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Selected AbstractsExperience-dependent plasticity in hypocretin/orexin neurones: re-setting arousal thresholdACTA PHYSIOLOGICA, Issue 3 2010X.-B. Gao Abstract The neuropeptide hypocretin is synthesized exclusively in the lateral hypothalamus and participates in many brain functions critical for animal survival, particularly in the promotion and maintenance of arousal in animals , a core process in animal behaviours. Consistent with its arousal-promoting role in animals, the neurones synthesizing hypocretin receive extensive innervations encoding physiological, psychological and environmental cues and send final outputs to key arousal-promoting brain areas. The activity in hypocretin neurones fluctuates and correlates with the behavioural state of animals and intensive activity has been detected in hypocretin neurones during wakefulness, foraging for food and craving for addictive drugs. Therefore, it is likely that hypocretin neurones undergo experience-dependent changes resulting from intensive activations by stimuli encoding changes in the internal and external environments. This review summarizes the most recent evidence supporting experience-dependent plasticity in hypocretin neurones. Current data suggest that nutritional and behavioural factors lead to synaptic plasticity and re-organization of synaptic architecture in hypocretin neurones. This may be the substrate of enhanced levels of arousal resulting from behavioural changes in animals and may help to explain the mechanisms underlying the changes in arousal levels induced by physiological, psychological and environmental factors. [source] Surgical Monotherapy Versus Surgery Plus Adjuvant Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma: A Systematic Review of OutcomesDERMATOLOGIC SURGERY, Issue 4 2009ANOKHI Jambusaria-PAHLAJANI MD BACKGROUND Adjuvant radiotherapy (ART) has been recommended for squamous cell carcinoma (SCC) with a high risk of recurrence, particularly perineurally invasive disease. The utility of ART is unknown. This study compares reported outcomes of high-risk SCC treated with surgical monotherapy (SM) with those of surgery plus ART (S+ART). METHODS The Medline database was searched for reports of high-risk SCC treated with SM or S+ART that reported outcomes of interest: local recurrence, regional or distant metastasis, or disease-specific death. RESULTS There were no controlled trials. Of the 2,449 cases of high-risk SCC included, 91 were treated with S+ART. Tumor stage and surgical margin status before ART were generally unreported. In 74 cases of perineural invasion (PNI), outcomes were statistically similar between SM and S+ART. In 943 high-risk SCC cases in which clear surgical margins were explicitly documented, risks of local recurrence, regional metastasis, distant metastasis, and disease-specific death were 5%, 5%, 1%, and 1%, respectively. CONCLUSIONS High cure rates are achieved in high-risk cutaneous SCC when clear surgical margins are obtained. Current data are insufficient to identify high-risk features in which ART may be beneficial. In cases of PNI, the extent of nerve involvement appears to affect outcomes, with involvement of larger nerves imparting a worse prognosis. [source] Successful administration of aggressive chemotherapy concomitant to tuberculostatic and highly active antiretroviral therapy in a patient with AIDS-related Burkitt's lymphomaHIV MEDICINE, Issue 1 2005C Lehmann Treatment of AIDS-related malignant lymphoma (ARL) remains a therapeutic challenge. There are concerns not only about infectious and haematological complications in HIV-infected patients during intensive chemotherapy, but also about potential interactions between chemotherapy and highly active antiretroviral therapy (HAART). Current data on patients treated concomitantly with intensive chemotherapy and HAART are limited, and no data exist on patients with ARL suffering from active opportunistic infections. We report the case of a 38-year-old man with advanced HIV-1 infection, pulmonary tuberculosis and Burkitt's lymphoma. Intensive chemotherapy was administered in parallel with tuberculostatic therapy and HAART. Six months later, the patient achieved not only a complete remission of Burkitt's lymphoma and sustained viral suppression, but also a full recovery from tuberculosis. This case report provides some useful observations on the successful application of intensive chemotherapy in addition to tuberculostatic therapy and HAART in HIV-infected patients. [source] Cytomegalovirus in inflammatory bowel disease: Pathogen or innocent bystander?INFLAMMATORY BOWEL DISEASES, Issue 9 2010Garrett Lawlor MD Abstract The role of cytomegalovirus (CMV) in exacerbations of inflammatory bowel disease (IBD) remains a topic of ongoing debate. Current data are conflicting as to whether CMV worsens inflammation in those with severe colitis, or is merely a surrogate marker for severe disease. The interpretation of existing results is limited by mostly small, retrospective studies, with varying definitions of disease severity and CMV disease. CMV colitis is rare in patients with Crohn's disease or mild-moderate ulcerative colitis. In patients with severe and/or steroid-refractory ulcerative colitis, local reactivation of CMV can be detected in actively inflamed colonic tissue in about 30% of cases. Where comparisons between CMV+ and CMV, steroid-refractory