bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing effective animal‐assisted intervention programs involving visiting dogs for institutionalized geriatric patients: a pilot study
Authors: BERRY Alessandra , BORGI Marta , TERRANOVA Livia , CHIAROTTI Flavia , ALLEVA Enrico , CIRULLI Francesca
Published: September 2012

Aim:  An ever increasing interest in the therapeutic aspects of the human‐animal bond has led to a proliferation of animal‐assisted interventions (AAI) involving dogs. However, most of these programs lack a solid methodological structure, and basic evaluative research is needed. The purpose of this study was to test the value of dog‐assisted interventions as an innovative tool to increase quality of life in the geriatric population.

Methods:  Nineteen patients (men and women) with a mean age of 85 years participated in the study. Interactions between patients and visiting dogs occurred either in a social situation (socialization sessions) or in a therapeutic context (physical therapy sessions). We derived and characterized a specific ethogram of elderly‐dog interactions aimed at evaluating the effectiveness of visiting dogs in improving mood, catalyzing social interactions and reducing their everyday apathetic state. Cortisol levels were also measured in the saliva, and depressive state was evaluated.

Results:  Overall, results show a time‐dependent increase in social behaviour and spontaneous interactions with the dogs. Dog‐mediated interactions affected the daily increase in cortisol levels, thus having an ‘activational effect’, in contrast to the apathetic state of institutionalized elderly.

Conclusions:  Dog‐mediated intervention programs appear to be promising tools to improve the social skills and enrich the daily activities of the institutionalized elderly.
Randomized controlled trial of home rehabilitation for patients with ischemic stroke: impact upon disability and elderly depression
Authors: CHAIYAWAT Pakaratee , KULKANTRAKORN Kongkiat
Published: September 2012

Background:  Patients with major stroke are often left with disability and may have depression and dementia during the recovery phase. Rehabilitation programmes have been shown to improve short‐term physical outcome, but their long‐term effectiveness and impact on dementia and depression are uncertain.

Methods:  We performed a 6‐month randomized controlled trial of a home rehabilitation programme and compared it with the standard care patients with recent ischemic stroke receive. The intervention group received home‐based physical therapy once a month for 6 months, along with educational support, counselling and audiovisual materials. The control group received rehabilitation as prescribed by a physician and educational materials upon discharge from hospital. The primary measurement was a change in Barthel Index. Secondary measurements were the Hospital Anxiety and Depression Scale (HADS) and Thai Mini‐Mental State Examination.

Results:  Of the 68 screened patients, 60 patients were enrolled. At baseline, there was no significant difference in patient characteristics between the two groups. Over 2 years, the mean Barthel Index and Hospital Anxiety and Depression Scale were significantly improved in the intervention group compared to the control group (Barthel Index mean: from 31.7 ± 5.9 to 97.2 ± 2.8 vs from 33.2 ± 4.8 to 76.4 ± 9.4, P < 0.001; Hospital Anxiety and Depression Scale mean: from 16.1 ± 7.6 to 9.1 ± 0.3 vs 16.4 ± 4.9 to 9.1 ± 0.3, P= 0.003). Depression was strongly associated with being dependent on others. However, the Thai Mini‐Mental State Examination in both groups did not significantly differ (Thai Mini‐Mental State Examination mean: from 24.4 ± 2.0 to 24.6 vs 23.8 ± 1.9 to 24.1 ± 0.3, P= 0.068). There was no significant interaction between baseline characteristics and treatment outcome.

