Episodic fevers and vasodilatory shock mimicking urosepsis in a patient with HIV-associated multicentric Castleman’s Disease: a case report

Background: Multicentric Castleman's disease (MCD) is a pre-malignancy that presents with lymphadenopathy and features of systemic inflammation. Human immunodeficiency virus (HIV)-associated MCD is associated with human herpesvirus-8 (HHV-8) infection. If untreated MCD has a relapsing and remitting course that is eventually fatal. Case presentation: A 67-year-old man had six hospital admissions over 20 months characterised by fever, urinary frequency and CRP >100 mg/L. The final admission was complicated by hypotension requiring intensive care unit admission and ionotropic support. His history included HIV and Hepatitis B virus (HBV) co-infection on suppressive therapy. Each presentation was managed as presumed urosepsis with use of empirical antibiotics, however numerous blood and urine cultures failed to identify a pathogen. A bone-marrow aspirate and trephine found no evidence of haematological malignancy. A positron emission tomography scan found active lymph nodes, one of which was biopsied and found to contain the plasma-cell variant of Castleman's disease. Ultimately the cause for the recurrent presentations was attributed to progressive MCD. The patient received rituximab monotherapy and has had no further related admissions. Conclusions: MCD should be considered in patients with chronic HIV infection presenting with recurrent sepsis-like episodes and/or vasodilatory shock, particularly if no pathogen is identified or lymphadenopathy is evident

Cost-effectiveness of the implantable cardioverter-defibrillator: Effect of improved battery life and comparison with amiodarone therapy

AbstractThe implantable cardioverter-defibrillator (ICD) greatly reduces the incidence of sudden cardiac death among patients with recurrent sustained ventricular tachycardia and fibrillation who do not respond to conventional antiarrhythmic therapy. A cost-effectiveness analysis was performed, comparing the ICD, amiodarone and conventional agents. Actual variable costs of hospitalization and follow-up care were used for 21 ICD- and 43 amiodarone-treated patients. Life expectancy and total variable costs were predicted with use of a Markov decision analytic model. Clinical event rates and probabilities were based on published reports or expert opinion.Life expectancy with an ICD (6.1 years) was 50% greater than that associated with treatment with amiodarone (3.9 years) and 2.5 times that associated with conventional treatment (2.5 years). Assuming replacement every 24 months, ICD lifetime treatment costs (in 1989 dollars) for a 55-year old patient are expected to be $89,600 compared with$24,800 for amiodarone and $16,100 for conventional therapy, yielding a marginal cost/effectiveness ratio for ICD versus amiodarone therapy of$29,200/year of life saved, which is comparable to that of other accepted medical treatments. If technologic improvements extend average battery life to 36 months, the marginal cost/effectiveness ratio would be $21,880/ year of life saved, and at 96 months it would be$13,800/year of life saved. Patient age at implantation did not significantly affect these results.If quality of life on amiodarone therapy is 30% lower than that with the ICD, the marginal cost/effectiveness ratio decreases by 35%. If the quality of life for patients receiving drugs is 40% lower than that of patients treated with an ICD, use of the defibrillator becomes the dominant strategy

Using exomarkers to assess mitochondrial reactive species in vivo

Background: The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. Scope of review: One approach towards achieving this goal is the use of exomarkers. In this, exogenous probe compounds are administered to the intact organism and are then transformed by the reactive molecules in vivo to produce a diagnostic exomarker. The exomarker and the precursor probe can be analysed ex vivo to infer the identity and amounts of the reactive species present in vivo. This is akin to the measurement of biomarkers produced by the interaction of reactive species with endogenous biomolecules. Major conclusions and general significance: Our laboratories have developed mitochondria-targeted probes that generate exomarkers that can be analysed ex vivo by mass spectrometry to assess levels of reactive species within mitochondria in vivo. We have used one of these compounds, MitoB, to infer the levels of mitochondrial hydrogen peroxide within flies and mice. Here we describe the development of MitoB and expand on this example to discuss how better probes and exomarkers can be developed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Abbreviations: EPR, electron paramagnetic resonance; GFP, green fluorescent protein; 4-HNE, 4-hydroxynonenal; MitoB, 3-(dihydroxyboronyl)benzyltriphenylphosphonium bromide; MitoP, (3-hydroxybenzyl)triphenylphosphonium bromide; ROS, reactive oxygen species; SOD, superoxide dismutase; TPMP, methyltriphenylphosphonium; TPP, triphenylphosphonium catio

Evidence for the protein leverage hypothesis in preschool children prone to obesity.

