bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking the Primary Sources of Fecal Pollution in a Tropical Watershed in a One-Year Study
Authors: Toledo-Hernandez Carlos , Ryu Hodon , Gonzalez-Nieves Joel , Huertas Evelyn , Toranzos Gary A. , Santo Domingo Jorge W.
Published: January 2013

A study was conducted to determine the primary sources of fecal pollution in a subtropical watershed using host-specific assays developed in temperate regions. Water samples (
n
= 534) from 10 different sites along the Rio Grande de Arecibo (RGA) watershed were collected mostly on a weekly basis (54 sampling events) during 13 months. DNA extracts from water samples were used in PCR assays to determine the occurrence of fecal bacteria (
Bacteroidales
,
Clostridium coccoides
, and enterococci) and human-, cattle-, swine-, and chicken-specific fecal sources. Feces from 12 different animals (
n
= 340) and wastewater treatment samples (
n
= 16) were analyzed to determine the specificity and distribution of host-specific assays. The human-specific assay (HF183) was found to be highly specific, as it did not cross-react with nontarget samples. The cattle marker (CF128) cross-reacted to some extent with swine, chicken, and turkeys and was present in 64% of the cattle samples tested. The swine assays showed poor host specificity, while the three chicken assays showed poor host distribution. Differences in the detection of host-specific markers were noted per site. While human and cattle assays showed moderate average detection rates throughout the watershed, areas impacted by wastewater treatment plants and cattle exhibited the highest prevalence of these markers. When conditional probability for positive signals was determined for each of the markers, the results indicated higher confidence levels for the human assay and lower levels for all the other assays. Overall, the results from this study suggest that additional assays are needed, particularly to track cattle, chicken, and swine fecal pollution sources in the RGA watershed. The results also suggest that the geographic stability of genetic markers needs to be determined prior to conducting applied source tracking studies in tropical settings.
Bradyzoite Pseudokinase 1 Is Crucial for Efficient Oral Infectivity of the Toxoplasma gondii Tissue Cyst
Authors: Buchholz Kerry R. , Bowyer Paul W. , Boothroyd John C.
Published: January 2013

The tissue cyst formed by the bradyzoite stage of
Toxoplasma gondii
is essential for persistent infection of the host and oral transmission. Bradyzoite pseudokinase 1 (BPK1) is a component of the cyst wall, but nothing has previously been known about its function. Here, we show that immunoprecipitation of BPK1 from
in vitro
bradyzoite cultures, 4 days postinfection, identifies at least four associating proteins: MAG1, MCP4, GRA8, and GRA9. To determine the role of BPK1, a strain of
Toxoplasma
was generated with the
bpk1
locus deleted. This BPK1 knockout strain (
Δbpk1
) was investigated
in vitro
and
in vivo
. No defect was found in terms of
in vitro
cyst formation and no difference in pathogenesis or cyst burden 4 weeks postinfection (wpi) was detected after intraperitoneal (i.p.) infection with
Δbpk1
tachyzoites, although the Δ
bpk1
cysts were significantly smaller than parental or BPK1-complemented strains at 8 wpi. Pepsin-acid treatment of 4 wpi
in vivo
cysts revealed that Δ
bpk1
parasites are significantly more sensitive to this treatment than the parental and complemented strains. Consistent with this, 4 wpi Δ
bpk1
cysts showed reduced ability to cause oral infection compared to the parental and complemented strains. Together, these data reveal that BPK1 plays a crucial role in the
in vivo
development and infectivity of
Toxoplasma
cysts.
Bacterial Community Morphogenesis Is Intimately Linked to the Intracellular Redox State
Authors: Dietrich Lars E. P. , Okegbe Chinweike , Price-Whelan Alexa , Sakhtah Hassan , Hunter Ryan C. , Newman Dianne K.
Published: January 2013

Many microbial species form multicellular structures comprising elaborate wrinkles and concentric rings, yet the rules governing their architecture are poorly understood. The opportunistic pathogen
Pseudomonas aeruginosa
produces phenazines, small molecules that act as alternate electron acceptors to oxygen and nitrate to oxidize the intracellular redox state and that influence biofilm morphogenesis. Here, we show that the depth occupied by cells within colony biofilms correlates well with electron acceptor availability. Perturbations in the environmental provision, endogenous production, and utilization of electron acceptors affect colony development in a manner consistent with redox control. Intracellular NADH levels peak before the induction of colony wrinkling. These results suggest that redox imbalance is a major factor driving the morphogenesis of
P. aeruginosa
biofilms and that wrinkling itself is an adaptation that maximizes oxygen accessibility and thereby supports metabolic homeostasis. This type of redox-driven morphological change is reminiscent of developmental processes that occur in metazoans.
Life-threatening piperacillin-induced immune haemolysis in a patient with cystic fibrosis
Authors: Marik Paul Ellis , Parekh Parth
Published: January 2013