patients can be made, most, but not all, studies show no difference in outcomes according to CMV status. Treatment with antiviral therapy has allowed some patients with severe colitis to avoid colectomy despite poor response to conventional IBD therapies. This article reviews the immunobiology of CMV disease, the evidence for CMV's role in disease severity, and discusses the outcomes with antiviral therapy. (Inflamm Bowel Dis 2010) [source] Profile of opportunistic infections among patients on immunosuppressive medicationINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2006Srinivas REDDY Abstract Background:, The widespread use of immunosuppressives in treating systemic autoimmune disorders has resulted in opportunistic infections (OIs) following such therapy. Current data regarding the possibility of infection due to these drugs or from the primary disease, per se, is conflicting. Objectives:, We aimed to analyse the profile of patients requiring hospitalization for OIs among those being treated with glucocorticoids and other immunosuppressive agents as part of management of systemic autoimmune disorders and to analyse the host factors in relation to OIs. Method:, In this descriptive analysis, all patients hospitalized the Postgraduate Institute of Medical Education and Research, Chandigarh, India, under medicinal units for OIs that occurred following and during treatment with corticosteroids and other immunosuppressive agents for treatment of systemic autoimmune disorders from February 2002 to January 2003, were studied. All hospitalized patients received antibiotics according to the nature of infection and sensitivity reports. All relevant clinical details were recorded in a standard pro forma. Descriptive statistics were used. The Institute Ethics Committee's permission was secured prior to study commencement. Results:, Nineteen patients (16 female) were admitted because of OIs. Their mean age (± SD) was 37.32 (± 19.9) years. Ten patients had systemic lupus erythematosus (SLE), two had SLE with overlap, five had rheumatoid arthritis, and one each had vasculitis and scleroderma with polymyositis. There were 28 infections. One (5.3%) patient had four infections, one (5.3%) had three, six (31.6%) had two, nine (47.4%) had one, and in two (10.5%) patients the infection was not localized. Of the 19 cases, 10 (52.6%) received > 10 mg of prednisolone each day (median = 1130 mg). The remaining nine (47.4%) were on < 10 mg prednisolone each day (median = 880 mg). Methylprednisolone was given to two (6.3%) patients. Bacteria accounted for most of the infections. There were two fungal infections and one patient each with tuberculosis and peritonitis. Infections occurred predominantly in the chest, urine and skin. Septicemia was diagnosed in three patients. There were two deaths, one each with SLE and rheumatoid arthritis. Conclusion:, Since infections can occur at low doses of corticosteroids, we suggest that these disorders may be, per se, responsible for an increased risk of infection. [source] Ochratoxin A impairs Nrf2-dependent gene expression in porcine kidney tubulus cellsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5 2009C. Boesch-Saadatmandi Summary The mycotoxin, ochratoxin A (OTA), which is produced by Aspergillus and Penicillium subspecies, is frequently present in feedstuffs. Ochratoxin A exhibits a wide range of toxic activities including nephrotoxicity. However, the underlying molecular mechanisms of OTA-induced cellular nephrotoxicity have yet not been fully elucidated. Nrf2 is a basic leucine zipper transcriptional activator essential for the coordinated transcriptional induction of antioxidant and xenobiotic metabolizing enzymes in the kidney. Therefore, in the present study, the effects of OTA on the nuclear translocation and transactivation of the transcription factor Nrf2 as well as mRNA levels of Nrf2 target genes including glutathione- S -transferase and ,-glutamylcysteinyl synthetase have been studied in cultured porcine kidney tubulus cells (LLC-PK1). Nrf2 was induced by sulforaphane, a well-known activator of this transcription factor. Ochratoxin A significantly decreased ,-glutamylcysteinyl synthetase and glutathione- S -transferase mRNA levels in LLC-PK1 cells. Decreased mRNA levels of ,-glutamylcysteinyl synthetase and glutathione- S -transferase were accompanied by a lowered nuclear translocation and transactivation of Nrf2. Furthermore, OTA also lowered Nrf2 mRNA levels. Current data indicate that OTA nephrotoxicity may be, at least partly, mediated by an Nrf2-dependent signal transduction pathway. [source] Diagnostic issues for adolescents and adults with ADHDJOURNAL OF CLINICAL PSYCHOLOGY, Issue 5 2005Jeanette WassersteinArticle first published online: 18 FEB 200 Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric syndrome once thought to disappear with maturation. Current data indicate that ADHD remains "hidden" in many of the grownups who had it as children. Adult prevalence rates range from 1% to 6% of the population. Research suggests the core childhood symptoms of hyperactivity, inattention, and impulsivity shift with development, perhaps transforming into more overt difficulties in executive functions and affect regulation. ADHD is also usually nestled with other comorbid psychiatric conditions, especially in adolescents and adults, further complicating diagnosis and treatment. This article discusses how to recognize and