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Obesity is an established risk factor for many cancers and has recently been found to alter the efficacy of T cell–based immunotherapies. Currently, however, the effects of obesity on immunometabolism remain unclear. Understanding these associations is critical, given the fact that T cell metabolism is tightly linked to effector function. Thus, any obesity‐associated changes in T cell bioenergetics are likely to drive functional changes at the cellular level, alter the metabolome and cytokine/chemokine milieu, and impact cancer immunotherapy outcomes. Here, we provide a brief overview of T cell metabolism in the presence and absence of solid tumor growth and summarize current literature regarding obesity‐associated changes in T cell function and bioenergetics. We also discuss recent findings related to the impact of host obesity on cancer immunotherapy outcomes and present potential mechanisms by which T cell metabolism may influence therapeutic efficacy. Finally, we describe promising pharmaceutical therapies that are being investigated for their ability to improve CD8 T cell metabolism and enhance cancer immunotherapy outcomes in patients, regardless of their obesity status. [ABSTRACT FROM AUTHOR]

Flow cytometry is a versatile and high throughput technique for rapid and efficient biological testing. It requires a high level of conceptual, technical, and analytical skills to properly design experiments, effectively operate flow cytometry machines, and analyze the data. A lack of training and development of any of these three skills can result in underutilization and improper use of flow cytometric machines that can impede research progress. Often students develop these conceptual, technical, and analysis skills from trial and error, but many students either do not use this powerful flow cytometry technology, use it improperly or ineffectively, or give up using it without proper training and support. Here we report on a course which teaches flow cytometry skills to undergraduate and graduate students. The design of this course is unique in that it teaches conceptual, technical, and analytical skills related to flow cytometry in a full semester format. Undergraduate and graduate students reported significant increases in their confidence levels over the course of the semester. Here we provide our findings and resources for others who may want to implement a similar course. [ABSTRACT FROM AUTHOR]

RNA sequencing ( RNA-seq) is a powerful tool for the evaluation and quantification of transcriptomes and expression patterns in animals, tissues, or pathological conditions. The purpose of this study was to determine the physiologic expression of cytochrome P450 ( CYP) mRNA transcripts in whole blood, kidney, duodenum, liver, and lung in healthy, adult male ( n = 4) and female ( n = 4) beagles via RNA-seq. mRNA expression was above background (transcripts per million) for 45 canine CYPs, with liver, duodenum, and lung expressing a high number of xenobiotic metabolizing CYPs, while prominent endogenous metabolizing CYP expression was present in blood and kidney. The relative expression pattern of CYP2A13, 2B11, 2C21, 2D15, 2E1, 3A12, and 27A1 in liver, lung, and duodenum was verified through qPCR. This is the first global profiling of physiologic CYP mRNA expression in multiple canine tissues, providing a platform for further studies characterizing canine CYPs and changes in gene expression in disease states. [ABSTRACT FROM AUTHOR]

PARR is widely used in the diagnostics of canine lymphoma. In human and veterinary medicine, melting curve analysis (MCA) has successfully been introduced to facilitate the process. Since visual interpretation of melting curves can be rather subjective, the purpose of this study was to develop an objective interpretation of melting curves by calculating the maximum fluorescence decrease (dFmax) within a defined rise of temperature. Lymph node aspirates and blood of 34 dogs with lymphoma and 28 control dogs were tested. 27/34 lymphoma cases were correctly detected to be monoclonal (sensitivity 79%). 2/28 control dogs showed a monoclonal rearrangement (specificity 93%). B- and T-cell neoplasia were still detectable using DNA amount as low as 10 ng. In serial dilutions of tumor DNA with DNA of normal tonsils, the detection limit was 25% for B-cell lymphomas and 100% for T-cell lymphoma, suggesting that PCR conditions could still be optimized. [ABSTRACT FROM AUTHOR]

