BACKGROUND & AIMS: :Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.

背景与目标： : 将含有茶碱，醋酸钙和微晶纤维素的球形颗粒挤出并球形化，然后通过界面络合用六种不同的果胶或藻酸盐包被。这项研究的目的是发现涂层对物理机械性能的影响，这对于确定颗粒作为持续释放系统的效用至关重要。在核心颗粒周围形成不溶性，光滑且均匀厚的钙多糖涂层。设计了析因实验，以研究颗粒大小，多糖类型和浓度对包封效率，机械性能和其他物理特性的影响。通过扫描电子显微镜观察到包被的颗粒，根据所用的特定多糖，发现干涂层的厚度为30-80微米。颗粒的大小，多糖的类型和浓度影响包衣颗粒中茶碱的产量。尽管通过施加任何凝胶涂层可以改善颗粒的机械性能，但使用具有高含量古罗糖醛酸的藻酸盐或酰胺化的果胶涂层可提供最佳结果。这可能是因为这两者都具有在凝胶涂层内形成非常稳定的交联的巨大潜力。

BACKGROUND & AIMS: Rabbits predominantly rearrange the most 3'VH gene (VH1); thus combinatorial diversity is very limited. In man and mouse, the most 3'DH gene, DQ52, is preferentially rearranged early in B-cell development. To test whether this preference for rearranging a DH gene segment based on 3' end proximity exists in rabbit, we cloned and sequenced the rabbit DQ52 gene. The 11 base pair coding region sequence is identical to a published mouse DQ52, and 81.8% similar to the human sequence. It is localized approximately 805 bp upstream of the JH1 gene. However, the 3' recombination signal sequence has an atypical nonamer. We prepared mRNA from 15- to 28-day fetal rabbits and amplified expressed VDJ sequences of mu mRNA by RT-PCR. The PCR products with VDJ rearrangements were cloned and sequenced. As expected, 44 of 45 VDJ sequences reflected use of the 3' VH1a2 gene, but the DQ52 gene was utilized very infrequently, if at all. We found only one VDJ sequence from 28-day fetal liver B-cells with 8 bp that matched the germline DQ52 sequence. Instead of expressing DQ52, another DH gene, Df was frequently expressed. We cloned the genomic Df gene and localized it about 32 kb upstream of the JH region. Thus, in contrast to man and mouse, rabbits preferentially express a DH gene located in the middle of the DH region early in B cell ontogeny. This may correlate with more frequent initial rearrangement of VH to DH in rabbit B cells.

背景与目标： 兔子主要重排最3'VH基因 (VH1); 因此组合多样性非常有限。在人和小鼠中，最3'DH基因DQ52在b细胞发育的早期优先重排。为了测试兔子中是否存在基于3' 末端邻近度重新排列DH基因片段的偏好，我们克隆并测序了兔子DQ52基因。11个碱基对编码区序列与已发表的小鼠DQ52相同，并且81.8% 类似于人序列。它位于JH1基因上游约805 bp。但是，3' 重组信号序列具有非典型的非amer。我们从15至28天的胎兔中制备了mRNA，并通过rt-pcr扩增了mu mRNA的VDJ表达序列。克隆并测序具有VDJ重排的PCR产物。正如预期的那样，在45个VDJ序列中，有44个反映了3'vh1a2基因的使用，但是DQ52基因很少被使用 (如果有的话)。我们从28天的胎儿肝b细胞中发现只有一个VDJ序列，其8 bp与种系DQ52序列匹配。Df不表达另一个DH基因DQ52，而是经常表达。我们克隆了基因组Df基因，并将其定位在JH区域上游约32 kb。因此，与人和小鼠相比，兔子在b细胞个体发育早期优先表达位于DH区域中部的DH基因。这可能与兔b细胞中VH到DH的更频繁的初始重排有关。

BACKGROUND & AIMS: Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male germinal cells show a highly abnormal adult spermatogenesis accompanied by sterility. This appears to result from the prevention of an early and massive wave of apoptosis in the testis, which occurs among germinal cells during the first round of spermatogenesis. In contrast, sporadic apoptosis among spermatogonia, which occurs in normal adult testis, is not prevented in adult transgenic mice. The physiological early apoptotic wave in the testis is coincident, in timing and localization, with a temporary high expression of the apoptosis-promoting protein Bax, which disappears at sexual maturity. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal mouse testis) in this early apoptotic wave is shown by the occurrence of a comparable testicular syndrome in mice defective in the bax gene. The apoptotic wave appears necessary for normal mature spermatogenesis to develop, probably because it maintains a critical cell number ratio between some germinal cell stages and Sertoli cells, whose normal functions and differentiation involve an elaborate network of communication.

