BACKGROUND & AIMS: :The failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to approximately 20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.

背景与目标： : 受损的轴突在哺乳动物中枢神经系统 (CNS) 中无法长距离再生不是由于中枢神经元无法再生，而是由于CNS组织环境的非宽松性质。例如，在周围神经内良好生长的再生CNS轴突不能穿透成熟的CNS组织超过约1毫米。最近的证据表明，这可能是由于与CNS少突胶质细胞和髓磷脂相关的抑制性膜蛋白所致。我们在此报告，植入成年大鼠兴奋性毒性病变纹状体的人类端脑神经母细胞可以逃避或中和成年CNS环境的这种抑制作用，并沿主要有髓纤维束延伸轴突，距离可达约20毫米。可以看到轴突沿着纹状体-黑质和皮质-脊髓束的路径伸长，到达黑质，桥脑核和颈脊髓，这是纹状体和皮质投射神经元的正常目标。这些植入物。

BACKGROUND & AIMS: :A prospective collection of positive antimicrobial cultures was performed over 12 consecutive months in the medical intensive care unit of a cancer hospital. In all, 144 infections and 163 pathogens were documented during 87 of the 528 admissions. Lung, urinary, ENT (ear, nose and throat) infections and bacteraemia were the most frequently documented. Staphylococcus species, Streptococcus species, Escherichia coli, Klebsiella species and Pseudomonas species were the most common pathogens. Gram-positive strains were observed predominantly during monomicrobial bacteraemia (48.9%). Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were found in 58% and 92% of the isolated strains respectively. No particular outbreak was identified. A further prospective study will be necessary to evaluate the impact of the antibiotic use on the selection of resistant strains in our ICU.

背景与目标： : 在癌症医院的医疗重症监护病房中连续12个月进行了阳性抗菌培养的前瞻性收集。在528的87例入院期间，共记录了144例感染和163例病原体。肺，泌尿，耳鼻喉科 (耳，鼻和喉) 感染和菌血症是最常见的记录。最常见的病原体是葡萄球菌，链球菌，大肠杆菌，克雷伯菌和假单胞菌。革兰氏阳性菌株主要在单株菌血症期间观察到 (48.9%)。分离株的58% 和92% 中分别发现了耐甲氧西林金黄色葡萄球菌 (MRSA) 和表皮葡萄球菌 (MRSE)。没有发现特别的爆发。需要进行进一步的前瞻性研究，以评估抗生素使用对我们ICU中耐药菌株选择的影响。

BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

背景与目标：

BACKGROUND & AIMS: Cytogenetic and molecular genetic studies were performed on a pleomorphic sarcoma removed from the left atrium of a 15-year-old girl. Histologic analysis was consistent with a storiform-pleomorphic malignant fibrous histiocytoma (MFH). Although MFH is the most common soft-tissue sarcoma of late adulthood. It is extremely rare in childhood and its existence in the pediatric population remains controversial. Cytogenetic analysis revealed several alterations previously associated with adult MFH, including abnormalities of chromosomal bands 11p11 and 19p13. Moreover, the tumor demonstrated homogeneously staining regions (HSR) and double minute chromosomes (dmin) suggestive of gene amplification. We therefore screened the case for amplification of genes localized to chromosomal bands 12q13-14, including the putative protooncogenes MDM2, CDK4, SAS, CHOP, and CLI, which are frequently amplified and overexpressed in adult MFH. Southern and Northern blot analysis confirmed the coamplification of MDM2, CDK4, SAS, and CHOP. To our knowledge, such coamplification studies of the 12q13-14 amplicon have not been previously detected in pediatric MFH. Our results provide cytogenetic and molecular genetic evidence that pediatric and adult MFH are histogenetically related entities.