We present a 24-year-old man with a history significant for cystic fibrosis and insulin-dependent diabetes mellitus who developed anaemia in the setting of piperacillin-induced immune haemolysis. This case provided a diagnostic challenge, a rare association of piperacillin-induced haemolysis in those suffering from cystic fibrosis.
Abnormal electrocardiographic findings in athletes: recognising changes suggestive of cardiomyopathy
Authors: Drezner Jonathan A , Ashley Euan , Baggish Aaron L , Börjesson Mats , Corrado Domenico , Owens David S , Patel Akash , Pelliccia Antonio , Vetter Victoria L , Ackerman Michael J , Anderson Jeff , Asplund Chad A , Cannon Bryan C , DiFiori John , Fischbach Peter , Froelicher Victor , Harmon Kimberly G , Heidbuchel Hein , Marek Joseph , Paul Stephen , Prutkin Jordan M , Salerno Jack C , Schmied Christian M , Sharma Sanjay , Stein Ricardo , Wilson Mathew
Published: January 2013

Cardiomyopathies are a heterogeneous group of heart muscle diseases and collectively are the leading cause of sudden cardiac death (SCD) in young athletes. The 12-lead ECG is utilised as both a screening and diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of an underlying pathological cardiac disorder. This article describes ECG findings present in cardiomyopathies afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.
Mapping English GP prescribing data: a tool for monitoring health-service inequalities
Authors: Rowlingson Barry , Lawson Euan , Taylor Benjamin , Diggle Peter J
Published: January 2013

Objective

The aim of this paper was to show that easily interpretable maps of local and national prescribing data, available from open sources, can be used to demonstrate meaningful variations in prescribing performance.

Design

The prescription dispensing data from the National Health Service (NHS) Information Centre for the medications metformin hydrochloride and methylphenidate were compared with reported incidence data for the conditions, diabetes and attention deficit hyperactivity disorder, respectively. The incidence data were obtained from the open source general practitioner (GP) Quality and Outcomes Framework. These data were mapped using the Ordnance Survey CodePoint Open data and the data tables stored in a PostGIS spatial database. Continuous maps of spending per person in England were then computed by using a smoothing algorithm and areas whose local spending is substantially (at least fourfold) and significantly (p<0.05) higher than the national average are then highlighted on the maps.

Setting

NHS data with analysis of primary care prescribing.

Population

England, UK.

Results

The spatial mapping demonstrates that several areas in England have substantially and significantly higher spending per person on metformin and methyphenidate. North Kent and the Wirral have substantially and significantly higher spending per child on methyphenidate.

Conclusions

It is possible, using open source data, to use statistical methods to distinguish chance fluctuations in prescribing from genuine differences in prescribing rates. The results can be interactively mapped at a fine spatial resolution down to individual GP practices in England. This process could be automated and reported in real time. This can inform decision-making and could enable earlier detection of emergent phenomena.
Are race-specific ERCC1 haplotypes in melanoma cases versus controls related to the predictive and prognostic value of ERCC1 N118N?
Authors: Gao Rui , Reece Kelie M , Sissung Tristan , Fu Samuel H , Venzon David J , Reed Eddie , Spencer Shawn D , Price Douglas K , Figg William D
Published: January 2013

Objectives

Although it does not alter the ERCC1 phenotype, theERCC1 500C>T(rs11615) polymorphism has undergone a myriad of investigations into its role as a marker for nucleotide excision repair (NER) function in different races, diseases and treatment outcomes. The goal of our study was to test the hypothesis that500C>Tis in linkage disequilibrium (LD) with causative alleles, and that these haplotypes are more frequent in Caucasians with melanoma than in healthy Caucasians or African Americans.

Design

In this case–control study, we selected race-specificERCC1single-nucleotide polymorphism (SNPs), conducted LD analysis withERCC1 500C>Tand compared the frequency ofERCC1diplotypes in Caucasians with melanoma (n=165), healthy Caucasians (n=150) and healthy African Americans (n=159). The haplotype was further studied using a fusion gene containing multipleERCC1SNPs.

Setting

Large cancer institute in the USA.

Participants

A total of 165 Caucasian melanoma patients, 159 healthy Caucasian controls and 159 African American healthy controls. Men and women were enrolled in the clinical trial; however, since the screening trial included prostate cancer screening in addition to screening for other cancers, only male controls were available.

Outcome measures

The outcome measures were melanoma risk in Caucasians, and LD between ERCC1 SNP, N118N and other race-specific allelic variants.

Results

When compared toERCC1 500C>Talone, a race-specific three-SNP variant haplotype inERCC1(comprised of rs11615, rs3212950 and rs3212948) was even more frequent in Caucasians with melanoma than in healthy Caucasians (p=0.0034) or African Americans (p<0.0001). A plasmid containing the variant haplotype was not differentially expressed.

Conclusions

We demonstrate thatERCC1 500C>Tparticipates in a previously characterised cancer-risk haplotype found more frequently in Caucasians, while LD is weak in African Americans; this haplotype appears to also be related to melanoma. It is therefore likely thatERCC1 500C>Tis only a valid NER, disease or treatment outcome marker in Caucasians.
Patient and family involvement in decision making for management of cancer patients at a centre in Singapore
Authors: Chong Jia An , Quah Yan Ling , Yang Grace Meijuan , Menon Sumytra , Radha Krishna Lalit Kumar
Published: January 2013

Background

The practice of patient autonomy within the prevailing bioethical framework in the West appears increasingly at odds with the prominent influence of the family in medical decision making in the Asian culture. The actual extent of involvement of patient versus the family in the decision making process for cancer management in clinical practice is largely unknown in Asia.

