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Sarcomatoid mesothelioma is an aggressive malignancy that can be challenging to distinguish from benign spindle cell mesothelial proliferations based on biopsy, and this distinction is crucial to patient treatment and prognosis. A novel deep learning based classifier may be able to aid pathologists in making this critical diagnostic distinction. SpindleMesoNET was trained on cases of malignant sarcomatoid mesothelioma and benign spindle cell mesothelial proliferations. Performance was assessed through cross-validation on the training set, on an independent set of challenging cases referred for expert opinion (‘referral’ test set), and on an externally stained set from outside institutions (‘externally stained’ test set). SpindleMesoNET predicted the benign or malignant status of cases with AUC’s of 0.932, 0.925, and 0.989 on the cross-validation, referral and external test sets, respectively. The accuracy of SpindleMesoNET on the referral set cases (92.5%) was comparable to the average accuracy of 3 experienced pathologists on the same slide set (91.7%). We conclude that SpindleMesoNET can accurately distinguish sarcomatoid mesothelioma from benign spindle cell mesothelial proliferations. A deep learning system of this type holds potential for future use as an ancillary test in diagnostic pathology.

The site of the gastrointestinal (GI) tract where biopsies are most likely to be diagnostic of graft-versus-host disease (GvHD) remains controversial. Recent reports have indicated that biopsies from the rectosigmoid have sufficient sensitivity and specificity for diagnosing GI GvHD and can be obtained via a less invasive flexible sigmoidoscopy procedure. While GvHD histologic grades 1–3 have little correlation with patients’ symptoms and overall clinical grade, histologic grade 4 GvHD does correlate with severe clinical presentation and a poor prognosis. We examined cases of lower GI biopsies obtained via a complete colonoscopy with ileal intubation for the evaluation of GvHD within a 2-year period from patients who underwent stem cell transplantation. In our study cohort, grade 4 GvHD was significantly more likely to be identified in a terminal ileum biopsy than in a biopsy from another site in the lower GI tract. Significantly, 5 of 6 patients with histologic grade 4 GvHD diagnosed on ileal biopsies died from complication of severe GI GvHD. Given the poor prognosis of histologic grade 4 GvHD in the terminal ileum, the detection of this finding may serve to inform clinicians that escalation or modification of treatment may need to be considered. Furthermore, our findings suggest that terminal ileal biopsies may help to increase sensitivity for identifying patients at high risk for poor outcome of GvHD.

Chronic infection with liver flukes (such as Clonorchis sinensis) can induce severe biliary injuries, which can cause cholangitis, biliary fibrosis, and even cholangiocarcinoma. The release of extracellular vesicles by C. sinensis (CsEVs) is of importance in the long-distance communication between the hosts and worms. However, the biological effects of EVs from liver fluke on biliary injuries and the underlying molecular mechanisms remain poorly characterized. In the present study, we found that CsEVs induced M1-like activation. In addition, the mice that were administrated with CsEVs showed severe biliary injuries associated with remarkable activation of M1-like macrophages. We further characterized the signatures of miRNAs packaged in CsEVs and identified a miRNA Csi-let-7a-5p, which was highly enriched. Further study showed that Csi-let-7a-5p facilitated the activation of M1-like macrophages by targeting Socs1 and Clec7a; however, CsEVs with silencing Csi-let-7a-5p showed a decrease in proinflammatory responses and biliary injuries, which involved in the Socs1- and Clec7a-regulated NF-κB signaling pathway. Our study demonstrates that Csi-let-7a-5p delivered by CsEVs plays a critical role in the activation of M1-like macrophages and contributes to the biliary injuries by targeting the Socs1- and Clec7a-mediated NF-κB signaling pathway, which indicates a mechanism contributing to biliary injuries caused by fluke infection. However, molecules other than Csi-let-7a-5p from CsEVs that may also promote M1-like polarization and exacerbate biliary injuries are not excluded.