背景与目标： 对一名15岁女孩左心房切除的多形性肉瘤进行了细胞遗传学和分子遗传学研究。组织学分析与多形性恶性纤维组织细胞瘤 (MFH) 一致。尽管MFH是成年后期最常见的软组织肉瘤。在儿童时期极为罕见，其在儿科人群中的存在仍然存在争议。细胞遗传学分析显示了先前与成人MFH相关的几种改变，包括染色体带11p11和19p13的异常。此外，肿瘤显示出均匀染色区域 (HSR) 和双分钟染色体 (dmin)，提示基因扩增。因此，我们筛选了扩增定位于染色体带12q13-14的基因的案例，包括假定的原癌基因MDM2，CDK4，SAS，CHOP和CLI，它们在成年MFH中经常被扩增和过表达。Southern和Northern印迹分析证实了MDM2，CDK4，SAS和CHOP的共扩增。据我们所知，这种12q13-14扩增子的共扩增研究以前尚未在小儿MFH中检测到。我们的结果提供了细胞遗传学和分子遗传学证据，表明儿科和成年MFH是与组织遗传学相关的实体。

BACKGROUND & AIMS: BACKGROUND:The major clinical feature of ataxia telangiectasia (A-T) is severe progressive neurodegeneration with onset in infancy. This classical A-T phenotype is caused by biallelic null mutations in the ATM gene, leading to the absence of ATM protein and increased cellular radiosensitivity. We report an unusual case of A-T in a 41-year-old mother, A-T210, who had very mild neurological symptoms despite complete loss of ATM protein. METHODS:A neurological examination was performed, cellular radiosensitivity was assessed, and the ATM gene was sequenced. Skin fibroblasts and a lymphoblastoid cell line (LCL) were assayed for ATM protein expression and kinase activity. RESULTS:Patient A-T210 showed mild chorea, dystonia, and gait ataxia, walked independently, and drove a car. LCL and skin fibroblasts were radiosensitive and did not express ATM protein. Two ATM-null mutations were identified. CONCLUSIONS:The severe neurodegeneration resulting from loss of ATM can be mitigated in some circumstances.

背景与目标：

BACKGROUND & AIMS: :Results from pharmacogenetic investigations of methylphenidate (MPH) response in patients with ADHD are still inconsistent, especially among adults. This study investigates the role of genetic variants (SLC6A4, HTR1B, TPH2, DBH, DRD4, COMT, and SNAP25) in the response to MPH in a sample of 164 adults. Genes were chosen owing to previous evidence for an influence in ADHD susceptibility. No significant differences in allele or genotype frequencies between MPH responders and nonresponders were detected. In conclusion, our findings do not support an effect of these genes in the pharmacogenetics of MPH among adults with ADHD.

背景与目标： : 多动症患者中哌醋甲酯 (MPH) 反应的药物遗传学研究结果仍然不一致，尤其是在成年人中。这项研究调查了164名成年人样本中遗传变异 (SLC6A4，HTR1B，TPH2，DBH，DRD4，COMT和SNAP25) 对MPH反应的作用。由于先前的证据对ADHD易感性有影响，因此选择了基因。在MPH应答者和非应答者之间未检测到等位基因或基因型频率的显着差异。总之，我们的发现不支持这些基因在ADHD成人中MPH的药物遗传学中的作用。

BACKGROUND & AIMS: BACKGROUND:The process and preparation of moving from child to adult services (transition) is a challenging period of time for young people and represents significant changes in care and support systems. The proliferation of mobile phone applications for health purposes suggests that it is an area for further investigation. OBJECTIVE:The review explores the potential to use mobile phone technology to help support young liver transplant recipients moving to adult services. It represents the first review conducted in this specialism and considers a new model of support for young liver patients. METHODS:A systematic rapid review of the published peer-reviewed literature. RESULTS:Two searches were conducted: Search 1: the use of technology to support transition to adult services (6 studies) and Search 2: how best to support liver transplant recipients during transition (6 studies). DISCUSSION:Research shows that to achieve positive transition young people need information about their condition and transition. The process needs to be guided by transition readiness, rather than the young persons' age. Although parents and support networks should be in place and are valued, transition should build upon self-management and independence. Results suggest that there appears to be scope to use mobile phone technology to support transition. This is the first time a review has explored the types of issues or concerns facing liver transplant patients and how these can be addressed through mobile phone technology.