Aims

(1) To describe patient and family involvement in healthcare decision making in actual practice, and to determine whether those practices are consistent with Singapore law; and (2) to act as a pilot for a larger prospective study examining the preferences of cancer patients on the decision making process, and the reasons for excluding patients from that process.

Methods

A retrospective review of patients who died in an oncology ward in Singapore General Hospital from February to April 2011. Patient and family involvement in discussions on (1) disclosure of diagnosis, (2) initial treatment decisions and (3) initiation of a ‘maximum ward management’ order was evaluated by reviewing case notes completed by healthcare professionals.

Results

Data were collected for 55 patients. Involvement of patients and families at first disclosure of diagnosis was noted in 61% and 64% of cases, respectively. In 12% of cases, the family requested withholding of the diagnosis from the patient. 86% of patients were involved in the initial treatment decisions, and their family was involved in 65% of cases. Only 9% of the 32 alert patients were consulted in end of life decisions. Factors associated with lower patient involvement were advanced age and inability to speak English.

Conclusions

While most cancer patients are involved in the healthcare decision making process during the early phase, familial involvement gains prominence as the disease progresses.
Who, why and when: stroke care unit patients seen by a palliative care service within a large metropolitan teaching hospital
Authors: Eastman Peter , McCarthy Gillian , Brand Caroline A , Weir Louise , Gorelik Alexandra , Le Brian
Published: January 2013

Objectives

To investigate factors associated with referral of patients from an Australian stroke care unit (SCU) to an inpatient palliative care service (PCS).

Methods

This retrospective observational cohort study included patients who were referred to the PCS after SCU admission between 1 January and 31 December 2008. Variables measured included patient demographics, premorbid functional status, premorbid living situation, stroke type, history of previous stroke and discharge outcomes. Group differences between all SCU patients seen and not seen by the PCS were compared using univariate analyses. Multivariate logistic regression analysis was undertaken to identify factors associated with PCS involvement. Group differences were also compared between deceased stroke patients seen and not seen by the PCS.

Results

544 patients were admitted to the SCU during the study period with 62 (11.4%) referred to the PCS. Assistance with end-of-life care was the commonest reason for referral. From univariate analyses, factors significantly associated with PCS involvement included age, gender, premorbid modified Rankin score, living situation prior to stroke and stroke type. Factors predicting PCS involvement for SCU patients from logistic regression were: increasing age, higher premorbid modified Rankin score and haemorrhagic stroke. 87 (16.0%) SCU patients died during their admission, with 49 (56.3%) seen by PCS. Deceased patients seen were significantly older, more disabled premorbidly and lived significantly longer.

Conclusions

This study indicates there are patient and condition-level factors associated with referral of stroke patients to PCS. It highlights factors that might better stratify hospitalised stroke patients to timely palliative care involvement, and adds an Australian perspective to limited data addressing this patient population.
Importance of proper patient selection and endpoint selection in evaluation of new therapies in acute stroke: further analysis of the SENTIS trial
Authors: Shuaib Ashfaq , Schwab Stefan , Rutledge J Neal , Starkman Sidney , Liebeskind David S , Bernardini Gary L , Boulos Alan , Abou-Chebl Alex , Huang David Y , Vanhooren Geert , Cruz-Flores Salvador , Klucznik Richard Paul , Saver Jeffrey L ,   for the SENTIS trial investigators
Published: January 2013

Background

The magnitude of treatment effect in acute stroke depends on several factors, including time from symptom onset (TFSO) to treatment and severity of the initial insult.

Objective

To report further evaluation of NeuroFlo therapy, focusing on the effect of time and stroke severity.

Methods

SENTIS was a prospective randomized trial (N=515) comparing standard medical therapy with/without NeuroFlo therapy. For this analysis, we evaluated outcomes in groups of patients based on TFSO and stroke severity: patients randomized <6 h, 6–10 h, and >10 h with mild (NIHSS<8), moderate (8–14), and severe (>14) symptoms at randomization. 90-Day mRS (modified Rankin Scale) scores and stroke-related death rates were compared between treatment groups.

Results

For patients randomized <6 h TFSO (n=128), the OR for mRS 0–2 was 3.11 (CI 1.30 to 7.46, p=0.011) for treated versus non-treated patients. In patients with disease of moderate severity (NIHSS 8–14, n=214), NeuroFlo-treated patients were more likely to have a good outcome (mRS 0–2; OR=1.84, CI 1.02 to 3.33, p=0.043). The stroke-related death rate was better in the treated group with TFSO >10 h and NIHSS >14 (n=42) (OR=7.10, CI 1.13 to 44.55, p=0.036).

Conclusions

The results of our analysis support the importance of careful selection of outcome measures and the impact that rapid treatment and initial stroke severity have on outcome.

Clinical trial registration URL://http.clinicaltrials.gov.Unique identifier:NCT00119717.
The cost of coils implanted in aneurysms: 2 years of clinical data
Authors: Wang Charlie , Hui Ferdinand K , Spiotta Alejandro M , Rasmussen Peter A
Published: January 2013

Objective

A study on factors of material costs in endovascular coil embolization has not been previously reported. The aim of this study was to assess the effect of aneurysm size and other factors on implanted coil costs.