Conclusions:  At 2 years follow‐up, it was evident that a 6‐month home rehabilitation programme after ischemic stroke improved functional outcome and reduced incidence of depression, but not dementia.
Antiepileptic drugs and suicidality: An expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology
Authors: Mula Marco , Kanner Andres M. , Schmitz Bettina , Schachter Steven
Published: September 2012

In 2008, the U.S. Food and Drug Administration (FDA) issued an alert to health care professionals about an increased risk of suicide ideation and suicide behavior in people treated with antiepileptic drugs (AEDs). Since then, a number of retrospective cohort and case–control studies have been published that are trying to address this issue, but gathered results are contradictory. This report represents an expert consensus statement developed by an ad hoc task force of the Commission on Neuropsychobiology of the International League Against Epilepsy (ILAE). Although some (but not all) AEDs can be associated with treatment‐emergent psychiatric problems that can lead to suicidal ideation and behavior, the actual suicidal risk is yet to be established, but it seems to be very low. The risk of stopping AEDs or refusing to start AEDs is significantly worse and can actually result in serious harm including death to the patient. Suicidality in epilepsy is multifactorial, and different variables are operant. Clinicians should investigate the existence of such risk factors and adopt appropriate screening instruments. If necessary, patients should be referred for a psychiatric evaluation, but AED treatment should not be withheld, even in patients with positive suicidal risks. When starting an AED or switching from one to other AEDs, patients should be advised to report to their treating physician any change in mood and suicidal ideation. Data on treatment‐emergent psychiatric adverse events need to be collected, in addition to general safety information, during controlled studies in order to have meaningful information for patients and their relatives when a new drug is marketed.
Optimal Simple Monetary and Fiscal Rules under Limited Asset Market Participation
Authors: MOTTA GIORGIO , TIRELLI PATRIZIO
Published: September 2012

The combination of limited asset market participation and consumption habits generates indeterminacy for empirically plausible calibrations of a business cycle model characterized by price and nominal wage rigidities. Equilibrium determinacy is restored by demand management policies based on simple fiscal rules. In this regard, fiscal control of nominal income growth is particularly effective. In addition the complementarity between the Taylor rule and the fiscal feedback on nominal income growth produces relatively large welfare gains, limiting both aggregate and intragroup volatilities.
Mortgage Choice as a Natural Field Experiment on Choice under Risk
Authors: BACON PHILOMENA M. , MOFFATT PETER G.
Published: September 2012

Data on approximately 280,000 borrowers from the UK Survey of Mortgage Lenders are used to model choices between variable and fixed rate mortgages. The choice is assumed to depend on three factors: risk attitude, interest‐rate expectations, and individual discount rate. The ordered probit model is used for estimation, while taking account of a number of econometric issues including missing counterfactuals, selectivity, and endogeneity. A large number of strong effects are found, including: higher income borrowers are less risk averse and have a lower discount rate, and risk aversion rises with the amount borrowed, providing evidence of increasing relative risk aversion.
Intracoronary Hemodynamic Effects of Pressure‐Controlled Intermittent Coronary Sinus Occlusion (PICSO): Results from the First‐In‐Man Prepare PICSO Study
Authors: VAN DE HOEF TIM P , NOLTE FROUKJE , DELEWI RONAK , HENRIQUES JOSE P.S , SPAAN JOS A.E , TIJSSEN JAN G.P , SIEBES MARIA , WYKRZYKOWSKA JOANNA J. , STONE GREGG W. , PIEK JAN J.
Published: September 2012

Background:
 Myocardial reperfusion is frequently suboptimal after ST‐segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). Using a balloon‐tipped catheter positioned in the coronary sinus (CS), pressure‐controlled intermittent coronary sinus occlusion (PICSO) results in an intermittent obstruction of coronary venous outflow of the left anterior descending artery (LAD), and may improve myocardial perfusion by augmenting redistribution of blood to the border zone of ischemic myocardium. We sought to document the intracoronary hemodynamic effects of PICSO during PCI.

Methods:
 We included 15 patients with stable angina scheduled for PCI of the LAD. Balloon occlusion of the LAD was performed twice, once with and once without PICSO and lasting maximally 3 minutes each, to document the effect of PICSO on CS pressure and LAD wedge pressure.