Background Celiac disease (CD) is characterized histologically by inflammation and villous atrophy. Villous atrophy is thought to result from a disruption of epithelial cellular proliferation and death. Epithelial cells in intestinal mucosa normally proliferate in the crypts and migrate towards the lumen, eventually dying. Apoptotic bodies in crypts are usually abnormal and are associated with certain disease states. The presence of crypt apoptosis in celiac disease has not been thoroughly examined by routine histologic assessment of crypt apoptotic body count (ABC). Methods We quantified the ABC in duodenal biopsies from celiac patients before and after initiation of a gluten-free diet (GFD). We examined twenty-three duodenal biopsies from adult patients with celiac disease at diagnosis and following GFD and determined the maximum ABC in 10 consecutive crypts. Fourteen biopsies from heartburn patients served as controls. Results Mean duration between paired biopsies was 2.9 (0.5–8.5) years. Mean maximum ABC in active celiac disease was 5.44 per crypt and decreased to 2.60 with GFD (p =

AimsSerous cystadenomata (SCAs) are benign pancreatic cystic neoplasms that present a diagnostic challenge despite many investigational approaches. Notwithstanding the promise of molecular diagnostics, these tests have limited accessibility in day-to-day surgical pathology practices. We aim to corroborate and build on recent evidence which suggests that positive α-inhibin immunohistochemistry (IHC) is a helpful adjunct in the biopsy confirmation of pancreatic SCA.MethodsWe retrospectively reviewed 22 fine-needle aspirates/biopsies from 14 patients (mean age 65 years, 47–83 years) with pancreatic multicystic lesions radiologically suspicious for SCA (location: 6 body, 2 head, 4 tail, 1 neck, 1 uncinate; cyst size: mean 3.7 cm, 2.0–7.6 cm), as well as an additional 10 pancreatic resection specimens with confirmed SCA; α-inhibin IHC was performed on all cell blocks, biopsy slides and representative resection specimen sections. Where available, associated cyst fluid was analysed for correlative vascular endothelial growth factor A (VEGF-A) and carcinoembryonic antigen levels.ResultsAn α-inhibin IHC sensitivity of 80% was observed in the cases with resection confirmed SCA. Of the fine-needle aspirate/biopsy specimens, 59% (13/22) contained epithelial cells strongly positive for α-inhibin. When selecting for specimens that exhibited distinct strips of epithelium, the α-inhibin strong positivity rate increased to 73% (8/11). VEGF-A values were supportive of false-negative α-inhibin IHC in three cases and true-negative α-inhibin IHC in one case.ConclusionThis study postulates a diagnostic algorithm to confirm pancreatic SCA which may help to decrease unnecessary follow-up endoscopy/surgical resection and would decrease the associated morbidity, mortality and financial costs in patients with this otherwise benign condition.

Context.— Serosal involvement (pT4a category) and lymphovascular invasion have prognostic significance in colorectal carcinoma, but are subject to interobserver variation in assessment. Objectives.— To provide the first large-scale assessment of interobserver variability in pT4a category and lymphovascular invasion reporting in real-world practice and to explore the impact of information from guidelines on variability in reporting these features. Design.— Analysis of 1555 consecutive synoptic reports of colorectal carcinoma was performed using multivariate logistic regression. Interobserver variability before and after the presentation of guideline information was assessed using an image-based survey. Results.— Significant differences in the odds of reporting pT4a versus pT3 category, detecting lymphovascular invasion of any type, and detecting large vessel invasion were identified among hospital sites and for individual pathologists compared with the median pathologist at the same site. Consistent with these results, interobserver agreement was only moderate in the image-based survey regarding T4a staging and lymphovascular invasion (all κ ≤ 0.57). The provision of information from guidelines did not tend to increase interobserver agreement in the survey, though responses in favor of using an elastic stain increased following recommendations for their use. However, when observers were provided with elastic-stained images, interobserver agreement remained only moderate (κ = 0.55). Conclusions.— Real-world reporting of pT4a category and lymphovascular invasion shows substantial variability at both local and regional levels. Our study underscores the need to address these features in quality initiatives, and provides a novel method through which existing synoptic data can be harnessed to monitor reporting patterns and provide individualized feedback.

