Seropositivity for pathogens associated with chronic infections is a risk factor for all-cause mortality in the elderly: findings from the Memory and Morbidity in Augsburg Elderly (MEMO) Study

GeroScience - Immunostimulation by chronic infection has been linked to an increased risk for different non-communicable diseases, which in turn are leading causes of death in high- and...     

Fertility-sparing surgery for patients with malignant ovarian germ cell tumors: 10 years of clinical experience from a tertiary referral center

Archives of Gynecology and Obstetrics - To describe a case series of patients with malignant ovarian germ cell tumors (MOGCT) treated exclusively with fertility-sparing surgery (FSS) with or...     

Robustness of diffuse reflectance spectra analysis by inverse adding doubling algorithm

Analysing diffuse reflectance spectra to extract properties of biological tissue requires modelling of light transport within the tissue, considering its absorption, scattering, and geometrical properties. Due to the layered skin structure, skin tissue models are often divided into multiple layers with their associated optical properties. Typically, in the analysis, some model parameters defining these properties are fixed to values reported in the literature to speed up the fitting process and improve its performance. In the absence of consensus, various studies use different approaches in fixing the model parameters. This study aims to assess the effect of fixing various model parameters in the skin spectra fitting process on the accuracy and robustness of a GPU-accelerated two-layer inverse adding-doubling (IAD) algorithm. Specifically, the performance of the IAD method is determined for noiseless simulated skin spectra, simulated spectra with different levels of noise applied, and in-vivo measured reflectance spectra from hyperspectral images of human hands recorded before, during, and after the arterial occlusion. Our results suggest that fixing multiple parameters to a priori known values generally improves the robustness and accuracy of the IAD algorithm for simulated spectra. However, for in-vivo measured spectra, these values are unknown in advance and fixing optical parameters to incorrect values significantly deteriorates the overall performance. Therefore, we propose a method to improve the fitting performance by pre-estimating model parameters. Our findings could be considered in all future research involving the analysis of diffuse reflectance spectra to extract optical properties of skin tissue.     

Genetic Characterization of Circulating African Swine Fever Viruses in Nigeria (2007–2015)

Sequencing and analysis of three discrete genome regions of African swine fever viruses (ASFV) from archival samples collected in 2007–2011 and active and passive surveillance between 2012 and 2015 in Nigeria were carried out. Analysis was conducted by genotyping of three single‐copy African swine fever (ASF) genes. The E183L and B646L genes that encode structural proteins p54 and p72, respectively, were utilized to delineate genotypes before intragenotypic resolution by characterization of the tetrameric amino acid repeat region within the hypervariable central variable region of the B602L gene. The results showed no variation in the p72 and p54 gene regions sequenced. Phylogeny of p72 sequences revealed that all the Nigerian isolates belonged to genotype I, while that of the p54 recovered the Ia genotype. Analysis of B602L gene revealed the differences in the number of tetrameric repeats. Four new variants (Tet‐15, Tet‐17a, Tet‐17b and Tet‐48) were recovered, while a fifth variant (Tet‐20) was the most widely distributed in the country displacing Tet‐36 reported previously in 2003–2006. The viruses responsible for ASF outbreaks in Nigeria are from very closely related but mutated variants of the virus that have been circulating since 1997. A practical implication of the genetic variability of the Nigerian viral isolates in this study is the need for continuous sampling and analysis of circulating viruses, which will provide epidemiological information on the evolution of ASFV in the field versus new incursion for informed strategic control of the disease in the country.     

