Αρχειοθήκη ιστολογίου

Τετάρτη 9 Μαρτίου 2016

Response to manuscript 'Is Opisthorchis viverrini an avian liver fluke?'



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Opisthorchis viverrini-like liver fluke in birds from Vietnam: morphological variability and rDNA/mtDNA sequence confirmation

Flukes were found in the bile ducts of domestic ducks (Anas platyrhynchos), necropsied in the Binh Dinh province of Central Vietnam. Following staining, morphological characteristics of the bird flukes were compatible with Opisthorchis viverrini, although some characteristics differed from those described in specimens collected from mammal hosts. Computation of the phylogenetic trees on the partial sequences of the second internal ribosomal spacer (ITS2) of the ribosomal DNA and cytochrome c oxidase subunit I (COI) markers of the mitochondrial DNA showed close similarity of the 'bird' Opisthorchis sp. with O. viverrini. We speculate that these bird flukes are O. viverrini that show intraspecies morphological and molecular variability compared to isolates from mammals. This demonstrates the complex epidemiological situation of opisthorchiasis in Vietnam and urges investigations on the potential of birds as a reservoir host of this zoonotic fluke.

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The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression

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Publication date: 15 May 2016
Source:Behavioural Brain Research, Volume 305
Author(s): Lanxiang Liu, Xinyu Zhou, Yuqing Zhang, Yiyun Liu, Lining Yang, Juncai Pu, Dan Zhu, Chanjuan Zhou, Peng Xie
Major depressive disorder, with serious impairment in cognitive and social functioning, is a complex psychiatric disorder characterized by pervasive and persistent low mood and a loss of interest or pleasure. However, the underlying molecular mechanisms of depression remain largely unknown. In this study, we used a non-targeted metabolomics approach based on gas chromatography–mass spectrometry of the prefrontal cortex in chronic restraint stress (CRS)-treated rats. CRS was induced in the stress group by restraining rats in a plastic restrainer for 6h every day. This stress paradigm continued for 21 days. Body weight measurement and behavior tests were applied, including the sucrose preference test for anhedonia, the forced swimming test for despair-like behavior, and open field test and the elevated plus-maze to test for anxiety-like behaviors in rats after CRS. Differentially expressed metabolites associated with CRS-treated rats were identified by combining multivariate and univariate statistical analysis and corrected for multiple testing using the Benjamini-Hochberg procedure. A heat map of differential metabolites was constructed using Matlab. Ingenuity Pathways Analysis was applied to identify the predicted pathways and biological functions relevant to the bio-molecules of interest. Our findings showed that CRS induces depression-like behaviors and not anxiety-like behaviors. Thirty-six metabolites were identified as potential depression biomarkers involved in amino acid metabolism, energy metabolism and lipid metabolism, as well as a disturbance in neurotransmitters. Consequently, this study provides useful insights into the molecular mechanisms of depression.



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Full title with Editorial board members

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Publication date: 1 May 2016
Source:Behavioural Brain Research, Volume 304





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Intensive care for cancer patients

Abstract

Every sixth to eighth European intensive care unit patient suffers from an underlying malignant disease. A large proportion of these patients present with cancer-related complications. This review explains why the prognosis of critically ill cancer patients has improved substantially over the last decades and which risk factors are of prognostic importance. Furthermore, the main reasons for intensive care unit admission – acute respiratory failure and septic complications – are discussed with regard to diagnostic and therapeutic specifics. In addition, we discuss potential intensive care unit admission criteria with respect to cancer prognosis. The successful management of critically ill cancer patients requires a close collaboration of intensivists with hematologists, oncologists and colleagues from other disciplines, such as infectious disease specialists, microbiologists, radiologists, surgeons, pharmacists, and others.



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memo—new frontiers to be reached



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Adjuvant medical treatment for breast cancer in elderly and old women

Abstract

The probability of developing breast cancer increases with age. Therefore, more than 50 % of women with breast cancer are older than 65 years at the time of diagnosis. However, elderly patients are often undertreated and clinical trials for elderly patients in the adjuvant setting are lacking. Elderly patients who are otherwise fit should receive the standard treatment regimen independent of age.

Endocrine therapy should not be withheld from patients by age alone. Thus, there are more adverse events in the elderly population.

The decision on adjuvant chemotherapy should be made taking into consideration the patient's comorbidities and frailty. A less toxic single-agent regimen may influence overall survival, but are associated with much less toxicity. Trastuzumab has a similar effect in elderly patients to that in younger patients. The risk of cardiotoxicity should be carefully considered in each patient.



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New approaches in graft versus host disease (GvHD) management

Abstract

Graft versus host disease (GVHD) remains the major cause of morbidity and nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (HSCT). Although the understanding of its biological basis is continuously improving and candidate target pathways therefore increasingly emerge, severe, steroid-refractory GVHD remains an unsolved issue with a rather poor prognosis in clinical practice thus far. With the exception of the Janus kinase (JAK) 1/2 inhibitor, ruxolitinib, which has demonstrated considerable effectiveness in steroid-refractory GVHD in a multicenter survey, few advances have been recognized in this field during recent years. Therefore, developments toward better, more individualized GVHD prophylaxis are needed. This, however, requires a more precise knowledge of risk factors for severe GVHD. One such emerging risk factor is the homozygosity for HLA-C group 1 killer cell immunoglobulin-like receptor (KIR) ligands. In addition, ongoing investigation into the predictive value of immunogenetic polymorphisms and post-transplant biomarkers will contribute to individually designed and adaptable GVHD management in the future, hopefully relying mainly on prophylactic and pre-emptive measures.