Due to limitations in early diagnosis and treatments of Parkinson's disease (PD), it is necessary to explore the neuropathological changes that occur early in PD progression and to design neuroprotective therapies to prevent or delay the ongoing degeneration process. Metabotropic glutamate receptor 5 (mGlu5) has shown both diagnostic and therapeutic potential in preclinical studies on PD. Clinical trials using mGlu5 negative allosteric modulators to treat PD have, however, raised limitations about the neuroprotective role of mGlu5. It is likely that mGlu5 has different regulatory roles in different stages of PD. Here, we investigated a protective role of cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in the progression of PD by differential regulation of mGlu5 expression and activity to protect against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. Following treatment with 6-OHDA, mGlu5 and CAL expressions were elevated in the early stage and reduced in the late stage, both in vitro and in vivo. Activation of mGlu5 in the early stage by (RS)-2-chloro-5-hydroxyphenylglycine, or blocking mGlu5 in the late stage by 2-methyl-6-(phenylethynyl) pyridine, increased cell survival and inhibited apoptosis, but these effects were significantly weakened by knockdown of CAL. CAL alleviated 6-OHDA-induced neurotoxicity by regulating mGlu5-mediated signaling pathways, thereby maintaining the physiological function of mGlu5 in different disease stages. In PD rat model, CAL deficiency aggravated 6-OHDA toxicity on dopaminergic neurons and increased motor dysfunction because of lack of regulation of mGlu5 activity. These data reveal a potential mechanism by which CAL specifically regulates the opposite activity of mGlu5 in progression of PD to protect against neurotoxicity, suggesting that CAL is a favorable endogenous target for the treatment of PD.

Immune checkpoint inhibitors such as programmed cell death-1 inhibitor pembrolizumab have been shown to be effective in metastatic malignancies such as advanced melanoma. Immune-related adverse effects on multiple organs have been described, such as colitis, skin rash, and hypothyroidism. We present the case of a 44-year-old man with advanced melanoma and recurrent lung metastases who developed symptoms of dyspepsia and gastroesophageal reflux disease after 1 month of therapy with pembrolizumab. Gastric biopsy showed histologic features consistent with lymphocytic gastritis, which was absent on a biopsy 2 months before initiation of therapy. Lymphocytic infiltrates likely secondary to increased autoimmunity after use of immunotherapy have been observed in the colon; however, such histologic findings in the upper gastrointestinal tract have yet to be described. Here, we present a case of lymphocytic gastritis in a patient treated with pembrolizumab, suggesting a new manifestation of toxicity.

In 2011, a new classification of lung adenocarcinoma was published. Since then there have been multiple studies regarding observer variability in predominant subtype determination, with levels of agreement generally in the weak to moderate range. In the 2011 and subsequent WHO 2015 classification, a recommendation was also made to visually assess and record the percentage of each subtype in 5% increments. The present study was initiated to determine the reproducibility of such gestalt assessments and to compare these data to a formal morphometric assessment. Five experienced pathologists reviewed multiple single images of 25 adenocarcinomas, taken at 2× and 10×, and estimated the percentage of lepidic, acinar, papillary, micropapillary, and solid components in 5% increments. After 2 months all the pathologists again reviewed the same images presented to them in a different order. We found that there was poor reproducibility within observers at 2× power using a 5% evaluation, but that this improved using 10% or 25% cutoffs. Use of 10× magnification allowed weak to moderate reproducibility at 5% increments, and this was again improved using 10% or 25% cutoffs. Correlation with morphometric assessment was poor except for the papillary and micropapillary subtypes. Differences among pathologists were generally low except for the acinar and, to a lesser degree, lepidic subtypes, which showed a wide spread of data. When estimating tumor subtype proportions, use of a 10× objective, and utilization of 10% or preferably 25% cutoffs provides a greater degree of consistency than a 5% cutoff.

Anabolic steroids are well-known to cause liver injury, which may manifest with jaundice and elevated liver enzymes. Selective androgen receptor modulators (SARMs) have been developed to enhance muscle bulk without the side effects associated with exogenous androgen steroids. We report a case of significant cholestatic liver injury associated with a SARM, ostarine (enobosarm), similar to that associated with anabolic steroids. Liver injury from SARMs has not been reported frequently, and we speculate that this may be seen more often as the consumption of SARMs increases in the athletic market.