背景与目标： 在雄性生发细胞中表达高水平BclxL或Bcl2蛋白的转基因小鼠显示出高度异常的成年精子发生并伴有不育。这似乎是由于防止了睾丸中早期大量的凋亡波，而这种凋亡波在第一轮精子发生期间发生在生发细胞中。相反，在成年转基因小鼠中，不能阻止正常成年睾丸中发生的精原细胞间的零星凋亡。睾丸中的生理性早期凋亡波在时间和定位上是重合的，与促凋亡蛋白Bax的暂时高表达，该蛋白在性成熟时消失。BclxL和Bax蛋白 (Bcl2显然在正常小鼠睾丸中未表达) 的细胞内平衡 (可能受激素控制) 在这种早期凋亡波中起关键作用，这表现为在小鼠中出现类似的睾丸综合征。bax基因。凋亡波似乎是正常成熟精子发生发展所必需的，可能是因为它在某些生发细胞阶段和支持细胞之间保持了临界的细胞数比，支持细胞的正常功能和分化涉及复杂的通讯网络。

BACKGROUND & AIMS: :A structure-activity relationship (SAR) study was performed principally at the N1 position of N1-arylsulfonyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes, a new family of calcilytics acting at the calcium sensing receptor (CaSR). The most active compound in this series was the 4-(trifluoromethoxy)benzenesulfonyl derivative 7e, which displayed an IC50 of 5.4 +/- 0.5 microM with respect to the inhibition of calcium-induced tritiated inositol phosphate ([3H]IP) accumulation in Chinese hamster ovarian (CHO) cells expressing the CaSR. Replacement of the sulfonamide linkage of this compound by a carboxamide led to a 6-fold increase in activity (7m, IC50 = 0.9 +/- 0.2 microM). Among the carboxamides synthesized, one of the most active compounds was the 4-chlorophenylcarboxamide (1S,2S,1'R)-7n (Calhex 231, IC50 = 0.33 +/- 0.02 microM). The absolute configuration of (1S,2S,1'R)-7n was deduced from an X-ray crystallographic study of one of the diastereomers of compound 7d. The stereochemical preference for the (1S,2S,1'R)-isomers can be rationalized on the basis of a three-dimensional model of the calcilytic binding pocket of the CaSR. Removal of the C-1' methyl group or replacement of the 1-naphthyl group by a 2-naphthyl or biphenyl moiety led to appreciable loss of calcilytic activity. Compounds 7e, 7m, and Calhex 231 did not stimulate [3H]IP accumulation in CHO cells expressing or not expressing the CaSR.

背景与目标： : 主要在N1-arylsulfonyl-N2-[1-(1-萘基) 乙基]-trans-1，2-二氨基环己烷的N1位置进行了构效关系 (SAR) 研究，作用于钙感应受体 (CaSR) 的新的钙离子家族。该系列中最具活性的化合物是4-(三氟甲氧基) 苯磺酰基衍生物7e，在表达CaSR的中国仓鼠卵巢 (CHO) 细胞中，对钙诱导的tri化肌醇磷酸 ([3H]IP) 积累的抑制作用显示出5.4/- 0.5微米的IC50。用甲酰胺代替该化合物的磺酰胺键导致6倍活动增加 (7m，IC50 = 0.9 +/- 0.2微米)。在合成的甲酰胺中，最具活性的化合物之一是4-氯苯基甲酰胺 (1S，2S，1'R)-7n (Calhex 231，IC50 = 0.33 +/- 0.02微米)。(1S，2S，1'R)-7n是根据对化合物7d的非对映异构体之一的x射线晶体学研究得出的。(1S，2S，1'R)-异构体可以在CaSR的煅烧结合袋的三维模型的基础上合理化。C-1甲基的去除或2-萘基或联苯部分取代1-萘基导致煅烧活性的明显损失。化合物7e，7m，并且Calhex 231不刺激表达或不表达CaSR的CHO细胞中的 [3H]IP积累。

BACKGROUND & AIMS: UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT-7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration and gamma-globin and EPO-receptor mRNA levels were significantly higher in EPO-treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically mature megakaryocytic characteristics such as a developed demarcation membrane in the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a bipotential cell line that can be induced to differentiate into erythroid and megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT-7/GM cells acquired a high hemoglobin concentration by treatment with TPO, suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results support the hypothesis that cytokines influence the programming of gene expression required for lineage commitment or differentiation.