BACKGROUND & AIMS The protein leverage hypothesis (PLH) proposed that strict regulation of protein intake drives energy overconsumption and obesity when diets are diluted by fat and/or carbohydrates. Evidence about the PLH has been found in adults, while studies in children are limited. Thus, we aimed to test the PLH by assessing the role of dietary protein on macronutrients, energy intake, and obesity risk using data from preschool children followed for 1.3 years. METHODS 553 preschool children aged 2-6 years from the 'Healthy Start' project were included. EXPOSURES The proportion of energy intake from protein, fat, and carbohydrates collected from a 4-day dietary record. OUTCOMES Energy intake, BMI z-score, fat mass (FM) %, waist- (WHtR) and hip-height ratio (HHtR). Power function analysis was used to test the leverage of protein on energy intake. Mixture models were used to explore interactive associations of macronutrient composition on all these outcomes, with results visualized as response surfaces on the nutritional geometry. RESULTS Evidence for the PLH was confirmed in preschool children. The distribution of protein intake (% of MJ, IQR: 3.2) varied substantially less than for carbohydrate (IQR: 5.7) or fat (IQR: 6.3) intakes, suggesting protein intake is most tightly regulated. Absolute energy intake varied inversely with dietary percentage energy from protein (L = -0.14, 95% CI: -0.25, -0.04). Compared to children with high fat or carbohydrate intakes, children with high dietary protein intake (>20% of MJ) had a greater decrease in WHtR and HHtR over the 1.3-year follow-up, offering evidence for the PLH in prospective analysis. But no association was observed between macronutrient distribution and changes in BMI z-score or FM%. CONCLUSIONS In this study in preschool children, protein intake was the most tightly regulated macronutrient, and energy intake was an inverse function of dietary protein concentration, indicating the evidence for protein leverage. Increases in WHtR and HHtR were principally associated with the dietary protein dilution, supporting the PLH. These findings highlight the importance of protein in children's diets, which seems to have significant implications for childhood obesity risk and overall health

Infrared Nonlinear Optics

Contains report on one research project.U.S. Air Force - Office of Scientific Research (Contract F49620-84-C-0010

Association of Changes in Neighborhood-Level Racial Residential Segregation With Changes in Blood Pressure Among Black Adults: The CARDIA Study

Importance: Despite cross-sectional evidence linking racial residential segregation to hypertension prevalence among non-Hispanic blacks, it remains unclear how changes in exposure to neighborhood segregation may be associated with changes in blood pressure. Objective: To examine the association of changes in neighborhood-level racial residential segregation with changes in systolic and diastolic blood pressure over a 25-year period. Design, Setting, and Participants: This observational study examined longitudinal data of 2280 black participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective investigation of adults aged 18 to 30 years who underwent baseline examinations in field centers in 4 US locations from March 25, 1985, to June 7, 1986, and then were re-examined for the next 25 years. Racial residential segregation was assessed using the Getis-Ord Gi* statistic, a measure of SD between the neighborhood\u27s racial composition (ie, percentage of black residents) and the surrounding area\u27s racial composition. Segregation was categorized as high (Gi* \u3e 1.96), medium (Gi* 0-1.96), and low (Gi* \u3c 0). Fixed-effects linear regression modeling was used to estimate the associations of within-person change in exposure to segregation and within-person change in blood pressure while tightly controlling for time-invariant confounders. Data analyses were performed between August 4, 2016, and February 9, 2017. Main Outcomes and Measures: Within-person changes in systolic and diastolic blood pressure across 6 examinations over 25 years. Results: Of the 2280 participants at baseline, 974 (42.7%) were men and 1306 (57.3%) were women. Of these, 1861 (81.6%) were living in a high-segregation neighborhood; 278 (12.2%), a medium-segregation neighborhood; and 141 (6.2%), a low-segregation neighborhood. Systolic blood pressure increased by a mean of 0.16 (95% CI, 0.06-0.26) mm Hg with each 1-SD increase in segregation score after adjusting for interactions of time with age, sex, and field center. Of the 1861 participants (81.6%) who lived in high-segregation neighborhoods at baseline, reductions in exposure to segregation were associated with reductions in systolic blood pressure. Mean differences in systolic blood pressure were -1.33 (95% CI, -2.26 to -0.40) mm Hg when comparing high-segregation with medium-segregation neighborhoods and -1.19 (95% CI, -2.08 to -0.31) mm Hg when comparing high-segregation with low-segregation neighborhoods after adjustment for time and interactions of time with baseline age, sex, and field center. Changes in segregation were not associated with changes in diastolic blood pressure. Conclusions and Relevance: Decreases in exposure to racial residential segregation are associated with reductions in systolic blood pressure. This study adds to the small but growing body of evidence that policies that reduce segregation may have meaningful health benefits

Some Constraints on The Formation of Globular Clusters

We explore the constraints on globular cluster formation provided by the observed conditions in starbursts where globulars are currently forming, and by the observed properties of young and old globular clusters. We note that the pressure in the ISM of starbursts and mergers implies that molecular clouds in these environments have radii similar to those of globular clusters. Such molecular clouds are therefore viable precursors to globular clusters if the star formation efficiency in the clouds is high. A high star formation efficiency may be a consequence of the high density and associated high binding energy and short dynamical timescale of molecular clouds in such environments. We also note that the apparent lack of a mass-radius relationship in young and old globular cluster systems places important constraints on globular cluster formation models. This is because molecular clouds are observed to follow a virial scaling relation between mass and radius. We suggest that a variable star formation efficiency may weaken or eliminate the mass-radius relation of molecular clouds as they fragment to form globular clusters. We attribute the absence of young globular clusters in the disks of ordinary galaxies such as the Milky Way to the relatively low ambient pressures in such systems.Comment: 12 pages. Accepted for publication in the Astronomical Journal, Oct 1st issu

Gemini/GMOS Imaging of Globular Cluster Systems in Five Early-type Galaxies

This paper presents deep high quality photometry of globular cluster (GC) systems belonging to five early-type galaxies covering a range of mass and environment. Photometric data were obtained with the Gemini North and Gemini South telescopes in the filter passbands g', r', and i'. The combination of these filters with good seeing conditions allows an excellent separation between GC candidates and unresolved field objects. Bimodal GC colour distributions are found in all five galaxies. Most of the GC systems appear bimodal even in the (g' -r') vs (r' -i') plane. A population of resolved/marginally resolved GC and Ultra Compact Dwarf candidates was found in all the galaxies. A search for the so-called "blue tilt" in the colour-magnitude diagrams reveals that NGC 4649 clearly shows that phenomenon although no conclusive evidence was found for the other galaxies in the sample. This "blue tilt" translates into a mass-metallicity relation given by Z \propto M^0.28\pm0.03 . This dependence was found using a new empirical (g' -i') vs [Z/H] relation which relies on an homogeneous sample of GC colours and metallicities. This paper also explores the radial trends in both colour and surface density for the blue (metal-poor) and red (metal-rich) GC subpopulations. As usual, the red GCs show a steeper radial distribution than the blue ones. Evidence of galactocentric colour gradients is found in some of the GC systems, being more significant for the two S0 galaxies in the sample. Red GC subpopulations show similar colours and gradients to the galaxy halo stars in their inner region. A GC mean colour-galaxy luminosity relation, consistent with [Z/H] \propto L_B ^0.26\pm0.08, is present for the red GCs. An estimate of the total GC populations and specific frequency SN values is presented for NGC 3115, NGC 3379, NGC 3923 and NGC 4649.Comment: 23 pages, 13 figures and 9 tables. Tables A1 and A2 will be published in full online only. Accepted for publication in MNRA

A Comparison of Components of Written Expression Abilities in Learning Disabled and Non-Learning Disabled Students at Three Grade Levels

Although written language plays a critical role in academic success, little empirical evidence exists on the normal development of processes involved in producing written products. Even less is known about the writing performance of LD children. This study empirically compared the written products of LD and normal students at three grade levels on The Test of Written Language. Results showed that LD subjects scored significantly lower than normal subjects on most written expression abilities, especially in the mechanical tasks of spelling, punctuation, and word usage.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Chronic hepatitis caused by persistent parvovirus B19 infection

<p>Abstract</p> <p>Background</p> <p>Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions.</p> <p>Case Presentation</p> <p>Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection.</p> <p>Conclusions</p> <p>In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual aetiology of chronic hepatitis, when other causes have been ruled out.</p