背景与目标：

BACKGROUND & AIMS: :Normal adult zebrafish can completely regenerate lost myocardium following partial amputation of the ventricle apex. We report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly impairs this regeneration. Adult male zebrafish were injected with vehicle (control) or TCDD (70ng/g, ip) 1 day prior to partial amputation of the ventricle apex. Gross observation and histological analysis of the amputated heart at 21 days postamputation revealed that TCDD-exposed fish had not progressed beyond the initial clot formation stage, whereas the vehicle control fish showed substantial recovery and almost complete resolution of the formed clot. In contrast, hearts that were not surgically wounded showed no signs of TCDD toxicity. Striking features in the TCDD-exposed hearts were the absence of the normal sheath of new tissue enveloping the wound and the absence of intense cell proliferation at the site of the wound. In addition, the patterns of collagen deposition at the wound site were different between the TCDD and vehicle groups. Because the receptor for TCDD is the aryl hydrocarbon receptor ligand-activated transcriptional regulator, we examined the effects of TCDD exposure on gene expression in the ventricle using DNA microarrays. Samples were collected just prior to amputation and at 6h and 7 days postamputation. TCDD-pretreated hearts had dysregulated expression of genes involved in heart function, tissue regeneration, cell growth, and extracellular matrix. Because embryonic, but not adult, hearts are major targets for TCDD-induced cardiotoxicity, we speculate that the need for embryonic-like cells in regeneration is connected with the effects of TCDD in inhibiting the response to wounding.

背景与目标： : 正常成年斑马鱼可以在部分截肢心室尖后完全再生丢失的心肌。我们报告2,3，7,8-四氯二苯并-对-二恶英 (TCDD) 显著损害这种再生。成年雄性斑马鱼在脑室尖部分截肢前1天注射赋形剂 (对照) 或TCDD (70ng/g，ip)。截肢后21天对截肢心脏的总体观察和组织学分析表明，暴露于TCDD的鱼没有进展超过最初的凝块形成阶段，而媒介物对照鱼则显示出实质性的恢复和形成的凝块的几乎完全消退。相反，未手术受伤的心脏没有TCDD毒性的迹象。暴露于TCDD的心脏的显着特征是没有包裹伤口的新组织的正常鞘，并且在伤口部位没有强烈的细胞增殖。此外，TCDD组和媒介物组在伤口部位的胶原沉积模式也不同。由于TCDD的受体是芳基烃受体配体激活的转录调节因子，因此我们使用DNA微阵列检查了TCDD暴露对心室中基因表达的影响。在截肢前以及截肢后6小时和7天收集样本。TCDD预处理的心脏与心脏功能，组织再生，细胞生长和细胞外基质有关的基因表达异常。由于胚胎而不是成年心脏是TCDD诱导的心脏毒性的主要靶标，因此我们推测再生中对胚胎样细胞的需求与TCDD抑制对创伤的反应有关。

BACKGROUND & AIMS: :Septic arthritis of the hip can be caused via a hematogenous route, by penetration of periarticular infections, open hip trauma, injections or operations. Ultrasound, hip puncture and elevation of inflammatory parameters lead to the diagnosis. Differentiation of septic arthritis from gout and chondrocalcinosis may be difficult. Nevertheless, early revision of the hip has to be performed to avoid joint destruction. Open revision is the therapy of choice in the majority of cases.

背景与目标： : 败血症性关节炎的髋部可通过血行途径，通过穿透关节周围感染，开放性髋部创伤，注射或手术引起。超声，髋部穿刺和炎症参数升高导致诊断。化脓性关节炎与痛风和软骨钙质病的鉴别可能很困难。尽管如此，必须对髋关节进行早期修复，以避免关节破坏。在大多数情况下，开放修订是首选疗法。

BACKGROUND & AIMS: :This case report describes the orthodontic treatment of an 18-year-old woman with a skeletal Class III malocclusion and a midline deviation. The treatment plan consisted of distalizing the mandibular dentition asymmetrically and producing space for retraction of the mandibular anterior teeth. Short Class III elastics, an open-coil spring, and the mulitloop edgewise archwire technique were used, combining the entire maxillary dentition as integrated anchorage. The active treatment period was 26 months. Normal overbite and overjet were obtained, and facial balance was improved.