Methods

Implanted coil costs were retrospectively obtained for all 387 consecutive aneurysm coiling procedures of saccular aneurysms performed in 342 patients over 2.5 years at the Cleveland Clinic. ANOVA and least squares linear regression were utilized to examine relationships.

Results

Linear regression analysis showed a significant relationship between log volume and log cost (p<0.0001). The fit relationship can be represented as normalized cost=1.6×volume0.36. Other factors (aneurysm geometry, recurrent vs primary, vendor/coil choice, procedure dates) were not shown to be significant at the p<0.05 level.

Conclusions

The costs associated with the coils implanted in an aneurysm vary in a predictable fashion as a function of aneurysm volume, suggesting that coiling costs can be modeled prior to actual embolization of a lesion and may be useful in refining the reimbursement models for endovascular aneurysm treatment.
NUMERICAL SIMULATION OF FIBER-OPTIC PHOTOACOUSTIC GENERATOR USING NANOCOMPOSITE MATERIAL
Authors: TIAN YE , WU NAN , SUN KAI , ZOU XIAOTIAN , WANG XINGWEI
Published: January 2013

Photoacoustic generation using an optical fiber is a promising approach to meet the challenges in most advanced ultrasonic non-destructive testing (NDT) applications. The energy-absorption layer coated on the fiber endface plays an important role in converting the laser energy into heat and exciting the acoustic wave. The selection of the absorption material and the optimization of the structure dimension are the keys for achieving high energy-conversion efficiency. A 2D-axisymmetric finite element analysis (FEA) model was established to simulate the photoacoustic generation process using a newly developed absorption material, polydimethylsiloxane/gold nanoparticle (PDMS/Au NPs) nanocomposites, with different thicknesses and laser pulse durations. The experimental results obtained using a similar set-up show a similar trend predicted by this FEA simulation. The FEA results provide practical clues to the design of the fiber-optic photoacoustic generator.
IMMERSIVE VR VISUALIZATIONS BY VFIVE PART 1: DEVELOPMENT
Authors: KAGEYAMA AKIRA , OHNO NOBUAKI
Published: January 2013

We have been developing a visualization application for CAVE-type virtual reality (VR) systems for more than a decade. This application, VFIVE, is currently used in several CAVE systems in Japan for routine visualizations. It is also used as a base system of further developments of advanced visualizations. The development of VFIVE is summarized.
Porcine Circovirus Type 2 (PCV2): Pathogenesis and Interaction with the Immune System
Authors: Meng Xiang-Jin
Published: January 2013

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus–associated disease (PCVAD). The virus preferentially targets the lymphoid tissues, which leads to lymphoid depletion and immunosuppression in pigs. The disease is exacerbated by immunostimulation or concurrent infections with other pathogens. PCV2 resides in certain immune cells, such as macrophage and dendritic cells, and modulates their functions. Upregulation of IL-10 and proinflammatory cytokines in infected pigs may contribute to pathogenesis. Pig genetics influence host susceptibility to PCV2, but the viral genetic determinants for virulence remain unknown. PCV2 DNA and proteins interact with various cellular genes that control immune responses to regulate virus replication and pathogenesis. Both neutralizing antibodies and cell-mediated immunity are important immunological correlates of protection. Despite the availability of effective vaccines, variant strains of PCV2 continue to emerge. Although tremendous progress has been made toward understanding PCV2 pathogenesis and immune interactions, many important questions remain.
Neuroimaging and Other Biomarkers for Alzheimer's Disease: The Changing Landscape of Early Detection
Authors: Risacher Shannon L. , Saykin Andrew J.
Published: January 2013

The goal of this review is to provide an overview of biomarkers for Alzheimer's disease (AD), with emphasis on neuroimaging and cerebrospinal fluid (CSF) biomarkers. We first review biomarker changes in patients with late-onset AD, including findings from studies using structural and functional magnetic resonance imaging (MRI), advanced MRI techniques (diffusion tensor imaging, magnetic resonance spectroscopy, perfusion), positron emission tomography with fluorodeoxyglucose, amyloid tracers, and other neurochemical tracers, and CSF protein levels. Next, we evaluate findings from these biomarkers in preclinical and prodromal stages of AD including mild cognitive impairment (MCI) and pre-MCI conditions conferring elevated risk. We then discuss related findings in patients with dominantly inherited AD. We conclude with a discussion of the current theoretical framework for the role of biomarkers in AD and emergent directions for AD biomarker research.
Surface-Enhanced Raman Spectroscopy Applied to Food Safety
Authors: Craig Ana Paula , Franca Adriana S. , Irudayaraj Joseph
Published: January 2013

