bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting coagulation as a pretreatment to ultrafiltration membranes
Authors: Ratajczak Marek J. , Exall Kirsten N. , Huck Peter M.
Published: November 2012

Low pressure membranes can be effective in treating various types of water, but are subject to fouling. In this work, chemical coagulation was studied as a pretreatment to ultrafiltration (UF), with the goal of mitigating fouling while maintaining high permeate water quality. Alum and ferric chloride were evaluated, as well as two polyaluminum chloride (PACl) products of different basicities and compositions. A bench-scale hollow fiber UF unit was developed to study the treatment of raw and pretreated water from two southern Ontario drinking water sources. The four coagulants were compared at optimal dosages, as well as at lower dosages. The roles of mixing and pH conditions were also evaluated. Membrane fouling was evaluated by observing changes in trans-membrane pressure (TMP) over 3-day experiments. Under optimal dose conditions, all four coagulants were able to reduce the rate at which the membrane fouled to varying degrees for each water source. Total organic carbon (TOC) removal by the membrane was also enhanced with coagulation pretreatment as would be expected. Experiments conducted with low coagulant dosages displayed under-dosing and a subsequent increase in membrane fouling. Experiments conducted with modified raw water pH improved both membrane performance and TOC removal, while experiments with modified mixing intensities proved ineffective.
Discharge of pharmaceuticals into municipal sewers from hospitals and long-term care facilities
Authors: ul Haq Muhammad Riaz , Metcalfe Chris , Li Hongxia , Parker Wayne
Published: November 2012

The presence of pharmaceutically active compounds in the aquatic environment has become well established, and their presence is of potential concern because they are designed to produce biological response in the target receptor, may bear intrinsic toxicity (e.g. cytostatic agents, antibiotics) and they possess the potential to foster and maintain drug resistance. For both risk assessment and risk management purposes, it is important to identify the major sources of pharmaceuticals in the environment. Healthcare facilities may be major sources of the discharges of these compounds into municipal sewers. In this study, we investigated the contributions to the wastewater treatment plant (WWTP) influents from two hospitals and two long-term care homes of nine compounds. Twenty-four hour composite samples were collected over 5 consecutive days from the effluents of these facilities. The WWTPs receiving sewage from these facilities were also sampled on the same days to facilitate mass balance calculations. The results showed that the healthcare facilities contributed a greater proportion of the antibiotic compounds to the WWTPs than the other target compounds; with maximum contributions of ciprofloxacin by hospitals and long-term care homes of 26.7 and 37%, respectively.
Characteristics of urban chemical spills in Southern Ontario
Authors: Cao Weihua , Li James , Joksimovic Darko
Published: November 2012

Thousands of chemical spills occur as a result of accidents or natural disasters each year worldwide and have the potential to harm human health and the environment. More than 700 recorded chemical spills involving more than 1,000 types of chemical occur every year in Southern Ontario, resulting in multiple environmental impacts. This paper presents characteristics of urban chemical spills (1988–2007) and an ArcGIS-based spatial distribution in Southern Ontario. Eleven regions involving 77 municipalities had experienced chemical spills during the study period. Industrial plants accounted for the majority of occurred spills. The St Clair River and the Humber River were the two major rivers encompassing higher spill areas owing to the high density of industry surrounding them. Pipe/hose leaks both accounted for the highest proportion of total chemical spills and resulted in a largest portion of chemical spills causing surface water impacts. The analysis results will provide information for a further study to develop a comprehensive urban chemical spill management strategy, which emphasizes spill prevention, control and emergency response. The strategy could also be used to assist both municipalities and industries to minimize the potential spill impacts to the environment and public health and to better protect water resources.
Laboratory study on the impact of pH and salinity on the fluorescence signal of Natural Organic Matter (NOM) relevant to groundwaters from a Canadian Shield sampling site
Authors: Borraro Vanessa , Riopel Rémi , Caron François , Siemann Stefan
Published: November 2012

Fluorescence spectroscopy with the spectral resolution routine PARAFAC is a leading tool to analyze Natural Organic Matter (NOM) in waters. This routine resolves spectra into humic-, fulvic- and protein-like components, which helps interpret the NOM dynamics in environmental systems. This work is one of the first systematic studies dealing with the impact of chemical perturbations on the fluorescence spectral interpretation of NOM. The samples, taken at two Canadian Shield locations (a shallow set and a deep set to ∼650 m), were perturbed for pH (‘titrations’ from pH 4 to 10) and salinity (from ∼0.02 to 3‰ salt content), then analyzed by fluorescence/PARAFAC. Our fluorescence signals for the three components showed no clear change with pH, as would be expected with a classic titration. The signals were reproducible between replicates for the humic- and protein-like components, but less so for the fulvic-like components. Changes of salinity only had a small impact on the fluorescence signal (a ∼2.7–3.4% signal decrease for each salinity unit, ‰) for the three components in this salinity range.
Treatment of wet peat mining process water with acrotelm peat
Authors: Walford Susanne E. , Lee Peter F. , Mackereth Robert W.
Published: November 2012