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Congress Report ESMO Asia 2015



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Catalog of genetic progression of human cancers: non-Hodgkin lymphoma

Abstract

The recent application of next-generation sequencing technologies lead to significant improvements in our understanding of genetic underpinnings of non-Hodgkin lymphomas with identification of an unexpectedly high number of novel mutation targets across the different B-cell lymphoma entities. These recently discovered molecular lesions are expected to have a major impact on development of novel biomarkers and targeted therapies as well as patient stratification based on the underlying genetic profile. This review will cover the major discoveries in B-cell lymphomas using next-generation sequencing technologies over the last few years, highlighting alterations associated with relapse and progression of these diseases.



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Biological underpinnings of psychogenic nonepileptic seizures: directions for future research

Abstract

Psychogenic nonepileptic seizures (PNES) are relatively common occurrences in epilepsy centers, but their pathophysiology is still poorly understood. Research that elucidates the pathophysiology of PNES, including their neurobiological basis and biomarkers, may have important clinical implications. The literature provides some evidence that genetic factors, intrinsic factors, and environmental factors probably play a significant role as the biological underpinnings of PNES. Researchers may be able to learn more about the pathophysiology of PNES by investigating the effects of each of these factors on functional and structural brain connectivity.



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Focal interictal epileptiform discharges in idiopathic generalized epilepsy

Abstract

Are idiopathic generalized epilepsies (IGEs) truly generalized? Do IGEs represent a continuum or rather distinct syndromes? Focal changes in the electroencephalography (EEG) have been reported in IGEs. The aim of this work is to investigate focal interictal epileptiform discharges (IEDs) in IGEs, and their relation to clinical variables. Forty-one IGE patients (classified according to ILAE, 2001) were recruited from a tertiary center (age 23 ± 10.938 years). Their files were reviewed and they were subjected to clinical examination and interictal EEG. Patients with focal IEDs were compared to those without focal IEDs. Nine patients had juvenile myoclonic epilepsy (JME) and 32 had idiopathic epilepsy with generalized tonic–clonic seizures only (EGTCSA). Focal IEDs were found in 20 patients, mostly in the frontal (45.5 %) and temporal (31.8 %) distribution. Patients with focal IEDs were treated with a larger number of combined antiepileptic drugs (AEDs) (p value = 0.022). No significant difference was found between the two groups regarding age, sex, age at onset, epilepsy syndrome, seizure frequency, family history, AEDs used (sodium valproate and carbamazepine) and their doses. Seventeen EGTCSA patients had focal IEDs. They were treated with larger number of combined AEDs (p value = 0.0142). No significant difference was found between the EGTCSA patients with and those without focal IEDs regarding age, sex, age at onset, seizure frequency, family history and AEDs doses. Caution must be applied in the interpretation of interictal focal IEDs. These focal changes may be related to prognosis, however this needs further investigation.



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Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars

Background: Huntington's disease is induced by CAG expansion in a single gene coding the huntingtin protein. The mutated huntingtin (mtHtt) primarily causes degeneration of neurons in the brain, but it also affects peripheral tissues, including testes. Objective: We studied sperm and testes of transgenic boars expressing the N-terminal region of human mtHtt. Methods: In this study, measures of reproductive parameters and electron microscopy (EM) images of spermatozoa and testes of transgenic (TgHD) and wild-type (WT) boars of F1 (24-48 months old) and F2 (12-36 months old) generations were compared. In addition, immunofluorescence, immunohistochemistry, Western blot, hormonal analysis and whole-genome sequencing were done in order to elucidate the effects of mtHtt. Results: Evidence for fertility failure of both TgHD generations was observed at the age of 13 months. Reproductive parameters declined and progressively worsened with age. EM revealed numerous pathological features in sperm tails and in testicular epithelium from 24- and 36-month-old TgHD boars. Moreover, immunohistochemistry confirmed significantly lower proliferation activity of spermatogonia in transgenic testes. mtHtt was highly expressed in spermatozoa and testes of TgHD boars and localized in all cells of seminiferous tubules. Levels of fertility-related hormones did not differ in TgHD and WT siblings. Genome analysis confirmed that insertion of the lentiviral construct did not interrupt any coding sequence in the pig genome. Conclusions: The sperm and testicular degeneration of TgHD boars is caused by gain-of-function of the highly expressed mtHtt.
Neurodegener Dis

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IL-10-Expressing Th2 Cells Contribute to the Elevated Antibody Production in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease associated with progressive disability, systemic complications, and early death. Multiple lines of evidence have placed adaptive immune responses in the center of RA pathogenesis. However, the functional roles of T helper cells are insufficiently described. Here, we examined the Th2 cell subsets and their functions in RA patients. A downregulation of IL-4+ cells in CD4+ T cells were observed in RA patients, indicating a downregulation of Th2 cells, and these results were confirmed by using and CXCR3 and CCR6 surface markers. We then found that CXCR3-CCR6 Th2 cells can be separated into IL-4+ (single positive), IL-10+ (single positive), and IL-4+IL-10+ (double positive) subsets. Further results showed that CXCR5 only expressed on IL-10+ Th2 cells. The CXCR5+ and CXCR5 Th2 cells each exhibited distinctive features in helping B cell antibody secretion. CXCR5+ Th2 cells were more potent at stimulating total Ig and IgM secretion, while CXCR5 Th2 cells were more potent at stimulating IgE. IL-10 was required for helping B cell total Ig, IgM, and IgE production, while IL-4 was required for total Ig and IgE. The frequencies of IL-10+ and IL-4+IL-10+ Th2 cells were positively correlated with rheumatoid factor titer in vivo. Together, our study demonstrated distinctive subsets within Th2 cells, each with different impacts on antibody production and RA disease.