diagnose ADHD in older patients. Key points include core symptoms present during childhood, appropriate family history in this strongly genetic condition, management of comorbidity, and the evolving role of diagnostic testing. Other medical causes for similar symptoms are considered. © 2005 Wiley Periodicals, Inc. J Clin Psychol/In Session 61: 535,547, 2005. [source] Life history and ecology of seahorses: implications for conservation and managementJOURNAL OF FISH BIOLOGY, Issue 1 2004S. J. Foster We present the first synthesis of the life history and ecology of seahorses, compare relationships for seahorses with other marine teleosts and identify research needs. Seahorses occurred primarily amidst temperate seagrasses and tropical coral reefs. Population densities were generally low, ranging from 0 to 0·51 individuals m,2, but reached 10 m,2 in some patches. Inferred life spans ranged from 1 to 5 years. Seahorses consumed live prey and possibly changed diet as they grew. Growth rates are poorly investigated to date. Reproduction and mating systems are the best-studied aspects of seahorse ecology. The relationship between size at first maturity and maximum size in seahorses conformed to that for other marine teleosts. All seahorse species were monogamous within a cycle, but some were polygamous across cycles. Direct transfer of clutches to the brood pouch of the male fish made it difficult to measure clutch size in live seahorses. After brooding, males released from c. 5 to 2000 young, depending on species and adult size. Newborn young measured from 2 to 20 mm in length, which was a narrower size range than the 17-fold difference that occurred in adult size. Newborn body size had no relationship to adult size. Both eggs and young were larger than expected among marine teleosts, even when considering only those with parental care, but brood size at release was lower than expected, perhaps because the young were more developed. The size of adults, eggs and young increased with increasing latitude, although brood size did not. Considerable research is needed to advance seahorse conservation and management, including (a) fisheries-dependent and fisheries-independent abundance estimates, (b) age- or stage-based natural and fishing mortalities, (c) growth rates and age at first maturity, and (d) intrinsic rates of increase and age- or size-specific reproductive output. Current data confirm that seahorses are likely to be vulnerable to high levels of exploitation. [source] Developmental roles for Homer: more than just a pretty scaffoldJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Lisa Foa Abstract Homer proteins are best known as scaffold proteins at the post-synaptic density where they facilitate synaptic signalling and are thought to be required for learning and memory. Evidence implicating Homer proteins in the development of the nervous system is also steadily accumulating. Homer is highly conserved and is expressed at key developmental time points in the nervous system of several species. Homer regulates intracellular calcium homeostasis, clustering and trafficking of receptors and proteins at the cytosolic surface of the plasma membrane, transcription and translation, and cytoskeletal organization. Each of these functions has obvious potential to regulate neuronal development, and indeed Homer is implicated in several pathologies associated with the developing nervous system. Current data justify more critical experimental approaches to the role of Homer in the developing nervous system and related neurological disorders. [source] A Review of the Clinical Efficacy and Safety of Cruciferous Vegetable PhytochemicalsNUTRITION REVIEWS, Issue 6 2007Deanna M. Minich PhD Supplementation with the crucifer-derived phytochemicals indole-3-carbinol (I3C) and 3,3, -diindolylmethane (DIM) has been an area of active interest due to their role in estrogen metabolism. This review addresses the debate about which cruciferous compound to use clinically by evaluating their efficacy and safety. Significantly more clinical trials are available for I3C than for DIM. I3C leads to beneficial shifts in hormone markers, and limited evidence suggests that DIM may result in a similar effect. More research in humans is needed to further address whether DIM poses any safety risk. Current data do not suggest that DIM provides enhanced clinical benefits over I3C. [source] Nonfatal work-related motor vehicle injuries treated in emergency departments in the United States, 1998,2002AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 9 2009Guang X. Chen MD Abstract Background Current data on nonfatal work-related motor vehicle injuries are limited and fragmented, often excluding government workers, self-employed workers, and workers on small farms. This study seeks to bridge the present data gap by providing a national profile of nonfatal work-related motor vehicle injuries across all industries and occupations. Methods Study subjects were people who suffered nonfatal work-related motor vehicle injuries and were treated in a hospital emergency department in the United States. Subjects were identified from a stratified probability sample of emergency departments. National estimates and rates were computed. Results From 1998 to 2002, the average annual rate of nonfatal work-related motor vehicle injuries was 7 injuries per 10,000 full-time equivalents. The rate was three times higher in men than in