RNAs, called microRNAs, are processed from hairpin precursors and regulate important genes involved in cell death, differentiation, and development. RNAi also protects the genome from invading genetic elements, encoded by transposons and viruses. When small double-stranded RNAs, called small interfering (si)RNAs, are introduced into cells, they bind to the endogenous RNAi machinery to disrupt the expression of mRNAs containing complementary sequences with high specificity. Any disease-causing gene and any cell type or tissue can potentially be targeted. This technique has been rapidly utilized for gene-function analysis and drug-target discovery and validation. Harnessing RNAi also holds great promise for therapy, although introducing siRNAs into cells in vivo remains an important obstacle. Pilot siRNA clinical studies began just three years after the discovery that RNAi works in mammalian cells. This review discusses recent progress and obstacles to using siRNAs as small molecule drugs.
    背景与目标: RNA干扰(RNAi)是一种保存良好,普遍存在的内源性机制,使用小的非编码RNA沉默基因表达。内源性小RNA(称为microRNA)是从发夹状前体加工而成的,并调节与细胞死亡,分化和发育有关的重要基因。 RNAi还保护基因组免受转座子和病毒编码的遗传成分的侵害。当将小的双链RNA(称为小干扰(si)RNA)引入细胞时,它们会与内源RNAi机制结合,从而破坏包含具有高特异性互补序列的mRNA的表达。任何致病基因和任何细胞类型或组织都可能成为目标。该技术已被迅速用于基因功能分析以及药物靶标的发现和验证。利用RNA干扰技术还具有广阔的治疗前景,尽管将siRNA体内引入细胞仍是一个重要的障碍。在发现RNAi在哺乳动物细胞中起作用后仅三年,便开始了siRNA试点临床研究。这篇综述讨论了使用siRNA作为小分子药物的最新进展和障碍。
  • 【转录因子遇到的表观遗传障碍:不计后果地重新编程。】 复制标题 收藏 收藏
    DOI:10.1016/j.gde.2012.08.002 复制DOI
    作者列表:Gifford CA,Meissner A
    BACKGROUND & AIMS: :Reprogramming of a somatic nucleus to an induced pluripotent state can be achieved in vitro through ectopic expression of Oct4 (Pou5f1), Sox2, Klf4 and c-Myc. While the ability of these factors to regulate transcription in a pluripotent context has been studied extensively, their ability to interact with and remodel a somatic genome remains underexplored. Several recent studies have begun to provide mechanistic insights that will eventually lead to a more rational design and improved understanding of nuclear reprogramming.
    背景与目标: :通过异位表达Oct4(Pou5f1),Sox2,Klf4和c-Myc可以在体外实现将体细胞核重编程为诱导性多能状态。尽管已经广泛研究了这些因素在多能环境中调节转录的能力,但它们与体细胞基因组相互作用和重塑的能力仍未得到充分研究。最近的一些研究已经开始提供机械的见解,这些见解最终将导致更合理的设计和对核重编程的更好的理解。
  • 13 Common obstacles in lipid management. 复制标题 收藏 收藏

    【脂质管理中的常见障碍。】 复制标题 收藏 收藏
    DOI:10.1016/j.ccell.2008.03.003 复制DOI
    作者列表:Elpers M
    BACKGROUND & AIMS: :This article provides the health care practitioner with some viable options to consider when starting a treatment plan for patients who have hyperlipidemia. These suggestions may increase patient compliance rates.
    背景与目标: :本文为医疗保健从业者提供了一些可行的选择,以便为高脂血症患者制定治疗计划。这些建议可能会提高患者的依从率。
  • 【欧洲对跨境医疗保健中电子处方的可能性和障碍的调查。】 复制标题 收藏 收藏
    DOI:10.1089/tmj.2006.12.484 复制DOI
    作者列表:Mäkinen M,Forsström J,Aärimaa M,Rautava P
    BACKGROUND & AIMS: :This study investigated the possibilities and obstacles for cross-border electronic prescriptions within the European internal market. Cross-border electronic prescribing requires interoperability of the systems and use of standardized solutions. We conducted a survey-based case study. A questionnaire on the use of electronic prescriptions was sent by e-mail to the delegates from 14 European Union (EU) member countries and 2 European Economic Area (EEA) countries during spring-summer 2003. A reply was received from 11 delegates in 11 countries contacted. Currently electronic prescriptions are in everyday use in only a few EU member countries, while many others are running or considering pilot projects. We found that electronic prescribing across national borders is impeded by many obstacles, which may relate to other systems or to lack of standardization. Information technology is likely to gradually spread to prescribing in Europe. Before more countries will integrate electronic prescribing into national healthcare, it would be important to ensure interoperability and common standards between national systems. Only then can electronic prescribing offer its full potential, and cross-border electronic prescribing can be realized at the EU level.
    背景与目标: :这项研究调查了欧洲内部市场中跨境电子处方的可能性和障碍。跨境电子处方需要系统的互操作性和标准化解决方案的使用。我们进行了基于调查的案例研究。在2003年春夏期间,通过电子邮件向来自14个欧盟(EU)成员国和2个欧洲经济区(EEA)国家的代表发送了有关使用电子处方的调查问卷。收到了来自11个国家的11个代表的答复联系的国家。目前,只有少数几个欧盟成员国每天都在使用电子处方,而其他许多国家正在运行或正在考虑进行试点项目。我们发现,跨越国界的电子处方受到许多障碍的阻碍,这些障碍可能与其他系统或缺乏标准化有关。信息技术很可能会逐渐传播到欧洲。在更多国家将电子处方集成到国家医疗保健之前,确保国家系统之间的互操作性和通用标准很重要。只有这样,电子处方才能发挥其全部潜力,并且可以在欧盟一级实现跨境电子处方。
  • 【BK病毒血清状态的移植前评估:意义,当前方法和障碍。】 复制标题 收藏 收藏
    DOI:10.3390/v11100945 复制DOI
    作者列表:Dakroub F,Touzé A,Akl H,Brochot E
    BACKGROUND & AIMS: :The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques' advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field).
    背景与目标: :肾移植患者中耐受移植所需的免疫抑制可触发潜在的BK多瘤病毒(BKPyV)激活,感染可发展为​​肾病和移植排斥。已经提出,供体和受体中的移植前BKPyV血清状态是移植后BKPyV复制的预测标记。研究实验室使用许多不同的测定技术来确定BKPyV血清状况的事实使这些数据分析变得复杂。即使基于相同技术的研究,其标准对照选择,用于检测的抗原结构类型以及血清阳性的临界值也有所不同。在这里,我们回顾了用于检测的不同BKPyV VP1抗原类型,并考虑了各种BKPyV血清状态检测技术的优缺点。最后,我们重点介绍了在诊所中实施共识性BKPyV血清学检测的障碍(例如,该领域中缺少指导原则)。

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