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Anti-HMG-CoA Reductase, Antioxidant, and Anti-Inflammatory Activities of Amaranthus viridis Leaf Extract as a Potential Treatment for Hypercholesterolemia

Inflammation and oxidative stress are believed to contribute to the pathology of several chronic diseases including hypercholesterolemia (elevated levels of cholesterol in blood) and atherosclerosis. HMG-CoA reductase inhibitors of plant origin are needed as synthetic drugs, such as statins, which are known to cause adverse effects on the liver and muscles. Amaranthus viridis (A. viridis) has been used from ancient times for its supposedly medically beneficial properties. In the current study, different parts of A. viridis (leaf, stem, and seed) were evaluated for potential anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities. The putative HMG-CoA reductase inhibitory activity of A. viridis extracts at different concentrations was determined spectrophotometrically by NADPH oxidation, using HMG-CoA as substrate. A. viridis leaf extract revealed the highest HMG-CoA reductase inhibitory effect at about 71%, with noncompetitive inhibition in Lineweaver-Burk plot analysis. The leaf extract showed good inhibition of hydroperoxides, 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and ferric ion radicals in various concentrations. A. viridis leaf extract was proven to be an effective inhibitor of hyaluronidase, lipoxygenase, and xanthine oxidase enzymes. The experimental data suggest that A. viridis leaf extract is a source of potent antioxidant and anti-inflammatory agent and may modulate cholesterol metabolism by inhibition of HMG-CoA reductase.

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Effect of Laser Acupuncture on Anthropometric Measurements and Appetite Sensations in Obese Subjects

Purpose. A patient-assessor-blinded, randomized, sham-controlled crossover trial was performed to investigate the effectiveness of laser acupuncture on anthropometric measurements and appetite sensation in obese subjects. Methods. Fifty-two obese subjects were randomly assigned to either the laser acupuncture group or the sham laser acupuncture group. Subjects within each group received the relevant treatment three times a week for 8 weeks. After a two-week washout period, the subjects then received the treatment of the opposite group for another 8 weeks. BMI, body fat percentage, waist-to-hip ratio (WHR), waist circumference, hip circumference, and appetite sensations were measured before and after 8 weeks of treatment. Results. BMI, body fat percentage, WHR, waist circumference, and hip circumference decreased significantly () in the laser acupuncture group compared to baseline but there was no decrease in those variables in the sham laser acupuncture group. Laser acupuncture significantly improved scores on the fullness, hunger, satiety, desire to eat, and overall well-being relative to the baseline (). Conclusions. Laser acupuncture is well tolerated and improves anthropometric measurements and appetite sensations in obese subjects.

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Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by Different Routes to Llamas (Lama glama)

We investigate the pharmacokinetics of two different cephalexin formulations administered to llamas by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of cephalexin against some Escherichia coli and staphylococci isolated from llamas, and we apply the PK/PD modelling approach, so that effective dosage recommendations for this species could be made. Six llamas received immediate (10 mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin. Pharmacokinetic parameters were calculated by noncompartmental approach. Immediate release SC administration produced a significantly longer elimination half-life as compared with the IV and IM administration ( versus and  h, resp.) and higher mean absorption time as compared with the IM administration ( versus  h). Absolute bioavailability was in the range of 72–89% for both formulations and routes of administration. Cephalexin MIC90 values against staphylococci and E. coli were 1.0 and 8.0 μg/mL, respectively. Our results show that the immediate release formulation (10 mg/kg) would be effective for treating staphylococcal infections administered every 8 h (IM) or 12 h (SC), whereas the sustained release formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h, respectively.

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Partial Response to First-Line Crizotinib in an Elderly Male Patient with ROS1 Translocation-Positive Lung Cancer

We report on a 90-year-old male patient with a ROS1-translocated adenocarcinoma of the lung who was treated with crizotinib as first-line therapy. After 11 months of treatment, we noticed complete metabolic response as measured by 18F-FDG-PET/CT scan and a partial response according to RECIST criteria. This patient indicates that ROS1 translocations are not restricted to young age, female gender and low stage. Furthermore, this case illustrates exemplarily that crizotinib therapy is effective and manageable even as first-line treatment in elderly patients with comorbidities. Based on our findings, we recommend to include elderly patients with advanced pulmonary adenocarcinomas in molecular screening approaches for ROS1 translocations.
Case Rep Oncol 2016;9:158-163

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Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001

Neuroendocrine tumors (NETs) are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903); serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration.
Case Rep Oncol 2016;9:164-170

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Adjusting to a Diagnosis of Cancer: Processes for Building Patient Capacity for Decision-Making

Abstract

This short report contributes to the expanding body of qualitative research literature about the cognitive processes of newly diagnosed cancer patients as they adjust to a diagnosis of cancer. The study is based on secondary qualitative analysis of audio records collected as part of a larger NIH study (RO1D: An Interdisciplinary Perspective: A Social Science Examination of Oncofertility RL1 HD058296). Core categories illustrate the processes of "naming it," "dealing with dealing with it," and finding the "new norm" and were based on nine patient experiences. We observe that our substantive conceptual categories have equivalents in bereavement and grief literature where researchers have posited the theory that processing the diagnosis of a terminal illness is the equivalent to adjusting to a bereavement. These findings emphasize the importance of understanding real-time patient thoughts and feelings as soon after diagnosis as was possible with full patient consent.