women. The rates were higher in workers 15,19 years of age and in workers 70 years or older. Justice, public order, and safety workers had the largest number of injuries, and taxicab service employees had the highest injury rate of all industries. Truck drivers had the largest number of injuries, and police and detectives, public service employees had the highest injury rate of all occupations. Conclusion Future efforts need to develop and enhance the use of surveillance information at the federal and state level for work-related nonfatal motor vehicle injuries. Prevention efforts need to address occupational motor vehicle safety for both commercial truck/bus drivers and workers who are not commercial drivers but who drive light motor vehicles on the job. Am. J. Ind. Med. 52:698,706, 2009. © 2009 Wiley-Liss, Inc. [source] The urinary proteome in diabetes and diabetes-associated complications: New ways to assess disease progression and evaluate therapyPROTEOMICS - CLINICAL APPLICATIONS, Issue 7-8 2008Kasper Rossing Abstract Diabetes represents one of the main chronic diseases worldwide. Diabetes and its associated complications may be detectable even at early stages in the urinary proteome. In this article we review the current literature on urinary proteomics applied to the study of diabetes and diabetic complications. Further, we present recent data that strongly indicate urinary proteome analysis may be a valuable tool in detecting diabetes-associated pathophysiological changes at an early stage, and also may enable assessment of disease progression and efficacy of therapy. Current data indicate that collagen-derived peptides represent one of the main peptidic components in urine, which are consistently found at reduced levels in diabetes. It is tempting to speculate that this decrease in urinary collagen-derived peptides is related to an increase in extracellular matrix deposition which is a major complication in diabetes. Therefore, urinary proteome analysis might enable noninvasive assessment of this process at an early stage via determination of specific collagen fragments. This may open an avenue towards targeted therapeutic intervention. [source] Fibromatosis of the Breast: Case Report and Current Concepts in the Management of an Uncommon LesionTHE BREAST JOURNAL, Issue 1 2006Graham S. Schwarz MD Abstract: Fibromatosis is an uncommon breast lesion that can mimic breast carcinoma in its clinical presentation. We present a case in which excisional biopsy was necessary to establish a diagnosis of fibromatosis. Clinical, diagnostic imaging, and pathologic features are discussed. Magnetic resonance imaging (MRI) has emerged as a tool for further characterization of breast lesions and as a screening modality in high-risk patient populations. Ours marks the second case in which dynamic MRI has been correlated with histologically confirmed primary mammary fibromatosis. Unlike the previous report, MRI in this case mimics breast carcinoma in its morphologic and pharmacokinetic features of enhancement. Wide local excision with clear margins remains the treatment of choice. Current data on radiotherapy and pharmacologic therapy for mammary fibromatosis are reviewed., [source] Protein Targeting into Secondary Plastids,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 1 2009KATHRIN BOLTE ABSTRACT. Most of the coding capacity of primary plastids is reserved for expressing some central components of the photosynthesis machinery and the translation apparatus. Thus, for the bulk of biochemical and cell biological reactions performed within the primary plastids, many nucleus-encoded components have to be transported posttranslationally into the organelle. The same is true for plastids surrounded by more than two membranes, where additional cellular compartments have to be supplied with nucleus-encoded proteins, leading to a corresponding increase in complexity of topogenic signals, transport and sorting machineries. In this review, we summarize recent progress in elucidating protein transport across up to five plastid membranes in plastids evolved in secondary endosymbiosis. Current data indicate that the mechanisms for protein transport across multiple membranes have evolved by altering pre-existing ones to new requirements in secondary plastids. [source] REVIEW ARTICLE: Tolerance Mechanisms in Pregnancy: A Reappraisal of the Role of Class I Paternal MHC Antigens,AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010David A. Clark Citation Clark DA, Chaouat G, Wong K, Gorczynski RM, Kinsky R. Tolerance mechanisms in pregnancy: a reappraisal of the role of class I paternal MHC antigens. Am J Reprod Immunol 2010; 63: 93,103 Problem, Allogeneic pregnancies have a survival advantage over syngeneic pregnancies, and paternal Class I MHC antigens have been implicated. In humans, HLA-C and HLA-G and E are expressed by subpopulations of fetal trophoblast. In mice, Qa-2, a Class Ib antigen, and classical H-2K antigens have been described. However, the mechanism of prevention of embryo demise in utero has not been critically assessed, and a number of conflicting ideas have not been addressed. The ,, T-cell receptor recognizes peptide bound to the groove in Class I MHC, and peptides have profound effects on the interaction of KIR receptors on T and NK cells with Class I MHC. Methods, Data on prevention of pregnancy loss (abortion) in poly IC-treated mice were reviewed along with