The diagnosis of canine intestinal lymphoma by morphological examination is challenging, especially when endoscopic tissue specimens are used. The utility of detection of antigen receptor gene rearrangement by polymerase chain reaction ( PARR) in canine lymphoma has been well established, but its usefulness to distinguish enteritis and intestinal lymphoma remains unclear. In this retrospective study we assessed clonality of 29 primary canine intestinal lymphoma, 14 enteritis and 15 healthy control cases by PARR analysis, using formalin-fixed, paraffin-embedded full-thickness tissue specimens. We could detect monoclonal rearrangements in 22 of 29 canine intestinal lymphomas [76%; 95% confidence interval ( CI) 56-90%] and polyclonal rearrangements in all of the enteritis and healthy control cases (100%; CI 88-100%). We revealed a predominance of T-cell phenotype compared to B-cell phenotype (85%; CI 65-96% and 15%; CI 4-35%, respectively). We showed that PARR analysis contributes to differentiation of canine intestinal lymphoma from enteritis and to phenotyping of lymphomas. [ABSTRACT FROM AUTHOR]

Aims To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and β-cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus. Methods Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n = 42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre-hepatic β-cell function, glucose tolerance index and C-peptide secretion within the first year of diabetes diagnosis and 2 years later. Associations of changes in serum concentrations of total adiponectin, high-molecular-weight adiponectin and their ratio with changes in the aforementioned metabolic variables were calculated using linear regression. Results Among people with Type 2 diabetes, 2-year increases in high-molecular-weight adiponectin and in high-molecular-weight/total adiponectin ratio were associated with decreases in glucose tolerance index of 0.1%/min ( P = 0.020) and 0.8%/min ( P = 0.013), respectively. Increases in high-molecular-weight/total adiponectin ratio were related to decreases in acute C-peptide secretion of 54.6% ( P = 0.020). Among people with Type 1 diabetes, 2-year increases in total adiponectin were associated with 2-year decreases in acute C-peptide secretion of 56.2% ( P = 0.035). Conclusions Increases in adiponectin concentrations in the first 2 years after diagnosis were related to a worsening of acute insulin secretion and glucose tolerance index in Type 1 and Type 2 diabetes. (Clinical Trials Registry no.: NCT01055093) [ABSTRACT FROM AUTHOR]

Aims To summarize the current knowledge on the phenomenon of dogs, both trained and untrained, sensing hypoglycaemia and alerting their owners to it. Methods Electronic databases were searched for all types of articles reporting on untrained or trained 'diabetes alert' dogs. Articles published up until December 2014 in the English or German language were included. Results Several case reports and observational studies provide evidence that animals can perform at a level above that attributable to chance, and may reliably detect low diurnal as well as nocturnal hypoglycaemic episodes. Behavioural changes in untrained dogs were reported during 38-100% of hypoglycaemic events experienced by their owners. The sensitivity and specificity of the performance of trained diabetes alert dogs sensing hypoglycaemia ranged from 22 to 100% and 71 to 90%, respectively. Additionally, 75-81% of patients with diabetes who owned a trained dog reported a subsequent improvement in their quality of life. Nevertheless, the available data are limited and heterogeneous because they rely on low patient numbers and survey-based studies prone to recall bias. Conclusion Further research is needed to confirm the preliminary data on the reliability and mechanism underlying the dogs' abilities to detect hypoglycaemia, and its impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Caffeine is the most widely used neurostimulant in the world. There is considerable debate on its effect on immune cells as it has been shown to antagonize adenosine receptors (ARs), which mediate an anti-inflammatory switch in activated immune cells. A second target is phosphodiesterase, where it acts as an inhibitor. If the primary effect of caffeine on mononuclear phagocytes were to antagonize ARs we would expect cells exposed to caffeine to have a prolonged proinflammatory response. The aim of this study was to investigate the effects and mechanism of action of caffeine in mononuclear phagocytes. Human mononuclear phagocytes were separated from whole blood and pretreated with protein kinase A inhibitor (PKA) and then exposed to micromolar physiological concentrations of caffeine. Phagocytosis and phagocytosis exhaustion were quantified using flow cytometry. Treatments were analyzed and compared to controls, using a beta regression controlling for factors of age, gender, caffeine intake, and exercise. We found that caffeine suppresses phagocytosis at micromolar physiological concentrations. This suppression was prevented when mononuclear phagocytes were pretreated with PKA inhibitor, suggesting that caffeine's phagocytic suppression may be due to its function as a phosphodiesterase inhibitor, pushing cells towards an anti-inflammatory response. Additionally, these effects are altered by regular caffeine intake and fitness level, emphasizing that tolerance and immune robustness are important factors in mononuclear phagocyte activation. These results demonstrate that caffeine may be acting as a phosphodiesterase inhibitor and suppressing phagocytosis in mononuclear phagocytes by promoting an anti-inflammatory response. [ABSTRACT FROM AUTHOR]

