Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis.

BACKGROUND: EGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance. METHODS: The expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test. RESULTS: HER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months). CONCLUSION: Our studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.

Diuretics in Different Samples: Update on the Pretreatment and Analysis Techniques.

Diuretics are drugs that promote the excretion of water and electrolytes in the body and produce diuretic effects. Clinically, they are often used in the treatment of edema caused by various reasons and hypertension. In sports, diuretics are banned by the World Anti-Doping Agency (WADA). Therefore, in order to monitor blood drug concentration, identify drug quality and maintain the fairness of sports competition, accurate, rapid, highly selective and sensitive detection methods are essential. This review provides a comprehensive summary of the pretreatment and detection of diuretics in various samples since 2015. Commonly used techniques to extract diuretics include liquid-liquid extraction, liquid-phase microextraction, solid-phase extraction, solid-phase microextraction, among others. Determination methods include methods based on liquid chromatography, fluorescent spectroscopy, electrochemical sensor method, capillary electrophoresis and so on. The advantages and disadvantages of various pretreatment and analytical techniques are elaborated. In addition, future development prospects of these techniques are discussed.

HIGHLIGHTSPretreatment and determination methods of diuretics in diverse samples are reviewed.Applications of novel materials and technologies for SPE and sensors are highlighted.Pros and cons of recent pretreatment and analysis techniques used for diuretics are discussed.Applications of high-resolution mass spectrometry are described in detail.

Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell activation and Klebsiella pneumonia liver translocation.

Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The effect and mechanism of diabetes on KP liver abscess was examined in streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP translocation to liver and plasma alaine transaminase levels were increased and liver clearance of KP was decreased in DM mice. Diabetic mice exhibited overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas growth in intestine, increased intestinal iNOS protein and nitrite levels in portal vein, and increased IL-1ß and TNF-α expression of Kupffer cells. Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation reversed diabetes-induced enteric dysbiosis, NO levels in portal vein, and KP translocation to liver. L-NAME treatment decreased intestinal iNOS protein expression as well as Kupffer cell activation and increased liver clearance of KP in DM mice. Dead E.coli (2×108 CFU/ml) feeding for one week induced iNOS and TLR4 expression of intestine in germ-free (GF) mice. Dead bacteria feeding induced IL-1ß and TNF-α expression of Kupffer cells in GF mice but not in GF TLR4-/- mice. In conclusion, balance of intestinal microflora is important for preventing intestinal iNOS expression, Kupffer cell activation, and KP liver translocation in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L. salivarius decreases diabetes-induced intestinal iNOS expression and KP liver translocation. Diabetes induces Kupffer cell activation and KP liver translocation through enteric dysbiosis and nitric oxide production.

The occipital white matter lesions in Alzheimer's disease patients with visual hallucinations.

PURPOSE: Investigators have suggested that lesions responsible for visual hallucinations (VHs) are situated in the visual association cortex. The aim of this study was to assess the relationship between occipital white matter lesions and VHs in Alzheimer's disease (AD) patients. METHODS: AD patients with a history of VHs (AD+VH) and those without (AD-VH) were retrospectively studied. The two groups of patients were matched by sex and mental state. All subjects underwent brain magnetic resonance image (MRI) scans. The periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWHs) on MRIs were rated by two raters using a semiquantitative scoring method (0=absent; 6=confluent). RESULTS: Five AD+VH patients and five AD-VH patients were enrolled into this study. The occipital PVH score was higher in the AD+VH patients than in the AD-VH patients. The occipital DWH score was zero in both groups. CONCLUSION: The presence of VHs in AD was associated with increased occipital PVHs and an absence of occipital DWHs on brain MRIs, implying that structural lesions in the geniculocalcarine region and preserved subcortical connections with visual association areas are involved in the genesis of VHs in AD.

Temporal patterns of body temperatures in the acute stage of stroke.