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Moderate and Vigorous Intensity Exercise During Pregnancy and Gestational Weight Gain in Women with Gestational Diabetes

Abstract

Objectives To estimate the associations of moderate and vigorous intensity exercise during pregnancy with the rate of gestational weight gain (GWG) from gestational diabetes (GDM) diagnosis to delivery, overall and stratified by prepregnancy overweight/obesity. Methods Prospective cohort study with physical activity reported shortly after the GDM diagnosis and prepregnancy weight and post-diagnosis GWG obtained from electronic health records (n = 1055). Multinomial logistic regression models in the full cohort and stratified by prepregnancy overweight/obesity estimated associations of moderate and vigorous intensity exercise with GWG below and above the Institute of Medicine's (IOM) prepregnancy BMI-specific recommended ranges for weekly rate of GWG in the second and third trimesters. Results In the full cohort, any participation in vigorous intensity exercise was associated with decreased odds of GWG above recommended ranges as compared to no participation [odds ratio (95 % confidence interval): 0.63 (0.40, 0.99)], with a significant trend for decreasing odds of excess GWG with increasing level of vigorous intensity exercise. Upon stratification by prepregnancy overweight/obesity, significant associations were only observed for BMI ≥ 25.0 kg/m2: any vigorous intensity exercise, as compared to none, was associated with 54 % decreased odds of excess GWG [0.46 (0.27, 0.79)] and significant trends were detected for decreasing odds of GWG both below and above the IOM's recommended ranges with increasing level of vigorous exercise (both P ≤ 0.03). No associations were observed for moderate intensity exercise. Conclusions for Practice In women with GDM, particularly overweight and obese women, vigorous intensity exercise during pregnancy may reduce the odds of excess GWG.



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Intimate Partner Violence Associated with Postpartum Depression, Regardless of Socioeconomic Status

Abstract

Objective This study examined whether socioeconomic status moderated the association between intimate partner violence (IPV) and postpartum depression among a community-based sample of women. Defining the role of poverty in the risk of postpartum depression for IPV victims enables prioritization of health promotion efforts to maximize the effectiveness of existing maternal-infant resources. Methods This cross-sectional telephone-survey study interviewed 301 postpartum women 2 months after delivery, screening them for IPV and depression [using Edinburgh Postnatal Depression Scale (EPDS)]. Socioeconomic status was defined by insurance (Medicaid-paid-delivery or not). This analysis controlled for the following covariates, collected through interview and medical-record review: demographics, obstetric history, prenatal health and additional psychosocial risk factors. After adjusting for significant covariates, multiple linear regression was conducted to test whether socioeconomic status confounded or moderated IPV's relationship with EPDS-score. Results Ten percent of participants screened positive for postpartum depression, 21.3 % screened positive for current or previous adult emotional or physical abuse by a partner, and 32.2 % met poverty criteria. IPV and poverty were positively associated with each other (χ2 (1) = 11.76, p < .001) and with EPDS score (IPV: beta 3.2 (CI 2.0, 4.5) p < .001, poverty: beta 1.3 (CI 0.2, 2.4) p = .017). In the multiple linear regression, IPV remained significantly associated, but poverty did not (IPV: adjusted beta 3.1 (CI 1.8, 4.3) p < .001, poverty: adjusted beta 0.8 (CI −0.3, 1.9) p = .141), and no statistically significant interaction between IPV and poverty was found. Conclusions Study findings illustrated that IPV was strongly associated with postpartum depression, outweighing the influence of socioeconomic status upon depression for postpartum women.



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The Impact of Balanced Counseling on Contraceptive Method Choice and Determinants of Long Acting and Reversible Contraceptive Continuation in Nepal

Abstract

Introduction Long-acting reversible contraceptives (LARCs) reduce rates of unintended pregnancies and repeat abortion. Uptake and continuation rates of LARCs are very low in Nepal, despite free provision from most health facilities. We sought to establish the effectiveness of a new approach to LARC promotion in Nepal. Methods We examined change in contraceptive method mix in Nepal using service data resulting from introduction of a balanced counseling (BC) approach to family planning (FP). All staff located at nine randomly selected FP sites were trained and began applying BC in April and May 2014. Women who accepted LARCs from a participating facility were re-contacted at 1, 3, 6 and 12 months. We estimated the LARC continuation rate and assessed determinants of continuation using descriptive analysis, Kaplan–Meier survival curves and univariate and multivariate Cox proportional hazard analysis. Results A total of 5744 women received BC between April and July 2014. 1580 women (27.5 %) took up LARCs, raising its contribution to contraceptive method mix at [organization] to 40 %, significantly higher than the 15 % recorded in 2013. 913 women were followed-up, and the LARC continuation rate at 12 months was 82 %. Women's reported satisfaction with LARC [AHR 0.23; 95 % CI 0.14–0.39, p = 0.000] was the single strongest determinant of LARC continuation after adjusting for all background characteristics. Discussion The findings suggest BC is an effective approach for increasing LARC uptake in Nepal. The rate of LARC continuation and its determinants are important inputs to strategies for improved delivery of FP services.



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High-resolution synchrotron X-ray analysis of bioglass-enriched hydrogels



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Biomimetic mineralization of hydrogels



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Pathogenese van Actinobacillus pleuropneumoniae-infecties bij het varken en het belang ervan voor vaccinontwikkeling

Contagious porcine pleuropneumoniae is caused by Actinobacillus pleuropneumoniae. The agent is able to adhere to the epithelium of the lower respiratory tract and lung alveoli. Type IV fimbriae play, amongst other virulence factors, an important role in the adhesion phase. Transferrin binding proteins mediate the uptake of iron by this bacterium, which is necessary for its multiplication. The typical hemorrhagic to necrotizing lesions in the lungs are primarily caused by the production of Apx toxins. By forming biofilms and producing proteases, Apx toxins and ammonia, A. pleuropneumoniae is able to circumvent the immune system of the host. Antibodies directed against the lipoprotein PalA may aggravate the course of infection, and counteract the protective effect of antibodies targeting the Apx toxins. In-depth knowledge on host-pathogen interactions may lead to the development of efficient vaccines. The protection observed after vaccination with bacterins, such as autologous vaccines, is serotype-specific and variable. This may be attributed to variable levels of PalA in these vaccines. Until now, the best results have been obtained using an experimental vaccine containing type IV fimbriae, transferrin binding proteins and Apx toxins.