A novel DNA-chip hybridization assay that uses the ras-related GTP-binding protein 1 gene ( Ypt1) was developed for the identification of several devastating Phytophthora species. The hybridization was conducted in a portable microfluidic lab-on-a-chip device for fast and accurate detection of 40 Phytophthora, two Pythium and one Phytopythium species. Moreover, the functionality of the Ypt1 region was examined in comparison to an array for the internal transcribed spacer ( ITS) region by in silico modelling. The difference in species-specific capture probe sequences was lower for the ITS than for the Ypt1 region. While ITS-probes of Phytophthora ramorum, Phytophthora fragariae and Phytophthora lateralis cross-reacted with up to 11 non-target species, Ypt1-probes were specific except for P. fragariae/ Phytophthora rubi. First analyses of artificially inoculated Rhododendron leaves successfully demonstrated the usability of the respective capture probes for the Ypt1 and the ras-related plant protein Rab1a gene region. The on-chip hybridization enabled the detection of up to 1 pg μL−1 target DNA depending on the species examined. Due to the complementarity of ITS and Ypt1 genetic features, the use of multiple loci is recommended to identify targets of different taxonomic rank. [ABSTRACT FROM AUTHOR]

A lean phenotype has been detected in vitamin D receptor (VDR) knockout mice; however, the gender differences in fat metabolism between male and female mice both with age and in response to a high-fat diet have not been studied before. The objective of our study was to assess changes in body and fat tissue weight, food intake and serum cholesterol and triglyceride in VDR knockout mice from weaning to adulthood and after a challenge of adult animals with a high-fat diet. Although VDR knockout mice of both sexes consumed more food than wild-type and heterozygous littermates, their body weight and the weight of fat depots was lower after 6 months on a diet with 5% crude fat content. When adult animals were challenged with a high-fat diet containing 21% crude fat content for 8 weeks, VDR knockout mice of both sexes had a significantly higher food intake but gained less weight than their wild-type littermates. Cholesterol levels were higher after 2 days on the high-fat diet in both sexes, but in the VDR knockout mice, less cholesterol was detected in the serum after 8 weeks. Wild-type male mice showed signs of fatty liver disease at the end of the experiment, which was not detected in the other groups. In conclusion, lack of the VDR receptor results in reduced fat accumulation with age and when adult mice are fed a high-fat diet, despite a higher food intake of VDR knockout mice relative to their wild-type littermates. These effects can be detected in both sexes. Wild-type male mice react with the highest weight gain and cholesterol levels of all groups and develop fatty liver disease after 8 weeks on a high-fat diet, while male VDR knockout mice appear to be protected. [ABSTRACT FROM AUTHOR]

Retraction: The article: “Justa N, Weber K, Klein D, Mueller RS, Sauter-Louis C, Hartmann K. Efficacy and adverse effects of (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine in Feline Immunodeficiency Virus-Infected Cats. Journal of Veterinary Internal Medicine 2012:26(6);1267–1273.” has been retracted from publication by the Editors in agreement with the authors and Wiley Periodicals, Inc. Retraction follows investigations by the Journal and the LMU University of Munich. The LMU investigation concluded that the allocation of cats to treatment groups was not random and that the investigators were not blinded to the nature of the treatment as indicated in the article by the authors.