Surface-enhanced Raman spectroscopy (SERS) is an advanced Raman technique that enhances the vibrational spectrum of molecules adsorbed on or in the vicinity of metal particles and/or surfaces. Because of its readiness, sensitivity, and minimum sample preparation requirements, SERS is being considered as a powerful technique for food inspection. Key aspects of food-safety assurance, spectroscopy methods, and SERS are briefly discussed in an extended introduction of this review. The recent and potential advances in SERS are highlighted in sections that deal with the (a) detection of food-borne pathogenic microorganisms and (b) the detection of food contaminants and adulteration, concentrated specifically on antibiotics, drugs, hormones, melamine, and pesticides. This review provides an outlook of the work done and a perspective on the future directions of SERS as a reliable tool for food-safety assessment.
The Adaptable Major Histocompatibility Complex (MHC) Fold: Structure and Function of Nonclassical and MHC Class I–Like Molecules
Authors: Adams Erin J. , Luoma Adrienne M.
Published: January 2013

The MHC fold is found in proteins that have a range of functions in the maintenance of an organism's health, from immune regulation to fat metabolism. Well adapted for antigen presentation, as seen for peptides in the classical MHC molecules and for lipids in CD1 molecules, the MHC fold has also been modified to perform Fc-receptor activity (e.g., FcRn) and for roles in host homeostasis (e.g., with HFE and ZAG). The more divergent MHC-like molecules, such as some of those that interact with the NKG2D receptor, represent the minimal MHC fold, doing away with the α3 domain and β2m while maintaining the α1/α2 platform domain for receptor engagement. Viruses have also co-opted the MHC fold for immune-evasive functions. The variations on the theme of a β-sheet topped by two semiparallel α-helices are discussed in this review, highlighting the fantastic adaptability of this fold for good and for bad.
Functional T Cell Immunodeficiencies (with T Cells Present)
Authors: Notarangelo Luigi D.
Published: January 2013

Severe combined immunodeficiency (SCID) comprises a group of disorders that are fatal owing to genetic defects that abrogate T cell development. Numerous related defects have recently been identified that allow T cell development but that compromise T cell function by affecting proximal or distal steps in intracellular signaling. These functional T cell immunodeficiencies are characterized by immune dysregulation and increased risk of malignancies, in addition to infections. The study of patients with these rare conditions, and of corresponding animal models, illustrates the importance of intracellular signaling to maintain T cell homeostasis.
Unnatural Amino Acids as Probes of Ligand-Receptor Interactions and Their Conformational Consequences
Authors: Pless Stephan A. , Ahern Christopher A.
Published: January 2013

G protein–coupled receptors and ion channels couple a wide range of external stimuli to cellular growth and division, metabolism, motility, and a myriad of intra- and intercellular signaling pathways. G protein–coupled receptors initiate complex, interrelated downstream signaling cascades, whereas rapid ionic flux through channels directly supports membrane excitability and mediates cellular functions through second messengers. Because of these characteristics, these ubiquitous transmembrane proteins are valuable therapeutic targets and have provided fertile ground for the development of leading-edge synthetic and chemical biological approaches. Here we summarize recent advances in the use of site-directed incorporation of unnatural amino acids and chemical probes to study ligand-receptor interactions, determine the location of binding sites, and examine the downstream conformational consequences of ligand binding in G protein–coupled receptors and ion channels.
Ring-Polymer Molecular Dynamics: Quantum Effects in Chemical Dynamics from Classical Trajectories in an Extended Phase Space
Authors: Habershon Scott , Manolopoulos David E. , Markland Thomas E. , Miller Thomas F.
Published: January 2013

This article reviews the ring-polymer molecular dynamics model for condensed-phase quantum dynamics. This model, which involves classical evolution in an extended ring-polymer phase space, provides a practical approach to approximating the effects of quantum fluctuations on the dynamics of condensed-phase systems. The review covers the theory, implementation, applications, and limitations of the approximation.
Cosolvent Effects on Protein Stability
Authors: Canchi Deepak R. , García Angel E.
Published: January 2013

Proteins are marginally stable, and the folding/unfolding equilibrium of proteins in aqueous solution can easily be altered by the addition of small organic molecules known as cosolvents. Cosolvents that shift the equilibrium toward the unfolded ensemble are termed denaturants, whereas those that favor the folded ensemble are known as protecting osmolytes. Urea is a widely used denaturant in protein folding studies, and the molecular mechanism of its action has been vigorously debated in the literature. Here we review recent experimental as well as computational studies that show an emerging consensus in this problem. Urea has been shown to denature proteins through a direct mechanism, by interacting favorably with the peptide backbone as well as the amino acid side chains. In contrast, the molecular mechanism by which the naturally occurring protecting osmolyte trimethylamine N-oxide (TMAO) stabilizes proteins is not clear. Recent studies have established the strong interaction of TMAO with water. Detailed molecular simulations, when used with force fields that incorporate these interactions, can provide insight into this problem. We present the development of a model for TMAO that is consistent with experimental observations and that provides physical insight into the role of cosolvent-cosolvent interaction in determining its preferential interaction with proteins.
Causal Inference in Public Health
Authors: Glass Thomas A. , Goodman Steven N. , Hernán Miguel A. , Samet Jonathan M.
Published: January 2013

Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action's consequences rather than the less precise notion of a risk factor's causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world.
Implementation Science and Its Application to Population Health
Authors: Lobb Rebecca , Colditz Graham A.
Published: January 2013

