Everyday problem solving in African Americans and European Americans with Alzheimer's disease: an exploratory study

In this exploratory study, we compared the performance of 10 African American and 26 European American persons with early- to mid-stage Alzheimer's disease (AD) to 20 nondemented elderly (NE), using a shortened version of the Test of Problem Solving (TOPS). The TOPS measures verbal reasoning to solve everyday problems in five areas: explaining inferences, determining causes, answering negative why questions, determining solutions, and avoiding problems. Six linguistic measures were also examined: total utterances, abandoned utterances, length of utterances, maze words, questions, and total words. NE performed better than AD subjects on all but one measure of verbal reasoning ability. AD subjects also showed a trend to use more total utterances and abandoned utterances than NE. For the AD group, no ethnic differences were found for verbal reasoning or linguistic measures. The findings from this preliminary investigation suggest that, compared to European Americans, African American persons with AD demonstrate similar everyday problem solving and linguistic skills. Thus, assessments such as TOPS that examine everyday problem solving may be a useful nonbiased evaluation tool for persons with AD in these two ethnic groups.     

Catalytic Activity of New Oxovanadium(IV) Microclusters with 2-Phenylpyridine in Olefin Oligomerization

So far, few microclusters containing vanadium have been described in the literature. In this report, the synthesis protocol for the preparation of oxovanadium (IV) microclusters with 2-phenylpyridine is shown for the first time. Moreover, the crystal structure of these microclusters is also studied through the use of X-rays. The morphology of the prepared crystals is investigated using a field-emission Scanning Electron Microscope (SEM). The new compound, after activation by modified methylaluminoxane as the catalytic system, is investigated regarding the oligomerizations of 3-buten-1-ol, 2-chloro-2-propen-1-ol, allyl alcohol, and 2,3-dibromo-2-propen-1-ol. The products of oligomerization are tested by the TG-FTIR and MALDI-TOF-MS methods. Moreover, the values of catalytic activities for the new oxovanadium(IV) microclusters with 2-phenylpyridine are determined for the 3-buten-1-ol, 2-chloro-2-propen-1-ol, allyl alcohol, and 2,3-dibromo-2-propen-1-ol oligomerizations. Oxovanadium(IV) microclusters with 2-phenylpyridine are shown to be very highly active precatalysts for the oligomerization of allyl alcohol, 2,3-dibromo-2-propen-1-ol, and 3-buten-1-ol. However, in the case of 2-chloro-2-propen-1-ol oligomerization, the new microclusters are seen as highly active precatalysts.     

Local Chemotherapy with Cisplatin-depot for Glioblastoma Multiforme

Glioblastoma multiforme (GBM) makes up as many as 30% of all primary brain tumors. Despite the employment of multimodal antitumor treatment, the overall survival is less than one year. Between 06/01/1998 and 06/01/2000 17 patients (Group A) with GBM (11 males, 6 females; median age 54.3 years) were administered local chemotherapy with cisplatin incorporated into biodegradable 6-carboxylcellulose polymer (cisplatin-depot (CDDP-D)). After the subtotal removal of GBM, twenty 1.5 × 1.5cm polymer plates with a total area of 45cm² (the density of cisplatin immobilization on 6-carboxylcellulose being 1mg/cm², a total cisplatin dose of 45mg) were implanted into the tumor bed. Group B (21 patients with GBM; 11 males, 10 females; median age 53.2 years) was control: the subtotal tumor ablation without CDDP-D implantation. Two to three weeks after the surgery all the patients of Groups A and B started a course of radiation therapy. A total dose of cranial irradiation was 20Gy (1 fraction/day, 5 days/week; a daily dose of 2Gy) followed by a boost tumor bed irradiation (1 fraction/day, 5 days/week; a daily dose of 2Gy) up to the conventional dose of 60Gy. Survival data for the patients were processed using the Kaplan–Meier method and analyzed by logrank test.All the patients of Group A tolerated surgical ablation of the brain tumor without side effects (brain edema, seizures, etc.). No patient of Group A had a reduction in blood cell counts during six weeks that would indicate systemic exposure to cisplatin. Blood chemistry and urinalysis did not show evidence of renal injury. No side effects of radiotherapy were registered in Group B either, regarding both the psychoneurological status of the patients and the basic values of homeostasis. Karnofsky performance scale (KPS) score of Group A and Group B patients demonstrated no significant differences before and after the surgery. The median overall survivals for patients of Group A and Group B were 427.5 and 211.0 days respectively (p=0.00001; overall logrank test). Conclusion. Local chemotherapy of GBM with CDDP-D followed by irradiation is well tolerated and effective.     