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Evaluatie van twee intensieve behandelingsschema's tegen Psoroptes ovis-schurft bij Belgisch witblauwe runderen op negen Vlaamse rundveebedrijven

Psoroptic mange, caused by Psoroptes ovis, is a problem on many Flemish farms where Belgian blue beef cattle are bred. Two intensive treatment schedules were evaluated on nine Belgian blue fauns with a-persistent mange problem. On farms 1 to 7, all animals were treated twice (with a seven-to-ten-days interval) with an injectable macrocyclic lactone (ML), while on the two remaining fauns, the initial treatment consisted of one injection with the long acting (LA) formulation of moxidectin (10%). Skin scrapings were taken after treatment, and when living mites were found on at least one animal, all animals (farms 1 to 7) or only positive animals (farms 8 and 9) were treated consecutively with an injectable ML. On all farms, the treated animals were clinically healthy and P ovis free at the end of winter, after two to nine treatment rounds (two injections with a seven to ten-days interval or one LA injection). Although mange reappeared on the first seven farms after the subsequent grazing season, the disease was less severe and easier to control.

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Understanding the occupational traveller profile towards malaria prevention enables directed health promotion and preventive practices

2016-03-09T02-58-29Z
Source: International Journal of Tropical Medicine and Public Health
Ana Gloria Fonseca, Susana Carvalho, Sara Simões Dias, Joao Luis Baptista, Jorge Torgal.
Aim/background: Increased migration and expatriation to malaria endemic countries has been appointed as contributing factor to the increasing imported malaria hospitalizations recently observed in Portugal. This study sought to profile this traveller and understand the knowledge, attitude and practice (KAP) towards malaria prevention as necessary first step to improve and suit risk reduction strategies. Methods: A cross sectional questionnaire based study was conducted at the Lisbon International Airport aiming to characterize the Portuguese occupational traveller to Angola. Travel and travellers characteristics associated to not seeking travel health advice and KAP towards malaria were specifically studied. Results: Occupational travellers represented 92,6% (n= 374/404) of the Portuguese travellers to Angola that participated in the survey. The profile found was that of an occupational traveller experienced in developing destinations to urban settings for long periods. The knowledge regarding malaria risk and prevention was good but the same was not observed for preventive practices. Those with chronic health conditions and those living in Angola or both in Portugal and Angola tend not to seek pre-travel medical advice and to be at higher malaria risk, considering their KAP towards malaria. Conclusions: Increasing watchfulness concerning occupational travellers and expatriates need to be in the public health agenda and suited interventions are needed.


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Abnormal Tilt Perception During Centrifugation in Patients with Vestibular Migraine

Abstract

Vestibular migraine (VM), defined as vestibular symptoms caused by migraine mechanisms, is very common but poorly understood. Because dizziness is often provoked in VM patients when the semicircular canals and otolith organs are stimulated concurrently (e.g., tilting the head relative to gravity), we measured tilt perception and eye movements in patients with VM and in migraine and normal control subjects during fixed-radius centrifugation, a paradigm that simultaneously modulates afferent signals from the semicircular canals and otoliths organs. Twenty-four patients (8 in each category) were tested with a motion paradigm that generated an inter-aural centrifugal force of 0.36 G, resulting in a 20° tilt of the gravito-inertial force in the roll plane. We found that percepts of roll tilt developed slower in VM patients than in the two control groups, but that eye movement responses, including the shift in the eye's rotational axis, were equivalent in all three groups. These results demonstrate a change in vestibular perception in VM that is unaccompanied by changes in vestibular-mediated eye movements and suggest that either the brain's integration of canal and otolith signals or the dynamics of otolith responses are aberrant in patients with VM.



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ARAS: an automated radioactivity aliquoting system for dispensing solutions containing positron-emitting radioisotopes

Abstract

Background

Automated protocols for measuring and dispensing solutions containing radioisotopes are essential not only for providing a safe environment for radiation workers but also to ensure accuracy of dispensed radioactivity and an efficient workflow. For this purpose, we have designed ARAS, an automated radioactivity aliquoting system for dispensing solutions containing positron-emitting radioisotopes with particular focus on fluorine-18 (18F).

Methods

The key to the system is the combination of a radiation detector measuring radioactivity concentration, in line with a peristaltic pump dispensing known volumes.

Results

The combined system demonstrates volume variation to be within 5 % for dispensing volumes of 20 μL or greater. When considering volumes of 20 μL or greater, the delivered radioactivity is in agreement with the requested amount as measured independently with a dose calibrator to within 2 % on average.

Conclusions

The integration of the detector and pump in an in-line system leads to a flexible and compact approach that can accurately dispense solutions containing radioactivity concentrations ranging from the high values typical of [18F]fluoride directly produced from a cyclotron (~0.1–1 mCi μL−1) to the low values typical of batches of [18F]fluoride-labeled radiotracers intended for preclinical mouse scans (~1–10 μCi μL−1).



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Data of a willingness to pay survey for national climate change mitigation policies in Germany

Publication date: Available online 9 March 2016
Source:Data in Brief
Author(s): Reinhard Uehleke
The dataset includes responses from a contingent valuation of the national climate change mitigation policies in Germany. The online survey was carried out in the spring of 2014. It assesses the willingness to pay for an increase of the national CO2 reduction target by 10 percentage points, which closely represents Germany's climate change mitigation strategy. Respondents were randomly allocated to one of the following three question formats: The dichotomous choice referendum, the dissonance minimizing referendum and the two-sided payment ladder. The data is used to estimate willingness to pay across different question formats in "The Role of Question Format for the Support for National Climate Change Mitigation Policies in Germany and the Determinants of WTP" [1]. The data can be used to investigate the influence of alternative statistical approaches on the willingness to pay measures and their comparison across question formats.