Implementation science studies the use of strategies to adapt and use evidence-based interventions in targeted settings (e.g., schools, workplaces, health care facilities, public health departments) to sustain improvements to population health. This nascent field of research is in the early stages of developing theories of implementation and evaluating the properties of measures. Stakeholder engagement, effectiveness studies, research synthesis, and mathematical modeling are some of the methods used by implementation scientists to identify strategies to embed evidence-based interventions in clinical and public health programs. However, for implementation science to reach its full potential to improve population health the existing paradigm for how scientists create evidence, prioritize publications, and synthesize research needs to shift toward greater stakeholder input and improved reporting on external validity. This shift will improve the relevance of the research that is produced and provide information that will help guide decision makers in their selection of research-tested interventions.
Commentary on the Symposium: Biological Embedding, Life Course Development, and the Emergence of a New Science
Authors: Hertzman Clyde
Published: January 2013

A new science of human development is emerging, which has the capacity to transform the way we understand the origins of health and disease; to increase the public health significance of early child development; and to call into question how and when society should act on a range of health problems. It builds on the multidisciplinary evidence that social environments and experiences during sensitive periods in brain and biological development affect health for the balance of the life course through a process called biological embedding. Despite the fact that biological embedding has established credibility in the scientific literature, the transformative power of the new science has yet to be fully realized in policy and practice. To further this transformation, this symposium offers a public health perspective on biological embedding.
High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment
Authors: Brunetti Giacomina , Faienza Maria Felicia , Piacente Laura , Ventura Annamaria , Oranger Angela , Carbone Claudia , Benedetto Adriana Di , Colaianni Graziana , Gigante Margherita , Mori Giorgio , Gesualdo Loreto , Colucci Silvia , Cavallo Luciano , Grano Maria
Published: January 2013

Children with 21-hydroxylase deficiency (21-OHD) need chronic glucocorticoid (cGC) therapy to replace congenital deficit of cortisol synthesis, and this therapy is the most frequent and severe form of drug-induced osteoporosis. In this study, we enrolled 18 patients (9 females) and 18 sex- and age-matched controls. We found in 21-OHD patients high serum and leukocyte levels of dickkopf-1 (DKK1), a secreted antagonist of the Wnt/β-catenin signaling pathway known to be a key regulator of bone mass. In particular, we demonstrated by flow cytometry, confocal microscopy, and real-time PCR that monocytes, T lymphocytes, and neutrophils from patients expressed high levels of DKK1, which may be related to the cGC therapy. In fact, we showed that dexamethasone treatment markedly induced the expression of DKK1 in a dose- and time-dependent manner in leukocytes. The serum from patients containing elevated levels of DKK1 can directly inhibit in vitro osteoblast differentiation and receptor activator of NF-κB ligand (RANKL) expression. We also found a correlation between both DKK1 and RANKL or COOH-terminal telopeptides of type I collagen (CTX) serum levels in 21-OHD patients on cGC treatment. Our data indicated that DKK1, produced by leukocytes, may contribute to the alteration of bone remodeling in 21-OHD patients on cGC treatment.
Compromised regulation of tissue perfusion and arteriogenesis limit, in an AT1R-independent fashion, recovery of ischemic tissue in Cx40−/−mice
Authors: Fang Jennifer S. , Angelov Stoyan N. , Simon Alexander M. , Burt Janis M.
Published: January 2013

Recently, we reported that recovery of tissue perfusion in the ischemic hindlimb was reduced, inflammatory response increased, and survival of distal limb tissue compromised in connexin 40 (Cx40)-deficient (Cx40−/−) mice. Here we evaluate whether genotype-specific differences in tissue perfusion, native vascular density, arteriogenesis, blood pressure, and chronic ANG II type 1 receptor (AT1R) activation contribute to poor recovery of ischemic hindlimb tissue in Cx40−/−mice. Hindlimb ischemia was induced in wild-type (WT), Cx40−/−, and losartan-treated Cx40−/−mice by using surgical procedures that either maintained (mild surgery) or compromised (severe surgery) perfusion of major collateral vessels supplying the distal limb. Pre- and postsurgical hindlimb perfusion was evaluated, and tissue survival, microvascular density, and macrophage infiltration were documented during recovery. Hindlimb perfusion was compromised in presurgical Cx40−/−versus WT mice despite comparable native microvascular density. Hindlimb perfusion 24 h postsurgery in Cx40−/−and WT mice was comparable after mild surgery (collateral vessels maintained), but compromised arteriogenesis in Cx40−/−animals nevertheless limited subsequent recovery of tissue perfusion and compromised tissue survival. Prolonged pre- and postsurgical treatment of Cx40−/−mice with losartan (an AT1R antagonist) normalized blood pressure but did not improve tissue perfusion or survival, despite reduced macrophage infiltration. Thus it appears Cx40 is necessary for normal tissue perfusion and for recovery of perfusion, arteriogenesis, and tissue survival in the ischemic hindlimb. Our data suggest that Cx40−/−mice are at significantly greater risk for poor recovery from ischemic insult due to compromised regulation of tissue perfusion, vascular remodeling, and prolonged inflammatory response.
T cell depletion protects against alveolar destruction due to chronic cigarette smoke exposure in mice
Authors: Podolin Patricia L. , Foley Joseph P. , Carpenter Donald C. , Bolognese Brian J. , Logan Gregory A. , Long Edward , Harrison Oliver J. , Walsh Patrick T.
Published: January 2013

