Enhanced cochlear responses after sound exposure

Alternating potentials produced in Hensen's cells of Mongolian gerbils by sinusoidal stimuli were enhanced or depressed after exposure to broad-band sound of moderately high intensity, depending on exposure- and stimulus intensities. Since Hensen's cell responses have been shown to be identical in phase and directly proportional in magnitude to outer hair cell (OHC) responses (Oesterle, E.C., Dallos, P., 1989, J. Acoust. Soc. Am. 86 (3), 1013–1032.; Zwislocki, J.J., Slepecky, N.B., Cefaratti, L., Smith, R.L., 1992, Hear. Res. 57, 175–194), it was assumed that these changes were reflections of changes in OHC receptor potentials, which were of main interest. The indirect method of intracellularly recording the Hensen's cell potentials rather than OHC potentials was used to minimize damage to the organ of Corti and reduce technical difficulties associated with repeated recordings from OHCs. Continuous magnitude and phase transfer functions (TFs) were obtained before and after the exposure over a range of sound pressure levels (SPLs) extending from 40–90 dB by using frequency sweeps ranging from 0.125–18 kHz. Cochlear microphonic (CM) TFs were also acquired over the same frequency and intensity ranges for monitoring purposes. The exposure stimuli were set at 80, 86, 90 or 100 dB SPL for periods ranging from 10–40 min. When response enhancement occurred, it was most clearly seen in the peak of the transfer function determined at 90 dB SPL. Enhancement ranged from approximately 12-230% of the original peak. In contrast, control Hensen's cell recordings obtained over periods of up to 130 min revealed great response stability. In all reliable recordings, response enhancement was associated with a phase lead or no phase change. The strongest exposure stimuli tended to produce sensitivity loss accompanied by phase lag at the lower SPLs, in agreement with previous work in this laboratory (Zhang and Zwislocki, 1995). In some preparations, both sensitivity loss at lower SPLs and enhancement at higher SPLs occurred simultaneously, suggesting involvement of two different mechanisms.     

A genome-wide association study of suicide severity scores in bipolar disorder

BackgroundSuicide claims one million lives worldwide annually, making it a serious public health concern. The risk for suicidal behaviour can be partly explained by genetic factors, as suggested by twin and family studies (reviewed in (Zai et al. 2012)). Recently, genome-wide association studies (GWASs) of suicide attempt on large samples of bipolar disorder (BD) patients from multiple sites have identified a number of novel candidate genes. GWASs of suicide behaviour severity, from suicidal ideation to serious suicide attempt, have not been reported for BD.MethodsWe conducted a GWAS of suicide behaviour severity in three independent BD samples:212 small nuclear families with BD probands from Toronto, Canada, 428 BD cases from Toronto, and 483 BD cases from the UK. We carried out imputation with 1000 Genome Project data as reference using IMPUTE2. Quality control and data analysis was conducted using PLINK and R. We conducted the quantitative analyses of suicide behaviour severity in the three samples separately, and derived an overall significance by a meta-analysis using the METAL software.ResultsWe did not find genome-wide significant association of any tested markers in any of the BD samples, but we found a number of suggestive associations, including regions on chromosomes 8 and 10 (p < 1e-5).ConclusionsOur GWAS findings suggest that likely many gene variants of small effects contribute collectively to the risk for suicidal behaviour severity in BD. Larger independent replications are required to strengthen the findings from the GWAS presented here.     

北京某二级甲等综合医院医务人员手卫生现状分析及对策

目的 了解临床医务人员手卫生状况,探讨提高医务人员手卫生依从性和洗手正确性的管理方法.方法 强化手卫生管理前后,采用随机抽查的方法,对医务人员手卫生依从性和洗手正确性进行调查.结果 强化手卫生管理后,医务人员手卫生依从性由43.23％提高至68.32％,洗手正确性由25.00％提高至38.61％;医务人员手卫生依从性和洗手正确性整体较低,护士高于医师.结论 采取相应的干预措施可以提高医务人员手卫生的依从性和正确性,但需要管理者持之以恒的严格管理.     

Histologic Characteristics of Hepatocellular Carcinomas Showing Atypical Enhancement Patterns on 4-Phase MDCT Examination

Objective

To retrospectively define which histologic characteristics of small-sized hepatocellular carcinomas (HCCs) are related to atypical dynamic enhancement on multi-detector computed tomography (MDCT) imaging.

Materials and Methods

Seventy-three patients with 83 HCCs (3 cm or less in diameter) were included in this study. All patients underwent 4-phase MDCT imaging and subsequent surgery within eight weeks. Two independent radiologists blinded to the histologic findings retrospectively classified the HCCs as either typical (showing increased enhancement on arterial phase images followed by washout in late phase images) or atypical lesions demonstrating any other enhancement pattern. From the original pathologic reports, various histologic characteristics including gross morphology, nuclear histologic grades, presence of capsule formation, and capsule infiltration when a capsule was present, were compared among the two groups.