information about prevention of losses in the abortion-prone CBA × DBA/2 model. This information was combined with data on paternal antigen expression at different times in pregnancy when key events determining outcome are thought to transpire, and role of tolerance signaling molecules such as CD200. Current data on models supporting a role for ,true' uterine NK cells (TuNKs) versus blood NK cells in the uterus (BuNKs) and role of MHC,KIR interaction were reviewed along with incompatible data in the literature. Results, Whilst paternal Class I MHC appears important, there is an important role for paternal non-MHC minor antigens (small peptides) that bind to the antigen-presenting groove of Class I MHC. BuNKs along with CD8+ T cells and Treg cells appear more important than TuNKs where the role of the latter appears primarily to promote angiogenesis. When during pregnancy the maternal immune system cells are first exposed to paternal Class I + peptide is uncertain, but at the time of implantation, if not earlier, seems likely. Conclusion, Suppression of pregnancy loss by paternal/embryo Class I MHC depends on the presence of paternal peptides. This greatly complicates existing models of Class I,KIR interactions in feto-maternal tolerance or rejection. It is important to consider all the data when devising explanatory models. [source] IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathwaysAPMIS, Issue 8 2009ANNA MISIAK-T, OCZEK Misiak-T,oczek A, Brzezi,ska-B,aszczyk E. IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: Involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathways. APMIS 2009; 117: 558,67. An increase in the number of mast cells within tissues is observed in many pathophysiological conditions. Current data indicate that migration of mature mast cells might be one of the key mechanisms responsible for rapid local accumulation of these cells. Considering that interleukin (IL)-6 and IL-4, as well as tumour necrosis factor (TNF), influence mast cell activity in various ways, the purpose of the current study was to examine whether these cytokines function as rat peritoneal mast cell chemoattractants. We showed that IL-4, in the concentration range from 10,6 to 10,3 ng/ml, did not induce a mast cell migratory response, even in the presence of laminin and fibronectin. Under the same experimental conditions, mast cells were shown to migrate in response to IL-6 stimulation in the presence of laminin. The optimal concentration of IL-6 for maximal migration of mast cells was 10,4 ng/ml (i.e. ,5 nM). In comparison, the optimal concentration of TNF for maximal migration of mast cells was 5 × 10,5 ng/ml (i.e. ,3 fM). IL-6-stimulated mast cell migration was the result of chemokinesis, whereas TNF-induced migration was the result of chemotaxis. Mast cell migratory responses to IL-6 and TNF were entirely blocked by specific anti-IL-6R and anti-TNFR1 antibodies. We also documented that the migration response of mast cells to stimulation with IL-6 and TNF was mediated through signal transduction pathways involving mitogen-activated protein kinases and phosphatidylinositol 3-kinase. Taken together, our results indicate that IL-6, as well as TNF, induces tissue mast cell migration. Thus, these proinflammatory cytokines can be responsible for mast cell accumulation at the site of diverse conditions accompanied by inflammation. [source] The physiological role of hormones in salivaBIOESSAYS, Issue 8 2009Michael Gröschl Abstract The assessment of hormones in saliva has gained wide acceptance in clinical endocrinology. To date, there is no hypothesis as to why some hormones can be found in saliva, while others cannot, and whether there is a physiological consequence of this fact. A number of carefully performed studies give examples of important physiological hormonal activity in saliva. Steroids, such as androgens, act as pheromones in olfactory communication of various mammalian species, such as facilitating mating behavior in swine or serving as odor cues for rodent nestlings. Salivary peptide hormones, such as epidermal growth factor (EGF) and transforming growth factor-, (TGF-,), and amines such as melatonin, are involved in the regulation of inflammatory processes and in the promotion of cell proliferation, and contribute to a rapid wound healing in the oropharyngeal epithelia. Current data provide evidence of the involvement of salivary cytokines, such as interleukin-8 and leptin, in tumorgenesis in the oral cavity and the salivary glands. The tumor tissues express and release significantly more of these cytokines than healthy glands. Consequently, the assessment of salivary hormone profiles may provide promising targets for diagnostic tumor markers. [source] Reference-Free Damage Classification Based on Cluster AnalysisCOMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 5 2008Hoon Sohn The ultimate goal of this study was to develop an in-site non-destructive testing (NDT) technique that can continuously and autonomously inspect the bonding condition between a carbon FRP (CFRP) layer and a host reinforced concrete (RC) structure, when the CRFP layer is used for strengthening the RC structure. The uniqueness of this reference-free NDT is two-fold: First, features, which are sensitive to CFRP debonding but insensitive to operational and environmental variations of the structure, have been extracted only from current data without direct comparison with previously