The role of T cells in chronic obstructive pulmonary disease (COPD) is not well understood. We have previously demonstrated that chronic cigarette smoke exposure can lead to the accumulation of CD4+and CD8+T cells in the alveolar airspaces in a mouse model of COPD, implicating these cells in disease pathogenesis. However, whether specific inhibition of T cell responses represents a therapeutic strategy has not been fully investigated. In this study inhibition of T cell responses through specific depleting antibodies, or the T cell immunosuppressant drug cyclosporin A, prevented airspace enlargement and neutrophil infiltration in a mouse model of chronic cigarette smoke exposure. Furthermore, individual inhibition of either CD4+T helper or CD8+T cytotoxic cells prevented airspace enlargement to a similar degree, implicating both T cell subsets as critical mediators of the adaptive immune response induced by cigarette smoke exposure. Importantly, T cell depletion resulted in significantly decreased levels of the Th17-associated cytokine IL-17A, and of caspase 3 and caspase 7 gene expression and activity, induced by cigarette smoke exposure. Finally, inhibition of T cell responses in a therapeutic manner also inhibited cigarette smoke-induced airspace enlargement, IL-17A expression, and neutrophil influx in mice. Together these data demonstrate for the first time that therapeutic inhibition of T cell responses may be efficacious in the treatment of COPD. Given that broad immunosuppression may be undesirable in COPD patients, this study provides proof-of-concept for more targeted approaches to inhibiting the role of T cells in emphysema development.
Relaxin Family Peptides and Their Receptors
Authors: Bathgate R. A. D. , Halls M. L. , van der Westhuizen E. T. , Callander G. E. , Kocan M. , Summers R. J.
Published: January 2013

There are seven relaxin family peptides that are all structurally related to insulin. Relaxin has many roles in female and male reproduction, as a neuropeptide in the central nervous system, as a vasodilator and cardiac stimulant in the cardiovascular system, and as an antifibrotic agent. Insulin-like peptide-3 (INSL3) has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. Although they are structurally related to insulin, the relaxin family peptides produce their physiological effects by activating a group of four G protein-coupled receptors (GPCRs), relaxin family peptide receptors 1–4 (RXFP1–4). Relaxin and INSL3 are the cognate ligands for RXFP1 and RXFP2, respectively, that are leucine-rich repeat containing GPCRs. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Relaxin-3 and INSL5 are the cognate ligands for RXFP3 and RXFP4 that are closely related to small peptide receptors that when activated inhibit cAMP production and activate MAP kinases. Although there are still many unanswered questions regarding the mode of action of relaxin family peptides, it is clear that they have important physiological roles that could be exploited for therapeutic benefit.
Rhabdomyolysis and Dengue Fever: A Case Report and Literature Review
Authors: Sargeant Tanya , Harris Tricia , Wilks Rohan , Barned Sydney , Galloway-Blake Karen , Ferguson Trevor
Published: January 2013

The medical literature contains only a few reports of rhabdomyolysis occurring in patients with dengue fever. We report the case of a 25-year-old Jamaican man who was admitted to a private hospital four days after the onset of an acute febrile illness with fever, myalgia, and generalized weakness. Dengue fever was confirmed with a positive test for the dengue antigen, nonstructural protein 1. He remained well and was discharged on day 6 of his illness. On day 8, he started to pass red urine and was subsequently admitted to the University Hospital of the West Indies. On admission he was found to have myoglobinuria and an elevated creatine phosphokinase (CPK) of 325,600 U/L, leading to a diagnosis of rhabdomyolysis. Dengue IgM was positive. He was treated with aggressive hydration and had close monitoring of his urine output, creatinine, and CPK levels. His hospital course was uneventful without the development of acute renal failure and he was discharged after 14 days in hospital, with a CPK level of 2463 U/L. This case highlights that severe rhabdomyolysis may occur in patients with dengue fever and that early and aggressive treatment may prevent severe complications such as acute renal failure and death.
Spectroscopic Detection of Caries Lesions
Authors: Ruohonen Mika , Palo Katri , Alander Jarmo
Published: January 2013

Background. A caries lesion causes changes in the optical properties of the affected tissue. Currently a caries lesion can be detected only at a relatively late stage of development. Caries diagnosis also suffers from high interobserver variance. Methods. This is a pilot study to test the suitability of an optical diffuse reflectance spectroscopy for caries diagnosis. Reflectance visible/near-infrared spectroscopy (VIS/NIRS) was used to measure caries lesions and healthy enamel on extracted human teeth. The results were analysed with a computational algorithm in order to find a rule-based classification method to detect caries lesions. Results. The classification indicated that the measured points of enamel could be assigned to one of three classes: healthy enamel, a caries lesion, and stained healthy enamel. The features that enabled this were consistent with theory. Conclusions. It seems that spectroscopic measurements can help to reduce false positives at in vitro setting. However, further research is required to evaluate the strength of the evidence for the method’s performance.
The Photocatalytic Property of Nitrogen-Doped TiO2Nanoball Film
Authors: Wang Haiying , Hu Yanchun
Published: January 2013