A 20-year-old woman presented with abdominal pain and MRI findings of intussusception of the distal small bowel with no identifiable lead point and no visualisation of the appendix. A diagnostic laparoscopy succeeded in manually reducing the intussusception but was unable to find any candidate lead point. Intraoperatively, hyperperistalsis was observed throughout the small bowel which seemed prone to transient intussusception. Incidental appendectomy revealed an uninflamed appendix with Enterobius vermicularis (pinworm) infestation, the most common parasite present in appendectomy specimens worldwide. Although intussusception in young adults is an uncommon occurrence, the unique nature of this case is amplified by the concurrent finding of E. vermicularis infection of the appendix in an adolescent in western Canada, a phenomenon normally observed in paediatric populations with higher incidence in tropical areas. Although the mechanism of intussusception in this patient remains unclear, it is hypothesised that E. vermicularis colonisation acted as an irritant stimulating intestinal hypercontractility with resulting intussusception. Successful medical eradication of the pinworm in this individual may prevent future recurrence.

Background: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD. Methods: A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. Results: A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. Conclusion: Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Fibrolamellar carcinoma is a rare primary hepatocellular malignancy arising in noncirrhotic livers of young individuals. Patients commonly present with a large solitary liver mass and nonspecific symptoms. Characteristic histologic features include large polygonal cells with oncocytic cytoplasm and prominent nucleoli separated into trabeculae and cords by dense parallel bands of collagen. Important differential diagnoses include classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which may be distinguished by a judicious panel of immunohistochemical studies, including cytokeratin 7, CD68, and hepatocyte paraffin 1 (HepPar-1). In addition, fibrolamellar carcinomas are characterized by activation of protein kinase A. Prognosis of fibrolamellar carcinoma is similar to classical hepatocellular carcinoma occurring in the absence of liver cirrhosis and is strongly correlated with tumor resectability. Other treatment options include liver transplant, chemotherapy, and hepatic artery embolization. In this article, we review the clinical features, gross and microscopic pathology, molecular genetics, differential diagnosis, treatment, and prognosis of this rare and interesting tumor.

Older asthmatic patients may develop fixed airway obstruction and clinical signs of chronic obstructive pulmonary disease (COPD). We investigated the added value of pathological evaluation of bronchial biopsies to help differentiate asthma from COPD, taking into account smoking, age, and inhaled corticosteroid (ICS) use. Asthma and COPD patients (24 of each category) were matched for ICS use, age, FEV1, and smoking habits. Five pulmonary and five general pathologists examined bronchial biopsies using an interactive website, without knowing patient information. They were asked to diagnose asthma or COPD on biopsy findings in both a pairwise and randomly mixed order of cases during four different phases, with intervals of 4–6 weeks, covering a maximal period of 36 weeks. Clinically concordant diagnoses of asthma or COPD varied between 63 %-73 %, without important differences between pairwise vs randomly mixed examination or between general vs pulmonary pathologists. The highest percentage of concordant diagnoses was in young asthmatic patients without ICS use and in COPD patients with ICS use. In non ICS users with fixed airway obstruction, a COPD diagnosis was favored if abnormal presence of glands, squamous metaplasia, and submucosal infiltrate was present and an asthma diagnosis in case of abnormal presence of goblet cells. In ICS users with fixed airway obstruction, abnormal presence of submucosal infiltrates, basement membrane thickening, eosinophils, and glands was associated with asthma. Histological characteristics in bronchial biopsies are reproducibly recognized by pathologists, yet the differentiation by histopathology between asthma and COPD is difficult without information about ICS use. Electronic supplementary material The online version of this article (doi:10.1007/s00428-015-1824-6) contains supplementary material, which is available to authorized users.