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Fluorescence-based thermal shift data on multidrug regulator AcrR from Salmonella enterica subsp. entrica serovar Typhimurium str. LT2

Publication date: Available online 9 March 2016
Source:Data in Brief
Author(s): Babu A. Manjasetty, Andrei S. Halavaty, Chi-Hao Luan, Jerzy Osipiuk, Rory Mulligan, Keehwan Kwon, Wayne F. Anderson, Andrzej Joachimiak
The fluorescence-based thermal shift (FTS) data presented here include Table S1 and Fig. S1, and are supplemental to our original research article describing detailed structural, FTS, and fluorescence polarization analyses of the Salmonella enterica subsp. entrica serovar Typhimurium str. LT2 multidrug transcriptional regulator AcrR (StAcrR) (doi:10.1016/j.jsb.2016.01.008.) [1]. Table S1 contains chemical formulas, a Chemical Abstracts Service (CAS) Registry Number (CAS No.), FTS rank (a ligand with the highest rank has the largest difference in the melting temperature (ΔTm), and uses as drug molecules against various pathological conditions of sixteen small-molecule ligands that increase thermal stability of StAcrR. Thermal stability of human enolase 1, a negative control protein, was not affected in the presence of various concentrations of the top six StAcrR binders (Fig. S1).



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Data for increase of Lymantria dispar male survival after topical application of single-stranded RING domain fragment of IAP-3 gene of its nuclear polyhedrosis virus

Publication date: Available online 9 March 2016
Source:Data in Brief
Author(s): Volodymyr V. Oberemok, Kateryna V. Laikova, Aleksei S. Zaitsev, Vladimir A. Gushchin, Oleksii A. Skorokhod
This data article is related to the research article entitled "The RING for gypsy moth control: topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide" [1]. This article reports on significantly higher survival of gypsy moth Lymantria dispar male individuals in response to topical application of single-stranded DNA, based on RING (really interesting new gene) domain fragment of LdMNPV (L. dispar multicapsid nuclear polyhedrosis virus) IAP-3 (inhibitor of apoptosis) gene and acted as DNA insecticide.



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Data and the associated R code used to estimate health and economic burden of neurocysticercosis in India

Publication date: Available online 9 March 2016
Source:Data in Brief
Author(s): B B Singh, M S Khatkar, J P S Gill, N K Dhand
This article contains epidemiological, demographic and other data used for estimating health and economic burden of neurocysticercosis (NCC)-associated active epilepsy in India [1]. Most of the data are embedded in the R-code used for analyses so that the reader is able to replicate the results or adapt the code to their own data. However, data used to conduct sensitivity analyses to evaluate the effect of changing important input values such as prevalence and per capita income on health and economic impact of NCC in India are included in tables. Results from sensitivity analyses are also presented in tables and figures. The paper also includes three scenarios with different age weighting (k) and time discounting (r) values used to estimate health and economic burden of NCC in India. The data for the scenario without any age weighting and time discounting are presented in "Estimation of the health and economic burden of neurocysticercosis in India" [1].



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Using Behavioral Risk Factor Data as a surveillance tool to monitor the prevalence of initiation, continuation and completion of Human Papilloma Virus Vaccination in Children

Publication date: Available online 9 March 2016
Source:Data in Brief
Author(s): Gia Elise Barboza, Silvia Dominguez
The Human Papilloma Virus ("HPV") is a common sexually transmitted disease that has infected approximately 79 million men and women in the United States alone. A vaccination is available but in order to be effective it must be received prior to becoming sexually active and recipients must complete a three-dose sequence. In this article we explore the predisposing, enabling and need-based factors associated with parents' or guardians' decision to have their child initiate, continue and complete the Human Papilloma Virus (HPV) vaccine. The data file includes 5,531 parents and guardians with presumptive knowledge regarding the number of HPV vaccination their child received. Data includes information on the child (e.g. child's age) as well as the adult respondent (e.g. health insurance status). A smaller subset of the dataset along with the code to run the model are supplied with this article. The interpretation of these data can be found in the research article published by the authors in the Journal of Preventive Medicine in 2015 http://ift.tt/1US4cyT].



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Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples

Publication date: Available online 9 March 2016
Source:Data in Brief
Author(s): Alessandro Tanca, Maria Filippa Addis, Salvatore Pisanu, Marcello Abbondio, Daniela Pagnozzi, Albino Eccher, Guido Rindi, Paolo Cossu-Rocca, Sergio Uzzau, Giuseppe Fanciulli
Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs). Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR < 1%. MS data are available in the PeptideAtlas repository at http://ift.tt/1US4cyL.



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The clinicopathological significance of Mortalin overexpression in invasive ductal carcinoma of breast

Abstract

Background

Mortalin/GRP75 is a ubiquitous mitochondrial chaperone which related to the cytosolic heat shock protein 70 (HSP70), and plays a role in carcinogenesis. This study aims to investigate the Mortalin expression in breast cancer and its correlation with the outcome of the patients with breast cancer.

Methods

A total of 155 invasive ductal carcinoma of breast patients with strict follow-up, 52 ductal carcinoma in situ (DCIS) and 45 adjacent non-tumor breast tissues were selected for immunohistochemical (IHC) staining of Mortalin protein. The localization of Mortalin protein was detected in MDA-MB231 breast cancer cells using immunofluorescence (IF) staining. The correlations between overexpression of Mortalin and the clinical features of patients with breast cancer were evaluated using chi-square test and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models.

Results

Mortalin protein showed a mainly cytoplasmic staining pattern in breast cancers by using IHC staining in paraffin embedded breast cancer tissues and IF staining in MDA-MB231 breast cancer cells. The strongly positive rate of Mortalin protein was 63.9 % (99/155) in invasive ductal carcinoma of breast and was significantly higher than in DCIS 34.6 % (18/52) and adjacent non-tumor tissues 15.6 % (7/45). Overexpression of Mortalin was closely correlated with histological grade, clinical stage, lymph node metastasis, lower disease free survival (DFS) and overall survival (OS) rates of patients with breast cancer. Moreover, multivariate analysis suggested that Mortalin emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer.

