Simultaneous Detection of Major Drug Resistance Mutations of HIV-1 Subtype B Viruses from Dried Blood Spot Specimens by Multiplex Allele-Specific Assay

A multiplex allele-specific (MAS) assay has been developed for the detection of HIV-1 subtype C drug resistance mutations (DRMs). We have optimized the MAS assay to determine subtype B DRMs in dried blood spots (DBS) collected from patients on antiretroviral therapy. The new assay accurately detected DRMs, including low-abundance mutations that were often missed by Sanger sequencing.     

Single-dose vaccine against tick-borne encephalitis

Tick-borne encephalitis (TBE) virus is the most important human pathogen transmitted by ticks in Eurasia. Inactivated vaccines are available but require multiple doses and frequent boosters to induce and maintain immunity. Thus far, the goal of developing a safe, live attenuated vaccine effective after a single dose has remained elusive. Here we used a replication-defective (single-cycle) flavivirus platform, RepliVax, to generate a safe, single-dose TBE vaccine. Several RepliVax-TBE candidates attenuated by a deletion in the capsid gene were constructed using different flavivirus backbones containing the envelope genes of TBE virus. RepliVax-TBE based on a West Nile virus backbone (RV-WN/TBE) grew more efficiently in helper cells than candidates based on Langat E5, TBE, and yellow fever 17D backbones, and was found to be highly immunogenic and efficacious in mice. Live chimeric yellow fever 17D/TBE, Dengue 2/TBE, and Langat E5/TBE candidates were also constructed but were found to be underattenuated. RV-WN/TBE was demonstrated to be highly immunogenic in Rhesus macaques after a single dose, inducing a significantly more durable humoral immune response compared with three doses of a licensed, adjuvanted human inactivated vaccine. Its immunogenicity was not significantly affected by preexisting immunity against WN. Immunized monkeys were protected from a stringent surrogate challenge. These results support the identification of a single-cycle TBE vaccine with a superior product profile to existing inactivated vaccines, which could lead to improved vaccine coverage and control of the disease.     

Study on the Implicit Attitude and Explicit Attitude of Heroin Abstainers

目的 了解海洛因戒断者对毒品的态度,探讨其对复吸行为的意义.方法 分别采用内隐联想测验和自陈式量表对戒断者和普通人对毒品的内隐态度和外显态度状况及其关系进行研究.结果 ①戒断者内隐态度取向的IAT效应显著(t=14.096,P＜0.001),其将毒品与积极的词联系的反应时短；②普通人内隐态度取向的IAT效应显著,其将毒品与消极词语联系的反应时短；③戒断者与普通人的外显态度没有显著差异(t=1.041,P＞0.05)；④内隐态度和外显态度的相关系数为0.003.结论 戒断者与普通人各自存在不同的内隐效应,戒断者对毒品的内隐态度为肯定倾向,普通人对毒品的内隐态度为否定倾向；戒断者与普通人对毒品的外显态度一致均为否定倾向；戒断者的内隐态度和外显态度倾向分离；内隐态度和外显态度相互独立.     

Apocrine Metaplasia Found at MR Biopsy: Is There Something to be Learned?