Thiosemicarbazones are cruzain inhibitors which have been identified as potential antitrypanosomal agents. In this work, several molecular properties were calculated at the density functional theory (DFT)/B3LYP/6-311G* level for a set of 44 thiosemicarbazones. Unsupervised and supervised pattern recognition techniques (hierarchical cluster analysis, principal component analysis, kth-nearest neighbors, and soft independent modeling by class analogy) were used to obtain structure-activity relationship models, which are able to classify unknown compounds according to their activities. The chemometric analyses performed here revealed that 12 descriptors can be considered responsible for the discrimination between high and low activity compounds. Classification models were validated with an external test set, showing that predictive classifications were achieved with the selected variable set. The results obtained here are in good agreement with previous findings from the literature, suggesting that our models can be useful on further investigations on the molecular determinants for the antichagasic activity. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives Cross-sectional studies in bipolar disorder (BD) suggested the presence of cognitive deficits and subtle magnetic resonance imaging (MRI) changes in limbic areas that may persist at euthymic stages. Whether or not cognitive and MRI changes represent stable attributes of BD or evolve with time is still matter of debate. To address this issue, we performed a 2-year longitudinal study including detailed neuropsychological and magnetic resonance imaging (MRI) analyses of 15 euthymic older BD patients and 15 controls. Methods Neuropsychological evaluation concerned working memory, episodic memory, processing speed, and executive functions. MRI analyses included voxel-based morphometry (VBM) analysis of gray matter including region of interest (ROI) analysis and tract-based spatial statistics (TBSS) analysis of white matter of diffusion tensor imaging derived fractional anisotropy (FA). Results BD patients displayed significantly lower performances in processing speed and episodic memory but not in working memory and executive functions compared to controls. However, BD patients did not differ from controls in the mean trajectory of cognitive changes during the 2 years follow-up. In the same line, longitudinal gray matter (VBM, ROI) and white matter (TBSS FA) changes did not differ between BD patients and controls. Conclusion The lack of distinction between BD patients and controls in respect to the 2-year changes in cognition and MRI findings supports the notion that this disorder does not have a significant adverse impact on cognitive and brain aging. From this point of view, the present results convey a message of hope for patients suffering from BD. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Currently there is no drug proven to effectively treat cats with feline infectious peritonitis ( FIP). Hypothesis Propentofylline ( PPF) can decrease vasculitis, and therefore prolong survival time in cats with FIP, and increase their quality of life. Animals Twenty-three privately owned cats with FIP. Methods Placebo-controlled double-blind trial. FIP was confirmed by histology or immunostaining of feline coronavirus ( FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with either PPF or placebo. All cats received additional treatment with glucocorticoids, antibiotics, and low molecular weight heparin according to methods. Results There was no statistically significant difference in the survival time of cats treated with PPF (8 days, 95% CI 5.4-10.6) versus placebo (7.5 days, 95% CI 4.4-9.6). The median survival time of all cats was 8 days (4-36 days). There was neither a difference in quality of life (day 7, P = .892), in the amount of effusion (day 7, P = .710), the tumor necrosis factor-alpha ( TNF-α) concentration (day 7, P = .355), nor in any other variable investigated in this study, including a complete blood count, and a small animal biochemistry profile. Conclusions and Clinical Importance This study did not detect an effect of PPF on the survival time, the quality of life, or any clinical or laboratory parameter in cats with FIP. Therefore, PPF does not appear to be an effective treatment option in cats with a late stage of the disease FIP. [ABSTRACT FROM AUTHOR]

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology 37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia. [ABSTRACT FROM AUTHOR]