背景与目标： UT-7是一种人类巨核细胞白血病细胞系，其生长和存活绝对依赖于interleukin-3，粒细胞-巨噬细胞集落刺激因子 (gm-csf) 或促红细胞生成素 (EPO)。在用gm-csf长期培养UT-7后，我们分离了一个新的子系UT-7/GM。在EPO处理的UT-7/GM细胞中，血红蛋白浓度以及 γ-珠蛋白和EPO受体mRNA水平显着高于未处理的细胞。相比之下，血小板生成素 (TPO) 处理的UT-7/GM细胞中的血小板因子4和糖蛋白IIb mRNA水平远高于未处理的细胞。某些经TPO处理的细胞具有形态成熟的巨核细胞特征，例如细胞质和多小叶核中的分界膜发达。这些发现表明，UT-7/GM是一种双能细胞系，可以分别通过EPO和TPO诱导分化为红系和巨核细胞系。此外，少数UT-7/GM细胞通过用TPO处理获得高血红蛋白浓度，表明TPO部分诱导了UT-7/GM细胞的红系分化。有趣的是，gm-csf抑制EPO或TPO诱导的红细胞分化和TPO诱导的UT-7/GM细胞的巨核细胞分化。这些结果支持以下假设: 细胞因子会影响谱系承诺或分化所需的基因表达编程。

BACKGROUND & AIMS: :Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4+ T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG. The effect of CD28 blockade on lupus nephritis onset, survival, production of anti-ds DNA antibodies and costimulatory molecules was evaluated. CD28 blockade prevented the development of lupus nephritis and prolonged survival during the 3-month treatment and 12 weeks after. Furthermore, the production of anti-ds DNA autoAbs was decreased. Lastly, the protective effect of CD28 blockade was associated with increased intrarenal expression of the immunoregulatory molecule, Indoleamine 2, 3-dioxygenase, of the co-inhibitory receptor programmed cell-Death - 1 (PD-1) and of its ligand programmed death ligand - 1 (PDL-1).In conclusion, CD28 blockade prevented the development of lupus nephritis in NZB/NZW F1 mice. This immunomodulatory strategy is a promising candidate for SLE therapy in humans.

背景与目标： 系统性红斑狼疮 (SLE) 是一种慢性全身性炎症性疾病。抗狼疮标志双链DNA (ds DNA) 的自身抗体 (autoAbs) 是通过自身反应性b细胞和CD4 T细胞之间的相互作用产生和维持的。该相互作用由CD28/CD80-86/CTLA-4轴控制。在这里，我们研究了在SLE的鼠模型中，选择性阻断CD28-CD80/86共刺激相互作用是否可以缓解狼疮性肾炎的发展。为此，用anti-CD28 Fab' 片段或对照Fab'-IgG处理NZB/nzwf1小鼠3个月。评估了CD28阻断对狼疮性肾炎发作，存活，抗ds DNA抗体和共刺激分子产生的影响。CD28阻断可防止狼疮性肾炎的发展，并在3个月的治疗和12周后延长生存期。此外，抗ds DNA autoAbs的产生减少了。最后，CD28阻断的保护作用与免疫调节分子吲哚胺2,3-双加氧酶，共抑制性受体程序性细胞死亡-1 (PD-1) 及其配体程序性死亡配体-1 (PDL-1) 的肾内表达增加有关。总之，CD28阻断阻止了NZB/NZW F1小鼠狼疮性肾炎的发展。这种免疫调节策略是人类SLE治疗的有希望的候选者。

BACKGROUND & AIMS: :Methionine adenosyltransferase (MAT) is involved in folate-mediated one-carbon metabolism, which is essential for preimplantation embryos in terms of both short-term periconceptional development and long-term phenotypic programming beyond the periconceptional period. Here, our immunofluorescence analysis of bovine oocytes and preimplantation embryos revealed the consistent expression of MAT2A (the catalytic subunit of the ubiquitously expressed-type of MAT isozyme) during this period. Addition of the MAT2A inhibitor FIDAS to the culture media of bovine preimplantation embryos reduced their blastocyst development, revealing the particular importance of MAT2A in successful blastocyst development. Exploration of MAT2A-associated genomic regions in bovine blastocysts using chromatin immunoprecipitation and sequencing (ChIP-seq) identified candidate MAT2A-associated genes implicated not only in short-term periconceptional embryo development, but also in long-term phenotypic programming during this period in terms of growth, metabolism, and immune functions. These results suggest the critical involvement of MAT2A in the periconceptional period in life-long programming of health and disease as well as successful preimplantation development.

