Russell bodies in a skin biopsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>The presence of eosinophilic bodies in a skin biopsy can be found in a variety of situations and this may present a challenge to the pathologist. The differential diagnosis of these eosinophilic structures include microorganisms such as histoplasmosis or cryptococcosis, fungi, Michaelis-Gutmann bodies, deposits of amyloid or immunoglobulins, colloid bodies or elastic bodies.</p> <p>Case presentation</p> <p>During a routine examination of a skin biopsy with actinic keratosis taken from the cheek of a 61-year-old man, clusters of eosinophilic bodies were seen within an inflammatory infiltrate in the dermis, both intracytoplasmic and extracellular. Using additional immunohistochemical staining, these structures were identified as polyclonal Russell bodies.</p> <p>Conclusion</p> <p>The differential diagnosis of intracytoplasmic eosinophilic structures in a skin biopsy includes Russell bodies, an uncommon finding that may be associated with chronic inflammatory conditions.</p

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial.

To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes

Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively active Akt construct markedly abrogated PEITC-mediated JNK activation, Mcl-1 downregulation, caspase activation, and apoptosis, and also interruption of the JNK pathway by pharmacological or genetically (e.g., siRNA) attenuated PEITC-induced apoptosis. Finally, administration of PEITC markedly inhibited tumor growth and induced apoptosis in U937 xenograft model in association with inactivation of Akt, activation of JNK, as well as downregulation of Mcl-1. Taken together, these findings represent a novel mechanism by which agents targeting Akt/JNK/Mcl-1 pathway potentiate PEITC lethality in transformed and primary human leukemia cells and inhibitory activity of tumor growth of U937 xenograft model

Radiation induced CNS toxicity – molecular and cellular mechanisms

Radiotherapy of tumours proximal to normal CNS structures is limited by the sensitivity of the normal tissue. Prior to the development of prophylactic strategies or treatment protocols a detailed understanding of the mechanisms of radiation induced CNS toxicity is mandatory. Histological analysis of irradiated CNS specimens defines possible target structures prior to a delineation of cellular and molecular mechanisms. Several lesions can be distinguished: Demyelination, proliferative and degenerative glial reactions, endothelial cell loss and capillary occlusion. All changes are likely to result from complex alterations within several functional CNS compartments. Thus, a single mechanism responsible cannot be separated. At least four factors contribute to the development of CNS toxicity: (1) damage to vessel structures; (2) deletion of oligodendrocyte-2 astrocyte progenitors (O-2A) and mature oligodendrocytes; (3) deletion of neural stem cell populations in the hippocampus, cerebellum and cortex; (4) generalized alterations of cytokine expression. Several underlying cellular and molecular mechanisms involved in radiation induced CNS toxicity have been identified. The article reviews the currently available data on the cellular and molecular basis of radiation induced CNS side effects.   http://www.bjcancer.com © 2001 Cancer Research Campaig

The appropriateness of prescribing antibiotics in the community in Europe: study design

Contains fulltext : 97417.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Over 90% of all antibiotics in Europe are prescribed in primary care. It is important that antibiotics are prescribed that are likely to be effective; however, information about antibiotic resistance in the community is incomplete. The aim of our study is to investigate the appropriateness of antibiotic prescribing in primary care in Europe by collecting and combining patterns of antibiotic resistance patterns and antibiotic prescription patterns in primary care. We will also evaluate the appropriateness of national antibiotic prescription guidelines in relation to resistance patterns. METHODS/DESIGN: Antibiotic resistance will be studied in an opportunistic sample from the community in nine European countries. Resistance data will be collected by taking a nose swab of persons (N = 4,000 per country) visiting a primary care practice for a non-infectious disease. Staphylococcus aureus and Streptococcus pneumoniae will be isolated and tested for resistance to a range of antibiotics in one central laboratory. Data on antibiotic prescriptions over the past 5 years will be extracted from the electronic medical records of General Practitioners (GPs). The results of the study will include the prevalence and resistance data of the two species and 5 years of antibiotic prescription data in nine European countries.The odds of receiving an effective antibiotic in each country will be calculated as a measure for the appropriateness of prescribing. Multilevel analysis will be used to assess the appropriateness of prescribing. Relevant treatment guidelines of the nine participating countries will be evaluated using a standardized instrument and related to the resistance patterns in that country. DISCUSSION: This study will provide valuable and unique data concerning resistance patterns and prescription behaviour in primary care in nine European countries. It will provide evidence-based recommendations for antibiotic treatment guidelines that take resistance patterns into account which will be useful for both clinicians and policy makers. By improving antibiotic use we can move towards controlling the resistance problem globally

Cognitive Defeasible Reasoning: the Extent to Which Forms of Defeasible Reasoning Correspond with Human Reasoning