Context Colorectal cancer is a heterogeneous disease resulting from different molecular pathways of carcinogenesis. Recent data evaluating the histologic features and molecular basis of the serrated polyp–carcinoma pathway have significantly contributed to more comprehensive classifications of and treatment recommendations for these tumors. Objective To integrate the most recent molecular findings in the context of histologic classifications of serrated lesions and their implications in diagnostic pathology and colorectal cancer surveillance. Data Sources Published literature focused on serrated polyps and their association with colorectal cancer. Conclusions Three types of serrated polyps are currently recognized: hyperplastic polyps, sessile serrated adenomas/polyps, and traditional serrated adenomas. The BRAF V600E mutation is one of the most frequent molecular abnormalities identified in hyperplastic polyps and sessile serrated adenomas. In contrast, in traditional serrated adenomas, either BRAF V600E or KRAS mutations can be frequently identified. CpG methylation has emerged as a critical molecular mechanism in the sessile serrated pathway. CpG methylation of MLH1 often leads to reduced or lost expression in dysplastic foci and carcinomas arising in sessile serrated adenomas/polyps.

The 3D Finite Element Method (FEM) model of engine connecting rod was established in this paper. And, nonlinear analysis of engine connecting rod was made, Stress distribution of the connecting rod under condition of maximum stretching and maximum compressing was simulated. The result shows that the results coincide with the actual results and connecting rod can satisfy the strength requirement, the method turns out to be very effective in practice.

In this paper, the finite method is applied and ABAQUS software is used, the vortex flow field is loaded as boundary condition of wraps. The stress and deformation in scroll under the action of gas pressure, temperature load and both of them is analyzed, the stress distribution and deformation of wraps in different shaft rotation angles is discussed, the stress distribution and deformation discipline of wraps are also respectively obtained. The results show that the overall stress and deformation in scroll are the largest when compression chamber is moving near the vent position and the thermal deformation is the main factor of affecting the overall deformation of scroll.

Mucinous cystic neoplasm (MCN) is characterized by mucinous epithelial lining and subepithelial ovarian-like stroma and is a precursor to invasive carcinoma. Type 1 autoimmune pancreatitis (AIP), on the other hand, is a form of IgG4-related disease (IgG4-RD) and can present as a pancreatic mass. There is no known causal relationship between these two entities in the current literature. Here, we report a case of a middle-aged female patient who was found to have an enlarging pancreatic mass and subsequently underwent a distal pancreatectomy. Gross examination of the pancreatectomy specimen showed a 4.3 cm mass with a central 3.4 cm cystic component, confirmed to be an MCN on microscopy. The immediately adjacent peritumoral tissue showed storiform fibrosis, obliterative phlebitis, and focal IgG4-positive plasma cell–rich infiltrates (≥75/HPF) with an IgG4+/IgG+ ratio of 80%. The background pancreas was histologically normal and these characteristic AIP findings were limited to the pericystic tissue. Clinical workup with CT scan and MRI did not show any evidence of systemic IgG4-RD, nor was the serum IgG4 level ever elevated. To our knowledge, this is only the second reported case of a pancreatic MCN associated with peritumoral AIP-like changes in a patient without systemic IgG4-RD. Awareness of these potential AIP-like changes surrounding pancreatic neoplasms may be helpful in preventing misdiagnosis in needle biopsy and aspiration specimens. Keywords: Type 1 autoimmune pancreatitis, IgG4-related disease, IgG4-RD, IgG4-related pancreatitis, Mucinous cystic neoplasm, MCN, Sclerosing pancreatitis

In order to choose a financial and suitable wind power system, the analysis of different wind power system is necessary. The paper reviewed several kinds of commonly used wind power system, given the topology structure same and different placesgenerator types respective advantages and disadvantages and applicable range of them. Compared and analysed direct-drive PMSG system and constant speed constant frequency SCIG system .Finally discussed the development trend of wind power generation system and the work emphasis in the future. It has certain reference value for research and choose of wind power system.

The mathematical model to determine the main parameters of the solar street lamp has been built. The structure and the main parameters of the solar street lamp were analyzed in the paper. The yearly average optimal tilted angle for the solar cell module used in Qujing is approximately 23.75o. For a 60 W high brightness DC LED lamp, the area of the solar cell and the battery capacity to meet the energy consumption of the solar street lamp are 3.67 m2 and 2.89 MJ, respectively.