Resveratrol is a natural stilbene synthesised by plants. This compound has been shown to inhibit the growth of Candida albicans TIMM 1768 efficiently. Till date, no information is available for other Candida species. The evaluation of the antimicrobial activity of resveratrol was analysed by the inhibition of the growth and metabolism assays. Our data indicate that resveratrol is not effective against Candida albicans and non- C. albicans species ( C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis and C. krusei) in vitro. The potential candidacidal activity could not be confirmed. [ABSTRACT FROM AUTHOR]

Diseases caused by Candida species are an increasing problem. Candida species are associated with high overall mortality, due to a variety of virulence factors such as the yeast-to-hyphal switch and proteolytic enzymes. The phenomenon of microbial communication known as quorum sensing also seems to play an important role. The main characteristics of the quorum-sensing molecule E, E-farnesol are well known for C. albicans. The present study focused on two questions. One of them concerned the secretion of E, E-farnesol by C. albicans and involved a close examination of the effect of the medium (serum) and the origin of the isolates used. The second one dealt with the activity of E, E-farnesol in non- C. albicans species, such as C. tropicalis and C. parapsilosis, e.g. its impact on biofilm formation and growth. Under serum conditions, C. albicans produced up to 58% more E, E-farnesol at 37 °C than at 30 °C. The growth of all isolates was reduced and delayed by the administration of E, E-farnesol. Of all Candida species, C. tropicalis isolates were most strongly affected by the addition of E, E-farnesol. Biofilm formation on polystyrene was affected by E, E-farnesol treatment in all non- C. albicans species and C. albicans. E, E-farnesol exerts its main effect by altering the metabolic activity and growth inhibition of treated Candida species. The results obtained indicate that the presence of E, E-farnesol in the environment not only regulates the morphology of the Candida species but also affects its fitness. In this regard, the secretion of E, E-farnesol might provide an advantage for members of the microbial community. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In addition to the sensitization of pain fibers in inflamed tissues, the increased excitability of the spinal cord is an important mechanism of inflammatory pain. Furthermore, spinal neuronal excitability has been suggested to play a role in modulating peripheral inflammation. This study was undertaken to test the hypothesis that spinal actions of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) add significantly to both hyperalgesia and maintenance of peripheral inflammation. METHODS: Rats with antigen-induced arthritis (AIA) were treated intrathecally with the TNFalpha-neutralizing compound etanercept continuously during the complete time course of AIA, which was 3 days for the acute phase and 21 days for the chronic phase. During this time, inflammation and pain-related behavior were monitored. Since a role for autonomic control of inflammation was proposed, measures from heart rate time series were obtained in the acute phase. Findings were compared with those in vehicle-treated animals and in animals receiving etanercept intraperitoneally. RESULTS: Spinally administered etanercept acutely reduced pain-related behavior, attenuated both the development and the maintenance of inflammation, and was superior to systemic administration. Parameters indicating autonomic modulation showed a shift toward a sympathetically dominated state in vehicle-treated animals, which was prevented by intrathecal etanercept. CONCLUSION: Our findings indicate that spinal TNFalpha plays an important role in both pain signaling and modulation of peripheral inflammation. Thus, neutralizing this cytokine at the spinal site not only represents a putative therapeutic option for different pain syndromes, but may be directly used to attenuate peripheral inflammation. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant trait in cats. The A31P single nucleotide polymorphism (SNP) in the myosin binding protein C 3 gene is thought to be the causative mutation in Maine Coon cats. Additionally, the A74T SNP is offered as a genetic test for HCM. Objectives: To evaluate the genetic association between the above-mentioned SNPs and phenotypes. Animals: Eighty-three Maine Coon cats and 68 cats of other breeds. Methods: The study was performed prospectively. Cats were phenotyped as healthy or HCM with echocardiography. Taqman genotyping assays were used for genotyping; results were confirmed by sequencing analysis. Results: A31P was found in 18/83 (22%) Maine Coon cats. Fifteen of 18 Maine Coons (83%) with the A31P mutation were healthy on echocardiographic examination (mean age 65 months). A74T was present in 28/79 (35%) of Maine Coons and in 42/68 (62%) of other cat breeds. Twenty-two of 28 (79%) of Maine Coons and 21/42 (62%) of other breed cats with the A74T mutation were healthy at a mean age of 72 months and 91 months, respectively. Of 12 Maine Coons with HCM, 9 (75%) were genotype-negative for A31P and 6 (50%) for A74T. Allele frequencies did not differ significantly ( P= .47) between phenotype groups. None of the evaluated genetic tests was able to provide useful predictive information of disease outcome. Conclusions and Clinical Importance: The value of currently available genetic tests is low in the cats of this study. The mutations analyzed appear to have a low penetrance, and even homozygote cats can remain healthy. [ABSTRACT FROM AUTHOR]