Classical logic forms the basis of knowledge representation and reasoning in AI. In the real world, however, classical logic alone is insufficient to describe the reasoning behaviour of human beings. It lacks the flexibility so characteristically required of reasoning under uncer- tainty, reasoning under incomplete information and reasoning with new information, as humans must. In response, non-classical extensions to propositional logic have been formulated, to provide non-monotonicity. It has been shown in previous studies that human reasoning exhibits non- monotonicity. This work is the product of merging three independent studies, each one focusing on a different formalism for non-monotonic reasoning: KLM defeasible reasoning, AGM belief revision and KM belief update. We investigate, for each of the postulates propounded to characterise these logic forms, the extent to which they have correspondence with human reasoners. We do this via three respective experiments and present each of the postulates in concrete and abstract form. We discuss related work, our experiment design, testing and evaluation, and report on the results from our experiments. We find evidence to believe that 1 out of 5 KLM defeasible reasoning postulates, 3 out of 8 AGM belief revi- sion postulates and 4 out of 8 KM belief update postulates conform in both the concrete and abstract case. For each experiment, we performed an additional investigation. In the experiments of KLM defeasible rea- soning and AGM belief revision, we analyse the explanations given by participants to determine whether the postulates have a normative or descriptive relationship with human reasoning. We find evidence that suggests, overall, KLM defeasible reasoning has a normative relationship with human reasoning while AGM belief revision has a descriptive rela- tionship with human reasoning. In the experiment of KM belief update, we discuss counter-examples to the KM postulates

Aerobic Training in Rats Increases Skeletal Muscle Sphingomyelinase and Serine Palmitoyltransferase Activity, While Decreasing Ceramidase Activity

Sphingolipids are important components of cell membranes that may also serve as cell signaling molecules; ceramide plays a central role in sphingolipid metabolism. The aim of this study was to examine the effect of 5 weeks of aerobic training on key enzymes and intermediates of ceramide metabolism in skeletal muscles. The experiments were carried out on rats divided into two groups: (1) sedentary and (2) trained for 5 weeks (on a treadmill). The activity of serine palmitoyltransferase (SPT), neutral and acid sphingomyelinase (nSMase and aSMase), neutral and alkaline ceramidases (nCDase and alCDase) and the content of sphingolipids was determined in three types of skeletal muscle. We also measured the fasting plasma insulin and glucose concentration for calculating HOMA-IR (homeostasis model assessment) for estimating insulin resistance. We found that the activities of aSMase and SPT increase in muscle in the trained group. These changes were followed by elevation in the content of sphinganine. The activities of both isoforms of ceramidase were reduced in muscle in the trained group. Although the activities of SPT and SMases increased and the activity of CDases decreased, the ceramide content did not change in any of the studied muscle. Although ceramide level did not change, we noticed increased insulin sensitivity in trained animals. It is concluded that training affects the activity of key enzymes of ceramide metabolism but also activates other metabolic pathways which affect ceramide metabolism in skeletal muscles

Treatment and survival of resected and unresected distal cholangiocarcinoma: a nationwide study

Background: Population-based data on distal cholangiocarcinoma (DCC) from the Western world are not available, albeit essential to identify areas for improvement. This study investigated the incidence, treatment and outcomes, including time trends and predictors for survival, in a nationwide cohort of DCC. Methods: This is a retrospective cohort study of patients diagnosed with DCC (2009–2016) derived from the Netherlands Cancer Registry. Overall survival (OS) and its predictors were analyzed using Kaplan–Meier and Cox regres

Physical activity as a possible mechanism behind the relationship between green space and health: A multilevel analysis

Background: The aim of this study was to investigate whether physical activity (in general, and more specifically, walking and cycling during leisure time and for commuting purposes, sports and gardening) is an underlying mechanism in the relationship between the amount of green space in people's direct living environment and self-perceived health. To study this, we first investigated whether the amount of green space in the living environment is related to the level of physical activity. When an association between green space and physical activity was found, we analysed whether this could explain the relationship between green space and health. Methods: The study includes 4.899 Dutch people who were interviewed about physical activity, self-perceived health and demographic and socioeconomic background. The amount of green space within a one-kilometre and a three-kilometre radius around the postal code coordinates was calculated for each individual. Multivariate multilevel analyses and multilevel logistic regression analyses were performed at two levels and with controls for socio-demographic characteristics and urbanicity. Results: No relationship was found between the amount of green space in the living environment and whether or not people meet the Dutch public health recommendations for physical activity, sports and walking for commuting purposes. People with more green space in their living environment walked and cycled less often and fewer minutes during leisure time; people with more green space garden more often and spend more time on gardening. Furthermore, if people cycle for commuting purposes they spend more time on this if they live in a greener living environment. Whether or not people garden, the time spent on gardening and time spent on cycling for commuting purposes did not explain the relationship between green space and health. Conclusion: Our study indicates that the amount of green space in the living environment is scarcely related to the level of physical activity. Furthermore, the amount of physical activity undertaken in greener living environments does not explain the relationship between green space and health.