OBJECTIVE: The present study aimed to describe the day-by-day temporal patterns of body temperatures in acute stroke and to delineate the differences in serial daily changes in body temperatures between intracerebral hemorrhage (ICH) and cerebral infarct (CI). METHODS: We retrospectively enrolled 90 patients (32 with ICH and 58 with CI), admitted within 12 hours after the onset of stroke. Body temperatures were measured as the tympanic temperatures during the initial 6 days of hospitalization. Patients with clinical infections were excluded. The severity of stroke was assessed by Scandinavian Stroke Scale (SSS). SSS score < or = 30 was defined as severe stroke, and SSS score >30 as mild-to-moderate stroke. RESULTS: Mean body temperature was significantly higher in patients with ICH than those with CI in 0 approximately 12 hours; 12 approximately 24 hours, 24 approximately 48 hours, and 48 approximately 72 hours (all p<0.05) after the onset of stroke. Among patients with ICH, the body temperature was significantly higher in the severe group than the mild-to-moderate group during 24 approximately 48 hours and 48 approximately 72 hours (both p<0.05) after the onset of stroke. No significant difference in body temperatures was observed between patients with severe stroke and patient with mild-to-moderate CI. CONCLUSIONS: The serial time course of body temperature in the acute stage of stroke differs between ICH and CI. This study showed that, in ICH but not in CI, the elevation of body temperature has significant association with the stroke severity. Our results may help in the management of hyperthermia during acute stroke.

Visualized analysis of mixed numeric and categorical data via extended self-organizing map.

Many real-world datasets are of mixed types, having numeric and categorical attributes. Even though difficult, analyzing mixed-type datasets is important. In this paper, we propose an extended self-organizing map (SOM), called MixSOM, which utilizes a data structure distance hierarchy to facilitate the handling of numeric and categorical values in a direct, unified manner. Moreover, the extended model regularizes the prototype distance between neighboring neurons in proportion to their map distance so that structures of the clusters can be portrayed better on the map. Extensive experiments on several synthetic and real-world datasets are conducted to demonstrate the capability of the model and to compare MixSOM with several existing models including Kohonen's SOM, the generalized SOM and visualization-induced SOM. The results show that MixSOM is superior to the other models in reflecting the structure of the mixed-type data and facilitates further analysis of the data such as exploration at various levels of granularity.

Development of a questionnaire on everyday navigational ability to assess topographical disorientation in Alzheimer's disease.

We developed a Questionnaire on Everyday Navigational Ability (QuENA) to detect topographical disorientation (TD) in patients with Alzheimer's disease (PwAD). In the QuENA, 3 items were designed to assess landmark agnosia, 2 for egocentric disorientation, 3 for heading disorientation, and 2 for inattention. The PwAD and their caregivers rated QuENA according to which TD symptoms would occur. Regarding the construct validity, confirmatory factor analysis showed that the caregiver version of the QuENA fits the proposed TD model well but the patient version does not. Regarding the internal consistency, the Cronbach's α for the caregiver version was 0.91 and that for the patient version was 0.87. A discrepancy existed between the appraisal of navigational abilities by PwAD and by caregivers, and it was correlated with the number of getting lost (GL) events. The caregiver version of QuENA is a feasible, reliable, and valid instrument to assess TD and it also discriminates well between the PwAD with GL and those without.

Rigidity of collagen fibrils controls collagen gel-induced down-regulation of focal adhesion complex proteins mediated by alpha2beta1 integrin.

Previous studies have shown that collagen gel overlay induced selective proteolysis of focal adhesion complex proteins in Madin-Darby canine kidney (MDCK) cells. In this study, we examined whether morphological and biochemical changes were present in cells cultured on collagen gel. We found that focal adhesion complex proteins, including focal adhesion kinase (FAK), talin, paxillin, and p130cas, but not vinculin, were decreased within 1 h when MDCK cells were cultured on collagen gel. Collagen gel-induced selective decrease of focal adhesion proteins was observed in all lines of cells examined, including epithelial, fibroblastic, and cancer cells. Matrigel also induced selective down-regulation of focal adhesion proteins. However, cells cultured on collagen gel- or matrigel-coated dishes did not show any changes of focal adhesion proteins. These data suggest that the physical nature of the gel, i.e. the rigidity, is involved in the expression of focal adhesion proteins. The collagen gel-induced down-regulation of focal adhesion complex proteins was caused by reduction of protein synthesis and activation of proteases such as calpain. Overexpression of a dominant negative mutant of discoidin domain receptor 1 (DDR1) or FAK-related non-kinase (FRNK) did not prevent collagen gel-induced down-regulation of the focal adhesion complex protein, whereas an anti-alpha2beta1 integrin-neutralizing antibody completely blocked it. Taken together, our results indicate that the rigidity of collagen gel controls the expression of focal adhesion complex proteins, which is mediated by alpha2beta1 integrin but not DDR1.