背景与目标： : 此病例报告描述了一名18岁女性的正畸治疗，该女性患有骨骼III类错牙合且中线偏离。治疗计划包括不对称地使下颌牙列远端，并为下颌前牙的缩回提供空间。使用了III类短弹性，开式螺旋弹簧和多环边沿弓丝技术，将整个上颌牙列结合为整体锚固。积极治疗期为26个月。获得了正常的咬合和过度喷射，并改善了面部平衡。

BACKGROUND & AIMS: OBJECTIVE:This pilot study was a comparison of dimensional models assessing personality traits and personality pathology in a clinical sample of adults diagnosed with ADHD and adults diagnosed with borderline personality disorder (BPD), and a nonclinical control sample of healthy adults. METHOD:Personality traits were assessed using the NEO-Personality Inventory-Revised (NEO-PI-R) and dimensional personality pathology with the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ). RESULTS:Adults with ADHD and BPD produced higher Emotional Dysregulation/Neuroticism and Dissocial Behavior scores than controls. For the Extraversion/Inhibitedness scale, adults with BPD produced significantly lower scores than adults with ADHD and controls. On the Conscientiousness/Compulsivity domains, Conscientiousness scores were lower for both disorders, whereas low Compulsivity values were specific to adult ADHD. CONCLUSION:Our results suggest that patients with adult ADHD and BPD have distinguishable profiles of personality traits and personality pathology.

背景与目标：

BACKGROUND & AIMS: Members of the Notch gene family are thought to be involved in the regulation of cell fate decisions in a variety of embryonic tissues, particularly in the developing central nervous system (CNS) in Drosophila and vertebrates. In goldfish the CNS continues to develop and add neurons well into adulthood and has the capacity to regenerate new neurons. Using probes derived from Xenopus Notch to screen an adult goldfish retinal cDNA library, followed by 5' RACE, we isolated a partial cDNA for a goldfish Notch homologue, G-Notch. Sequence alignment supported assignment of G-Notch to the Notch-3 class. Northern blot analysis revealed a single transcript of > 8 kb, and RNase protection assays indicated that G-Notch is expressed in eye and brain but not muscle of adult goldfish. The spatiotemporal pattern of expression of G-Notch was defined from early embryonic stages to adulthood by in situ hybridization. Expression in the embryonic CNS was localized to neurogenic regions and was downregulated in differentiated cell populations. In adult goldfish, expression persisted in and adjacent to the germinal zones in the retina and the brain. Weak expression was seen in scattered cells in the inner nuclear layer of the retina, which might include neurogenic stem cells. Following retinal lesions (puncture wounds or laser lesions restricted to photoreceptors in the outer nuclear layer), G-Notch was upregulated in proliferating cell populations throughout the retina, in association with a generalized mitogenic response. In the region of the laser lesion, where earlier studies have demonstrated that photoreceptors are regenerating at 1-3 weeks following the lesion, G-Notch expressing cells were abundant in the outer nuclear layer. These observations suggest that retinal regeneration involves the re-expression of an important developmental signaling molecule in neuroepithelial cells resident in the differentiated retina.

背景与目标： Notch基因家族的成员被认为参与了多种胚胎组织中细胞命运决定的调节，尤其是果蝇和脊椎动物发育中的中枢神经系统 (CNS)。在金鱼中，中枢神经系统继续发育并增加神经元到成年，并具有再生新神经元的能力。使用源自非洲爪蟾Notch的探针筛选成年金鱼视网膜cDNA文库，然后进行5' 竞赛，我们分离了金鱼Notch同源物G-Notch的部分cDNA。序列比对支持将G-Notch分配给Notch-3类。Northern印迹分析显示单个转录本> 8 kb，RNase保护试验表明G-Notch在成年金鱼的眼睛和大脑中表达，但在肌肉中不表达。通过原位杂交定义了从胚胎早期到成年的G-Notch表达的时空模式。胚胎CNS中的表达定位于神经源性区域，并在分化的细胞群体中下调。在成年金鱼中，表达持续存在于视网膜和大脑的生发区并与其相邻。在视网膜内核层的分散细胞中观察到弱表达，其中可能包括神经源性干细胞。视网膜病变 (穿刺伤口或激光损伤仅限于外核层的光感受器) 后，G-Notch在整个视网膜的增殖细胞群中被上调，并伴有普遍的促有丝分裂反应。在激光病变区域，较早的研究表明，光感受器在病变后1-3周再生，在外核层中表达G-Notch的细胞丰富。这些观察结果表明，视网膜再生涉及驻留在分化视网膜中的神经上皮细胞中重要的发育信号分子的重新表达。