Results:
 Catheter delivery was successful in all patients. The study protocol could not be conducted in 5 patients due to initial calibration difficulties (n = 3), a pressure wire problem (n = 1), and a vagal response at the start of the procedure (n = 1). In the remaining 10 patients, CS occlusion caused a marked increase in mean CS pressure (4.1 ± 7.3 mmHg vs. 22.0 ± 12.6 mmHg; P < 0.001) and CS pulse pressure (4.3 ± 0.8 mmHg vs. 36.1 ± 6.3 mmHg; P < 0.001). Concomitantly, mean distal LAD wedge pressure and wedge pulse pressure increased (32.4 ± 12.2 mmHg vs. 35.5 ± 12.6 mmHg; P < 0.001 and 39.1 ± 27.2 mmHg vs. 45.9 ± 26.0 mmHg; P < 0.001, respectively). At 30 day follow‐up, no device‐related events occurred.

Conclusions:
 PICSO safely augments CS pressure, thereby increasing LAD coronary wedge pressure. These findings support further evaluation of PICSO in the setting of STEMI. (J Interven Cardiol 2012;25:549–556)
Analysis of Longitudinal Clinical Trials with Missing Data Using Multiple Imputation in Conjunction with Robust Regression
Authors: Mehrotra Devan V. , Li Xiaoming , Liu Jiajun , Lu Kaifeng
Published: September 2012

SummaryIn a typical randomized clinical trial, a continuous variable of interest (e.g., bone density) is measured at baseline and fixed postbaseline time points. The resulting longitudinal data, often incomplete due to dropouts and other reasons, are commonly analyzed using parametric likelihood‐based methods that assume multivariate normality of the response vector. If the normality assumption is deemed untenable, then semiparametric methods such as (weighted) generalized estimating equations are considered. We propose an alternate approach in which the missing data problem is tackled using multiple imputation, and each imputed dataset is analyzed using robust regression (M‐estimation;Huber, 1973,Annals of Statistics 1,799–821.) to protect against potential non‐normality/outliers in the original or imputed dataset. The robust analysis results from each imputed dataset are combined for overall estimation and inference using either the simpleRubin (1987,Multiple Imputation for Nonresponse in Surveys, New York: Wiley) method, or the more complex but potentially more accurateRobins and Wang (2000,Biometrika 87,113–124.) method. We use simulations to show that our proposed approach performs at least as well as the standard methods under normality, but is notably better under both elliptically symmetric and asymmetric non‐normal distributions. A clinical trial example is used for illustration.
Sorrow: A Therapist's Reflection on the Inevitable and the Unknowable
Authors: Weingarten Kaethe
Published: September 2012

People who live with a painful gap between who they have been and who they are now, of who they dreamt themselves to be and who they still long to be, are living with chronic sorrow. Chronic sorrow is a normal, nonpathological state of pervasive, continuing, periodic, and resurgent sadness related to the ongoing losses associated with illness and disability, in this case not loss of an other, but loss of self (Roos, 2002). Focusing on the lives of four women, one of whom committed suicide, I explore the macroprocesses that invade the experience of even so personal an experience as self‐loss. The role of the therapist is made transparent through anecdotes and by discussing implications for clinical practice.
Quality of Life and Adjustment in Youths with Asthma: The Contributions of Family Rituals and the Family Environment
Authors: Santos Susana , Crespo Carla , Silva Neuza , Canavarro Maria Cristina
Published: September 2012