Conclusions

Mortalin is upregulated in breast cancer, and may be a useful poor prognostic biomarker as well as a potential therapeutic target for patients with breast cancer.



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Mixed-reality simulation for orthognathic surgery

Abstract

Background

Mandibular motion tracking system (ManMoS) has been developed for orthognathic surgery. This article aimed to introduce the ManMoS and to examine the accuracy of this system.

Methods

Skeletal and dental models are reconstructed in a virtual space from the DICOM data of three-dimensional computed tomography (3D-CT) recording and the STL data of 3D scanning, respectively. The ManMoS uniquely integrates the virtual dento-skeletal model with the real motion of the dental cast mounted on the simulator, using the reference splint. Positional change of the dental cast is tracked by using the 3D motion tracking equipment and reflects on the jaw position of the virtual model in real time, generating the mixed-reality surgical simulation. ManMoS was applied for two clinical cases having a facial asymmetry. In order to assess the accuracy of the ManMoS, the positional change of the lower dental arch was compared between the virtual and real models.

Results

With the measurement data of the real lower dental cast as a reference, measurement error for the whole simulation system was less than 0.32 mm. In ManMoS, the skeletal and dental asymmetries were adequately diagnosed in three dimensions. Jaw repositioning was simulated with priority given to the skeletal correction rather than the occlusal correction. In two cases, facial asymmetry was successfully improved while a normal occlusal relationship was reconstructed. Positional change measured in the virtual model did not differ significantly from that in the real model.

Conclusions

It was suggested that the accuracy of the ManMoS was good enough for a clinical use. This surgical simulation system appears to meet clinical demands well and is an important facilitator of communication between orthodontists and surgeons.



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Histopathologic Diagnosis of Multifactorial Alopecia

Abstract

Establishing a definitive diagnosis for any form of alopecia can be challenging. Adding to the diagnostic complexity is the fact that many patients have more than one form of alopecia contributing to their hair loss. We conducted a review of 1360 consecutive scalp biopsy specimens submitted for the evaluation of scalp hair loss over a 16-month period, demonstrating that 12.5% of cases had a combination of diagnoses (multifactorial alopecia) accounting for their hair loss. An approach to the histopathologic diagnosis of multifactorial alopecia, particularly multiple forms of alopecia found in a single biopsy, is here presented.



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Revisiting histopathologic findings in Goltz syndrome

Abstract

Goltz syndrome (focal dermal hypoplasia) is an X-linked dominant disorder that is classically associated with yellowish papules representing fat herniation (superficial adipocytes). We report a series of 3 cases, with clinicopathologic correlation of biopsies from Blaschkoid streaks. A range of histopathologic features, including some underreported findings (increased papillary dermal blood vessels, decreased thickness of the dermis, and adipocytes high in the dermis), are reproducible and can strongly point to the correct diagnosis of Goltz syndrome.



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Clear Cell Atypical Fibroxanthoma: a Case Report and Review of the Literature

ABSTRACT

Atypical fibroxanthoma (AFX) is a group of cutaneous tumors characterized by a population of fusiform, epithelioid, and pleomorphic cells. Clinically, AFX is commonly found on the head and neck of older adults as a solitary ulcerated nodule. Clear cell atypical fibroxanthoma is a very rare variant of AFX, with only thirteen cases reported to date. The differential diagnoses often include dermal neoplasms composed of clear cells, such as squamous cell carcinoma, basal cell carcinoma, metastatic renal cell carcinoma, and balloon cell malignant melanoma. These diagnoses can be ruled out by the typical immunohistochemical profile of clear cell AFX, which is negative for specific epithelial and melanocytic markers. Herein, we describe a rare and unusual case of clear cell AFX arising on the ear of a relatively young adult patient. Histologically, the dermis was completely replaced by an atypical population of vacuolated cells with numerous atypical mitoses. Immunohistochemical stains were negative forpancytokeratin, CK5/6, CK7, and p63, S100 and Melan-A stains. CD10 and CD68 stainswerepositive, making the findings consistent with the diagnosis of clear cell atypical fibroxanthoma.



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Skin involvement as the first manifestation of breast implant-associated anaplastic large cell lymphoma

Abstract

Breast implant–associated large cell anaplastic lymphoma (ALCL) is a newly described clinical and pathologic entity that typically presents as seroma in the fibrous scar around the implant. Less frequently, it presents as a solid peri-implant mass, and there have been no reports to date of cutaneous lesions as the presenting manifestation.

We report the case of a 56-year-old woman with a history of bilateral breast reconstruction following breast cancer of the right breast who consulted with several papules on the right breast suggestive of metastasis. Histopathology showed a proliferation of large epithelioid lymphocytes with highly pleomorphic cells and nuclei. The neoplastic cells were CD15 and CD30 positive and ALK-1 negative. The epithelial markers were all negative except for epithelial membrane antigen (EMA), which was weakly positive. Molecular analysis showed monoclonal T-cell receptor (TCR) γ gene rearrangement, confirming a diagnosis of breast implant–associated ALCL.

The nonspecific morphology of the skin lesions, the epithelioid nature of the neoplastic cells, and the expression of EMA can lead to an erroneous diagnosis of skin metastases from a poorly differentiated adenocarcinoma of the breast. We recommend immunohistochemical staining for CD30 and ALK-1 for patients with breast implants who develop anaplastic lesions.