obtained baseline data. Second, damage classification is performed instantaneously without relying on predetermined decision boundaries. The extraction of the reference-free features is accomplished based on the concept of time reversal acoustics, and the instantaneous decision-making is achieved using cluster analysis. Monotonic and fatigue load tests of large-scale CFRP-strengthened RC beams are conducted to demonstrate the potential of the proposed reference-free debonding monitoring technique. Based on the experimental studies, it has been shown that the proposed reference-free NDT technique may minimize false alarms of debonding and unnecessary data interpretation by end users. [source] REVIEW: The phosphate regulating hormone fibroblast growth factor-23ACTA PHYSIOLOGICA, Issue 2 2010R. Marsell Abstract Over the last decade, the regulation of phosphate (Pi) homeostasis has been under intense investigation. By utilizing modern biochemical and genetic tools, the pathophysiological mechanisms behind several known hereditary and acquired hypo- and hyperphosphatemic diseases have been clarified. The results of these efforts have opened new insights into the causes of Pi dysregulation and hereby also the physiological mechanisms determining Pi homeostasis. Although several potential Pi-regulating proteins have been discovered and investigated, current data strongly argues for fibroblast growth factor-23 (FGF23), a hormonal factor produced in bone, as a particularly important regulator of Pi homeostasis. In this article, we review the discovery of the FGF23 protein, as well as its biochemistry, localization of production, receptor specificity and mechanisms of action. [source] Arm and leg substrate utilization and muscle adaptation after prolonged low-intensity trainingACTA PHYSIOLOGICA, Issue 4 2010J. W. Helge Abstract This review will focus on current data where substrate metabolism in arm and leg muscle is investigated and discuss the presence of higher carbohydrate oxidation and lactate release observed during arm compared with leg exercise. Furthermore, a basis for a possible difference in substrate partitioning between endogenous and exogenous substrate during arm and leg exercise will be debated. Moreover the review will probe if differences between arm and leg muscle are merely a result of different training status rather than a qualitative difference in limb substrate regulation. Along this line the review will address the available studies on low-intensity training performed separately with arm or legs or as whole-body training to evaluate if this leads to different adaptations in arm and leg muscle resulting in different substrate utilization patterns during separate arm or leg exercise at comparable workloads. Finally, the influence and capacity of low-intensity training to influence metabolic fitness in the face of a limited effect on aerobic fitness will be challenged. [source] The Use of B-Type Natriuretic Peptides in the Intensive Care UnitCONGESTIVE HEART FAILURE, Issue 2008Christian Mueller MD B-type natriuretic peptide levels are quantitative markers of cardiac stress and heart failure that summarize the extent of systolic and diastolic left ventricular dysfunction, valvular dysfunction, and right ventricular dysfunction. Initial observational pilot studies have addressed 7 potential indications in the intensive care unit: identification of cardiac dysfunction, diagnosis of hypoxic respiratory failure, risk stratification in severe sepsis and septic shock, evaluation of patients with shock, estimation of invasive measurements, weaning from mechanical ventilation, as well as perioperative and postoperative risk prediction. Although additional studies are required to better define the clinical utility of B-type natriuretic peptide values in the intensive care unit, current data suggest that the diagnosis of hypoxic respiratory failure and timing of extubation seem to be the most promising indications. Congest Heart Fail. 2008;14(4 suppl 1):43,45. ©2008 Le Jacq [source] UNITED STATES V. BOOKER AS A NATURAL EXPERIMENT: USING EMPIRICAL RESEARCH TO INFORM THE FEDERAL SENTENCING POLICY DEBATE,CRIMINOLOGY AND PUBLIC POLICY, Issue 3 2007PAUL J. HOFER Research Summary: In United States v. Booker, the U.S. Supreme Court held that the federal sentencing guidelines must be considered advisory, rather than mandatory, if they are to remain constitutional under the Sixth Amendment. Since the decision, the U.S. Sentencing Commission has provided policy makers with accurate and current data on changes and continuity in federal sentencing practices. Unlike previous changes in legal doctrine, Booker immediately increased the rates of upward and downward departures from the guideline range. Government-sponsored downward departures remain the leading category of outside,the-range sentences. The rate of within-range sentences, although lower than in the period immediately preceding Booker, remains near rates observed earlier in the guidelines era. Despite the increase in departures, average sentence lengths for the overall caseload remain stable, because of offsetting increases in the seriousness of the crimes being sentenced and in the severity of penalties for those crimes. Analyses of the reasons that judges reported for downward departures suggest that treatment of criminal history and offender characteristics are the two leading areas of dissatisfaction with the