Background: It has been reported that coronary slow flow (CSF) is associated with acute myocardial infarction, ventricular tachycardia, ventricular fibrillation, and even sudden cardiac death. Although studies concerning the etiopathogenesis of CSF are scarce, diffuse atherosclerosis and endothelial dysfunction are thought to play important roles. It has been suggested that a high plasma thrombomodulin (TM) level seems to play an important role in the pathogenesis of atherosclerosis and endothelial dysfunction. Objectives: We hypothesized that a high plasma TM level might be associated with CSF and aimed to research the relationship between plasma TM level and CSF. Methods: Fifty-two CSF patients with angiographically proven CSF and 44 cases with normal coronary flow were included in this study. Coronary flow velocity was determined by the thrombolysis in myocardial infarction (TIMI) frame count method. Plasma TM levels were measured in all the study subjects. Results: Plasma TM levels were significantly higher in the CSF group compared to the control group (3.9 ± 0.5 vs. 3.6 ± 0.3 ng/mL, p = 0.01). There was a positive relationship (r = 0.31, p = 0.002) between plasma TM level and mean TIMI frame count (TFC). Factors associated with mean TFC were plasma TM level (β = 0.206, p = 0.038) and red cell distribution width (β = 0.088, p = 0.009) in multiple linear regression analysis. Conclusions: Patients with CSF have a higher plasma TM level, and this may play an important role in the pathogenesis of CSF. An elevated plasma TM level may be a predictor of CSF. Future studies are needed to confirm these results.

In order to improve electric efficiency of solar cell arrays and obtain available heat energy, the solar trough concentration photovoltaic/thermal system has been constructed and the experiment performance and analysis of solar cell arrays have been carried out. The results show that in concentration the thermal efficiency of system linearly decreases with the temperature of cell arrays increasing. In non-concentration, the maximum power output (Pm) temperature coefficients of single crystalline silicon solar cell, polycrystalline silicon cell array and super cell array are -0.2 W/(m2·°C), -0.15 W/(m2·°C) and -0.16 W/(m2·°C), respectively. In concentration, the Pm temperature coefficients are -11.8 W/(m2·°C), -5.9 W/(m2·°C) and -5.1 W/(m2·°C).

Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy of disputed histogenesis that arises in the sinonasal tract and has an extremely poor prognosis. Despite multimodality treatment with surgical resection, radiation, and chemotherapy, recurrence is common. The tumor spreads by direct local extension, but also metastasizes to lymph nodes, brain, lung and bone. To date, reports of metastasis to the skin have not been published. We report a case of a 58-year-old woman diagnosed with SNUC who underwent surgical resection of the tumor followed by chemoradiation. The tumor soon recurred, and she required wide re-excision. Two months after this procedure, she developed multiple dermal nodules in the head and neck region, clinically suspicious for metastases. Biopsy of a nodule from the right neck revealed a poorly differentiated carcinoma, with morphological and immunohistochemical findings consistent with a metastasis of the patient's known SNUC. We conclude that the skin may be a rare site of metastasis of SNUC, and in some cases may be the presenting sign of tumor recurrence despite aggressive multimodality treatment.

Inhalation of residual oil fly ash (ROFA), a component of ambient particulate matter, has been shown to increase pulmonary morbidity and impair lung defense mechanisms in exposed workers. Our objective was to evaluate the effect of ROFA preexposure on lung defense and injury after pulmonary challenge with a bacterial pathogen. Male Sprague-Dawley rats were dosed intratracheally at day 0 with saline (control) or ROFA (0.2 or 1 mg/100 g body weight). Three days later, a low (5 x 10(3)) or high (5 x 10(5)) dose of Listeria monocytogenes was instilled intratracheally into the ROFA- and saline-treated rats. Bronchoalveolar lavage was performed on the right lungs at days 6, 8, and 10. The recovered cells were differentiated, and chemiluminescence (CL) and nitric oxide (NO) production, two indices of alveolar macrophage (AM) function, were measured. At the same time points, the left lung and spleen were removed, homogenized, and cultured, and colony-forming units were counted after an overnight incubation. Exposure to ROFA and the high dose of L. monocytogenes led to marked lung injury and inflammation as well as to an increase in mortality, compared with rats treated with saline and the high dose of L. monocytogenes. Preexposure to ROFA significantly enhanced injury and delayed the pulmonary clearance of L. monocytogenes at both bacterial doses when compared to the saline-treated control rats. ROFA had no effect on AM CL but caused a significant suppression of AM NO production, as compared to the saline control rats. We have demonstrated that acute exposure to ROFA slowed the pulmonary clearance of L. monocytogenes. The suppression in AM NO production by ROFA pretreatment likely plays an important role. These results suggest that pulmonary exposure to ROFA may alter AM function and lead to increased susceptibility to lung infection in exposed populations.