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Polymorphous sweat gland carcinoma: a report of two cases

ABSTRACT

Polymorphous sweat gland carcinoma (PSGC) is a rare adnexal neoplasm with characteristic variegated histopathologic findings and low-grade clinical behavior. First described in 1994, only eleven cases have been reported in the literature. It is named for the multiplicity of architectural patterns that may be present: solid, tubular, trabecular, pseudopapillary and cylindromatous. Due to the multiple architectural patterns, the differential diagnosis is broad, including metastatic adenocarcinoma and other adnexal neoplasms with ductular differentiation. We present two new cases of PSGC and review the literature on this rare tumor.



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Pigmented Desmoplastic trichilemmoma



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Postirradiation pseudosclerodermatous panniculitis with involvement of breast parenchyma: A dramatic example of a rare entity and a pitfall in diagnosis

Abstract

Postirradiation pseudosclerodermatous panniculitis is a rare complication of external beam radiotherapy. This inflammatory process typically presents as an erythematous indurated plaque in a previously irradiated region of skin. To date, 13 cases have been reported worldwide. We present a case of a 70 year-old female who received breast irradiation following conservation surgery for invasive breast carcinoma. In her third year of follow-up she developed an enlarging mass, involving the subcutis and underlying breast tissue, associated with mammographically-detected coarse calcifications and density, at the surgical site. This was deemed highly suspicious of recurrent malignancy. Following several benign needle core biopsies, she had an excision of the mass. This revealed a lobular panniculitis and irradiation-induced vascular changes affecting subcutaneous fat and underlying breast tissue. This is the 14th reported case of this rare entity. It is unique in the degree of involvement, affecting breast parenchyma as well as subcutaneous fat, and in its corresponding dramatic clinical and radiographic manifestations.



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Histopathology of keratotic papules of the limbs in frontal fibrosing alopecia

Abstract

Frontal fibrosing alopecia (FFA) is a scarring type of alopecia that presents clinically as progressive frontotemporal hairline regression and eyebrow loss, mainly in postmenopausal women. An additional common finding is keratotic papules on the face or (less commonly) on the trunk and extremities. The histopathology of the facial keratotic papules associated with FFA is the same as that of lichen planopilaris. There are very few FFA cases with biopsies from extrafacial sites and no cases of folliculocentric keratotic papules with biopsies from extrafacial sites. In the current report, we describe the histopathology of one such keratotic papule from the arm of a 75-year-old woman with FFA and demonstrate that the morphology is that of lichen planopilaris and that the papules are identical to those found in Graham-Little-Piccardi syndrome.



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Methotrexate-associated EBV-positive vasculitis in the skin: a report of two cases simulating rheumatoid vasculitis

Abstract

Rheumatoid vasculitis (RV) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), generally treated with a high dose of immunosuppressive drugs. Recently, we encountered two cases of ulcerative vasculitis in methotrexate (MTX)-prescribed RA patients, which simulated RV; however, Epstein-Barr virus (EBV)-encoded RNA in situ hybridization on their skin biopsies revealed many EBV-positive lymphocytes (over 50 cells/high-power field) within the vessel walls and perivascular stroma, which led us to the diagnosis of EBV-related vasculitis instead of RV. Subsequently, both ulcers regressed after the discontinuation of MTX and no recurrence was noted during the follow-up period. To prevent unnecessary treatment, EBV-positive vasculitis should be added in the differential diagnosis of lymphocytic vasculitis observed in MTX-administered RA patients.



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Spindle B-cell lymphoma: a rare variant of follicle center lymphoma

Abstract

Primary cutaneous follicle center lymphoma (PCFCL) is a common subtype of primary cutaneous B-cell lymphoma (PCBCL). The prognosis of this subtype is favorable and recurrence is observed in up to 50% of patients. The dissemination to lymph nodes or internal organs is rare. In this study, two cases of rare variant of PCFCL are reported. Both cases presented with multiple erythematous nodules , plaques and some annular configurations . Histopathological examination revealed dermal lymphocytic infiltrates consisting of admixed centrocytes and centroblasts. Interestingly, spindle-shaped cells with elongated nuclei, dispersed chromatin and scant cytoplasm were also detected. Immunohistochemical analysis revealed that all cells including the spindle cells were positive for CD20 and negative for CD3, CD43, CD10, CD34, CD68 and CD138. They were also negative for desmin and S-100. They consistently expressed nuclear bcl-6, but did not express bcl-2. The histopathological and immunohistochemical examination suggest a rare case of primary cutaneous spindle cell B-cell lymphoma (PCSBCL).

Although few data is published about this rare subtype, PCSBCL is recently considered as a rare subtype of PCFCL. The prognosis and the nature of this peculiar subtype are not yet cleared. This indicates a great need for more investigations.



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Eruptive Angiokeratomas and Porokeratosis in the setting of Sclerodermatous Graft-Versus-Host Disease

Abstract

Porokeratosis and angiokeratomas are both seen in the setting of chronic graft-versus-host-disease (GVHD), but rarely occur together. We present a case of a patient with lichen planus-like (LPL) and sclerodermatous chronic GVHD manifesting after allogeneic bone marrow transplant with concomitant eruptive angiokeratomas and porokeratosis.



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An unusual presentation of Dermatofibrosarcoma Protuberans with pleomorphic sarcomatous transformation: potential pitfall and diagnostic strategy

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a low grade, superficial sarcoma characterized by a proliferation of monomorphous, spindle cells arranged in a storiform pattern and infiltrating the subcutaneous tissue. The tumor is typically CD34 positive, and shows the characteristic COL1A1-PDGFB fusion gene, detectable either by FISH and PCR. We describe a case of DFSP with a focus of peculiar pleomorphic sarcomatous transformation. The focus constituted the entire bioptic tissue that was initially excised, raising considerable diagnostic problems for pathologist. The use of FISH as an ancillary technique allowed the right diagnosis.



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