guidelines. Policy Implications: Assessment of changes in sentencing practices following Booker by different observers depends partly on competing institutional perspectives and on different degrees of trust in the judgment of judges, prosecutors, the Sentencing Commission, and Congress. No agreement on whether Booker has bettered or worsened the system can be achieved until agreement exists on priorities among the purposes of sentencing and the goals of sentencing reform. Both this lack of agreement and an absence of needed data make consensus on Booker's effects on important sentencing goals, such as reduction of unwarranted disparity, unlikely in the near future. Similarly, lack of baseline data before Booker on the effectiveness of federal sentencing at crime control makes before-after comparisons impossible. Despite these limitations, research provides a sounder framework for policy making than do anecdotes or speculation and sets valuable empirical parameters for the federal sentencing policy debate. [source] No Smoking Gun: Findings From a National Survey of Office-Based Cosmetic Surgery Adverse Event ReportingDERMATOLOGIC SURGERY, Issue 11 2003Rajesh Balkrishnan PhD Background. Because of recent press reports of adverse outcomes, office-based cosmetic surgery has come under intense scrutiny and associated legislative regulatory action. Objective. To assess the safety of office-based cosmetic surgery through a national survey of state agencies that collect information on adverse patient outcomes. Methods. Medical boards or other responsible authorities were contacted in 48 states to obtain records on adverse outcomes from cosmetic surgery procedures performed in an office-based setting. Results. Five states were able to provide complete information regarding 13 cases of adverse outcomes that resulted from office-based cosmetic surgery procedures. Thirteen states had incomplete information or were unable to provide information. The remaining states reported no adverse outcomes. Information collected by state agencies varies greatly and is inadequate to define the safety of office-based cosmetic surgery practice. Conclusions. The need to regulate physician office surgery on the basis of hospital privileges and office certification is not supported by current data. Mandatory reporting of adverse outcomes from office-based surgery is warranted to identify modifiable risk factors and to reduce the risk of adverse outcomes. [source] Schizophrenia treatment: content versus deliveryACTA PSYCHIATRICA SCANDINAVICA, Issue 2009J. Van Os Objective:, To review the evidence supporting the importance of ensuring that patients with psychiatric disorders receive an optimal and appropriate level of non-pharmacological treatment, and how Assertive Community Treatment (ACT) may be able to contribute to this aim. Method:, Analysis of data from selected individual published studies on ACT, in addition to reviews from the Cochrane Library, and other study groups. Results:, Treatment management using ACT appears to offer benefits in terms of reduction in hospitalisation, although there is some debate as to whether this is the most representative outcome measure. Preliminary indications using remission as an outcome measure have also shown promising results in favour of ACT. Conclusion:, While further investigation and validation are necessary, current data indicate that ACT may be an appropriate strategy to facilitate the delivery of treatment to patients with psychotic disorders. [source] Fitness and body size in mature odonatesECOLOGICAL ENTOMOLOGY, Issue 2 2000Natalia Sokolovska Summary The relationship between body size and fitness components in odonates was examined using a meta-analysis of 33 published studies. There was a positive and significant overall effect of body size on mating rate and lifetime mating success among males. There was also a weaker but still significant positive effect of body size on survivorship of males. The relationship between body size, mating rate, longevity, and lifetime mating success differed significantly between males of territorial and nonterritorial species. The effect of body size was significant for all fitness components in territorial species but significant only for longevity and lifetime mating success in nonterritorial species. Effect sizes appeared to be strongest on longevity in both sexes, and on male mating rate in territorial species. Other effect sizes, even when significant, were small. Despite a much smaller data set, female fitness also increased significantly with body size. Both clutch size and longevity showed a significant positive relationship with body size. These results suggest that there is a general fitness benefit to large size in odonates. Nevertheless, significant heterogeneity is apparent in this effect, which can be attributed to sex, mating system, and fitness component. Finally, these analyses point to inadequacies in the current data that need further study before the potentially rich patterns in size effects on fitness can be explored more thoroughly. [source] Angiopoietin/tie-2 as mediators of angiogenesis: a role in congestive heart failure?