Study objectives To examine the lung defensemechanisms of both young and aged rats before and after pulmonarychallenge with a bacterial pathogen. Design Male Fischer 344 rats, either 2.5 months or 20 months of age, wereintratracheally inoculated with 5 × 10 3 ,5 × 10 4 , or 5 × 10 5 Listeriamonocytogenes , and the effects on mortality, lung inflammation, pulmonary bacterial clearance, alveolar macrophage (AM) function, and T-lymphocyte characterization were determined. Measurementsand results In noninfected control animals, the older rats hadlower numbers of AMs on lavage and a lower percentage of total T, CD4+, and CD8+ cells. No difference was observed between noninfected youngand old rats in AM function, assessing both chemiluminescence andnitric oxide (NO) production. After bacterial challenge, aged ratsexhibited an increase in mortality, pulmonary infection, and edema, andlung lesions, which were more extensive than those observed in theyounger rats. Interestingly, AM chemiluminescence was enhanced, while AM NO, a highly important antibacterial defense product, was abrogatedin the aged rats as compared to the young rats. Conclusions This study demonstrated that advanced age isassociated with alterations in lung defense mechanisms and increasedsusceptibility to pulmonary bacterial infection marked by elevatedmortality, slowed pulmonary bacterial clearance, and altered AMfunction, specifically a decrease in NO production. These observationsare indicative of reduced pulmonary defense function in an olderpopulation of rats.

Dysfunction of adenosinergic systems has been implicated in the development of multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in animals. Caffeine, a non-selective antagonist of adenosine receptors, has been shown to provide protection against myelin oligodendroglia glycoprotein (MOG)-induced EAE in mice. In this study, we showed that chronic caffeine similarly imparts neuroprotection against EAE induced in rats by guinea pig spinal cord homogenates (GPSCH). GPSCH-induced EAE is characterized by extensive tissue inflammation with a typical chronic disease course. We showed that caffeine decreases the incidence of EAE and attenuates EAE pathology at behavioral, histological (inflammatory cell infiltration and demyelination) and neurochemical (expression of inflammatory cytokines) levels. The attenuation of GPSCH-induced pathology by chronic caffeine treatment was observed at doses of 10 and 30 mg/kg and during both peak and recovery phases of EAE. Furthermore, it was showed that chronic treatment with caffeine up-regulated A1 receptor and TGF-beta mRNAs and suppressed interferon-gamma mRNA in EAE rats. Together with previous reports, our data demonstrates that chronic treatment with caffeine exerts a neuroprotective effect against EAE, possibly through an A(1) receptor-mediated shift from Th1 to Th2 cell function, and provides a neurobiological basis for epidemiological investigation into the possible relationship between caffeine consumption and development of multiple sclerosis in humans.

Idazoxan, an imidazoline 2 receptor (I(2)R) ligand, has been shown to protect against brain injury in several animal models of neurological disorders. In the present study we investigated the effect of idazoxan on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced by immunizing Wistar rats with guinea pig spinal cord homogenates emulsified in CFA, followed by daily treatment of idazoxan (0, 0.5 mg/kg, 1.5 mg/kg, 4.5 mg/kg, i.p, bid) for 10 days. The results showed that the treatment of idazoxan (1.5 mg/kg and 4.5 mg/kg) significantly decreased the incidence and alleviated inflammatory cell infiltration and demyelination in spinal cords and cerebral cortex. Furthermore, the protective effect of idazoxan on EAE was associated with the enhanced astrocytic activation and attenuated microglial activation and with the subsequent down-regulated expression of proinflammatory cytokines IL-12p40 and IFN-gamma and up-regulated expression of anti-inflammatory cytokines IL-10 and TGF-beta(1). Thus, the daily treatment of the I(2)R ligand idazoxan for 10 days attenuates EAE pathology by differential modulation of astrocytic and microglial activations, raising a possibility that the I(2)R ligand may be a novel strategy for treating EAE.