Objective Total mesorectal excision (TME) as proposed by R.J. Heald more than 20 years ago, is nowadays accepted worldwide for optimal rectal cancer surgery. This technique is focused on an intact package of the tumour and its main lymphatic drainage. This concept can be translated into colon cancer surgery, as the mesorectum is only part of the mesenteric planes which cover the colon and its lymphatic drainage like envelopes. According to the concept of TME for rectal cancer, we perform a concept of complete mesocolic excision (CME) for colonic cancer. This technique aims at the separation of the mesocolic from the parietal plane and true central ligation of the supplying arteries and draining veins right at their roots. Method Prospectively obtained data from 1329 consecutive patients of our department with RO-resection of colon cancer between 1978 and 2002 were analysed. Patient data of three subdivided time periods were compared. Results By consequent application of the procedure of CME, we were able to reduce local 5-year recurrence rates in colon cancer from 6.5% in the period from 1978 to 1984 to 3.6% in 1995 to 2002. In the same period, the cancer related 5-year survival rates in patients resected for cure increased from 82.1% to 89.1%. Conclusion The technique of CME in colon cancer surgery aims at a specimen with intact layers and a maximum of lymphnode harvest. This is translated into lower local recurrence rates and better overall survival. [ABSTRACT FROM AUTHOR]

The article describes the case of a 5-month-old female domestic short hair cat that was diagnosed with Vitamin D-dependent hereditary rickets type 1. The cat was examined for a 1-month history of generalized pain. The results of the diagnostic procedures performed on the cat, such as electrocadiography are presented. The cat was treated with meloxicam and with lactose and a sodium chloride enema.

Background and purpose:Transient receptor potential (TRP) V3 is a thermosensitive ion channel expressed predominantly in the skin and neural tissues. It is activated by warmth and the monoterpene camphor and has been hypothesized to be involved in skin sensitization. A selection of monoterpenoid compounds was tested for TRPV3 activation to establish a structure-function relationship. The related channel TRPM8 is activated by cool temperatures and a number of chemicals, among them the monoterpene (-)-menthol. The overlap of the receptor pharmacology between the two channels was investigated.Experimental approach:Transfected HEK293 cells were superfused with the test substances. Evoked currents were measured in whole cell patch clamp measurements. Dose-response curves for the most potent agonists were obtained in Xenopus laevis oocytes.Key results:Six monoterpenes significantly more potent than camphor were identified: 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol and (+)-borneol. Their EC50 is up to 16 times lower than that of camphor. All of these compounds carry a ring-located hydroxyl group and neither activates TRPM8 to a major extent.Conclusions and implications:Terpenoids have long been recognized as medically and pharmacologically active compounds, although their molecular targets have only partially been identified. TRPV3 activation may be responsible for several of the described effects of terpenoids. We show here that TRPV3 is activated by a number of monoterpenes and that a secondary hydroxyl-group is a structural requirement.British Journal of Pharmacology (2007) 151, 530–540; doi:10.1038/sj.bjp.0707245; published online 10 April 2007 [ABSTRACT FROM AUTHOR]