This cross‐sectional study explored the relationships among family ritual meaning, cohesion, conflict, and health‐related quality of life (both specific to chronic health conditions and in general), and the emotional and behavioral problems reported by youths with asthma. Participants included 149 Portuguese children and adolescents between the ages of 8 and 18 who had been diagnosed with asthma and attended outpatient services at three public hospitals. The results showed that stronger family ritual meaning predicted a more positive family environment (i.e., higher cohesion levels and lower conflict levels), better health‐related quality of life, and fewer emotional and behavior problems in youths. Furthermore, family cohesion and conflict mediated the links between family ritual meaning and health‐related quality of life, and emotional and behavioral problems. These results did not change after controlling for participant age, gender, and asthma severity. The findings of this study suggest that family ritual meaning contributes to the adaptation of youths with asthma via its positive association with the family environment. The implications for multicontextual interventions with families are briefly discussed with regard to the positive role of family rituals and of their potential as a modifiable factor in families with increased health challenges.
Implementation of Parent Management Training—Oregon Model (PMTOTM) in Iceland: Building Sustained Fidelity
Authors: Sigmarsdóttir Margrét , Guðmundsdóttir Edda Vikar
Published: September 2012

Bringing empirically supported treatments (ESTs) into community settings is a challenge because of threats to therapy adherence. The nationwide implementation of Parent Management Training—the Oregon Model (PMTO) in Iceland was studied by comparing therapists' competent adherence to PMTO across three generations of therapists. To assess therapists' competence and adherence to the PMTO method, the Fidelity of Implementation Rating System (FIMP) was used as the measuring device. Of 16 therapists across three generations who entered training, 12 completed with certification. As expected, each of the three generations obtained adequate FIMP scores. Generations 1 and 3 showed equivalent levels of performance on FIMP scores at certification. A small drop in FIMP scores for Generation 2 was explained in terms of translating and culturally adjusting materials and strengthening training procedures. Results are parallel to earlier findings from the nationwide PMTO implementation in Norway and support the idea that PMTO can be implemented in community settings with high fidelity even when resources are scarce.
Alternate Light Sources in the Detection of Bone After an Accelerated Fire: A Pilot Study
Authors: Gallant Amber S.
Published: September 2012

This study examines the ability of alternate light sources to detect bone that has been exposed to fire when identification of bone remains is difficult to ascertain. It is intended as a tool for fire investigators to quickly determine whether an area should be considered a forensic scene. After being subjected to a test burn, pig bones were viewed and photographed with the use of a laser, and later compared with aUVlight source. A secondary study observing stages of a human cremation was conducted to assess how various levels of burnt flesh affect the ability of bone to fluoresce utilizing a laser. Both studies demonstrated success in detecting bone while fluorescing with a molten lava type of appearance that has the potential to distinguish bone from its surrounding environment. Limitations and recommendations are discussed by the author including the need for future studies to expand on this research.
Stereotactic body radiotherapy for prostate cancer: A preliminary report
Authors: Lee Yun Hee , Son Seok Hyun , Yoon Sei Chul , Yu Mina , Choi Byung Ock , Kim Yeon Sil , Jang Hong Seok , Lee Sang Nam , Jang Ji Sun , Hwang Tae Kon
Published: September 2012

Aims

We report the results of a retrospective study of stereotactic body radiotherapy (SBRT) using a Cyberknife for prostate cancer.

Methods

In all 29 patients were treated with hypofractionated SBRT using a Cyberknife at median 36 Gy in five fractions. All the patients were treated with a radical aim. Prostate‐specific antigen (PSA) was evaluated at baseline and after radiotherapy. Acute (≤3 months) and late (>3 months) urinary and rectal toxicities were recorded according to the CTCAE version 4.0.

Results

The median duration of follow up was 41 months. PSA values decreased in a time‐dependent way. The median PSA nadir was 0.329 ng/mL, achieved after a median of 23 months’ follow up. Two patients had a PSA failure according to the definition of nadir + 2 ng/mL. Eight patients (28%) had a benign PSA bounce at median 9 months after radiotherapy. CTCAE Grade 2 and 3 late urinary toxicities were reported in 3 and 3%, respectively. One patient had exacerbated urinary symptoms and received an operation. There were no severe late rectal toxicities.