倒T形切口缩乳术在乳房肥大或合并乳腺癌患者中的应用

目的探讨倒T形切口缩乳术在乳房肥大患者，特别是合并乳腺癌的患者手术中的应用及其临床意义。 方法本回顾性研究共纳入2007年10月到2017年10月分别在同济大学附属东方医院及附属同济医院乳腺外科行缩乳术的39例乳房肥大女性患者，均采用倒T形切口(内侧蒂25例，垂直蒂5例，外侧蒂9例)。其中，包括18例符合保留乳房手术指征的乳腺癌患者(内侧蒂10例，垂直蒂4例，外侧蒂4例)。术后6、12个月评价美容效果(乳腺癌患者待放射治疗结束后进行评价)。评估患者的术后并发症、满意度以及复发转移情况。 结果39例患者术后乳房外形自然、对称，明显缩小上提，乳头、乳晕血供和感觉良好，瘢痕不明显，患者满意度高。1例术后2周出现一侧乳房的乳头乳晕区坏死，经过清创换药后愈合。5例术后双侧乳头乳晕感觉减退，其中4例在术后6个月左右恢复正常感觉，1例在术后12个月恢复。5例出现术后局部乳房组织硬结，其中3例为接受过放射治疗的乳腺癌患者，二次手术切除硬结后无再次发生。3例出现瘢痕处猫耳畸形，再次局部麻醉手术修整后效果良好，3例瘢痕增粗，其余患者瘢痕正常。乳腺癌患者中有3例出现放射治疗后患侧乳房皮肤水肿，术后12个月消退。术后6个月进行了美容效果评价，极好25例，良好10例，中等4例，差0例(18例乳腺癌患者中，极好9例，良好6例，中等3例，差0例)。术后12个月的美容效果评价显示：极好25例，良好13例，中等1例，差0例(18例乳腺癌患者中，极好9例，良好8例，中等1例，差0例)。随访时间最长的1例患者(双侧乳房单纯性重度肥大)术后观察了10年，乳房外形无明显变化。全部患者术后随访15～120个月，中位随访61个月，18例乳腺癌患者均无局部复发转移。 结论对于乳房肥大，特别是合并乳腺癌的患者，采用倒T形切口缩乳术，既可切除病变，又可缩小并悬吊乳房。     

Protein Binder (ProBi) as a New Class of Structurally Robust Non-Antibody Protein Scaffold for Directed Evolution

Engineered small non-antibody protein scaffolds are a promising alternative to antibodies and are especially attractive for use in protein therapeutics and diagnostics. The advantages include smaller size and a more robust, single-domain structural framework with a defined binding surface amenable to mutation. This calls for a more systematic approach in designing new scaffolds suitable for use in one or more methods of directed evolution. We hereby describe a process based on an analysis of protein structures from the Protein Data Bank and their experimental examination. The candidate protein scaffolds were subjected to a thorough screening including computational evaluation of the mutability, and experimental determination of their expression yield in E. coli, solubility, and thermostability. In the next step, we examined several variants of the candidate scaffolds including their wild types and alanine mutants. We proved the applicability of this systematic procedure by selecting a monomeric single-domain human protein with a fold different from previously known scaffolds. The newly developed scaffold, called ProBi (Protein Binder), contains two independently mutable surface patches. We demonstrated its functionality by training it as a binder against human interleukin-10, a medically important cytokine. The procedure yielded scaffold-related variants with nanomolar affinity.     

Regulation of vascular guanylyl cyclase by endothelial nitric oxide-dependent posttranslational modification

In isolated cells, soluble guanylyl cyclase (sGC) activity is regulated by exogenous nitric oxide (NO) via downregulation of expression and posttranslational S-nitrosylation. The aim of this study was to investigate whether such regulatory mechanism impact on endothelium-dependent vasodilation in a newly developed mouse strain carrying an endothelial-specific overexpression of eNOS (eNOS⁺⁺). When compared with transgene negative controls (eNOSⁿ), eNOS⁺⁺-mice showed a 3.3-fold higher endothelial-specific aortic eNOS expression, increased vascular cGMP and VASP phosphorylation, a L-nitroarginine (L-NA)-inhibitable decrease in systolic blood pressure, but normal levels of peroxynitrite and nitrotyrosine formation, endothelium-dependent aortic vasodilation and vasodilation to NO donors. Western blot analysis for sGC showed similar protein levels of sGC-α1 and sGC-β1 subunits in eNOSⁿ and eNOS⁺⁺. In striking contrast, the activity of isolated sGC was strongly decreased in lungs of eNOS⁺⁺. Semiquantitative evaluation of sGC-β1-S-nitrosylation demonstrated that this loss of sGC activity is associated with increased nitrosylation of the enzyme in eNOS⁺⁺, a difference that disappeared after L-NA-treatment. Our data suggest the existence of a physiologic NO-dependent posttranslational regulation of vascular sGC in mammals involving S-nitrosylation as a key mechanism. Because this mechanism can compensate for reduction in vascular NO bioavailability, it may mask the development of endothelial dysfunction.     

Physical inactivity causes endothelial dysfunction in healthy young mice

OBJECTIVES: We sought to determine if physical inactivity affects endothelial function in young healthy individuals. BACKGROUND: Recent studies have linked exercise training to increased bioavailability of vascular nitric oxide (NO) and to improved endothelial function in patients with cardiovascular disorders. The effects of physical inactivity on normal vascular endothelial function are not known. METHODS: Healthy young male C57Bl/6 mice living in groups of five in large cages, where they were running, climbing, and fighting during their active cycle, were randomly assigned to stay there or to live alone in small cages where they were predominantly resting. After five and nine weeks citrate synthase activity (a measure of mitochondrial respiratory chain activity), heart weight/body weight ratio, vascular reactivity, and protein expression of endothelial nitric oxide synthase (eNOS) were assessed. RESULTS: Singularized mice showed a reduction of citrate synthase activity (p < 0.05), of endothelium-dependent vasorelaxation (to 65 +/- 5% of control levels; p < 0.001), and of eNOS protein expression (to 53 +/- 8% of control levels; p < 0.01). In striking contrast, vascular responses to potassium chloride, phenylephrine, and the NO-donor racemic S-nitroso-N-acetylpenicillamine were unchanged. The alterations of vascular eNOS-activity were completely reversible when singularized mice underwent exercise. In mice living in groups, exercise showed only a small effect on aortic eNOS expression. CONCLUSIONS: In young healthy individuals physical inactivity induces endothelial dysfunction, which is completely reversible by a short period of moderate exercise training. We suggest that physical inactivity, the so-called sedentary lifestyle, increases cardiovascular risk in young healthy individuals by inducing endothelial dysfunction.