Mechanical dewatering of wet mined peat produced peat mining process water (PMPW) with low pH (5.49) and high total suspended solids (TSS 432 mg L−1), Al (1.39 mg L−1), Fe (4.36 mg L−1), Hg (37.1 ng L−1), MeHg (0.485 ng L−1), Zn (55 μg L−1), total nitrogen (TN 7.92 mg L−1), total phosphorus (TP 303 μg L−1) and true colour (532 TCU). High removal efficiencies were calculated for acrotelm peat filters (mesocosms) used to treat PMPW (TSS 45–83%; particulate organic carbon (POC) 47–89%; metals 53–100%; TN 85%; TP 81%), though final mesocosm leachate concentrations did not all achieve Canadian Water Quality Guidelines. In one study, mesocosm leachate had higher colour and dissolved organic carbon (DOC) concentrations than PMPW. Our mesocosm studies suggest an initial reduction in PMPW solids be considered by industry before peatlands are used as treatment systems.
Role of the rpoS gene in the survival of Salmonella enterica serovar Typhimurium in the marine environmentRôle du gène rpoS pour la survie de Salmonella enterica serovar Typhimurium dans l'environnement marin
Authors: Zaafrane S. , Maatouk K.
Published: November 2012

The survival of Salmonella enterica serovar Typhimurium rpoS+ and rpoS− exposed to sunlight or incubated in the dark was studied in a seawater microcosm and a diffusion chamber. The total number of bacteria and physiologically active ones were estimated by direct counting using epifluorescence microscopy, while cultivable bacteria were enumerated by plating onto an agar culture medium. The results obtained showed that the bacteria exposed to sunlight, either in the microcosm or in the diffusion chamber, exhibited a fast decline of cultivable cells, whereas the epifluorescence enumeration revealed a conservation of physiological activity after a total loss of cultivability. In a transparent diffusion chamber, the evolution of cultivable and physiological active bacteria was characterized by a diurnal decrease and a nocturnal stabilization in the count levels, reflecting the effect of phototoxicity on the survival of Salmonella. The transformation and persistence of a physiological active state and cellular integrity in the diffusion chamber or the microcosm showed a clear dependence on the presence of the rpoS gene. Survival in the dark was also characterized by a decrease of cultivability; however, this was significantly inferior to that observed in bacteria exposed to sunlight. This loss of cultivability was accompanied by the preservation of a physiologically active state. The study of seasonal survival carried out in the transparent diffusion chamber was characterized by an enhanced survival of the rpoS+ strain in comparison with the rpoS– mutant. The highest survival rates were obtained in the autumn, thus highlighting the relevant effect of temperature and exposure to sunlight on the persistence of bacteria in seawater.
Decision making with uncertainty: an example of water treatment approach selection
Authors: Chowdhury Shakhawat
Published: November 2012

Decision makers often encounter uncertainty in selecting the best available option. Fuzzy multicriteria decision making aggregates different basic criteria through a hierarchy structure. This aggregation combines fuzzy assessment and priority matrices. When available data are imprecise, the assessment and priority matrices for different hierarchy level criteria are developed from expert judgments. In fuzzy aggregation, uncertainties in the assessment matrix are captured with fuzzy membership functions. The priority matrix is developed through pairwise comparison, in which the relative importance of the criteria is represented in crisp values; thus uncertainties associated with priority assignments are not incorporated in traditional fuzzy aggregation. This paper presents the application of a methodology to incorporate fuzziness in developing a priority matrix for environmental decision making. Fuzzy α-cut technique for different confidence intervals has been incorporated. The gradient eigenvector method has been followed to obtain consistency in constructing the priority matrix for different hierarchy level criteria. The max-min paired elimination method for hierarchical aggregation has been used to obtain the final fuzzy set. A case study for drinking water treatment technology evaluation is performed to present the potential environmental application of this approach, leading to the identification of the best treatment technology.
Communication Skills Training for Dialysis Decision-Making and End-of-Life Care in Nephrology
Authors: Schell Jane O. , Green Jamie A. , Tulsky James A. , Arnold Robert M.
Published: November 2012

Nephrology fellows often face difficult conversations about dialysis initiation or withdrawal but are frequently unprepared for these discussions. Despite evidence that communication skills are teachable, few fellowship programs include such training. A communication skills workshop for nephrology fellows (NephroTalk) focused on delivering bad news and helping patients define care goals, including end-of-life preferences. This 4-hour workshop, held in October and November 2011, included didactics and practice sessions with standardized patients. Participants were nephrology fellows at Duke University and the University of Pittsburgh (n=22). Pre- and post-workshop surveys evaluated efficacy of the curriculum and measured changes in perceived preparedness on the basis on workshop training. Overall, 14% of fellows were white and 50% were male. Less than one-third (6 of 22) reported prior palliative care training. Survey response rate varied between 86% and 100%. Only 36% (8 of 22) and 38% (8 of 21) of respondents had received structured training in discussions for dialysis initiation or withdrawal. Respondents (19 of 19) felt that communication skills were important to being a “great nephrologist.” Mean level of preparedness as measured with a five-point Likert scale significantly increased for all skills (range, 0.5–1.14; P<0.01), including delivering bad news, expressing empathy, and discussing dialysis initiation and withdrawal. All respondents (21 of 21) reported they would recommend this training to other fellows. NephroTalk is successful for improving preparedness among nephrology fellows for having difficult conversations about dialysis decision-making and end-of-life care.
Urinary Angiotensinogen and Risk of Severe AKI
Authors: Alge Joseph L. , Karakala Nithin , Neely Benjamin A. , Janech Michael G. , Tumlin James A. , Chawla Lakhmir S. , Shaw Andrew D. , Arthur John M.
Published: November 2012

Background

Biomarkers of AKI that can predict which patients will develop severe renal disease at the time of diagnosis will facilitate timely intervention in populations at risk of adverse outcomes.