Conclusions

The preliminary findings of our study suggest SBRT is feasible for prostate cancer treatment. Further studies with more patients and longer follow‐up duration are required.
Ancillary approaches to plasminogen activators
Authors: Bavarsad Shahripour Reza , Alexandrov Andrei V.
Published: September 2012

Acute ischemic stroke develops from an interruption in focal cerebral blood flow. In many cases, it is caused by an acute thromboembolism. Although systemic fibrinolytic therapy for acute ischemic stroke has been a significant breakthrough in the management of this disease, additional agents and methods that could improve or restore cerebral flow are necessary. Similarly to findings in acute myocardial infarction, combination pharmacotherapy has the potential to improve current thrombolytic treatment in acute ischemic stroke. In recent years, research efforts were directed toward various combination therapy with pharmacological and nonpharmacological methods. Several trials tested tissue plasminogen activator (t‐PA) in combination with antiplateletes and anticoagulants. Combination of t‐PA with nonpharmacological agents included sonothrombolysis (amplifying the thrombolytic effect), laser (neuro‐recovery), hypothermia (cytoprotection and decreasing brain swelling), and blood flow augmentation (increasing residual flow and recruitment of collateral vessels). This paper will review ongoing clinical trials and safety of these promising combinatory treatments.
Timing of thrombolysis for acute ischemic stroke: “timing is everything” or “everyone is different”
Authors: Grotta James
Published: September 2012

It is indisputable that in the first 2 to 3 hours of an acute ischemic, the best strategy to maximize recovery is robustly time‐based and depends on getting the artery open as soon as possible. The second law of thermodynamics and the underappreciated effect of clot consistency and size must be accounted for in our efforts to minimize time to recanalization within the first 2 to 3 hours. It is also clear that at later time intervals, beyond 4.5 hours, few patients completely recover even with sustained complete recanalization, and that the ability to recover depends more on physiologic tissue issues than on the duration of the occlusion. Clinical factors as well as imaging should be used to select patients who may benefit from delayed attempts at reperfusion.
Why a Macroeconomic Perspective Is Critical to the Prevention of Noncommunicable Disease
Authors: Smith Richard
Published: September 2012

Effective prevention of noncommunicable diseases will require changes in how we live, and thereby effect important economic changes across populations, sectors, and countries. What we do not know is which populations, sectors, or countries will be positively or negatively affected by such changes, nor by how much. Without this information we cannot know which policies will produce effects that are beneficial both for economies and for health.
Structural Basis for Microtubule Binding and Release by Dynein
Authors: Redwine William B. , Hernández-López Rogelio , Zou Sirui , Huang Julie , Reck-Peterson Samara L. , Leschziner Andres E.
Published: September 2012

Motoring Along

Dyneins are large and complex molecular motors that transport cargo along cellular microtubules and power the movement of cilia. An enigma is how microtubule binding and nucleotide hydrolysis are coordinated between sites separated by 25 nm.

Redwine
et al.

(p.
1532
) report an electron microscopy structure of the dynein microtubule-binding domain bound to microtubules in a high-affinity state and combined this with molecular dynamics and existing x-ray structures to provide a model for how dynein couples its affinity for microtubules with the nucleotide-bound state of the motor domain.
Neighborhood Effects on the Long-Term Well-Being of Low-Income Adults
Authors: Ludwig Jens , Duncan Greg J. , Gennetian Lisa A. , Katz Lawrence F. , Kessler Ronald C. , Kling Jeffrey R. , Sanbonmatsu Lisa
Published: September 2012

Location, Location, Location

It seems obvious that a person's residential neighborhood will influence their sense of well-being, but it has been difficult to nail down cause and effect.Ludwiget al.(p.1505; see the Perspective bySampson) describe the analysis, 10 to 15 years onward, of a large-scale social experiment carried out in five U.S. cities in the mid 1990s. Several thousand residents of poor neighborhoods were given housing vouchers that could only be used if they moved into much less poor neighborhoods. In comparison to a similar group of individuals who did not move, those who did experienced substantial improvement in their subjective well-being.
Response to Comment on “A Common Pesticide Decreases Foraging Success and Survival in Honey Bees”
Authors: Henry Mickaël , Béguin Maxime , Requier Fabrice , Rollin Orianne , Odoux Jean-François , Aupinel Pierrick , Aptel Jean , Tchamitchian Sylvie , Decourtye Axel
Published: September 2012

