Karyotyping chromosomes by electron microscopy. Condensation-inhibition of G bands in human and Chinese hamster chromosomes by a BrdU-Hoechst 33258 treatment

A BrdU-Hoechst 33258 treatment of living cells, which selectively induced condensation-inhibition of G-band chromatin in human and Chinese hamster chromosomes, is presented. As a consequence mitotic chromosomes showed high resolution R-banding patterns when examined by light and electron microscopy. Besides each whole chromosome identification, this procedure also permitted the electron microscopic study of specific structures, such as satellites, secondary constrictions, telomeres, centromeres, as well as G and R bands, some of them not visible by light microscopy. We have also observed that the chromatin of G and R bands behave as blocks of chromatin condensation and that G-band chromatin develops condensation along G₂. Under the BrdU-Hoechst 33258 treatment, chromatin fibers seem to invert their spontaneous pattern of condensation within the chromosomes.     

The influence of molecular structure on the affinity and efficacy of some β-adrenoceptor agonists

Summary The affinity and efficacy of a number of sympathomimetic amines structurally related to prenalterol and the selective ₁-adrenoceptor agonist RO 363 were determined using a combination of radioligand binding and organ bath techniques. Affinity of the molecules (pK _D) was calculated from their ability to displace the radioligand [¹²⁵I]iodocyanopindolol ([¹²⁵I]CYP) from -adrenoceptor sites in left atrial (₁) and uterine (₂) membrane homogenates. These pK _D values were used to calculate efficacy from the positive inotropic and uterine relaxant responses elicited by the drugs in organ bath experiments. The drugs studied were either arylethanolamines i.e., (–)-isoprenaline (ISO), p-hydroxyisoprenaline (pOH-ISO), compounds XIV and XVI or aryloxypropanolamine-derivatives, i.e., oxymethylene-isoprenaline (OM-ISO), prenalterol and Compound XI which possessed ap-phenol or catechol ring and an isopropyl or a homoveratryl amine substituent. Only ISO, OM-ISO, pOH-ISO and Compound XVI were active as agonists in both tissue preparations. These drugs were partial agonists which exhibited a wide range of pD₂ values and did not display any marked selectivity for either -adrenoceptor subtype. Compound XI and prenalterol were inactive as agonists and together with the partial agonists behaved as competitive antagonists to ISO in the two preparations. All drugs tested displaced [¹²⁵I]CYP from -adrenoceptor sites, however, there was also a wide range of potency amongst the drugs.Analysis of the structure-affinity and structure-efficacy relationships indicated that removal of the 3-hydroxyl group from the catechol ring reduces both affinity and efficacy without altering the selectivity of the drug for either -adrenoceptor subtype. While aryloxypropanolamine derivatives have generally higher affinities than arylethanol-amines, especially at -adrenoceptor sites, their efficacies are generally reduced at both -adrenoceptors. The presence of a homoveratryl group in aryloxypropanolamines enhances slightly the affinity for ₁- and reduces affinity for ₂-adrenoceptors. With this amine group, efficacy is markedly reduced at ₂- as opposed to ₂-adrenoceptor sites.Thus for prenalterol, the small degree of cardioselectivity can be attributed to the oxymethylene group whilst its lack of agonist activity (i.e., efficacy) reflects a combined action of this group and the absence of the 3-hydroxyl group on the phenyl ring. In RO363 it can be deduced that the oxymethylene group, together with the homoveratryl substituent are responsible for the observed selective affinity of the drug for ₁- as opposed to ₂-adrenoceptors.     

Component-Resolved Diagnosis of Hazelnut Allergy in Children

Hazelnuts commonly elicit allergic reactions starting from childhood and adolescence, with a rare resolution over time. The definite diagnosis of a hazelnut allergy relies on an oral food challenge. The role of component resolved diagnostics in reducing the need for oral food challenges in the diagnosis of hazelnut allergies is still debated. Therefore, three electronic databases were systematically searched for studies on the diagnostic accuracy of specific-IgE (sIgE) on hazelnut proteins for identifying children with a hazelnut allergy. Studies regarding IgE testing on at least one hazelnut allergen component in children whose final diagnosis was determined by oral food challenges or a suggestive history of serious symptoms due to a hazelnut allergy were included. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Eight studies enrolling 757 children, were identified. Overall, sensitivity, specificity, area under the curve and diagnostic odd ratio of Cor a 1 sIgE were lower than those of Cor a 9 and Cor a 14 sIge. When the test results were positive, the post-test probability of a hazelnut allergy was 34% for Cor a 1 sIgE, 60% for Cor a9 sIgE and 73% for Cor a 14 sIgE. When the test results were negative, the post-test probability of a hazelnut allergy was 55% for Cor a 1 sIgE, 16% for Cor a9 sIgE and 14% for Cor a 14 sIgE. Measurement of IgE levels to Cor a 9 and Cor a 14 might have the potential to improve specificity in detecting clinically tolerant children among hazelnut-sensitized ones, reducing the need to perform oral food challenges.     

Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in Hamp KO Mice

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including ⁵⁹Fe (as FeCl₃) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40–50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.     

A qualitative exploration of the mechanisms,pathways and public health outcomes of a city centre 20mph speed limit intervention: The case of Belfast,United Kingdom

Twenty miles per hour (mph) speed limits can impact the health of the public (e.g., road safety, active travel). However, a better understanding of how individuals experience 20mph limits is required, to ensure interventions are cognisant of perceptions and potential un/intended outcomes. Focus groups (n = 9, 60 participants) to explore the Belfast 20mph intervention highlighted divergent perspectives and experiences including: 12 mechanisms (e.g., limited awareness), 15 pathways (e.g., reduced driving speed→improved liveability) and 10 public health outcomes (e.g., increased cyclist safety). Future interventions should consider un/intended outcomes and implement strategies to enhance effectiveness and mitigate harms (e.g., through training, enforcement).     

胃镜治疗与内科治疗对消化性溃疡出血的应用效果比较分析

目的:探究胃镜治疗与内科治疗对消化性溃疡出血的应用效果对比。方法:在2018年9月~2019年9月这个时间段中,选取本院收治的45例消化性溃疡出血患者作为本次研究的观察组,给予胃镜治疗;同期选取本院收治的45例消化性溃疡出血患者作为本次研究的对照组,给予内科治疗;对两组疗效进行对比。结果:观察组治疗总有效率(95.6%)显著高于对照组(77.8%),有统计学意义,P<0.05。观察组住院时间、止血时间与再次出血率均优于对照组,P<0.05。结论:在消化性溃疡出血患者中采用胃镜治疗的效果优于内科治疗效果,且止血效果较好,促使患者尽早康复,在临床上的应用价值较高。     

炎症细胞与淋巴细胞在鼻息肉发病机理中的相关性研究

目的：探讨炎症细胞、淋巴细胞及浆细胞在鼻息肉发病中的作用;方法：采用免疫组化SP法及HE、甲苯胺兰染色对34例鼻息肉和30例正常中鼻甲粘膜进行研究;结果：鼻息肉中嗜酸性粒细胞阳性率显著高于对照组织（P＜0.01）;鼻息肉中肥大细胞数量显著多于对照组织（P＜0.01）,肥大细胞数量在吸入性变应原皮肤试验阳性组与阴性组间无显著性差异;鼻息肉中T淋巴细胞阳性细胞（CD43）和B淋巴细胞阳性细胞（CD20）、浆细胞数量显著多于对照组织（P＜0.01）,鼻息肉中T淋巴细胞与B淋巴细胞之间无显著性差异;结论：鼻息肉中存在活跃的细胞免疫和体液免疫,与嗜酸性粒细胞、肥大细胞及中性粒细胞共同参与鼻息肉的发病。     

脑梗死患者血清脂蛋白a含量的变化及其意义

目的研究血清脂蛋白a(1ipoprotein(a),LP(a))在脑梗死形成中的作用及意义.方法采用双抗体夹心法检测血清中LP(a)的浓度.结果脑梗死组(n=71)LP(a)浓度显著高于健康对照组(n=37),p＜0.05.脑梗死组与健康对照组中不同性别,年龄组LP(a)水平无显著差异,p＞0.05.脑梗死组中,有无糖尿病及高血压,LP(a)水平无显著差异,P＞0.05.结论LP(a)是与遗传有关的血浆脂蛋白,血清LP(a)水平高低在估计脑梗死患病风险上有参考意义.     

高校师资队伍建设的构想

师资是一所高校最重要的资源 ,是高校实现人才培养、科学研究和社会服务三大功能的主体力量 ,也是一所高校在人才培养、科学创造与学术成就以及社会影响力等方面获得竞争优势的决定性因素。在新的历史时期 ,高等院校师资队伍建设的总体目标 ,是建设一支素质良好、结构优化、富有活力、具有创新能力的师资队伍。其具体措施是完善选人机制 ,优化教师资源配置 ;采取得力措施 ,优化教师队伍成才环境 ;建立激励机制 ,加强学科带头人和骨干教师队伍建设 ;强化竞争机制 ,实施和完善教师聘任制 ;强化教师培训 ,全面提高教师素质 ;加大投入 ,确保教师队伍建设落到实处