靶向性自杀基因治疗系统联合放射线治疗前列腺癌移植瘤的实验研究

目的初步判断针对整合素αv的靶向性自杀基因治疗系统(RGD4C AAVP HSV-TK/ GCV)是否能提高前列腺癌细胞株DU145移植瘤的放射效应。方法建立移植性前列腺癌细胞株DU145的裸鼠肿瘤模型48只。当位于每只裸鼠右大腿的肿瘤直径达6.0mm(5.8～6.3 mm)时,开始实验。实验共分成6组(每组8只),分别为对照组、单纯放射组、单纯RGD-4C AAVP HSV-TK/GCV组(RGD-4C组)、单纯AAVP HSV-TK/GCV组(无RGD-4C组)、RGD-4C AAVP HSV-TK/GCV联合放射组(XRT RGD4C组)和AAVP HSV-TK/GCV联合放射组(XRT 无RGD-4C组)。观察指标为肿瘤生长延迟时问(肿瘤从6.0 mm生长至12.0 mm所需时间)和肿瘤治愈情况。结果除5只在实验过程中死亡外,单纯放射组、RGD-4C组、无RGD-4C组各有1只和XRT RGD-4C组3只肿瘤被治愈。统计分析余下37只肿瘤生长情况发现,RGD-4C组、无RGD-4C组和单纯放射组的绝对延迟时间分别为(24.4±9.0)、(22.6±11.3)和(28.3±5.5)d;当RGD4C AAVP HSV-TK/GCV和AAVP HSV-TK/ GCV分别联合放射时,其绝对延迟时间分别为(64.7±23.8)和(35.4±9.6)d,而标准化的延迟时间则分别为(40.3±23.8)和(12.8±9.6)d,它们对放射的增益因子分别为1.42和0.45。结论针对整合素αv的靶向性自杀基因治疗系统RGD-4C AAVP HSV-TK/GCV能显著提高前列腺癌细胞株DU145移植瘤的放射效应,值得进一步研究。     

CHARACTERIZATION OF A HUMAN HERPES VIRUS－6（HHV－6） AND EPSTEIN－BARR VIRUS（EBV） ASSOCIATED LEUKEMIC CELL LINE，J6－1

ＣＨＡＲＡＣＴＥＲＩＺＡＴＩＯＮＯＦＡＨＵＭＡＮＨＥＲＰＥＳＶＩＲＵＳ－６（ＨＨＶ－６）ＡＮＤＥＰＳＴＥＩＮ－ＢＡＲＲＶＩＲＵＳ（ＥＢＶ）ＡＳＳＯＣＩＡＴＥＤＬＥＵＫＥＭＩＣＣＥＬＬＬＩＮＥ，Ｊ６－１ＷｕＫｅｆｕ吴克复；ＪａｎｏｓＬｕｋａ；Ｓｈａｎｔ...     

Induction of apoptosis in murine tumors by cyclophosphamide

Whereas there have been several recent reports of the induction of apoptosis by chemotherapy agents in cell culture systems, much less is known about the role of this mode of cell death in tumors treated in vivo. We therefore quantitated the proportion of apoptotic cells induced as a function of time and dose in two murine tumors treated with cyclophosphamide in vivo. The two tumors were a mammary adenocarcinoma, MCa-4, and an ovarian adenocarcinoma, OCa-1. The percent apoptosis was scored from stained histological sections of the tumors using a system based on the characteristic features of the apoptotic nuclei. The kinetics of apoptosis development were determined over a 5-day period following treatment of the mice with 200 mg/kg. The percent apoptosis peaked between 10–18 h in both tumors and then slowly declined to background levels by 5 days after treatment. The dose responses showed that even much lower doses, 25 mg/kg, could induce significant apoptosis and that the proportion of apoptotic cells plateaued at doses higher than 100 mg/kg. These results are compared and contrasted with our previous reports on apoptosis induction in these same tumors with ionizing radiation.The Work reported in this paper was supported by research grants CA-06294 and CA-16672 awarded by the National Cancer Institute, Department of Health and Human Services, and by the Katharine Unsworth Memorial Fund     

Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma

A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled in a Phase III trial and randomized to receive conventional radiotherapy. The study population comprised 155 of 268 (58%) randomized patients with sufficient pretreatment biopsy specimens for immunohistochemical assay. The specimens were dewaxed and incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly counterstained with Mayer's hematoxylin. Quantitative EGFR immunohistochemistry (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and quick score (QS). These EGFR IHC parameters were correlated with the T stage, N stage, combined stage grouping, and recursive partitioning analysis classes. Subsequently, the EGFR parameters were correlated with the outcome end points, i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR) relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide variation in EGFR expression (MOD, 0.2-66.0; SI, 0.3-97.0; QS, 0.01-69.9) with a relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There was no correlation between EGFR expression and T stage, N stage, stage grouping, and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse rate was highly significantly higher (P = 0.0031) compared with those of patients with low EGFR-expressing HNSCCs. However, there was no difference in the distant metastasis rate between the two groups (P = 0.96). Significant correlations, although somewhat less robust than MOD, were also observed between SI and QS and the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR expression was an independent determinant of survival and a robust independent predictor of LR relapse. In summary, this correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis. The data suggest that EGFR IHC should be considered for selecting patients for more aggressive combined therapies or enrollment into trials targeting EGFR signaling pathways.     

In vitro enhancement of tumor cell radiosensitivity by a selective inhibitor of cyclooxygenase-2 enzyme: mechanistic considerations

PURPOSE: Selective cyclooxygenase-2 inhibitors have been reported to enhance the tumor response to radiation in vivo, but the cellular mechanisms underlying the radiosensitizing effect are not understood. In the present study, we investigated several possible mechanisms using a murine sarcoma cell culture system. METHODS AND MATERIALS: Cells derived from a murine sarcoma, designated NFSA, were cultured in vitro and exposed to different (either single or split) doses of radiation with and without a pretreatment of SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-l-yl] benzene sulfonamide), a selective cyclooxygenase-2 (COX-2) inhibitor. The cells were assayed for clonogenic survival to determine the radiosensitizing effect of SC-236. In addition, MTT assay and TUNEL assay were performed to determine the effects of SC-236 and radiation on the cell survival and cell cycle distribution. RNase protection assay was performed on the total RNA extract using probes that encoded for selected cell cycle regulatory proteins, such as cyclins and cyclin-dependent kinases. To monitor the extent of COX-2 activity and its role in radiosensitization, the cellular content of prostaglandin E2, a major metabolite of COX-2 activity on arachidonic acid, was also determined. RESULTS: The cell clonogenic survival assay showed that SC-236 significantly enhanced tumor cell radiosensitivity: 50 microM SC-236 increased it by a factor of 1.51 at the 0.1 cell survival level. Treatment with SC-236 (50 microM, 3 days) removed the "shoulder" region on the radiation survival curve, suggesting that the drug inhibited repair of sublethal radiation damage. The inhibition was confirmed by split-dose experiments where two doses (3 Gy each) of radiation were given 4 h apart. The cells exposed to radiation only repaired the damage by a factor of 1.44, whereas those treated with SC-236 plus radiation repaired it by a factor of 1.1 only. Whereas SC-236 induced apoptosis in these NFSA cells, radiation did not. No further increase in apoptosis was observed when the cells were exposed to both SC-236 and radiation, suggesting that SC-236 did not render tumor cells more susceptible to radiation-induced apoptosis. The RNase protection assay showed that SC-236 (50 microM, 3 days) inhibited the expression of cyclins A and B, as well as cyclin-dependent kinase-1. Inhibition of these cell cycle regulatory elements by SC-236 was associated with the arrest of cells in the radiosensitive G2-M phase (67%), determined by flow cytometry. CONCLUSIONS: SC-236 significantly enhanced radiosensitivity of tumor cells; the magnitude of sensitivity was dependent on the drug's concentration. The likely mechanisms involve accumulation of cells in the radiosensitive G2-M phase of the cell cycle and inhibition of repair from sublethal radiation damage.     

Progression of corpus callosum atrophy in Alzheimer disease

BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. METHODS: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex-matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.