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2004A. Y. Chong Abstract Angiogenic factors, in particular vascular endothelial growth factor (VEGF) and the angiopoietins, Ang-1 and -2, have recently generated significant interest, especially in oncology. The process of angiogenesis is also thought to occur in response to ischaemic conditions, which lie at the core of cardiovascular disease states such as coronary artery disease and congestive heart failure. However, current data do not conclusively show evidence of angiogenesis per se in these conditions, despite (for example) the presence of high levels of VEGF and Ang-2. High levels of these angiogenic factors in heart disease also have not translated into clinically significant new vessel formation, as in accelerated cancer growth or proliferative retinopathy. Indeed, we would hypothesize that these angiogenic markers , especially the angiopoietins , do not necessarily translate into new vessel formation in congestive heart failure (CHF), but may well reflect disturbances of endothelial integrity in CHF. [source] Molecular imaging in hereditary forms of parkinsonismEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2007M. C. Shih The development of in vivo molecular imaging to evaluate the dopamine (DA) system with positron-emission tomography and single photon emission computed tomography has been of key importance on monitoring in vivo nigrostriatal neuronal loss in Parkinson's disease (PD), mostly through assessments of pre- and post-synaptic DA receptors. The discoveries of genes related to hereditary forms of parkinsonism (PARK1, PARK2, PARK6, PARK7 and PARK8) have increased our understanding either of distinct subtypes of clinical expression in PD or its etiology. This article revises current data on molecular neuroimaging of genetic forms of parkinsonism comparing and contrasting its main features with the classical sporadic forms. Awareness of the spectrum variance in the genotype and its respective PD phenotype are useful to distinguish different pathophysiological mechanisms of PD. [source] Creutzfeldt,Jakob disease risk and PRNP codon 129 polymorphism: necessity to revalue current dataEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2005E. Mitrová The polymorphism at codon 129 (M129V) of the prion protein gene (PRNP) is a recognized genetic marker for susceptibility to Creutzfeldt,Jakob disease (CJD) in the Caucasians. The distribution of this polymorphism in healthy individuals provides an important starting point for the evaluation of CJD risk in the general population. Early studies of reference population cohorts demonstrated that methionine/valine heterozygosity was the most frequent genotype. These studies were performed in relatively small numbers of control subjects and do not correspond with the findings of more recent investigations. In this study, we present an analysis of the codon M129V distribution in 613 corneal donors, representing one of the largest control groups examined to date. Methionine homozygotes represented 48.1%, valine homozygotes 8.7% and methionine/valine heterozygotes 43.2%. While age-related difference was not significant, differentiation according to the gender showed significant difference. The observed highest proportion of methionine homozygotes and statistically significant difference between genders as well as comparison with results obtained in other countries underline the need to re-evaluate the generally used reference data on M129V, including consideration of the gender, age and geographical distribution. [source] Deep brain stimulation mechanisms: beyond the concept of local functional inhibitionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Jean-Michel Deniau Abstract Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. [source] Potential clinical relevance of the ,little brain' on the mammalian heartEXPERIMENTAL PHYSIOLOGY, Issue 2 2008J. A. Armour It is hypothetized that the heart possesses a nervous system intrinsic to it that represents the final relay station for the co-ordination of regional cardiac indices. This ,little brain' on the heart is comprised of spatially distributed sensory (afferent), interconnecting (local circuit) and motor (adrenergic and cholinergic efferent) neurones that communicate with others in intrathoracic extracardiac ganglia, all under the tonic influence of central neuronal command and circulating catecholamines. Neurones residing from the level of the heart to the insular cortex form temporally dependent reflexes that control overlapping, spatially determined cardiac indices. The emergent properties that most of its components display depend primarily on sensory transduction of the cardiovascular milieu. It is further hypothesized that the stochastic nature of such neuronal interactions represents a stabilizing feature that matches cardiac output to normal corporal blood flow demands. Thus, with regard to cardiac disease states, one must consider not only cardiac myocyte dysfunction but also the fact that components within this neuroaxis may interact abnormally to alter myocyte function. This review emphasizes the stochastic behaviour displayed by most peripheral cardiac neurones, which appears to be a consequence of their predominant cardiac chemosensory inputs, as well as their complex functional interconnectivity. Despite our limited understanding of the whole, current data indicate that the emergent properties displayed by most neurones comprising the cardiac neuroaxis will have to be taken into consideration when contemplating the targeting of its individual components if predictable, long-term therapeutic benefits are to accrue. 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