背景与目标： : 蛋氨酸腺苷转移酶 (MAT) 参与叶酸介导的单碳代谢，这对于植入前胚胎的短期围术期发展和围术期以后的长期表型编程都是必不可少的。在这里，我们对牛卵母细胞和植入前胚胎的免疫荧光分析揭示了在此期间MAT2A (MAT同工酶普遍表达类型的催化亚基) 的一致表达。在牛植入前胚胎的培养基中添加MAT2A抑制剂FIDAS会降低其胚泡发育，从而揭示了MAT2A在成功胚泡发育中的特殊重要性。使用染色质免疫沉淀和测序 (ChIP-seq) 探索牛囊胚中的MAT2A-associated基因组区域，确定了候选MAT2A-associated基因，不仅涉及短期内胚胎发育，而且还涉及在此期间生长，代谢和免疫功能方面的长期表型编程。这些结果表明，MAT2A在围手术期的关键参与了健康和疾病的终生规划以及成功的植入前发展。

BACKGROUND & AIMS: BACKGROUND:The Nutrition Embedded Evaluation Programme Impact Evaluation (NEEP-IE) study is a cluster randomised controlled trial designed to evaluate the impact of a childcare centre-based integrated nutritional and agricultural intervention on the diets, nutrition and development of young children in Malawi. The intervention includes activities to improve nutritious food production and training/behaviour-change communication to improve food intake, care and hygiene practices. This paper presents the rationale and study design for this randomised control trial. METHODS:Sixty community-based childcare centres (CBCCs) in rural communities around Zomba district, Malawi, were randomised to either (1) a control group where children were attending CBCCs supported by Save the Children's Early Childhood Health and Development (ECD) programme, or (2) an intervention group where nutritional and agricultural support activities were provided alongside the routine provision of the Save the Children's ECD programme. Primary outcomes at child level include dietary intake (measured through 24-h recall), whilst secondary outcomes include child development (Malawi Development Assessment Tool (MDAT)) and nutritional status (anthropometric measurements). At household level, primary outcomes include smallholder farmer production output and crop-mix (recall of last production season). Intermediate outcomes along theorised agricultural and nutritional pathways were measured. During this trial, we will follow a mixed-methods approach and undertake child-, household-, CBCC- and market-level surveys and assessments as well as in-depth interviews and focus group discussions with project stakeholders. DISCUSSION:Assessing the simultaneous impact of preschool meals on diets, nutrition, child development and agriculture is a complex undertaking. This study is the first to explicitly examine, from a food systems perspective, the impact of a preschool meals programme on dietary choices, alongside outcomes in the nutritional, child development and agricultural domains. The findings of this evaluation will provide evidence to support policymakers in the scale-up of national programmes. TRIAL REGISTRATION:ISRCTN registry, ID: ISRCTN96497560 . Registered on 21 September 2016.

背景与目标：

BACKGROUND & AIMS: :Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty-seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow-up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue.

背景与目标： : 在1981年2月26日和1987年7月30日之间，有36例患者因溃疡性结肠炎相关的原发性硬化性胆管炎接受了原位肝移植。36名接受者中有3名因移植物无功能或手术并发症而在3个月内死亡。其他33人 (92%) 至少活了1年。33例中的2例分别在移植前未诊断出的复发性胆管癌分别在12和14个月后死亡。另外4例患者在14、21、36和44个月后死于复发性肝衰竭 (3例) 或免疫母细胞肉瘤 (1例)。移植后23至81个月，有27 (75%) 例患者仍然存活。两名患者在移植后分别被诊断为结直肠癌11和21个月，如果排除了由胆管癌引起的三例早期死亡和两例晚期死亡，则总发生率为5.6% 例 (36例中的2例) 和6.5% 例的校正发生率 (31例中的2例)。尚不清楚是否存在结直肠恶性肿瘤，但在移植时未发现，或者其后是否发展。很明显，接受肝移植治疗与溃疡性结肠炎相关的原发性硬化性胆管炎的患者应仔细随访结肠，包括结肠镜检查和结肠粘膜的多次活检。肝移植后是否应预防性考虑直肠结肠切除术是一个尚未解决的问题。

BACKGROUND & AIMS: BACKGROUND:Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic. CONTENT:We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs. SUMMARY:With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.