BACKGROUND & AIMS: :Mesial temporal lobe epilepsy (mTLE) is a neurological condition characterized by the occurrence of spontaneous recurrent seizures originating from mesial structures involving the hippocampus within the temporal lobe. This condition is often associated with pathological features in the hippocampus such as neuronal cell loss, widening of the granule cell layer, astrogliosis and mossy fibre spouting. At present, the mechanisms underlying these pathological features are unclear. However, recent advances in adult neurogenesis studies in mTLE animals and patients suggest that newly generated neurons may contribute to the pathogenesis of ongoing epileptogenesis. This article will review the recent animal and human studies on adult neurogenesis in mTLE and discuss how these results suggests that adult endogenous neurogenesis may not always be reparative in the mTLE and may be targeted in new therapeutic strategies for mTLE.

背景与目标： : 颞叶内侧癫痫 (mTLE) 是一种神经系统疾病，其特征是发生自发性复发性癫痫发作，起源于颞叶内海马的内侧结构。这种情况通常与海马的病理特征有关，例如神经元细胞丢失，颗粒细胞层变宽，星形胶质细胞增生和苔藓状纤维喷出。目前，这些病理特征的机制尚不清楚。然而，在mTLE动物和患者中进行的成人神经发生研究的最新进展表明，新生的神经元可能有助于正在进行的癫痫发生的发病机理。本文将回顾最近有关mTLE中成人神经发生的动物和人类研究，并讨论这些结果如何表明成人内源性神经发生可能并不总是在mTLE中修复，并且可能在mTLE的新治疗策略中靶向。

BACKGROUND & AIMS: PURPOSE:To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patients with hepatic impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. EXPERIMENTAL DESIGN:Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to 130 mg/m(2) every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepatic dysfunction: control group A [bilirubin, AST, and AP < or = upper limit of normal (ULN)], mild dysfunction group B (bilirubin < or = ULN, ULN < AST < or = 2.5 x ULN, or ULN < AP < or = 5 x ULN), moderate dysfunction group C (ULN < bilirubin < or = 3.0 mg/dL, AST > 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. RESULTS:Dose escalation of single-agent oxaliplatin to 130 mg/m(2) was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patients with a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. CONCLUSIONS:Oxaliplatin at 130 mg/m(2) every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction.

背景与目标：

BACKGROUND & AIMS: :The efficacy of cognitive behavioral treatments (CBT) for anxiety in adults has been supported by multiple meta-analyses. However, most have focused on only 1 diagnosis, thereby disallowing diagnostic comparisons. This study examined the efficacy of CBT across the anxiety disorders. One hundred eight trials of CBT for an anxiety disorder met study criteria. Cognitive therapy and exposure therapy alone, in combination, or combined with relaxation training, were efficacious across the anxiety disorders, with no differential efficacy for any treatment components for any specific diagnoses. However, when comparing across diagnoses, outcomes for generalized anxiety disorder and posttraumatic stress disorder were superior to those for social anxiety disorder, but no other differences emerged. CBT effects were superior to those for no-treatment and expectancy control treatments, although tentative evidence suggested equal effects of CBT when compared with relaxation-only treatments.

背景与目标： : 认知行为治疗 (CBT) 对成年人焦虑的功效已得到多项荟萃分析的支持。然而，大多数只关注1个诊断，因此不允许进行诊断比较。这项研究检查了CBT在焦虑症中的功效。针对焦虑症的CBT试验达到了研究标准。单独使用认知疗法和暴露疗法，或与放松训练相结合，在焦虑症中是有效的，对于任何特定诊断的任何治疗成分都没有不同的功效。然而，当比较各种诊断时，广泛焦虑症和创伤后应激障碍的结果优于社交焦虑症，但没有其他差异。CBT效果优于无治疗和预期对照治疗，尽管初步证据表明CBT与仅松弛治疗相比具有相同的效果。