We compared the interobserver reproducibility of the 1990 and 2004 International Society for Heart and Lung Transplantation (ISHLT) grading system for cardiac rejection. The 2004 ISHLT grading system for cardiac allograft rejection did not improve reproducibility partly due to pathologists' disagreement in diagnosing Grades 1B/1R and 3A/2R rejection. To achieve better reproducibility, better criteria for defining 1B/1R vs. 3A/2R rejection and markers of myocyte injury are needed.

Background Pulmonary vein stenosis is a recognized complication of catheter ablation of arrhythmias emanating from the pulmonary vein; however, there is little information on secondary effects of pulmonary vein stenosis on lung tissue. Methods and results A 55-year-old man with a history of paroxysmal atrial fibrillation refractory to antiarrhythmic medication had radiofrequency ablation in April 2003 and July 2003. Although these procedures were successful in resolving the patient's arrhythmia, they were complicated by the development of pulmonary vein stenosis of all four veins and pulmonary hypertension requiring patch annuloplasty of the pulmonary veins in October 2003. The patient was referred to our center for pulmonary vein stent placement in December 2003, June 2004, and August 2004, each time for recurrent hemoptysis. Due to persistent hemoptysis over the next several months, the patient underwent left lower lung lobectomy in September 2005. Microscopic examination of the lung showed marked medial thickening and intimal hyperplasia of large and small pulmonary veins and arteries, as well as focal organizing thrombi in the small arteries. The lung tissue showed extensive hemosiderin deposition indicative of prior hemorrhage. Conclusion Chronic pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation results in irreversible venous and arterial morphologic changes throughout the lung, including areas both close to, and remote from, the site of catheter ablation. Because there are persistent pathological changes remote from the ablation site causing the pulmonary hypertension, stenting the site of ablation to reopen large pulmonary veins may not be effective in treating the pulmonary hypertension.

A 28-year-old woman presented with diarrhoea, haematochezia, tenesmus and rectal pain for 2 months. She was diagnosed with systemic lupus erythematosus (SLE) 8 years ago and remained on prednisone, azathioprine and hydroxychloroquine. Blood work revealed a positive ANA (antinuclear antibody test), anti-dsDNA 749 IU/mL (0-300 IU/mL), C3 0.22 g/L (0.65-1.65 g/L) and C4 0.05 g/L (0.16-0.60 g/L). Stool studies were unremarkable. MRI of the pelvis showed a rectum with eccentric wall thickening. Flexible sigmoidoscopy showed severe proctitis with multiple deep ulcers and diffuse submucosal haemorrhage. Rectal biopsy revealed crypt architectural distortion and reactive fibrosis in the lamina propria. The patient was given mesalamine suppository for 2 weeks with minimal improvement. Repeat flexible sigmoidoscopy showed a coalesced 3×4 cm full-thickness rectal ulcer. Therefore, the patient was given intravenous methylprednisolone for 3 days, followed by intravenous cyclophosphamide for 2 weeks. Her symptoms resolved and repeat flexible sigmoidoscopy showed fibrotic healing of the rectal ulcers.

The bandwidth properties of chaotic signals generated by semiconductor lasers subject to strong chaotic optical injection (COI) are investigated numerically. The chaotic output of an injection master laser (ML) is injected into the slave laser (SL). The effects of feedback strength, injection strength and bias current on the bandwidth properties are discussed in detail. Some novel results are found, the bandwidth for SL increases with the injection strength firstly until reaches a maximum, and then decrease to approach the bandwidth of ML due to the injection-locking chaos synchronization. Large feedback strength and bias current contributes to higher maximum chaotic bandwidth in the range of injection strength. That is to say, for given parameters, optimal injection strength exists contributing to highest chaotic bandwidth, and moves to a large value for a large feedback strength and bias current, which is extremely useful for increasing the transmission rate of the optical chaotic communication system.