背景与目标：

BACKGROUND & AIMS: :Proteins encoded by MADS-box genes are important transcription factors involved in the regulation of flowering plant growth and development. Currently, no systematic information exists regarding the MADS-box family in the important tropical fruit banana. Ninety-six MADS-box genes were identified from the banana (Pahang) A genome. Phylogenetic analysis indicated that Musa acuminata MCM1-AGAMOUS- DEFICIENS-SRF (MaMADS) could be divided into MIKCc, MIKC*, Mα/β and Mγ groups. MIKCc could be further divided into 11 subfamilies, which was further supported by conserved motif and gene structure analyses. Transcriptome analysis on the Feng Jiao (FJ) and BaXi Jiao (BX) banana cultivars revealed that MaMADS genes are differentially expressed in various organs, at different fruit development and ripening stages, indicating the involvement of these genes in fruit development and ripening processes. Interactive network analysis indicated that MaMADS24 and 49 not only interacted with MaMADS proteins themselves, but also interacted with hormone-response proteins, ethylene signal transduction and biosynthesis-related proteins, starch biosynthesis proteins and metabolism-related proteins. This systematic analysis identified candidate MaMADS genes related to fruit development and ripening for further functional characterization in plants, and also provided new insights into the transcriptional regulation of MaMADS genes, facilitating the future genetic manipulation of MADS-mediated fruit development and ripening.

背景与目标： : MADS-box基因编码的蛋白质是参与调节开花植物生长发育的重要转录因子。目前，尚无有关重要热带水果香蕉中MADS-box家族的系统信息。从香蕉 (Pahang) A基因组中鉴定出96个MADS-box基因。系统发育分析表明，尖锐湿疣MCM1-AGAMOUS-SRF (MaMADS) 可分为MIKCc，MIKC *，m α/β 和m γ 组。MIKCc可以进一步分为11个亚科，这得到了保守基序和基因结构分析的进一步支持。对Feng Jiao (FJ) 和BaXi Jiao (BX) 香蕉品种的转录组分析表明，MaMADS基因在不同的果实发育和成熟阶段在各个器官中差异表达，表明这些基因参与了果实的发育和成熟过程。交互网络分析表明，MaMADS24和49不仅与MaMADS蛋白本身相互作用，而且还与激素反应蛋白，乙烯信号转导和生物合成相关蛋白，淀粉生物合成蛋白和代谢相关蛋白相互作用。该系统分析确定了与果实发育和成熟相关的候选MaMADS基因，以进一步表征植物的功能，并为MaMADS基因的转录调控提供了新的见解，从而促进了MADS介导的果实发育和成熟的未来遗传操作。

BACKGROUND & AIMS: OBJECT:The purpose of this study was to provide an evidence-based algorithm for the design, development, and implementation of a new checklist for the response to an intraoperative neuromonitoring alert during spine surgery. METHODS:The aviation and surgical literature was surveyed for evidence of successful checklist design, development, and implementation. The limitations of checklists and the barriers to their implementation were reviewed. Based on this review, an algorithm for neurosurgical checklist creation and implementation was developed. Using this algorithm, a multidisciplinary team surveyed the literature for the best practices for how to respond to an intraoperative neuromonitoring alert. All stakeholders then reviewed the evidence and came to consensus regarding items for inclusion in the checklist. RESULTS:A checklist for responding to an intraoperative neuromonitoring alert was devised. It highlights the specific roles of the anesthesiologist, surgeon, and neuromonitoring personnel and encourages communication between teams. It focuses on the items critical for identifying and correcting reversible causes of neuromonitoring alerts. Following initial design, the checklist draft was reviewed and amended with stakeholder input. The checklist was then evaluated in a small-scale trial and revised based on usability and feasibility. CONCLUSIONS:The authors have developed an evidence-based algorithm for the design, development, and implementation of checklists in neurosurgery and have used this algorithm to devise a checklist for responding to intraoperative neuromonitoring alerts in spine surgery.