In the present study, the aim was to select electronic properties responsible for free radical scavenging ability of a set of 25 flavonoid compounds employing chemometric methods. Electronic parameters were calculated using the AM1 semiempirical method, and chemometric methods (principal component analysis, hierarchical cluster analysis, and k-nearest neighbor) were used with the aim to build models able to find relationships between electronic features and the antioxidant activity presented by the compounds studied. According to these models, four electronic variables can be considered important to discriminate more and less antioxidant flavonoid compounds: polarizability (α), charge at carbon 3 (QC3), total charge at substituent 5 (QS5), and total charge at substituent 3′ (QS3′). The features found as being responsible for the antioxidant activity of the flavonoid compounds studied are consistent with previous results found in the literature. The results obtained can also bring improvements in the search for better antioxidant flavonoid compounds. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [ABSTRACT FROM AUTHOR]

To review the initial clinical results of photodynamic diagnosis (PDD) using hypericin (a new photosensitizer for PDD that helps to label flat urothelial tumours to facilitate biopsy) for the early detection of superficial bladder carcinoma, as flat noninvasive tumours of the bladder may be missed during conventional white-light cystoscopy (WLC) if there is bladder overdistension or ongoing cystitis. Between 1 January 2001 and 30 October 2004, 41 consecutive patients (mean age 66.1 years,sd 9.1, range 46–81) had transurethral resection for bladder cancer. Hypericin was introduced intravesically for 2 h before cystoscopy. Immediately after WLC, fluorescence cystoscopy (FC) was used at the same location and the same bladder site inspected using violet light. FC findings, e.g. positive or negative red fluorescence, were documented for each specific bladder site examined, and the exact location sampled for biopsy. The mean (sd, range) bladder capacity of the patients was 431 (86, 300–650) mL. In all, 179 biopsies were taken from the 41 patients; urothelial cancers were found in 41% (74) and 80% (33) had macroscopically visible bladder tumours; 40% (71) of the biopsies were positive under FC and 86% (61) of the 71 FC-positive biopsies showed cancer on histology. Twenty-five biopsies (14%) were positive on FC but not WLC. PDD testing with hypericin had a sensitivity of 82% (61/74) and specificity of 91% (95/105), vs WLC, at 62% (46/74) and 98% (103/105), respectively. The PDD test had a positive predictive value of 86% (61/71) and a negative predictive value of 88% (95/108), vs 96% (46/48) and 79% (103/131), respectively for WLC. There were no reports of significant complications after the procedure. PDD using hypericin shows promise, as it has a higher sensitivity but equivalent specificity than WLC. It can be used to detect flat lesions not seen on WLC. PDD testing is also well tolerated with minimal side-effects. [ABSTRACT FROM AUTHOR]

The Early Cretaceous Brandberg and Okenyenya igneous complexes provide ideal locations to quantify the postbreakup denudation history of the continental margin of central Namibia. Apatite fission track analysis has been applied to vertical sample profiles extending over 1-2 km of relief to constrain the denudation history of this region. An advantage of vertical profiles is that they allow the inference of the paleogeothermal gradient directly from the data. An independent, data-consistent thermal gradient estimate is essential to determine the amount of denudation as well as to resolve phases of slow and accelerated denudation. We obtained independent paleogeothermal gradient estimates for the two vertical profiles from 26 ± 32°C to 23 ± 16°C. The uncertainties are large but are considered pessimistic. The best fit values agree well with each other, and the present-day gradients of 22°C. The total amount of denudation since the Late Cretaceous has been estimated as 5 km in the Brandberg area and 4 km for the Okenyenya area. The data from the two vertical profiles imply a phase of rapid exhumation in the Late Cretaceous between 80 and 60 Ma, at rates between 0.2 and 0.125 km/m.y. These decline rapidly in the Early Tertiary to a maximum denudation rate between 0.023 and 0.015 km/m.y. The denudation chronology inferred from the new apatite fission track data is consistent with the observation of a major influx of clastic sediment to offshore basins about 50 m.y. after continental breakup. The study shows that vertical fission track profiles provide key insights into postbreakup tectonic and geomorphic processes in the Central Damara Zone in Namibia, where no Phanerozoic sedimentary record has been preserved. [ABSTRACT FROM AUTHOR]

