优选短串联重复序列应用于脊肌萎缩症产前诊断的连锁分析

目的 建立完整的适合汉族人群的脊肌萎缩症(SMA)产前基因诊断体系.方法 对30名正常汉族人的外周血样本进行基因多态性分析,评估位于运动神经元存活基因1(SMN1)两侧的短串联重复序列(STR)位点的多态信息含量;并通过在6个SMA产前诊断家系连锁中的应用,优选出STR位点,并结合PCR-酶切法(PCR-RFLP)进一步评价STR位点与SMN1基因的连锁紧密性.结果 从7个STR位点中优选出D5S435、D5S629、D5S610和D5S351四个STR位点用于家系连锁分析,联合PCR-RFLP,在6名待检胎儿中检出2例患者和4例携带者.结论 通过优选出的4个多态性强、与SMN1基因紧密连锁的STR位点,联合家系连锁和PCR-RFLP,建立起稳定可靠的适合汉族人群的SMA产前基因诊断体系.     

Screening and Quantification of Depression in Mild-to-Moderate Dementia Through the GDS Short Forms

Abstract

We evaluated the validity of the 1-, 4- and 15-item versions of the GDS in 51 patients affected by mild to moderate dementia, using the long form as standard. The following sensitivity and specificity values were obtained: 66% and 91% for GDS-1, 93% and 87% for GDS-4, 79% and 100% for GDS-15. GDS-15 also showed good agreement with GDS-30 in defining the severity of depression. These findings support the use of GDS-4 for the screening of depression and of GDS-15 for its severity assessment.     

Angiotensinogen mRNA and Pressor Reactions to Angiotensin in Brain Stem Areas of Spontaneously Hypertensive Rats

The role of angiotensin (ANG II) at the tissue level, particularly in the brain, remains imperfectly defined. We measured angiotensinogen (A°) mRNA in the brain stems, sensory and sympathetic ganglia, and blood vessels of Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHR-SP) by quantitative, liquid hybridization. We micro-injected ANG II and glutamate into the brain stems of these rats to gain insight into the functional significance of our findings. A° mRNA was found in the dorsolateral, dorsomedial, and ventrolateral pons, as well as in the dorsolateral, dorsomedial, and ventrolateral medulla of both strains. A° mRNA was 8–10 pg/μg total mRNA higher (p<0.05) in the dorsomedial medulla (nucleus tractus solitarii) in WKY and SHR-SP (28.27 ± 1.26 and 33.50 ± 1.42 pg/μg RNA respectively) than in the other areas. SHR-SP had higher values (27.22±1.77 vs. 21.53±0.57 pg/μg mRNA) than WKY (p<0.05) in the dorsolateral pons (locus coeruleus). A° mRNA was also identified in the optic nerves and chiasm, trigeminal and coeliac ganglia, arteries and veins. Injections of glutamate and ANG II into the dorsomedial, dorsolateral, and ventrolateral.     

Safety assessment of food and feed from biotechnology-derived crops employing RNA-mediated gene regulation to achieve desired traits: A scientific review

Gene expression can be modulated in plants to produce desired traits through agricultural biotechnology. Currently, biotechnology-derived crops are compared to their conventional counterparts, with safety assessments conducted on the genetic modification and the intended and unintended differences. This review proposes that this comparative safety assessment paradigm is appropriate for plants modified to express mediators of RNA-mediated gene regulation, including RNA interference (RNAi), a gene suppression mechanism that naturally occurs in plants and animals. The molecular mediators of RNAi, including long double-stranded RNAs (dsRNA), small interfering RNAs (siRNA), and microRNAs (miRNA), occur naturally in foods; therefore, there is an extensive history of safe consumption. Systemic exposure following consumption of plants containing dsRNAs that mediate RNAi is limited in higher organisms by extensive degradation of ingested nucleic acids and by biological barriers to uptake and efficacy of exogenous nucleic acids. A number of mammalian RNAi studies support the concept that a large margin of safety will exist for any small fraction of RNAs that might be absorbed following consumption of foods from biotechnology-derived plants that employ RNA-mediated gene regulation. Food and feed derived from these crops utilizing RNA-based mechanisms is therefore expected to be as safe as food and feed derived through conventional plant breeding.     

室间隔缺损封堵术对心脏重构近、中期的影响

目的:应用超声心动图评价室间隔缺损封堵术后心脏结构与大小的近、中期变化.方法:观察30例室间隔缺损患者封堵术前、术后第3天,术后3个月和术后6个月左室舒张末期内径(LVEDD)、左室舒张末期容积(LVEDV)、左房内径(LAd)和右室内径(RVd)大小及变化.结果:封堵术后第3天,LVEDD与LVEDV较术前缩小,术后3个月、术后6个月随访时,LVEDD与LVEDV进一步缩小.封堵术后3个月、术后6个月,LAd较术前缩小,术后6个月与术后3个月比较无明显变化.术后第3天RVd较术前增大,术后3个月、术后6个月与术前比较无明显差异.结论:经导管室间隔缺损封堵术能有效改善室间隔缺损患者近、中期心脏重构.     

Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice

PurposeWe aimed to clarify the role of particulate allergen exposure to the conjunctiva in the development of allergic conjunctivitis.MethodsWe administered ragweed pollen suspension, pollen extract, pollen shell, particulate air pollutants, and their combinations to the mouse conjunctiva five days a week without prior sensitization. Clinical signs were scored. Histological changes, cellular infiltrations, mRNA expressions, lymph node cell recall responses, and serum immunoglobulin levels were assessed. Immune cell-depleting antibodies and ST2 knockout mice were used to investigate the cellular and molecular requirements.ResultsPollen suspension, but not the extract or shell alone, induced robust eosinophilic conjunctivitis, accompanied by a proliferative response of epithelial cells. A combination of pollen extract and shell completely restored eosinophil accumulation. In addition, eosinophilic conjunctivitis was induced by a mixture of particulate air pollutants and pollen extract. Mechanistically, eosinophil accumulation was ameliorated by deficiency of the IL-33 receptor ST2 and abolished by depleting CD4⁺ T cells. Pollen shells, but not the extract, induced IL-33 release from conjunctival epithelial cells in vivo.ConclusionsOur results indicate the non-redundant roles for the allergens’ particulate properties and soluble factors in the development of allergic conjunctivitis.     

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

Genicular Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis

PurposeTo evaluate the efficacy and safety of embolization of hyperemic synovial tissue for the treatment of knee pain secondary to osteoarthritis (OA).Materials and MethodsTwenty patients with radiographic knee OA and moderate-to-severe pain refractory to conservative therapy were enrolled in a prospective, 2-site pilot study. Genicular artery embolization (GAE) was performed with 75- or 100-μm spherical particles. Patients were assessed with magnetic resonance imaging at baseline and at 1 month and with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and at 1, 3, and 6 months. Adverse events were recorded at all timepoints.ResultsEmbolization of at least 1 genicular artery was achieved in 20/20 (100%) patients. Mean VAS improved from 76 mm ± 14 at baseline to 29 mm ± 27 at 6-month follow-up (P < .01). Mean WOMAC score improved from 61 ± 12 at baseline to 29 ± 27 at 6-month follow-up (P < .01). Self-limiting skin discoloration occurred in 13/20 (65%) patients. Two of 20 (10%) patients developed plantar sensory paresthesia that resolved within 14 days.ConclusionsGAE to treat knee pain secondary to OA can be performed safely and demonstrates potential efficacy. Further randomized comparative studies are needed to determine true treatment effect versus placebo effect.