背景与目标：

BACKGROUND & AIMS: :A microsomal butyrylesterase (L-I) was purified from the livers of male W rats treated with phenobarbital, and an antiserum against this purified L-I was raised in a rabbit. By the Ouchteriony double-diffusion test, a precipitin line was observed between the anti-L-I antiserum and each Triton X-100 extract of livers during development, regeneration after partial hepatectomy, and carcinogenesis and of hyperplastic nodules and hepatomas, all of which revealed L-I in their esterase isoenzyme patterns. These precipitin lines exhibited esterase activity. The fusion of the lines of these tissue extracts and that of the purified L-I indicated the presence of an antigen site common to their esterases. The extracts of adult and fetal livers and also of hepatomas resembling fetal liver in the esterase isoenzyme pattern did not produce a precipitin line with anti-L-I antiserum.

背景与目标： : 从用苯巴比妥处理的雄性W大鼠的肝脏中纯化了微粒体丁酸酯酶 (l-i)，并在兔子中产生了针对该纯化的l-i的抗血清。通过Ouchteriony双扩散试验，在肝脏的发育，部分肝切除术后的再生，癌变以及增生性结节和肝癌的发育过程中，在抗L-I抗血清和每个Triton X-100提取物之间观察到沉淀蛋白线，所有这些都在其酯酶同工酶模式中显示了L-I。这些沉淀素系表现出酯酶活性。这些组织提取物的品系与纯化的l-i品系的融合表明存在其酯酶共有的抗原位点。在酯酶同工酶模式下，成年和胎儿肝脏以及类似胎儿肝脏的肝癌的提取物不会产生具有抗L-I抗血清的沉淀蛋白。

BACKGROUND & AIMS: :A brief 21-item symptom rating scale, the Psychiatric Outpatient Rating Scale (PORS), was developed for use in outpatient clinics. On the basis of its initial use with 86 patients, it was shown to have high internal and interjudge reliability and evidence of concurrent and construct validity. Scores on the PORS correlated significantly with the Global Assessment Scale and with the number of sessions of psychotherapy. For a subsample of 45 patients rated on the PORS at the beginning and termination of psychotherapy, seven symptoms revealed highly significant improvement. The PORS appears to be a potentially useful measure of change in outpatient clinics.

背景与目标： : 开发了一个简短的21项症状评定量表，即精神科门诊评定量表 (PORS)，用于门诊。根据86例患者的首次使用，它被证明具有较高的内部和中间信度以及并发和结构效度的证据。PORS的得分与全球评估量表和心理治疗次数显着相关。对于在心理治疗开始和终止时对PORS进行评分的45名患者的子样本，有7种症状显示出显着改善。PORS似乎是衡量门诊诊所变化的潜在有用指标。

BACKGROUND & AIMS: :Cervical screening attendance among women aged 25-29 years in England is lower than at older ages. There is some evidence that pre-notification leaflets motivate women who have not yet considered their response to a health intervention. We aimed to identify key information to motivate young women at their first cervical screening invitation. Six focus groups were conducted, five with young women aged 17-25 registered with a General Practice in Manchester, UK, and one with Practice nurses. Some women took part in two further groups to discuss leaflet design. There was low awareness of the purpose or procedures of cervical screening, and most women were de-motivated by reports of bad experiences. Some intended to be screened, but not immediately after invitation. Screening was viewed as a test for a cancer that affected older women. Since none of the participants believed that they had cervical cancer, screening seemed unnecessary. We conclude that the perception that screening is unimportant when you are young needs to be challenged. Women also need to be better informed of screening procedures. A pre-notification leaflet incorporating key information was designed and will be tested in a randomized trial of complex interventions within the routine cervical screening programme.

背景与目标： : 英格兰25-29岁女性的子宫颈筛查出勤率低于老年人。有证据表明，预先通知的传单会激励尚未考虑对健康干预措施做出反应的妇女。我们的目标是确定关键信息，以激励年轻女性首次接受子宫颈筛查邀请。进行了六个重点小组，其中五个是在英国曼彻斯特注册的17-25岁的年轻女性，其中一个是执业护士。一些妇女参加了另外两个小组，讨论传单设计。人们对宫颈筛查的目的或程序的认识不足，大多数妇女因不良经历的报道而缺乏动力。有些人打算放映，但不是在邀请后立即放映。筛查被视为对影响老年妇女的癌症的测试。由于没有参与者相信自己患有宫颈癌，因此筛查似乎没有必要。我们得出的结论是，年轻时筛查不重要的看法需要受到挑战。妇女还需要更好地了解筛查程序。设计了包含关键信息的预通知传单，并将在常规子宫颈筛查计划中进行复杂干预的随机试验中进行测试。