Abstract Background Because there is reason to assume that also in Austria calcium and vitamin D malnutrition is wide-spread, we initiated a comprehensive study on calcium and vitamin D status in relation to bone health in a large group of the normal adult population. Subjects and methods We assessed dietary calcium and vitamin D intake, serum concentrations of Ca2+ , phosphate, alkaline phosphatase, 25(OH)D, 1,25(OH) 2 D, parathyroid hormone (PTH), follicle-stimulating hormone (FSH), sex hormones and bone mineral density (BMD) by double-energy X-ray absorptiometry at five different skeletal sites in 648 females and 400 males (age 21–76 years). Results Mean daily intake of vitamin D (101 IU, range 0·2–320) and calcium (569 mg, range 40–2170) was significantly less than the respective recommended dietary allowances. Two hundred and seventy-one (26%) individuals had hypovitaminosis D with serum 25(OH)D < 12 ng mL-1 , while serum Ca 2+ was less than normal in 82 (7·8%) subjects. Multiple regression analysis revealed significant correlations between mean calcium intake and BMD in the femoral region in the men ( r = 0·13, P < 0·05) though not in the women. No consistent data could be obtained for associations between BMD and vitamin D status, except for 25(OH)D and BMD at the spine in the men ( r = 0·10, P < 0·05). 25(OH)D correlated negatively ( P < 0·05) with age in the women ( r = -0·11) and with PTH in the women ( r = -0·11) and men ( r = -0·16). Inversely, a significant ( P < 0·001) age-related increase in PTH was observed in both sexes (men, r = 0·19; women, r = 0·14). Conclusions Prevalence of hypovitaminosis D in adult Austrians is an imminent risk for development of secondary hyperparathyroidism with advancing age, and requires timely correction of nutritional deficits. [ABSTRACT FROM AUTHOR]

Abstract Background There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database. Methods We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21–76 years, who had been recruited by 17 centres across Austria. Results Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = -0·23), total hip ( r = -0·07), trochanter ( r = -0·10), femoral neck ( r = -0·30) and Ward's triangle ( r = -0·40) in the women but only at the femoral neck ( r = -0·23) and at Ward's triangle ( r = -0·40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7·6–27·4% of the women and 16–41% of the men in our study group had low bone mass, whereas 0·6–2·7% of the female and 0·2–1·0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4–9-fold more females and 5–15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems. Conclusion Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis. [ABSTRACT FROM AUTHOR]

The Gonzaga University's behaviorally based Department of Special Education offers an undergraduate major in special education for the completion of a Bachelor of Education degree, as well as a Master of Education in Special Education. The basic behavioral, data-based model, philosophy, and courses are outlined at both the undergraduate and graduate levels. Outcome data gathered from the program's consumers indicated high levels of student and employer satisfaction with the program, the faculty, and the curricular content. The manner in which the program is viewed as compatible with state and national accrediting bodies is discussed. Copyright © 1999 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Some red clover vein mosaic virus (RCVMV) strains have exhibited two characteristics considered atypical for carlaviruses. Strains RK31 and P-42 exhibited multiple components in sucrose density gradients (Bos et al. 1972), and RNA preparation of the American Type Culture Collection (ATCC/ PV110) contained a noninfectious subgenomic 12-15S RNA in addition to the infectious 39S component (Veerisetty and Brakke 1977). We found that ATCC/PV110 exhibited particle and NA disparities and present evidence that this culture is a mixture of, at least, two strains, where one produces, in addition to long particles, short particles from which a small RNA can be isolated. [ABSTRACT FROM AUTHOR]