Design, setting, participants, & measurements

Liquid chromatography/tandem mass spectrometry was used to identify 30 potential prognostic urinary biomarkers of severe AKI in a group of patients that developed AKI after cardiac surgery. Angiotensinogen had the best discriminative characteristics. Urinary angiotensinogen was subsequently measured by ELISA and its prognostic predictive power was verified in 97 patients who underwent cardiac surgery between August 1, 2008 and October 6, 2011.

Results

The urine angiotensinogen/creatinine ratio (uAnCR) predicted worsening of AKI, Acute Kidney Injury Network (AKIN) stage 3, need for renal replacement therapy, discharge >7 days from sample collection, and composite outcomes of AKIN stage 2 or 3, AKIN stage 3 or death, and renal replacement therapy or death. The prognostic predictive power of uAnCR was improved when only patients classified as AKIN stage 1 at the time of urine sample collection (n=79) were used in the analysis, among whom it predicted development of stage 3 AKI or death with an area under the curve of 0.81. Finally, category free net reclassification improvement showed that the addition of uAnCR to a clinical model to predict worsening of AKI improved the predictive power.

Conclusions

Elevated uAnCR is associated with adverse outcomes in patients with AKI. These data are the first to demonstrate the utility of angiotensinogen as a prognostic biomarker of AKI after cardiac surgery.
Renal Function and Proteinuria after Successful Immunosuppressive Therapies in Patients with FSGS
Authors: Hogg Ronald J. , Friedman Aaron , Greene Tom , Radeva Milena , Budisavljevic Milos N. , Gassman Jennifer , Gipson Debbie S. , Jefferson J. Ashley , John Eunice G. , Kaskel Frederick J. , Moudgil Asha , Moxey-Mims Marva , Ortiz Luis A. , Schelling Jeffrey R. , Schnaper William , Srivastava Tarak , Trachtman Howard , Vehaskari V. Matti , Wong Craig , Woronieki Robert P. , Van Why Scott K. , Zolotnitskaya Anna
Published: November 2012

Background and objectives

In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined.

Design, setting, participants, and measurements

The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2–40 years, with eGFR ≥40 ml/min per 1.73 m2 and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout the study. UP/C and eGFR were measured at 0, 26, 52, and 78 weeks.

Results

The median UP/C in the cyclosporine- and mycophenolate/dexamethasone-responsive patients fell by 89.8% and 82.7% at 52 weeks; the fall was largely sustained at 78 weeks (74.7% and 80.3%, respectively). The mean eGFR fell by 19.4% in the cyclosporine group and rose by 7.0% in the mycophenolate mofetil/dexamethasone group at 52 weeks, but subsequently rose by 16.4% and fell by 2.6%, respectively, in the two groups from 52 to 78 weeks.

Conclusions

In this subset of responding FSGS patients, the improvement in UP/C after cyclosporine or mycophenolate/dexamethasone treatment was largely sustained for 6 months after therapy. Reduction in eGFR in the cyclosporine group was improved 6 months after cyclosporine was stopped although the levels were lower than baseline in seven patients who entered the study with decreased eGFR.
Indicative levels of PM in the ambient air in the surrounding villages of the copper smelter complex Bor, Serbia
Authors: Tasic Visa , Milosevic Novica , Kovacevic Renata , Jovasevic-Stojanovic Milena , Dimitrijevic Mile
Published: November 2012

While information on air pollution in the form of particulate matter (PM) has
been monitored for longer period for EU countries, availability of PM data
sets in the Western Balkan countries including the Republic of Serbia are
still limited. Studies, related to the particulate pollution research, have
been only carried out in the past several years. The main objective of this
paper is to present PM levels measured in the ambient air in the surrounding
settlements of the Copper Smelter Complex Bor. Also, one of the goals is a
comparison of PM levels in the surrounding settlements with those measured in
Bor town. The ambient levels of PM particles (PM10, PM2.5) were measured by
automatic PM monitors at 4 nearby settlements: Slatina, Ostrelj, Krivelj and
Brezonik in the time interval from 2005 to 2010. According to the measurement
results, PM10 and PM2.5 levels in the ambient air were higher in the cold,
heating, (October-March) than in the warm no heating period
(April-September). The exceeding of the daily limit of PM10 and PM2.5 mass
concentration levels was observed at all measuring points. A higher number of
exceedances were detected in the cold period. The results indicate that there
is a significant seasonal change in the level of fine particles at all
measuring places in surroundings. In addition, the PM levels in Bor town are
more influenced by the air pollution from the Copper Smelter Complex than
settlements in the vicinity, where the PM concentrations were greatly
influenced by the presence of domestic heating in the cold period.
Short-term effects of black smoke on cardiovascular hospitalization in elderly in Nis, Serbia
Authors: Stankovic Aleksandra , Nikolic Maja , Bogdanovic Dragan
Published: November 2012

In past few years numerous epidemiological studies bring new evidence on the
effects of particle air pollution on cardiovascular hospitalizations. The
aim of our paper was to investigate the association between ambient
concentrations of black smoke (BS) and daily total non-accidental
cardiovascular hospitalizations in elderly in Nis. The daily mean number of
all age cardiovascular hospitalizations was 12.46?6.26 (0 to 38) and
5.92?3.29 (0 to 20) among person ? 65 yrs. Daily measurements for black
smoke (BS) and SO2, as well as the daily number of cardiovascular
hospitalization among person ? 65 yrs of age, have been collected. BS
(?g/m3) was measured by the refractometry method and SO2 (?g/m3) by
spectrophotometer. Generalized linear model extending Poisson regression was
applied. The effects of time trend, seasonal variations, day of week,
temperature, relative humidity and barometric pressure were adjusted.
Estimated OR of unipolutant regression model for among person ? 65 yrs was
1.00135 (95% CI: 0,97835 to 1,02489), and estimated OR of bipolutant model
was 1,00975 (95% CI: 0,99457 to 1,02394) per 10?g/m3. The results do not
support findings from previous studies that had shown an increase in the
number of cardiovascular hospitalization in elderly in association with
black smoke.
Receptor modeling studies for the characterization of PM10 pollution sources in Belgrade
Authors: Mijic Zoran , Stojic Andreja , Perisic Mirjana , Rajsic Slavica , Tasic Mirjana
Published: November 2012

The objective of this study is to determine the major sources and potential
source regions of PM10 over Belgrade, Serbia. The PM10 samples were collected
from July 2003 to December 2006 in very urban area of Belgrade and
concentrations of Al, V, Cr, Mn, Fe, Ni, Cu, Zn, Cd and Pb were analyzed by
atomic absorption spectrometry. The analysis of seasonal variations of PM10
mass and some element concentrations reported relatively higher
concentrations in winter, what underlined the importance of local emission
sources. The Unmix model was used for source apportionment purpose and the
four main source profiles (fossil fuel combustion; traffic exhaust/regional
transport from industrial centers; traffic related particles/site specific
sources and mineral/crustal matter) were identified. Among the resolved
factors the fossil fuel combustion was the highest contributor (34%) followed
by traffic/regional industry (26%). Conditional probability function (CPF)
results identified possible directions of local sources. The potential source
contribution function (PSCF) and concentration weighted trajectory (CWT)
receptor models were used to identify spatial source distribution and
contribution of regional-scale transported aerosols.
Short-term health effects of particulate air pollution with special reference to the needs of southern European countries
Authors: Katsouyanni Klea
Published: November 2012

Exposure to air pollution, especially from particulate matter, is generally
accepted to be one of the most important public health problems in Europe and
worldwide. The effects caused in the general population are associated with
relatively small relative risks, but if the ubiquity of exposure is
considered, the attributable number of events is large. Furthermore, there is
evidence that the effects in sensitive population subgroups (such as the
elderly, those with chronic diseases and children) are stronger. Within large
European Union funded collaborative projects (such as the Air Pollution and
Health: a European Approach-APHEA), effect modification by geographical
characteristics has been investigated and it was found that in warmer
countries, in locations where particles come from traffic and where the
proportion of the elderly is greater, particle toxicity is increased. These
characteristics are particularly relevant to Southern European locations.
From other projects we know that meteorological, climatic, environmental and
socioeconomic factors are effect modifiers of the effects of specific air
pollutants. In this presentation we will show the evidence on the short-term
health effects of particulate and gaseous air pollutants and emphasize
particularly results concerning southern Europe and potential effect
modifiers. The gaps in knowledge and the need to study air pollution in
Southern European countries more extensively will be demonstrated. To conduct
useful research, good quality air pollution and health data are needed.
Air quality management planning (AQMP)
Authors: Sivertsen Bjarne , Bartonova Alena
Published: November 2012

In most urban areas of the world, particulate matter (PM) levels pose severe
problems, addressed in several policy areas (air quality, climate change, and
human health). PM presents multiple challenges due to the multitude of its
sources, spanning many sectors of economic activity as well as nature, and
due to the complexity of atmospheric processes involved in its transport and
secondary formation. For the authorities, the goal is to assure minimal
impacts of atmospheric PM levels, in practice represented by compliance with
existing regulations and standards. This may be achieved through an air
quality management plan (AQMP). In Northern America and in parts of Europe,
comprehensive research programs have guided development of AQMP over the last
forty years. This cumulated experience can be utilized by others who face the
same problems, but have yet to develop their own substantial research base.
The main purpose of the AQMP development process is to establish an effective
and sound basis for planning and management of air quality in a selected
area. This type of planning will ensure that significant sources of impacts
are identified and controlled in a most cost-effective manner. The choice of
tools, methods and input information is often dictated by their availability,
and should be evaluated against current best practices. Important elements of
the AQMP are the identification of sources and development of a complete
emission inventory, the development and operation of an air quality
monitoring programme, and the development and application of atmospheric
dispersion models. Major task is to collect the necessary input data. The
development of the AQMP will take into account: - Air Quality Management
System (AQMS) requirements; - Operational and functional structure
requirements; - Source identification through emission inventories; - Source
reduction alternatives, which may be implemented; - Mechanisms for
facilitating interdepartmental cooperation in order to assure that actions
are being taken; - Institutional building and training requirements This
paper offers a practical guide through the different parts of the air quality
management and planning procedures.
Health effects of long-term exposure to air pollution: An overview of major respiratory and cardiovascular diseases and diabetes
Authors: Jovanovic-Andersen Zorana
Published: November 2012

Large number of studies provided convincing evidence for adverse effects of
exposure to outdoor air pollution on human health, and served as basis for
current USA and EU Air Quality Standards and limit values. Still, new
knowledge is emerging, expanding our understanding of vast effects of
exposure to air pollution on human health of this ubiquitous exposure
affecting millions of people in urban setting. This paper focuses on the
studies of health effects of long-term (chronic) exposures to air pollution,
and includes major chronic and acute diseases in adults and especially
elderly, which will present increasing public health burden, due to improving
longevity and projected increasing numbers of elderly. The paper gives
overview over the most relevant and latest literature presented by different
health outcomes: chronic obstructive pulmonary disease, asthma, pneumonia,
cardiovascular disease, and diabetes.
System for automatically preventing the raising of ash from dedicated landfills
Authors: Milutinovic Predrag , Grsic Zoran , Zivkovic Nenad , Dramlic Dragan , Velikic Zoran , Dramlic Stefan
Published: November 2012

The paper presents a system for automatic prevention of raising of ashes from
dedicated landfills based on a simple mathematical model which has modest
entry requirements for meteorological data. Such an approach is efficient
enough and enables fast information retrieval, i.e. zones with different
concentrations of dust in the air, enabling quick start of counter measures
to reduce emissions of ashes into the air. The system hardware consists of
an automatic weather station, set of meters that determine moisture of ash,
set of remotely managed sprinklers, computers, microprocessor and
microcontroller based elements for the local acquisition and management of
the executive elements and modules for wireless data transfer. An original
software application for the system management has been developed. Within
the application there is a module that allows entering of all data necessary
to configure the system, as well as data about sensors and sprinklers. Based
on the meteorological input data, measured moisture content of the ashes,
and on the basis of determined functional dependencies, special software
module operates sprinklers for soaking the surfaces from which the ashes is
emitted into the air, in order to eliminate these emissions. The system,
based on the developed mathematical model, predicts the propagation of ashes
through the air, as well as dry and wet deposition, in real-time. The system
automatically stores all the data relevant to the future analyses and
reporting. The system is designed and implemented as modular and open. A
custom developed graphical user interface serves as Man-Machine Interface
(MMI). By using the TCP/IP connection it could be easily connected with the
other information systems.
A validated stability-indicating RP-HPLC method for paracetamol and lornoxicam: Application to pharmaceutical dosage forms
Authors: Karunakaran Kulandaivelu , Navaneethan Gurusamy , Pitchaimuthu Kuppanagounder
Published: November 2012

A new method for the simultaneous determination of paracetamol (PR) and
lornoxicam (LR) has been developed by reversed phase HPLC from the
combination drug product. The separation achieved on C18 column using
acetonitrile and 0.02 M potassium dihydrogen phosphate was in the ratio of
35:65 (v/v) as mobile phase at a flow rate of 1.0 mL/min. Both the components
were monitored at a single wavelength at 260 nm and the column temperature
was maintained at 30?C throughout the analysis. A linear response was found
in the concentration range of 125-375 ?g/mL for PR and 2-6 ?g/mL for LR, with
the correlation coefficient of more than 0.999. Although the tablet contained
a high dose of PR (500 mg) and a low dose of LR (8 mg), the single HPLC
method was developed and the intra as well as inter day precision was
obtained at less than 2% of RSD. The accuracy results obtained were between
98% and 102%. The drug was intentionally degraded under acidic, basic,
peroxide, thermal, and photolytic conditions. The major degradation observed
for both PR and LR under peroxide condition indicated that the drug product
is susceptible to oxidation. The degraded peaks were properly resolved from
PR and LR. Hence, the method is stability indicating.
Identification of Cross-Species Shared Transcriptional Networks of Diabetic Nephropathy in Human and Mouse Glomeruli
Authors: Hodgin Jeffrey B. , Nair Viji , Zhang Hongyu , Randolph Ann , Harris Raymond C. , Nelson Robert G. , Weil E. Jennifer , Cavalcoli James D. , Patel Jignesh M. , Brosius Frank C. , Kretzler Matthias
Published: November 2012

Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared human–mouse cross-species glomerular transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db), and 162 (Human-BKS eNOS−/− db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetes complications, such as elements of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and vascular endothelial growth factor receptor (VEGFR) signaling pathways. In addition, novel pathways not previously associated with DN and cross-species gene nodes and pathways unique to each of the human–mouse networks were discovered. The human–mouse shared glomerular transcriptional networks will assist DN researchers in selecting mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans.
Neuronal Androgen Receptor Regulates Insulin Sensitivity via Suppression of Hypothalamic NF-κB–Mediated PTP1B Expression
Authors: Yu I-Chen , Lin Hung-Yun , Liu Ning-Chun , Sparks Janet D. , Yeh Shuyuan , Fang Lei-Ya , Chen Lumin , Chang Chawnshang
Published: November 2012

Clinical investigations highlight the increased incidence of metabolic syndrome in prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT). Studies using global androgen receptor (AR) knockout mice demonstrate that AR deficiency results in the development of insulin resistance in males. However, mechanisms by which AR in individual organs coordinately regulates insulin sensitivity remain unexplored. Here we tested the hypothesis that functional AR in the brain contributes to whole-body insulin sensitivity regulation and to the metabolic abnormalities developed in AR-deficient male mice. The mouse model selectively lacking AR in the central nervous system and AR-expressing GT1-7 neuronal cells were established and used to delineate molecular mechanisms in insulin signaling modulated by AR. Neuronal AR deficiency leads to reduced insulin sensitivity in middle-aged mice. Neuronal AR regulates hypothalamic insulin signaling by repressing nuclear factor-κB (NF-κB)–mediated induction of protein-tyrosine phosphatase 1B (PTP1B). Hypothalamic insulin resistance leads to hepatic insulin resistance, lipid accumulation, and visceral obesity. The functional deficiency of AR in the hypothalamus leads to male mice being more susceptible to the effects of high-fat diet consumption on PTP1B expression and NF-κB activation. These findings suggest that in men with PCa undergoing ADT, reduction of AR function in the brain may contribute to insulin resistance and visceral obesity. Pharmacotherapies targeting neuronal AR and NF-κB may be developed to combat the metabolic syndrome in men receiving ADT and in elderly men with age-associated hypogonadism.
Inhibition of Carnitine Palmitoyltransferase-1 Activity Alleviates Insulin Resistance in Diet-Induced Obese Mice
Authors: Keung Wendy , Ussher John R. , Jaswal Jagdip S. , Raubenheimer Monique , Lam Victoria H.M. , Wagg Cory S. , Lopaschuk Gary D.
Published: November 2012

Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated what effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice were fed a high-fat diet (60% calories from fat) for 12 weeks to develop insulin resistance. Subsequent treatment of mice for 4 weeks with the carnitine palmitoyltransferase-1 inhibitor, oxfenicine (150 mg/kg i.p. daily), resulted in improved whole-body glucose tolerance and insulin sensitivity. Exercise capacity was increased in oxfenicine-treated mice, which was accompanied by an increased respiratory exchange ratio. In the gastrocnemius muscle, oxfenicine increased pyruvate dehydrogenase activity, membrane GLUT4 content, and insulin-stimulated Akt phosphorylation. Intramyocellular levels of lipid intermediates, including ceramide, long-chain acyl CoA, and diacylglycerol, were also decreased. Our results demonstrate that inhibition of mitochondrial fatty acid uptake improves insulin sensitivity in diet-induced obese mice. This is associated with increased carbohydrate utilization and improved insulin signaling in the skeletal muscle, suggestive of an operating Randle Cycle in muscle.
White Matter Microstructural Integrity in Youth With Type 1 Diabetes
Authors: Antenor-Dorsey Jo Ann V. , Meyer Erin , Rutlin Jerrel , Perantie Dana C. , White Neil H. , Arbelaez Ana Maria , Shimony Joshua S. , Hershey Tamara
Published: November 2012

Decreased white and gray matter volumes have been reported in youth with type 1 diabetes mellitus (T1DM), but the effects of hyperglycemia on white matter integrity have not been quantitatively assessed during brain development. We performed diffusion tensor imaging, using two complimentary approaches—region-of-interest and voxelwise tract-based spatial statistics—to quantify white matter integrity in a large retrospective study of T1DM youth and control participants. Exposure to chronic hyperglycemia, severe hyperglycemic episodes, and severe hypoglycemia, as defined in the Diabetes Control and Complications Trial (DCCT), were estimated through medical records review, HbA1c levels, and interview of parents and youth. We found lower fractional anisotropy in the superior parietal lobule and reduced mean diffusivity in the thalamus in the T1DM group. A history of three or more severe hyperglycemic episodes was associated with reduced anisotropy and increased diffusivity in the superior parietal lobule and increased diffusivity in the hippocampus. These results add microstructural integrity of white matter to the range of structural brain alterations seen in T1DM youth and suggest vulnerability of the superior parietal lobule, hippocampus, and thalamus to glycemic extremes during brain development. Longitudinal analyses will be necessary to determine how these alterations change with age or additional glycemic exposure.
Metabolite Profiling Reveals Normal Metabolic Control in Carriers of Mutations in the Glucokinase Gene (MODY2)
Authors: Spégel Peter , Ekholm Ella , Tuomi Tiinamaija , Groop Leif , Mulder Hindrik , Filipsson Karin
Published: November 2012

Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The disease does not progress over time, and diabetes complications rarely develop. It has therefore been suggested that GCK-MODY represents a metabolically compensated condition, but experimental support for this notion is lacking. Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY patients revealed a metabolite pattern similar to that of healthy individuals, while other forms of diabetes differed markedly in their metabolite profiles. Furthermore, despite elevated glucose concentrations, carriers of GCK mutations showed lower levels of free fatty acids and triglycerides than healthy control subjects. The metabolite profiling was confirmed by enzymatic assays and replicated in a cohort of 11 GCK-MODY patients. Elevated levels of fatty acids are known to associate with β-cell dysfunction, insulin resistance, and increased incidence of late complications. Our results show that GCK-MODY represents a metabolically normal condition, which may contribute to the lack of late complications and the nonprogressive nature of the disease.
Structured Type 1 Diabetes Education Delivered Within Routine Care
Authors: Cooke Debbie , Bond Rod , Lawton Julia , Rankin David , Heller Simon , Clark Marie , Speight Jane ,   for the U.K. NIHR DAFNE Study Group
Published: November 2012

OBJECTIVE

To determine whether improvements in glycemic control and diabetes-specific quality of life (QoL) scores reported in research studies for the type 1 diabetes structured education program Dose Adjustment For Normal Eating (DAFNE) are also found when the intervention is delivered within routine U.K. health care.

RESEARCH DESIGN AND METHODS

Before and after evaluation of DAFNE to assess impact on glycemic control and QoL among 262 adults with type 1 diabetes.

RESULTS

There were significant improvements in HbA1c from baseline to 6 and 12 months (from 9.1 to 8.6 and 8.8%, respectively) in a subgroup with suboptimal control. QoL was significantly improved by 3 months and maintained at both follow-up points.

CONCLUSIONS

Longer-term improved glycemic control and QoL is achievable among adults with type 1 diabetes through delivery of structured education in routine care, albeit with smaller effect sizes than reported in trials.
ABC Transporter Genes and Risk of Type 2 Diabetes
Authors: Schou Jesper , Tybjærg-Hansen Anne , Møller Holger J. , Nordestgaard Børge G. , Frikke-Schmidt Ruth
Published: November 2012

OBJECTIVE

Alterations of pancreatic β-cell cholesterol content may contribute to β-cell dysfunction. Two important determinants of intracellular cholesterol content are the ATP-binding cassette (ABC) transporters A1 (ABCA1) and -G1 (ABCG1). Whether genetic variation in ABCA1 and ABCG1 predicts risk of type 2 diabetes in the general population is unknown.

RESEARCH DESIGN AND METHODS

We tested whether genetic variation in the promoter and coding regions of ABCA1 and ABCG1 predicted risk of type 2 diabetes in the general population. Twenty-seven variants, identified by previous resequencing of both genes, were genotyped in the Copenhagen City Heart Study (CCHS) (n = 10,185). Two loss-of-function mutations (ABCA1 N1800H and ABCG1 g.-376C>T) (n = 322) and a common variant (ABCG1 g.-530A>G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415).

RESULTS

Only one of the variants examined, ABCG1 g.-530A>G, predicted a decreased risk of type 2 diabetes in the CCHS (P for trend = 0.05). Furthermore, when validated in the CGPS or in the CCHS and CGPS combined (n = 40,600), neither the two loss-of-function mutations (ABCA1 N1800H, ABCG1 g.-376C>T) nor ABCG1 g.-530A>G were associated with type 2 diabetes (P values >0.57 and >0.30, respectively).

CONCLUSIONS

Genetic variations in ABCA1 and ABCG1 were not associated with increased risk of type 2 diabetes in the general population. These data were obtained in general population samples harboring the largest number of heterozygotes for loss-of-function mutations in ABCA1 and ABCG1.
Right Ventricular Involvement in Diabetic Cardiomyopathy
Authors: Widya Ralph L. , van der Meer Rutger W. , Smit Johannes W.A. , Rijzewijk Luuk J. , Diamant Michaela , Bax Jeroen J. , de Roos Albert , Lamb Hildo J.
Published: November 2012

OBJECTIVE

To compare magnetic resonance imaging-derived right ventricular (RV) dimensions and function between men with type 2 diabetes and healthy subjects, and to relate these parameters to left ventricular (LV) dimensions and function.

RESEARCH DESIGN AND METHODS

RV and LV volumes and functions were assessed in 78 men with uncomplicated type 2 diabetes and 28 healthy men within the same range of age using magnetic resonance imaging. Steady-state free precession sequences were used to assess ventricular dimensions. Flow velocity mapping across the pulmonary valve and tricuspid valve was used to assess RV outflow and diastolic filling patterns, respectively. Univariate general linear models were used for statistical analyses.

RESULTS

RV end-diastolic volume was significantly decreased in patients compared with healthy subjects after adjustment for BMI and pulse pressure (177 ± 28 mL vs. 197 ± 47 mL, P < 0.01). RV systolic function was impaired: peak ejection rate across the pulmonary valve was decreased (433 ± 54 mL/s vs. 463 ± 71 mL/s, P < 0.01) and pulmonary flow acceleration time was longer (124 ± 17 ms vs. 115 ± 25 ms, P < 0.05). Indexes of RV diastolic function were impaired: peak filling rate and peak deceleration gradient of the early filling phase were 315 ± 63 mL/s vs. 356 ± 90 mL/s (P < 0.01) and 2.3 ± 0.8 mL/s2 × 10−3 vs. 2.8 ± 0.8 mL/s2 × 10−3 (P < 0.01), respectively. All RV parameters were strongly associated with its corresponding LV parameter (P < 0.001).

CONCLUSIONS

Diabetic cardiomyopathy affects the right ventricle, as demonstrated by RV remodeling and impaired systolic and diastolic functions in men with type 2 diabetes, in a similar manner as changes in LV dimensions and functions. These observations suggest that RV impairment might be a component of the diabetic cardiomyopathy phenotype.
The Fate of Taspoglutide, a Weekly GLP-1 Receptor Agonist, Versus Twice-Daily Exenatide for Type 2 Diabetes
Authors: Rosenstock Julio , Balas Bogdan , Charbonnel Bernard , Bolli Geremia B. , Boldrin Mark , Ratner Robert , Balena Raffaella ,   for the T-emerge 2 Study Group
Published: November 2012

OBJECTIVE

Taspoglutide is a long-acting glucagon-like peptide 1 receptor agonist developed for treatment of type 2 diabetes. The efficacy and safety of once-weekly taspoglutide was compared with twice-daily exenatide.

RESEARCH DESIGN AND METHODS

Overweight adults with inadequately controlled type 2 diabetes on metformin ± a thiazolidinedione were randomized to subcutaneous taspoglutide 10 mg weekly (n = 399), taspoglutide 20 mg weekly (n = 398), or exenatide 10 µg twice daily (n = 392) in an open-label, multicenter trial. The primary end point was change in HbA1c after 24 weeks.

RESULTS

Mean baseline HbA1c was 8.1%. Both doses of taspoglutide reduced HbA1c significantly more than exenatide (taspoglutide 10 mg: –1.24% [SE 0.09], difference –0.26, 95% CI –0.37 to –0.15, P < 0.0001; taspoglutide 20 mg: –1.31% [0.08], difference –0.33, –0.44 to –0.22, P < 0.0001; exenatide: –0.98% [0.08]). Both taspoglutide doses reduced fasting plasma glucose significantly more than exenatide. Taspoglutide reduced body weight (taspoglutide 10 mg, –1.6 kg; taspoglutide 20 mg, –2.3 kg) as did exenatide (–2.3 kg), which was greater than with taspoglutide 10 mg (P < 0.05). HbA1c and weight effects were maintained after 52 weeks. More adverse events with taspoglutide 10 and 20 mg than exenatide developed over time (nausea in 53, 59, and 35% and vomiting in 33, 37, and 16%, respectively). Allergic and injection-site reactions were more common with taspoglutide. Discontinuations were greater with taspoglutide. Antitaspoglutide antibodies were detected in 49% of patients.

CONCLUSIONS

Once-weekly taspoglutide demonstrated greater glycemic control than twice-daily exenatide with comparable weight loss, but with unacceptable levels of nausea/vomiting, injection-site reactions, and systemic allergic reactions.
Reliability and Responsiveness of the Gross Motor Function Measure-88 in Children With Cerebral Palsy
Authors: Ko Jooyeon , Kim MinYoung
Published: November 2012

Background

The Gross Motor Function Measure (GMFM-88) is commonly used in the evaluation of gross motor function in children with cerebral palsy (CP). The relative reliability of GMFM-88 has been assessed in children with CP. However, little information is available regarding the absolute reliability or responsiveness of GMFM-88.

Objective

The purpose of this study was to determine the absolute and relative reliability and the responsiveness of the GMFM-88 in evaluating gross motor function in children with CP.

Design

A clinical measurement design was used.

Methods

Ten raters scored the GMFM-88 in 84 children (mean age=3.7 years, SD=1.9, range=10 months to 9 years 9 months) from video records across all Gross Motor Function Classification System (GMFCS) levels to establish interrater reliability. Two raters participated to assess intrarater reliability. Responsiveness was determined from 3 additional assessments after the baseline assessment. The interrater and intrarater intraclass correlation coefficients (ICCs) with 95% confidence intervals, standard error of measurement (SEM), smallest real difference (SRD), effect size (ES), and standardized response mean (SRM) were calculated.

Results

The relative reliability of the GMFM was excellent (ICCs=.952–1.000). The SEM and SRD for total score of the GMFM were acceptable (1.60 and 3.14, respectively). Additionally, the ES and SRM of the dimension goal scores increased gradually in the 3 follow-up assessments (GMFCS levels I and II: ES=0.5, 0.6, and 0.8 and SRM=1.3, 1.8, and 2.0; GMFCS levels III–V: ES=0.4, 0.7, and 0.9 and SRM=1.5, 1.7, and 2.0).

Limitations

Children over 10 years of age with CP were not included in this study, so the results should not be generalized to all children with CP.

Conclusions

Both the reliability and the responsiveness of the GMFM-88 are reasonable for measuring gross motor function in children with CP.