The purpose of this study was to determine (a) the frequency of apocrine metaplasia (ApoM) found on MR core biopsy of suspicious findings, and (b) to determine if there are specific MR imaging features that might obviate the need for biopsy. This HIPAA‐compliant retrospective study was performed under IRB exemption for quality assurance studies. Patient demographics, MR imaging features, and pathology were reviewed. Breast lesions which underwent MR‐guided biopsy, yielding ApoM on pathology analysis were included. Retrospective review of MR imaging features of these lesions was performed by two radiologists blinded to pathology results except for the presence of ApoM. Imaging features on MR assessed included location, size, morphology, T1 and T2 signals, and enhancement kinetics. Full pathology results were subsequently reviewed during data analysis. The pathology slides and imaging was subsequently reviewed by two fellowship trained radiologists and a breast pathologist to categorize the finding of ApoM into target lesion (imaging corresponds to size of lesion on pathology) versus incidental lesion. Target lesion characteristics were assessed to determine specific MRI features of ApoM. Between January 2011 to November 2012, 155 distinct breast lesions suspicious for malignancy successfully underwent MR‐guided biopsy. Of the 155 lesions biopsied, 123 (79%) were benign and 32 (21%) were malignant. Of the 123 benign biopsies, ApoM was found in 57 (46%), of which 35 (61%) had no associated atypia and 22 (39%) had associated atypia. Of the 32 malignant biopsies, three (9%) had associated ApoM (DCIS in two cases and DCIS/LCIS in one case). Of the 60 cases with ApoM, only 11 (18.3%) were target lesions and 49 were incidental lesions (81.7%). Of the 60 cases with ApoM, 35 (58%) were masses (average size 0.8 cm for both with or without atypia) and 25 (42%) were nonmass enhancement (NME) (average size 2.1 cm with and 1.0 cm without atypia). Only five (14%) of 35 masses demonstrated spiculated margins, of which four were associated with atypia (80%). Of 22 lesions with atypia or other high‐risk lesion, 14 (64%) were masses, most commonly with irregular margins (64%). Of the 12 T2 hyperintense lesions, only two (1.7)% had associated atypia or high‐risk lesion, and none were associated with malignancy. Of the 11 target lesions, seven were T2 hyperintense. Enhancement kinetics were variable: 30 (50%) showed mixed persistent and plateau kinetics, eight (13%) persistent delayed enhancement, 10 (17%) plateau kinetics, four (7%) washout kinetics, and eight (13%) were below threshold for kinetic analysis. ApoM is a common benign pathologic result at MR‐guided core biopsy for both masses and NME accounting for 39% of all biopsy results in this series. Although there is considerable variability in imaging characteristics on MR, our results suggest biopsy may be safely obviated for lesions that are subcentimeter T2 hyperintense areas of NME and short term follow‐up imaging may be a reasonable alternative for these lesions.     

1例Graves眼病并象皮病型胫前黏液性水肿病人的护理

胫前黏液性水肿是Graves病合并的一种少见的皮肤损害,偶可见于桥本氏甲状腺炎,一般好发于胫骨前下1/3处,皮肤损害呈对称性.早期皮肤呈广泛性红肿,之后出现皮肤的增厚、变粗伴有广泛大小不等的棕褐色突起,不平的斑块或结节,边界清楚,皮肤毛孔增粗,可伴角化过度、色素沉着、多汗、下肢粗大似象皮腿.多数合并Graves眼病,占Grvaes眼病病人的13%[1].     

Rhein lysinate inhibits cell growth by modulating various mitogen-activated protein kinases in cervical cancer cells

In previous studies, we found that rhein lysinate (RHL; the salt of rhein and lysine, easily dissolved in water) inhibited the growth of tumor cells in breast and ovarian cancer and hepatocellular carcinoma. This study aimed to investigate the effect of RHL on the growth of human cervical carcinoma HeLa cells and any underlying mechanisms. RHL inhibited the growth of HeLa cells in a dose- and time-dependent manner. It was also noted that RHL induced apoptosis in HeLa cells in a dose-dependent manner. Mechanistically, RHL triggered HeLa cell apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, the activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was a critical mediator in RHL-induced growth inhibition. Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed RHL-induced growth inhibition by decreasing the level of cleaved PARP and caspase-3/7. Phosphorylation of the extracellular signal-related kinase (ERK) was increased by RHL; conversely, the MEK inhibitor which inhibits ERK activity, synergistically enhanced RHL-induced growth inhibition in HeLa cells. The results showed that RHL inhibits Hela cell growth through the activation of p38 MAPK and JNK, and is a potential chemotherapeutic agent for cervical cancer.