Prevalence of cortical superficial siderosis in patients with cognitive impairment

Cortical superficial siderosis (cSS) is a magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. cSS has further been identified as a risk marker for future intracranial hemorrhage. Although uncommon in the general population, cSS may be much more prevalent in high risk populations for amyloid pathology. We aimed to determine the frequency of cSS in patients with cognitive impairment presenting to a memory clinic. We prospectively evaluated consecutive patients presenting to our memory clinic between April 2011 and April 2013. Subjects received neuropsychological testing using the Consortium to Establish a Registry for Alzheimer’s Disease battery (CERAD-NP). Two hundred and twelve patients with documented cognitive impairment further underwent a standardized 3T-MR-imaging protocol with T2*-weighted gradient-echo sequences for detection of cSS. Thirteen of 212 patients (6.1 %) displayed cSS. In seven of them (54 %) cSS was the only imaging sign of CAA. Patients with cSS did not differ from patients without cSS with regard to medical history, age or cardiovascular risk profile. Subjects with cSS performed worse in the mini-mental state examination (p = 0.001), showed more white matter hyperintensities (p = 0.005) and more often had microbleeds (p = 0.001) compared to those without cSS. cSS is common in patients with cognitive impairment. It is associated with lower cognitive scores, white matter hyperintensities and microbleeds and can be the only imaging sign for CAA in this patient group.     

Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling

Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.     

不同牵引位点进行骨性支抗上颌前方牵引时骨缝应力分布特征

目的 分析不同牵引位点进行骨性支抗前牵引上颌时骨缝应力分布特征,以指导临床上患者选择合适的前方牵引位点。方法 建立包含种植体的儿童颅面三维有限元模型,根据种植体植入部位设定牵引位点,共分4种工况。工况1:乳侧切牙牙冠远中面远中2 mm与颈缘龈向5 mm交点处牙槽骨;工况2:第1乳磨牙牙冠近中面近中2 mm与颈缘龈向5 mm交点处牙槽骨;工况3:第1磨牙牙冠近中面近中2 mm与颈缘龈向5 mm交点处牙槽骨;工况4:第1磨牙牙冠远中面远中2 mm与颈缘龈向5 mm交点处牙槽骨。分析比较在不同牵引位点前牵引力(与合平面前下成角30°,500 g/侧)作用下各骨缝的应力分布。结果 额颌缝应力在工况2中最大(1 477～28 190 Pa),鼻颌缝应力在工况1中最大(5.296～924 Pa),颧颌缝应力在工况4中最大(394.7～13 130 Pa),颧额缝应力在工况4中最大(495.2～31 690 Pa),颧颞缝应力在工况3中最大(1 148～15 870 Pa),腭中缝应力在工况1中最大(6.479～730 Pa)。结论 当牵引位点置于乳侧切牙远中和第1乳磨牙近中时,对改善鼻根部凹陷明显...     

更欣汤治疗心肾不交型围绝经期失眠症的临床疗效研究

目的：观察更欣汤治疗心肾不交型围绝经期失眠症的临床疗效。方法：选取2019年6月至2021年1月就诊于北京中医药大学东直门医院妇科门诊的心肾不交型围绝经期失眠患者40例作为研究对象,随机分为观察组和对照组,每组20例。其中观察组给予更欣汤中药颗粒剂治疗,对照组给予西药佐匹克隆治疗,2组疗程均为4周。收集患者一般资料及临床基本情况,以匹兹堡睡眠质量指数(PSQI)评分变化为主要疗效指标,以改良Kupperman量表、中医证候量表评分变化以及睡眠监测项目中的睡眠潜伏期和睡眠时间变化为次要疗效指标,以血常规、尿常规、生化检验结果中的指标变化及有无不良反应的发生作为安全性指标,分别于治疗前后进行临床治疗效果及安全性指标的评价,采用SPSS 20.0统计软件进行数据分析。结果：更欣汤与第3代环吡咯酮类催眠药佐匹克隆都能有效改善妇女围绝经期失眠症状,延长患者睡眠时间,提高睡眠效率,2组疗效比较,差异无统计学意义(P>0.05);同时更欣汤还能安全有效地改善患者其他围绝经期综合征相关症状,疗效显著优于佐匹克隆,2组疗效比较,差异有统计学意义(P<0.05)。结论：更欣汤能有效改善妇女围绝...     

Effects of dexamethasone on selective lymphocyte subpopulations in hypercortisolemic patients with anorexia nervosa and with bulimia nervosa: Preliminary report

The studies reported here describe the effects of intravenous (IV) administration of the synthetic glucocorticoid dexamethasone (DEX) on certain neuroendocrine and immunological measures in hypercortisoiemic patients with anorexia nervosa (AN) and with bulimia nervosa (BN). The results demonstrate that failure to suppress cortisol levels after DEX administration in patients with AN is associated with failure to reduce the level of adrenocorticotropic hormone (ACTH), the ratio of CD4-to-CD8 lymphocytes, the percent and number of circulating CD4 lymphocytes, and the percent and number of virgin CD4 cells (CD4+CD45RA+). Administration of DEX to patients with BN suppressed plasma ACTH and cortisol levels, reduced the CD4/CD8 ratio and the percent and number of CD4 and of CD4 + CD45RA+ lymphocytes, and increased the percent and number of circulating CD8 lymphocytes. Administration of DEX failed to alter other immune measures in either patient population, including circulating populations of B and natural killer cells, the proliferative response to T-cell mitogen, and the number of glucocorticoid receptors in circulating lymphocytes.     

An essential review of Singapore’s response to out-of-hospital cardiac arrests: improvements over a ten-year period

Care for patients who experience out-of-hospital cardiac arrest (OHCA) has rapidly evolved in the past decade. Increased sophistication of care in the community, emergency medical services (EMS) and hospital setting is associated with improved patient-centred outcomes. Notably, Utstein survival doubled from 11.6% to 23.1% between 2011 and 2016. These achievements involved collaboration between policymakers, clinicians and researchers, and were made possible by a strategic interplay of policy, research and implementation. We review the development and current state of OHCA in Singapore using primary population-based data from the Pan-Asian Resuscitation Outcomes Study and an unstructured search of research databases. We discuss the roles of important milestones in policy, community, dispatch, EMS and hospital interventions. Finally, we relate these interventions to relevant processes and outcomes, such as the relationship between the strategic implementation of bystander cardiopulmonary resuscitation and placement of automated external defibrillator with return of spontaneous circulation, survival to discharge and survival with favourable neurological outcomes.     

基于冰山模型构建护士综合素质测评指标体系

[目的] 基于冰山模型构建护士综合素质测评指标体系,为临床护士综合素质测评提供可视化工具。[方法] 在冰山模型的基础上,通过查阅国内外文献、小组讨论和运用德尔菲法对16名专家进行2轮专家函询,建立了系统、全面的护士综合素质测评体系。[结果] 最终确定了护士综合素质测评指标体系,包括3项一级指标,8项二级指标和31项三级指标。两轮专家有效应答率均为100%,第2轮函询专家权威系数为0.887 5,二级、三级指标的Kendall W系数分别为0.492和0.387（P<0.05）。[结论] 基于冰山模型的护士综合素质测评指标体系科学、客观、内容全面,可用于对临床护士综合素质的测评,并对其他医院护理团队建设有借鉴价值。     

IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer

Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib.     

Novel Mutations Including Deletions of the Entire OFD1 Gene in 30 Families with Type 1 Orofaciodigital Syndrome: A Study of the Extensive Clinical Variability

OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X‐linked condition with lethality in males. Mutations in OFD1 also cause X‐linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X‐inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability.