bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV gp120 H375 Is Unique to HIV-1 Subtype CRF01_AE and Confers Strong Resistance to the Entry Inhibitor BMS-599793, a Candidate Microbicide Drug
Authors: Schader Susan M. , Colby-Germinario Susan P. , Quashie Peter K. , Oliveira Maureen , Ibanescu Ruxandra-Ilinca , Moisi Daniela , Mespléde Thibault , Wainberg Mark A.
Published: May 2012

BMS-599793 is a small molecule entry inhibitor that binds to human immunodeficiency virus type 1 (HIV-1) gp120, resulting in the inhibition of CD4-dependent entry into cells. Since BMS-599793 is currently considered a candidate microbicide drug, we evaluated its efficacy against a number of primary patient HIV isolates from different subtypes and circulating recombinant forms (CRFs) and showed that activity varied between ∼3 ρM and 7 μM at 50% effective concentrations (EC50s). Interestingly, CRF01_AE HIV-1 isolates consistently demonstrated natural resistance against this compound. Genotypic analysis of >1,600 sequences (Los Alamos HIV sequence database) indicated that a single amino acid polymorphism in Env, H375, may account for the observed BMS-599793 resistance in CRF01_AE HIV-1. Results of site-directed mutagenesis experiments confirmed this hypothesis, andin silicodrug docking simulations identified a drug resistance mechanism at the molecular level. In addition, CRF01_AE viruses were shown to be resistant to multiple broadly neutralizing monoclonal antibodies. Thus, our results not only provide insight into how Env polymorphisms may contribute to entry inhibitor resistance but also may help to elucidate how HIV can evade some broadly neutralizing antibodies. Furthermore, the high frequency of H375 in CRF01_AE HIV-1, and its apparent nonoccurrence in other subtypes, could serve as a means for rapid identification of CRF01_AE infections.
Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components
Authors: Barnhill Alison E. , Brewer Matt T. , Carlson Steve A.
Published: May 2012

This minireview explores mitochondria as a site for antibiotic-host interactions that lead to pathophysiologic responses manifested as nonantibacterial side effects. Mitochondrion-based side effects are possibly related to the notion that these organelles are archaic bacterial ancestors or commandeered remnants that have co-evolved in eukaryotic cells; thus, this minireview focuses on mitochondrial damage that may be analogous to the antibacterial effects of the drugs. Special attention is devoted to aminoglycosides, chloramphenicol, and fluoroquinolones and their respective single side effects related to mitochondrial disturbances. Linezolid/oxazolidinone multisystemic toxicity is also discussed. Aminoglycosides and oxazolidinones are inhibitors of bacterial ribosomes, and some of their side effects appear to be based on direct inhibition of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial ribosomes and gyrases/topoisomerases, respectively, both of which are present in mitochondria. However, the side effects of chloramphenicol and the fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria. Nonetheless, it appears that mitochondrion-associated side effects are a potential aspect of antibiotics whose targets are shared by prokaryotes and mitochondria—an important consideration for future drug design.
A Chimeric Toxin Vaccine Protects against Primary and Recurrent Clostridium difficile Infection
Authors: Wang Haiying , Sun Xingmin , Zhang Yongrong , Li Shan , Chen Kevin , Shi Lianfa , Nie Weijia , Kumar Raj , Tzipori Saul , Wang Jufang , Savidge Tor , Feng Hanping
Published: May 2012

The global emergence of
Clostridium difficile
infection (CDI) has contributed to the recent surge in severe antibiotic-associated diarrhea and colonic inflammation.
C. difficile
produces two homologous glucosylating exotoxins, TcdA and TcdB, both of which are pathogenic and require neutralization to prevent disease occurrence. However, because of their large size and complex multifunctional domain structures, it has been a challenge to produce native recombinant toxins that may serve as vaccine candidates. Here, we describe a novel chimeric toxin vaccine that retains major neutralizing epitopes from both toxins and confers complete protection against primary and recurrent CDI in mice. Using a nonpathogenic
Bacillus megaterium
expression system, we generated glucosyltransferase-deficient holotoxins and demonstrated their loss of toxicity. The atoxic holotoxins induced potent antitoxin neutralizing antibodies showing little cross-immunogenicity or protection between TcdA and TcdB. To facilitate simultaneous protection against both toxins, we generated an active clostridial toxin chimera by switching the receptor binding domain of TcdB with that of TcdA. The toxin chimera was fully cytotoxic and showed potent proinflammatory activities. This toxicity was essentially abolished in a glucosyltransferase-deficient toxin chimera, cTxAB. Parenteral immunization of mice or hamsters with cTxAB induced rapid and potent neutralizing antibodies against both toxins. Complete and long-lasting disease protection was conferred by cTxAB vaccinations against both laboratory and hypervirulent
C. difficile
strains. Finally, prophylactic cTxAB vaccination prevented spore-induced disease relapse, which constitutes one of the most significant clinical issues in CDI. Thus, the rational design of recombinant chimeric toxins provides a novel approach for protecting individuals at high risk of developing CDI.
Neutrophils Are Essential for Containment of Vibrio cholerae to the Intestine during the Proinflammatory Phase of Infection
Authors: Queen Jessica , Satchell Karla J. Fullner
Published: May 2012

Cholera is classically considered a noninflammatory diarrheal disease, in comparison to invasive enteric organisms, although there is a low-level proinflammatory response during early infection withVibrio choleraeand a strong proinflammatory reaction to live attenuated vaccine strains. Using an adult mouse intestinal infection model, this study examines the contribution of neutrophils to host defense to infection. Nontoxigenic El Tor O1V. choleraeinfection is characterized by the upregulation of interleukin-6 (IL-6), IL-10, and macrophage inflammatory protein 2 alpha in the intestine, indicating an acute innate immune response. Depletion of neutrophils from mice with anti-Ly6G IA8 monoclonal antibody led to decreased survival of mice. The role of neutrophils in protection of the host is to limit the infection to the intestine and control bacterial spread to extraintestinal organs. In the absence of neutrophils, the infection spread to the spleen and led to increased systemic levels of IL-1β and tumor necrosis factor alpha, suggesting the decreased survival in neutropenic mice is due to systemic shock. Neutrophils were found not to contribute to either clearance of colonizing bacteria or to alter the local immune response. However, when genes for secreted accessory toxins were deleted, the colonizing bacteria were cleared from the intestine, and this clearance is dependent upon neutrophils. Thus, the requirement for accessory toxins in virulence is negated in neutropenic mice, which is consistent with a role of accessory toxins in the evasion of innate immune cells in the intestine. Overall, these data support that neutrophils impact disease progression and suggest that neutrophil effectiveness can be manipulated through the deletion of accessory toxins.
Antiphagocytic Function of an IgG Glycosyl Hydrolase from Streptococcus equi subsp.
equi
and Its Use as a Vaccine Component
Authors: Flock Margareta , Frykberg Lars , Sköld Markus , Guss Bengt , Flock Jan-Ingmar
Published: May 2012

EndoSe from
Streptococcus equi
subsp.
equi
is an enzyme hydrolyzing glycosyl groups on IgG, analogous to EndoS from
Streptococcus pyogenes
. We here show that the activity of EndoSe leads to an antiphagocytic function and may thus be a contributory factor to immune evasion of
S. equi
. Despite the damaging effect that EndoSe has on IgG, antibodies against EndoSe can neutralize its function. Antibodies against EndoSe restored the opsonic activity of specific opsonizing antibodies. Mice infected with either
S. equi
subsp.
equi
or subsp.
zooepidemicus
or
S. pyogenes
could be protected by vaccination with EndoSe. It is speculated that EndoSe could be a suitable vaccine candidate against streptococcal infections.
Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study
Authors: Lombard Zané , Crowther Nigel J , van der Merwe Lize , Pitamber Punita , Norris Shane A , Ramsay Michèle
Published: May 2012

Background

Obesity is a complex trait with both environmental and genetic contributors. Genome-wide association studies have identified several variants that are robustly associated with obesity and body mass index (BMI), many of which are found within genes involved in appetite regulation. Currently, genetic association data for obesity are lacking in Africans—a single genome-wide association study and a few replication studies have been published in West Africa, but none have been performed in a South African population.

Objective

To assess the association of candidate loci with BMI in black South Africans. The authors focused on single nucleotide polymorphisms (SNPs) in theFTO,LEP,LEPR,MC4R,NPY2RandPOMCgenes.

Design

A genetic association study.

Participants

990 randomly selected individuals from the larger Birth to Twenty cohort (a longitudinal birth cohort study of health and development in Africans).

Measures

The authors genotyped 44 SNPs within the six candidate genes that included known BMI-associated SNPs and tagSNPs based on linkage disequilibrium in an African population forFTO,LEPandNPY2R. To assess population substructure, the authors included 18 ancestry informative markers. Weight, height, sex, sex-specific pubertal stage and exact age collected during adolescence (13 years) were used to identify loci that predispose to obesity early in life.

Results

Sex, sex-specific pubertal stage and exact age together explain 14.3% of the variation in log(BMI) at age 13. After adjustment for these factors, four SNPs were individually significantly associated with BMI:FTOrs17817449 (p=0.022),LEPrs10954174 (p=0.0004),LEPrs6966536 (p=0.012) andMC4Rrs17782313 (p=0.045). Together the four SNPs account for 2.1% of the variation in log(BMI). Each risk allele was associated with an estimated average increase of 2.5% in BMI.

Conclusions

The study highlighted SNPs inFTOandMC4Ras potential genetic markers of obesity risk in South Africans. The association with two SNPs in the 3′ untranslated region of theLEPgene is novel.
Discontinuation of statin therapy in older people: does a cancer diagnosis make a difference? An observational cohort study using data linkage
Authors: Stavrou Efty P , Buckley Nicholas , Olivier Jake , Pearson Sallie-Anne
Published: May 2012

Objective

The aim was to examine statin discontinuation rates in a cohort of elderly Australians with newly diagnosed cancer using population-based secondary health data.

Design

Observational cohort study.

Setting

New South Wales, the largest jurisdiction in Australia. The Pharmaceutical Benefits and Repatriation Pharmaceutical Benefits Schemes are national programmes subsidising prescription drugs to the Australian population and Australian Government Department of Veterans' Affairs clients.

Participants

The cohort comprised 1731 cancer patients aged ≥65 years with evidence of statin use in the 90 days prior to diagnosis. They were matched to 3462 non-cancer patients prescribed statins in the same period.

Main outcome measure

The authors compared statin discontinuation rates up to 4 years post-diagnosis and examined the factors associated with statin discontinuation.

Results

The proportion of cancer patients discontinuing statin therapy at 4 years (27%) was comparable to the comparison cohort; however, significantly higher proportions of the cancer cohort discontinued statins than the comparison cohort at 3, 6 and 12 months of follow-up (9.7% vs 7.4% at 12 months, respectively). More than 30% of cancer patients who died were dispensed statins within 30 days of death. Discontinuation of statin therapy in cancer patients was associated with regionalised and distant disease spread at diagnosis (p<0.001), older age (p=0.006), upper gastrointestinal organs and liver cancer (aHR 2.95, 95% CI 1.92 to 4.53) and cancer of the lung, bronchus and trachea (aHR 1.99, 95% CI 1.32 to 3.00) and poorer survival.

Conclusions

Medications should be rationalised at the time of a cancer diagnosis, especially in the setting of a poor prognosis. At least for some patients in our cohort, statin therapy may be inappropriately continued which adds unnecessarily to therapeutic burden.
Palliative care for the management of chronic illness: a systematic review study protocol
Authors: Effiong Andem , Effiong Andem I
Published: May 2012

Introduction

Chronic illnesses are marked by fluctuations and variations over time. Individuals with chronic illness experience pain and other symptoms that are not always adequately managed. Their caregivers often have to deal with enormous burden as the illness progresses. Palliative care can serve as an intervention to manage chronic illness, not just at the end of life but also in the early phases of illness.

Methods and analysis

Randomised and non-randomised studies will be included in the systematic review. The focus will be on non-cancer chronic illness. Sources of data will be from PubMed and other databases and will include the reference list of studies included in the systematic review. The primary outcome will be to assess the efficacy of palliative care on chronic illness. Secondary outcomes will include health-related quality of life, care giver burden, quality of care and cost-effectiveness of interventions. The study population will consist of patients aged 18 years or over.

Ethics and dissemination

For purposes of privacy and confidentiality, the systematic review will be limited to studies with de-identified data. The systematic review will be published in a peer-reviewed journal. It will also be disseminated electronically and in print. Brief reports of review findings will be disseminated directly to appropriate audiences via email and other modes of communication. Updates of the review will be conducted to inform and guide healthcare practice and policy.

Trial registration number

PROSPEROCRD42011001794.
The International Community-Acquired Pneumonia (CAP) Collaboration Cohort (ICCC) study: rationale, design and description of study cohorts and patients
Authors: Myint Phyo Kyaw , Kwok Chun Shing , Majumdar Sumit R , Eurich Dean T , Clark Allan B , España Pedro P , Man Shin Yan , Huang David T , Yealy Donald M , Angus Derek C , Capelastegui Alberto , Rainer Timothy H , Marrie Thomas J , Fine Michael J , Loke Yoon K
Published: May 2012

Objective

To improve the understanding of the determinants of prognosis and accurate risk stratification in community-acquired pneumonia (CAP).

Design

Multicentre collaboration of prospective cohorts.

Setting

6 cohorts from the USA, Canada, Hong Kong and Spain.

Participants

From a published meta-analysis of risk stratification studies in CAP, the authors identified and pooled individual patient-level data from six prospective cohort studies of CAP (three from the USA, one each from Canada, Hong Kong and Spain) to create the International CAP Collaboration Cohort. Initial essential inclusion criteria of meta-analysis were (1) prospective design, (2) in English language, (3) reported 30-day mortality and transfer to an intensive or high dependency care and (4) minimum 1000 participants. Common baseline patient characteristics included demographics, history and physical examination findings, comorbidities and laboratory and radiographic findings.

Primary and secondary outcome measures

This paper reports the rationale, hypotheses and analytical framework and also describes study cohorts and patients. The authors aim to (1) compare the prognostic accuracy of existing CAP risk stratification tools, (2) assess patient-level determinants of prognosis, (3) improve risk stratification by combined use of scoring systems and (4) understand prognostic factors for specific patient groups.

Results

The six cohorts assembled from 1991 to 2007 included 13 784 patients (median age 71 years, 54% men). Aside from one randomised controlled study, the remaining five were cohort studies, but all had similar inclusion criteria. Overall, there was 0%–6% missing data. A total of 6159 (44%) had severe pneumonia by Pneumonia Severity Index class IV/V. Mortality at 30 days was 8% (1036). Admission to intensive care or high dependency unit was also 8% (1059).

Conclusions

International CAP Collaboration Cohort provides a pooled multicentre data set of patients with CAP, which will help us to better understand the prognosis of CAP.
STABILITY ANALYSIS FOR SOLITON SOLUTIONS IN A GAUGED CP(1) THEORY
Authors: SOURROUILLE LUCAS
Published: May 2012

We analyze the stability of soliton solutions in a Chern–Simons-CP(1) model. We show a condition for which the soliton solutions are stable. Finally we verified this result numerically.
STATE-SPACE GEOMETRY, NONEXTREMAL BLACK HOLES AND KALUZA–KLEIN MONOPOLES
Authors: BELLUCCI STEFANO , TIWARI BHUPENDRA NATH
Published: May 2012

We examine the statistical nature of the charged anticharged nonextremal black holes in string theory. From the perspective of the intrinsic Riemannian geometry, the first principle of the statistical mechanics shows that the stability properties of general nonextremal nonlarge charged black brane solutions are divulged from the positivity of the corresponding principle minors of the space-state metric tensor. Under the addition of the Kaluza–Klein monopoles, a novel aspect of the Gaussian fluctuations demonstrates that the canonical fluctuations can be ascertained without any approximation. We offer the state-space geometric implication for the most general nonextremal black brane configurations in string theory.
PULSED LASER SURFACE MODIFICATION OF AZ31B WITH Al-Si
Authors: DU BAOSHUAI , PAITAL SAMEER R. , DAHOTRE NARENDRA B.
Published: May 2012

A pulsed Nd:YAG laser was used to modify the surface properties of Mg alloy (AZ31B) for wear application with Al-Si as precursor material. Highly refined microstructure consisting of Mg2Si, Mg, Al12Mg17 and Al2O3 was obtained. Phase constituent was correlated with thermodynamic calculation by employing Thermocalc™. The evolution of phase amount in the coatings was associated with the laser processing parameters. Due to the presence of highly refined microstructure and hard intermetallic reinforcements, substantial improvement of microhardness has been found in the coating region.
A STUDY ON MICROSTRUCTURE CHARACTERISTICS OF IN SITU FORMED TiC REINFORCED COMPOSITE COATINGS
Authors: LIU PENG , GUO WEI , LUO HUI
Published: May 2012

In situ synthesized TiC reinforced composite coating was fabricated by laser cladding of Al-Ni-Cr-C powders on titanium alloys, which can greatly improve the surface performance of the substrate. In this study, the Al-Ni-Cr-C laser-cladded composite coatings have been researched by means of X-ray diffraction, scanning electron microscope (SEM) and electron probe micro-analyzer (EPMA). There was a metallurgical combination between the Al-Ni-Cr-C laser-cladded coating and the Ti-6Al-4V substrate, and the micro-hardness of the Al-Ni-Cr-C laser-cladded coating was in the range of ~1200–1450 HV0.2, which was ~3–4 times higher than that of Ti-6Al-4V substrate. Furthermore, the reinforcement of the Al-Ni-Cr-C laser-cladded coating were mainly contributed to the action of the TiC , Ti3Al , Cr7C3 , Al8Cr5 phases and the solution strengthening.
THE POTENTIAL POINT OF VIEW FOR RENORMALIZATION
Authors: BARAVIERA ALEXANDRE , LEPLAIDEUR RENAUD , LOPES ARTUR O.
Published: May 2012

For the shift σ in Σ = {0, 1}ℕ, we define the renormalization for potentials by [Formula: see text] We show that for a good H, there is a unique fixed point for [Formula: see text]. It is the Hofbauer potential V*.

We show that the stable set of the Hofbauer potential, i. e. the set of potentials V such that [Formula: see text] converges to V* is characterized by the germ of these potentials close to 0∞= 000….

Then, we make connections with the Manneville–Pomeau map f : [0, 1]↺. In particular we show that the lift in Σ of log f′ is in the stable set of V*.

In the second part, we characterize "good" H, such that σ2◦ H = H ◦ σ.

In the last part, we study the thermodynamic formalism for some special potentials in the stable set of V*. They are called virtual Manneville–Pomeau maps.
Membrane Fission: The Biogenesis of Transport Carriers
Authors: Campelo Felix , Malhotra Vivek
Published: May 2012

Membrane-bound transport carriers are used to transfer cargo between membranes of the secretory and the endocytic pathways. The generation of these carriers can be classified into three steps: segregation of cargo away from the residents of a donor compartment (cargo sorting), generation of membrane curvature commensurate with the size of the cargo (membrane budding or tubulation), and finally separation of the nascent carrier from the donor membrane by a scission or membrane fission event. This review summarizes advances in our understanding of some of the best-characterized proteins required for the membrane fission that separates a transport carrier from its progenitor compartment: the large GTPase dynamin, the small guanine nucleotide-binding (G) proteins of the Arf family, BAR (Bin-amphiphysin-Rvs) domain proteins, and protein kinase D. These proteins share their ability to insert into membranes and oligomerize to create the large curvatures; however, the overall process of fission that involves these proteins appears to be quite different.
Emerging Paradigms for Complex Iron-Sulfur Cofactor Assembly and Insertion
Authors: Peters John W. , Broderick Joan B.
Published: May 2012

[FeFe]-hydrogenses and molybdenum (Mo)-nitrogenase are evolutionarily unrelated enzymes with unique complex iron-sulfur cofactors at their active sites. The H cluster of [FeFe]-hydrogenases and the FeMo cofactor of Mo-nitrogenase require specific maturation machinery for their proper synthesis and insertion into the structural enzymes. Recent insights reveal striking similarities in the biosynthetic pathways of these complex cofactors. For both systems, simple iron-sulfur cluster precursors are modified on assembly scaffolds by the activity of radical S-adenosylmethionine (SAM) enzymes.

Radical SAM enzymes are responsible for the synthesis and insertion of the unique nonprotein ligands presumed to be key structural determinants for their respective catalytic activities. Maturation culminates in the transfer of the intact cluster assemblies to a cofactor-less structural protein recipient. Required roles for nucleotide binding and hydrolysis have been implicated in both systems, but the specific role for these requirements remain unclear. In this review, we highlight the progress on [FeFe]-hydrogenase H cluster and nitrogenase FeMo-cofactor assembly in the context of these emerging paradigms.
GTPase Networks in Membrane Traffic
Authors: Mizuno-Yamasaki Emi , Rivera-Molina Felix , Novick Peter
Published: May 2012

Members of the Rab or ARF/Sar branches of the Ras GTPase superfamily regulate almost every step of intracellular membrane traffic. A rapidly growing body of evidence indicates that these GTPases do not act as lone agents but are networked to one another through a variety of mechanisms to coordinate the individual events of one stage of transport and to link together the different stages of an entire transport pathway. These mechanisms include guanine nucleotide exchange factor (GEF) cascades, GTPase-activating protein (GAP) cascades, effectors that bind to multiple GTPases, and positive-feedback loops generated by exchange factor-effector interactions. Together these mechanisms can lead to an ordered series of transitions from one GTPase to the next. As each GTPase recruits a unique set of effectors, these transitions help to define changes in the functionality of the membrane compartments with which they are associated.
The Fires of Life
Authors: Schatz Gottfried
Published: May 2012

This retrospective recounts the hunt for the mechanism of mitochondrial ATP synthesis, the early days of research on mitochondrial formation, and some of the colorful personalities dominating these often dramatic and emotional efforts. The narrative is set against the backdrop of postwar Austria and Germany and the stream of young scientists who had to leave their countries to receive postdoctoral training abroad. Many of them—including the author—chose the laboratory of a scientist their country had expelled a few decades before. The article concludes with some thoughts on the uniqueness of U.S. research universities and a brief account of the struggles to revive science in Europe.
Introduction to Theme “Chromatin, Epigenetics, and Transcription”
Authors: Conaway Joan W.
Published: May 2012

Transcriptional regulation in eukaryotes depends on a complex network of interactions between RNA polymerases and a host of transcription factors and coregulators that control their activity during transcription initiation and elongation. Among these are an enormous variety of enzymes and proteins that modulate chromatin structure via changes in DNA methylation, histone modifications, and nucleosome location. This volume of the Annual Review of Biochemistry contains a set of four reviews addressing the interplay between mechanisms that regulate DNA methylation, chromatin structure, and transcription.
Molecular Pathways: Interferon/Stat1 Pathway: Role in the Tumor Resistance to Genotoxic Stress and Aggressive Growth
Authors: Khodarev Nikolai N. , Roizman Bernard , Weichselbaum Ralph R.
Published: May 2012

STAT1 is activated by IFNs and other cell signals. Following activation, STAT1 is translocated to the nuclei and activates transcription of IFN-stimulated genes. Although the activation of STAT1 by IFNs is classically associated with antiviral defense and tumor-suppressive functions, emerging data indicate that expression of the STAT1 pathway confers cellular resistance to DNA-damaging agents and mediates aggressive tumor growth. Recent advances in the development of Janus-activated kinase/Stat inhibitors and peptide inhibitors specific for individual Stat proteins may provide new insights into the controversial functions of this pathway. Clin Cancer Res; 18(11); 3015–21. ©2012 AACR.
Electrocardiographic Characteristics of Potential Organ Donors and Associations With Cardiac Allograft Use
Authors: Khush Kiran K. , Menza Rebecca , Nguyen John , Goldstein Benjamin A. , Zaroff Jonathan G. , Drew Barbara J.
Published: May 2012

Background—

Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation.

Methods and Results—

A single experienced reviewer interpreted the first ECG obtained after brain stem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002 to 2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft use for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy, prolongation of the corrected QT interval, and repolarization changes (ST/T wave abnormalities). Fifty-seven percent of potential cardiac allografts in this cohort were accepted for transplantation. Left ventricular hypertrophy on ECG was a strong predictor of allograft nonuse. No significant associations were seen among corrected QT interval prolongation, repolarization changes, and allograft use for transplantation after adjusting for donor clinical variables and echocardiographic findings.

Conclusions—

We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brain stem herniation and are not associated with allograft use for transplantation.
Immediate Antioxidant and Antiplatelet Effect of Atorvastatin via Inhibition of Nox2
Authors: Pignatelli Pasquale , Carnevale Roberto , Pastori Daniele , Cangemi Roberto , Napoleone Laura , Bartimoccia Simona , Nocella Cristina , Basili Stefania , Violi Francesco
Published: May 2012

Background—

Statins exert an antithrombotic effect in patients at risk of or with acute thrombosis, but no study has investigated whether this effect is immediate and whether there is an underline mechanism.

Methods and Results—

Patients with hypercholesterolemia were randomly allocated to a Mediterranean diet with low cholesterol intake (<300 mg/d; n=15) or atorvastatin (40 mg/d; n=15). Oxidative stress, as assessed by serum Nox2 and urinary isoprostanes, and platelet activation, as assessed by platelet recruitment, platelet isoprostanes, and thromboxane A
2
, platelet Nox2, Rac1, p47
phox
, protein kinase C, vasodilator-stimulated phosphoprotein, nitric oxide, and phospholipase A
2
, were determined at baseline and after 2, 24, and 72 hours and 7 days of follow-up. An in vitro study was also performed to see whether atorvastatin affects platelet oxidative stress and activation. The atorvastatin-assigned group showed a significant and progressive reduction of urinary isoprostanes and serum Nox2, along with inhibition of platelet recruitment, platelet isoprostanes, Nox2, Rac1, p47
phox
, and protein kinase C, starting 2 hours after administration. Platelet phospholipase A
2
and thromboxane A
2
significantly decreased and vasodilator-stimulated phosphoprotein and nitric oxide increased after 24 hours. Low-density lipoprotein cholesterol decreased significantly after 72 hours and further declined after 7 days. No changes were observed in the Mediterranean diet group. In vitro experiments demonstrated that atorvastatin dose-dependently inhibited platelet Nox2 and phospholipase A
2
activation, along with inhibition of platelet recruitment, platelet isoprostanes, and thromboxane A
2
, and increased vasodilator-stimulated phosphoprotein and nitric oxide.

Conclusions—

The study provides the first evidence that atorvastatin acutely and simultaneously decreases oxidative stress and platelet activation by directly inhibiting platelet Nox2 and ultimately platelet isoprostanes and thromboxane A
2
. These findings provide a rationale for the use of statins to prevent or modulate coronary thrombosis.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01322711.
Effects of Hunter-Gatherer Subsistence Mode on Arterial Distensibility in Cameroonian Pygmies
Authors: Lemogoum Daniel , Ngatchou William , Janssen Christophe , Leeman Marc , Van Bortel Luc , Boutouyrie Pierre , Degaute Jean Paul , Van de Borne Philippe
Published: May 2012

We aimed to assess whether arterial distensibility estimated by pulse wave velocity (PWV) and augmentation index (AI) differs between Cameroon traditional pygmies (TPs) on hunter-gather subsistence mode, contemporary pygmies who migrated to semiurban area, and the Bantou farmers (BFs) sharing the same environment. For that purpose, we recorded carotid-femoral PWV (ComplioR) in age and sex carefully matched 20 TPs, 20 contemporary pygmies, and 22 BFs. Aortic AI corrected for heart rate and blood pressures were generated from pressure wave analysis (SphygmoCor). Lipid profile was determined in TP and BF participants. TPs were shorter (
P
=0.02) with lower body weight (
P
<0.01) in comparison with contemporary pygmies and BFs. TPs had lower low-density lipoprotein cholesterol but higher high-density lipoprotein cholesterol than BFs (
P
<0.01). Their PWV (5.81±0.21 m/s) was slower (
P
=0.006) than that of contemporary pygmies (6.82±0.36 m/s) or BFs (6.93±0.29 m/s); however, after its adjustment for age, mean arterial pressure, and heart rate, the difference was slightly attenuated (
P
=0.051). PWV adjusted for weight did not differ between groups (
P
=0.10). In the whole study population but not in TPs taken separately, multivariate regression analysis revealed that PWV was independently associated with mean arterial pressure, age, and TP status (
P
<0.001), whereas age, mean arterial pressure, and height emerged as independent determinants of aortic AI corrected for heart rate (
P
<0.001). Aortic AI corrected for heart rate did not differ in the 3 groups. In conclusion, hunter-gather lifestyle is associated with low atherosclerosis risk translated by lower aortic stiffness attributed at least partly to low weight and blunted effects of aging and blood pressures on TP arterial structure and function.
Effect of Home Blood Pressure Telemonitoring With Self-Care Support on Uncontrolled Systolic Hypertension in Diabetics
Authors: Logan Alexander G. , Irvine M. Jane , McIsaac Warren J. , Tisler Andras , Rossos Peter G. , Easty Anthony , Feig Denice S. , Cafazzo Joseph A.
Published: May 2012

Lowering blood pressure reduces cardiovascular risk, yet hypertension is poorly controlled in diabetic patients. In a pilot study we demonstrated that a home blood pressure telemonitoring system, which provided self-care messages on the smartphone of hypertensive diabetic patients immediately after each reading, improved blood pressure control. Messages were based on care paths defined by running averages of transmitted readings. The present study tests the system's effectiveness in a randomized, controlled trial in diabetic patients with uncontrolled systolic hypertension. Of 244 subjects screened for eligibility, 110 (45%) were randomly allocated to the intervention (n=55) or control (n=55) group, and 105 (95.5%) completed the 1-year outcome visit. In the intention-to-treat analysis, mean daytime ambulatory systolic blood pressure, the primary end point, decreased significantly only in the intervention group by 9.1±15.6 mmHg (SD;
P
<0.0001), and the mean between-group difference was 7.1±2.3 mmHg (SE;
P
<0.005). Furthermore, 51% of intervention subjects achieved the guideline recommended target of <130/80 mmHg compared with 31% of control subjects (
P
<0.05). These improvements were obtained without the use of more or different antihypertensive medications or additional clinic visits to physicians. Providing self-care support did not affect anxiety but worsened depression on the Hospital Anxiety and Depression Scale (baseline, 4.1±3.76; exit, 5.2±4.30;
P
=0.014). This study demonstrated that home blood pressure telemonitoring combined with automated self-care support reduced the blood pressure of diabetic patients with uncontrolled systolic hypertension and improved hypertension control. Home blood pressure monitoring alone had no effect on blood pressure. Promoting patient self-care may have negative psychological effects.
Hypertension Induces Brain β-Amyloid Accumulation, Cognitive Impairment, and Memory Deterioration Through Activation of Receptor for Advanced Glycation End Products in Brain Vasculature
Authors: Carnevale Daniela , Mascio Giada , D'Andrea Ivana , Fardella Valentina , Bell Robert D. , Branchi Igor , Pallante Fabio , Zlokovic Berislav , Yan Shirley ShiDu , Lembo Giuseppe
Published: May 2012

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease.
A Theory of the Interhemispheric Meridional Overturning Circulation and Associated Stratification
Authors: Nikurashin Maxim , Vallis Geoffrey
Published: May 2012

A quantitative theoretical model of the meridional overturning circulation and associated deep stratification in an interhemispheric, single-basin ocean with a circumpolar channel is presented. The theory includes the effects of wind, eddies, and diapycnal mixing and predicts the deep stratification and overturning streamfunction in terms of the surface forcing and other parameters of the problem. It relies on a matching among three regions: the circumpolar channel at high southern latitudes, a region of isopycnal outcrop at high northern latitudes, and the ocean basin between.

The theory describes both the middepth and abyssal cells of a circulation representing North Atlantic Deep Water and Antarctic Bottom Water. It suggests that, although the strength of the middepth overturning cell is primarily set by the wind stress in the circumpolar channel, middepth stratification results from a balance between the wind-driven upwelling in the channel and deep-water formation at high northern latitudes. Diapycnal mixing in the ocean interior can lead to warming and upwelling of deep waters. However, for parameters most representative of the present ocean mixing seems to play a minor role for the middepth cell. In contrast, the abyssal cell is intrinsically diabatic and controlled by a balance between the deep mixing-driven upwelling and the residual of the wind-driven and eddy-induced circulations in the Southern Ocean.

The theory makes explicit predictions about how the stratification and overturning circulation vary with the wind strength, diapycnal diffusivity, and mesoscale eddy effects. The predictions compare well with numerical results from a coarse-resolution general circulation model.
The Wavy Ekman Layer: Langmuir Circulations, Breaking Waves, and Reynolds Stress
Authors: McWilliams James C. , Huckle Edward , Liang Jun-Hong , Sullivan Peter P.
Published: May 2012

Large-eddy simulations are made for the canonical Ekman layer problem of a steady wind above a uniformly rotating, constant-density ocean. The focus is on the influence of surface gravity waves: namely, the wave-averaged Stokes-Coriolis and Stokes-vortex forces and parameterized wave breaking for momentum and energy injection. The wave effects are substantial: the boundary layer is deeper, the turbulence is stronger, and eddy momentum flux is dominated by breakers and Langmuir circulations with a vertical structure inconsistent with both the conventional logarithmic layer and eddy viscosity relations. The surface particle mean drift is dominated by Stokes velocity with Langmuir circulations playing a minor role. Implications are assessed for parameterization of the mean velocity profile in the Ekman layer with wave effects by exploring several parameterization ideas. The authors find that the K-profile parameterization (KPP) eddy viscosity is skillful for the interior of the Ekman layer with wave-enhanced magnitude and depth scales. Furthermore, this parameterization form is also apt in the breaker and Stokes layers near the surface when it is expressed as a Lagrangian eddy viscosity (i.e., turbulent Reynolds stress proportional to vertical shear of the Lagrangian mean flow, inclusive of Stokes drift) with a derived eddy-viscosity shape and with a diagnosed vertical profile of a misalignment angle between Reynolds stress and Lagrangian mean shear.
Tropical Cyclone Contribution to Rainfall over Australia
Authors: Dare Richard A. , Davidson Noel E. , McBride John L.
Published: May 2012

Tropical cyclone (TC) rainfall over the Australian continent is studied using observations from 41 TC seasons 1969/70 to 2009/10. A total of 318 storms, whose centers either crossed the coastline or were located within 500 km of the coast, are considered in this study. Mean seasonal (November/April) contributions by TCs to the total rainfall are largest along the northern coastline from 120°–150°E. However, the percentage contributions by TCs are greatest west of 125°E, with mean coastal values of 20%–40% and inland values of approximately 20%. Farther east, percentages near the coast are only around 10%, and even lower inland. Inland penetration by TC rainfall is generally greatest over western portions of the continent, associated with greater inland penetration of TC tracks. During the peak of the TC season (January–March), TCs contribute around 40% to the rainfall total of coastal regions west of 120°E, while during December, TCs contribute approximately 60%–70% to the total rainfall west of 115°E. Rain from TCs varies sharply between TC seasons, with some longitude bands receiving no TC rain during some seasons. For the 110°–115°E longitude band the TC rain contribution is quite inconsistent, varying interannually from 0%–86%. This has an impact on water supplies, with storage dams falling to low levels during some years, while filling to capacity during TC-related flood events in other years. These large interannual variations and their impacts underline why it is important to understand TC rainfall characteristics over the Australian continent.
Challenges in End-of-Life Care Management for Low-Income Frail Elders
Authors: Kwak Jung , Kramer Betty J. , Lang Josh , Ledger Maria
Published: May 2012

The need for well-coordinated care at the end of life is an important priority for meeting the needs of the growing number of low-income frail elders who are advancing in age. Partially integrated (Medicaid only) models of managed long-term care (MMLTC) are viewed as one promising and financially viable approach to enhance care coordination, yet we know little about the challenges that care managers face in managing the end-of-life care needs of poor elders. A case study design was used to explore challenges encountered in the provision of end-of-life care management for low-income elders enrolled in an innovative partially integrated model of long-term care, in Wisconsin, the Milwaukee County Family Care program. Data were collected via in-depth interviews with county administrators ( n = 4) and selected lead supervisors or care managers ( n = 7) and two focus groups with care management team members ( n = 17). We identified five major themes representing essential challenges: (1) complexity of care and high level of support needs; (2) communication constraints in advance care planning; (3) family conflicts in end-of-life decision making for elders; (4) insufficient communication and collaboration between elders, families, teams, and service providers; and (5) limited bereavement and grief related support for families and teams after elders die. We discuss similarities and difference in the challenges reported here as compared to challenges reported in studies of other models of care and offer recommendations for program and policy development.
The Analytic Group as an Arena for the Resolution of Shame
Authors: Rathbone Gillian
Published: May 2012

Although shame has been extensively explored in recent psychotherapeutic literature the role of shame in group analysis as described by Foulkes remains unclear. Based on a narrative literature review conducted for a master’s degree (Rathbone, 2010), the author draws together theory and evidence and explores its relevance to the practice of group analytic psychotherapy. She argues that the social nature of the original trauma and the particular configuration of the analytic group gives it the potential to be an ideal arena for a reparative ‘good enough’ experience of attunement and thus for resolution of shame-based psychopathology. She concludes that this may be considered an additional therapeutic factor alongside socialization, mirroring, activation of the collective unconscious and exchange, which Foulkes identified.
Solid waste management in Croatia in response to the European Landfill Directive
Authors: Stanic-Maruna Ira , Fellner Johann
Published: May 2012

The European Landfill Directive 99/31/EC represents the most influential piece of waste legislation on the management of municipal solid waste. In addition to technical standards regarding the design and location of landfills, it calls for a decrease in the amount of biodegradable waste landfilled. In order to meet the reduction targets set in the Landfill Directive, national solid waste strategies need to be changed. This article outlines the impact of the Landfill Directive on the Croatian waste management strategy and discusses the key challenges of its implementation. In addition, three scenarios of future waste management (mechanical biological pre-treatment, waste-to-energy and landfilling) have been investigated and evaluated regarding environmental impacts and affordability. The results of the analysis show that Croatia has transposed the said Directive into its own legislation in an exemplary way. The developed national waste management strategy foresees the set up of a separate collection of recyclables, waste pre-treatment of MSW, as well as the upgrading of existing disposal sites to sanitary landfills. However, the practical progress of carrying out provisions implemented on paper is lagging behind. Concerning the investigated scenarios the results of the evaluation indicate that mechanical biological pre-treatment in conjunction with separate collection of recyclables appears to be the most feasible option (in terms of economic and ecologic parameters). This result is in line with the proposed national waste management strategy.
Intersectional Normalization Processes in a Swedish Family Assessment Home
Authors: Sawyer Lena S.
Published: May 2012

This article focuses on normalization processes within a Swedish family assessment home. It discusses how normality is constructed by personnel working at Family House, a fictive name for an assessment home of parental care. The article focuses on the ways in which meanings of race/ethnicity, class, and gender are an implicit part of the normativity constructed by personnel in these institutional settings and are used to position themselves as different from the families who are there to be evaluated. The term Svensson is shown to be a key term that is imbued with normative understandings of an “orderly life” in the Swedish welfare state.