Results

An atypical enhancement pattern was seen in 30 (36.2%) of the 83 HCCs. The mean size of atypical HCCs (1.71 ± 0.764) was significantly smaller than that of typical HCCs (2.31 ± 0.598, p < 0.001). Atypical HCCs were frequently found to be vaguely nodular in gross morphology (n = 13, 43.3%) and to have grade I nuclear grades (n = 17, 56.7%). Capsule formation was significantly more common in typical HCCs (p < 0.001). Capsular infiltration was also more common in typical HCCs (p = 0.001).

Conclusion

HCCs showing atypical dynamic enhancement on MDCT imaging are usually smaller than typical HCCs, vaguely nodular type in gross morphology in most cases, and well-differentiated in nuclear grades, and they lack of capsule formation or capsular infiltration.     

胰腺癌免疫治疗的现状及前景CSCD

胰腺癌(胰腺导管腺癌)是一种恶性程度较高,诊断和治疗都较困难的消化系统恶性肿瘤。近年来,肿瘤免疫治疗在多种肿瘤中如黑色素瘤、膀胱癌、乳腺癌、非小细胞肺癌和肾癌等均取得了令人振奋的治疗效果,但是胰腺癌的免疫治疗策略尚在不断探索中。目前针对胰腺癌独特的肿瘤微环境设计了多种免疫治疗策略,包括强化/提高自身免疫反应(免疫调节剂、单克隆抗体、肿瘤疫苗和细胞治疗)以及抑制肿瘤免疫逃逸(免疫检查点抑制剂和肿瘤微环境)等。本文就胰腺癌免疫治疗的研究进展进行综述,着重探讨PD-1/PD-L1抑制剂在胰腺癌中的应用,并分析免疫治疗联合其他方式治疗胰腺癌的前景。     

急性胰腺炎CT诊断价值的评价(附64例分析)

目的:评价CT对急性胰腺炎的诊断准确性。材料与方法:64例急性胰腺炎。男性24例,女性40例,年龄29～78岁,平均53.2岁,于临床症状出现2小时至7天内均经CT扫描。其中55例还经增强扫描。结果:64例中经CT诊断为急性水肿性胰腺炎49例,急性坏死性胰腺炎15例。5例经手术证实,59例经临床、实验及腹膜穿刺证实。结论:CT是目前诊断急性胰腺炎的最敏感的方法。特别是增强扫描对鉴别急性胰腺炎的病变类型具有很高的敏感性,值得首选。     

Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma

The regional chemotherapy of the human malignant melanomas (SK-MEL-2, -3, -5, -24) implanted in NMRInu/nu mice with a combination of the hyaluronic-acid-cleaving enzyme hyaluronidase (HYase) and vinblastine is a very effective therapeutic procedure. In three out of four melanoma models (SK-MEL-2,-3, -5) the weekly peritumoral administration of high-dose HYase (100 000 IU/kg) 4 h prior to the injection of 0.3 mg/kg vinblastine in the vicinity of the tumor (seven weekly therapeutic cycles) caused marked antitumor effects, while HYase and vinblastine were inactive when given alone. The pretreatment with HYase, which is well tolerated by the test animals, prevented local inflammation reactions commonly seen after subcutaneous vinblastine administration. Tumor growth and metastatic behavior of the melanomas used were neither increased nor reduced by HYase after peritumoral administration without subsequent vinblastine injection. The curative activity of the regional chemotherapy with HYase/vinblastine could be demonstrated on the SK-Mel-3 melanoma. After an observation time of 18 weeks tumor cells could no longer be detected in the subcutaneous region of the former lesion. Only macrophages, which had abundantly incorporated melanin, gave evidence of previously growing tumors. In contrast to the controls, no metastases could be observed in the axillary lymph nodes of the test animals.Abbreviations HA hyaluronic acid - T/C 100 X [median tumor area of therapy group (mm²)]/[median tumor area of control group (mm²)] - n number of animals per group     

Antibodies targeting dengue virus envelope domain III are not required for serotype-specific protection or prevention of enhancement in vivo

The envelope (E) protein of dengue virus (DENV) is composed of three domains (EDI, EDII, EDIII) and is the main target of neutralizing antibodies. Many monoclonal antibodies that bind EDIII strongly neutralize DENV. However in vitro studies indicate that anti-EDIII antibodies contribute little to the neutralizing potency of human DENV-immune serum. In this study, we assess the role of anti-EDIII antibodies in mouse and human DENV-immune serum in neutralizing or enhancing DENV infection in mice. We demonstrate that EDIII-depleted human DENV-immune serum was protective against homologous DENV infection in vivo. Although EDIII-depleted DENV-immune mouse serum demonstrated decreased neutralization potency in vitro, reduced protection in some organs, and enhanced disease in vivo, administration of increased volumes of EDIII-depleted serum abrogated these effects. These data indicate that anti-EDIII antibodies contribute to protection and minimize enhancement when present, but can be replaced by neutralizing antibodies targeting other epitopes on the dengue virion.