TiO2nanoball films of nitrogen doping and no doping were prepared by anodic oxidation method. The nitrogen-doped samples exhibited significant enhanced absorption in visible light range, narrowing band gap from 3.2 eV to 2.8 eV and the smaller nanoball diameter size. The concentrations of methyl blue reduce to nearly 44% after 4-hour photodecomposition test by nitrogen-doped sample. It is indicated that there may be two main reasons for the enhanced photocatalytic activity: the increase of O vacancy and photocatalytic reactivity surface area in nitrogen-doped samples.
Infectious Keratitis: Secreted Bacterial Proteins That Mediate Corneal Damage
Authors: Marquart Mary E. , O'Callaghan Richard J.
Published: January 2013

Ocular bacterial infections are universally treated with antibiotics, which can eliminate the organism but cannot reverse the damage caused by bacterial products already present. The three very common causes of bacterial keratitis—Pseudomonas aeruginosa,Staphylococcus aureus, andStreptococcus pneumoniae—all produce proteins that directly or indirectly cause damage to the cornea that can result in reduced vision despite antibiotic treatment. Most, but not all, of these proteins are secreted toxins and enzymes that mediate host cell death, degradation of stromal collagen, cleavage of host cell surface molecules, or induction of a damaging inflammatory response. Studies of these bacterial pathogens have determined the proteins of interest that could be targets for future therapeutic options for decreasing corneal damage.
Antimicrobial Potential and Chemical Characterization of Serbian Liverwort (Porella arboris-vitae): SEM and TEM Observations
Authors: Kumar Tyagi Amit , Bukvicki Danka , Gottardi Davide , Veljic Milan , Guerzoni Maria Elisabetta , Malik Anushree , Marin Petar D.
Published: January 2013

The chemical composition ofPorella arboris-vitaeextracts was determined by solid phase microextraction, gas chromatography-mass spectrometry (SPME GC-MS), and 66 constituents were identified. The dominant compounds in methanol extract ofP.arboris-vitaewereβ-caryophyllene (14.7%),α-gurjunene (10.9%),α-selinene (10.8%),β-elemene (5.6%),γ-muurolene (4.6%), and allo-aromadendrene (4.3%) and in ethanol extract,β-caryophyllene (11.8%),α-selinene (9.6%),α-gurjunene (9.4%), isopentyl alcohol (8.8%), 2-hexanol (3.7%),β-elemene (3.7%), allo-aromadendrene (3.7%), andγ-muurolene (3.3%) were the major components. In ethyl acetate extract ofP.arboris-vitae, undecane (11.3%),β-caryophyllene (8.4%), dodecane (6.4%),α-gurjunene (6%), 2-methyldecane (5.1%), hemimellitene (4.9%), and D-limonene (3.9%) were major components. The antimicrobial activity of differentP.arboris-vitaeextracts was evaluated against selected food spoilage microorganisms using microbroth dilution method. The Minimal Inhibitory Concentration (MIC) varied from 0.5 to 1.5 mg/mL and 1.25 to 2 mg/mL for yeast and bacterial strains, respectively. Significant morphological and ultrastructural alterations due to the effect of methanolic and ethanolicP.arboris-vitaeextracts onS. Enteritidis have also been observed by scanning electron microscope and transmission electron microscope, respectively. The results provide the evidence of antimicrobial potential ofP.arboris-vitaeextracts and suggest its potential as natural antimicrobial agents for food preservation.
Tissue Reactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Tumors of Neuroectodermal, Mesodermal, and Epithelial Origin
Authors: Blanco Rancés , Quintana Yisel , Blanco Damián , Cedeño Mercedes , Rengifo Charles E. , Frómeta Milagros , Ríos Martha , Rengifo Enrique , Carr Adriana
Published: January 2013

The expression of N-glycolylneuraminic acid forming the structure of gangliosides and/or other glycoconjugates (Hanganutziu-Deicher antigen) in human has been considered as a tumor-associated antigen. Specifically, some reports of 14F7 Mab (a highly specific Mab raised against N-glycolyl GM3 ganglioside) reactivity in human tumors have been recently published. Nevertheless, tumors of epithelial origin have been mostly evaluated. The goal of the present paper was to evaluate the immunohistochemical recognition of 14F7 Mab in different human tumors of neuroectodermal, mesodermal, and epithelial origins using an immunoperoxidase staining method. Samples of fetal, normal, and reactive astrocytosis of the brain were also included in the study. In general, nontumoral tissues, as well as, low-grade brain tumors showed no or a limited immunoreaction with 14F7 Mab. Nevertheless, high-grade astrocytomas (III-IV) and neuroblastomas, as well as, sarcomas and thyroid carcinomas were mostly reactive with 14F7. No reaction was evidenced in medulloblastomas and ependymoblastomas. Our data suggest that the expression of N-glycolyl GM3 ganglioside could be related to the aggressive behavior of malignant cells, without depending on the tumor origin. Our data could also support the possible use of N-glycolyl GM3 as a target for both active and passive immunotherapies of malignancies expressing this molecule.