Cresswell and Thompson have suggested an elegant way to improve honey bee colony simulations when forecasting the fate of colonies exposed to pesticides. Following their recommendations, we rescaled the model on a sound empirical data set. The adjusted forecast is bleaker than their tentative scenario.
Nanometer-Scale Printing
Authors: Rogers John A.
Published: September 2012

A method using rubber stamps and molecular-scale fracture can produce patterns with feature sizes in the nanometer range.
Despite Setbacks, Optimism on Drugs for Hepatitis C
Authors: Cohen Jon
Published: September 2012

Researchers have hit speed bumps on the road they hope will soon lead to a safe, short course of treatment that will rid the body of this liver-damaging virus.
Tackling America's Eating Habits, One Store at a Time
Authors: Couzin-Frankel Jennifer
Published: September 2012

Several initiatives are evaluating if easing access to healthy food will change how Americans eat—and reduce obesity around the country.
Chronic Disease Vaccines Need Shot in the Arm
Authors: Trivedi Bijal
Published: September 2012

Whether vaccines to prevent obesity, asthma, smoking-related illnesses, and other chronic diseases will ever work remains an open question.
Single Nucleotide Polymorphisms in the Mycobacterium bovis Genome Resolve Phylogenetic Relationships
Authors: Joshi Deepti , Harris N. Beth , Waters Ray , Thacker Tyler , Mathema Barun , Krieswirth Barry , Sreevatsan Srinand
Published: September 2012

Mycobacterium bovis
isolates carry restricted allelic variation yet exhibit a range of disease phenotypes and host preferences. Conventional genotyping methods target small hypervariable regions of the
M. bovis
genome and provide anonymous biallelic information that is insufficient to develop phylogeny. To resolve phylogeny and establish trait-allele associations, we interrogated 75
M. bovis
and 61
M. tuberculosis
genomes for single nucleotide polymorphisms (SNPs), using iPLEX MassArray (Sequenom Inc., CA) technology. We indexed nucleotide variations in 306 genic and 44 intergenic loci among isolates derived from outbreaks in the United States from 1991 to 2010 and isolated from a variety of mammalian hosts. Two hundred six variant SNPs classified the 136 isolates and 4 previously sequenced strains (AF2122/97, BCG Pasteur, H37Rv, and CDC1551) into 5 major “SNP cluster groups.”
M. bovis
isolates clustered into three major lineages based on 118 variant SNPs, while 84 SNPs differentiated the
M. bovis
BCG lineage from the virulent isolates. Forty-nine of the 51 human
M. tuberculosis
isolates were identical at all 350 loci studied. Thus, SNP-based analyses resolved the genotypic differences within
M. bovis
strains and differentiated these strains from
M. tuberculosis
strains representing diversity in time and space, providing population genetic frameworks that may aid in identifying factors responsible for the wide host range and disease phenotypes of
M. bovis
.
Evaluation of the FTA Carrier Device for Human Papillomavirus Testing in Developing Countries
Authors: Gonzalez Paula , Cortes Bernal , Quint Wim , Kreimer Aimée R. , Porras Carolina , Rodríguez Ana Cecilia , Jimenez Silvia , Herrero Rolando , Struijk Linda , Hildesheim Allan , Melchers Willem
Published: September 2012

Liquid-based methods for the collection, transportation, and storage of cervical cells are cumbersome and expensive and involve laborious DNA extraction. An FTA cartridge is a solid carrier device, easier to handle and allowing simple DNA elution for human papillomavirus (HPV) testing. HPV-DNA results from cervical specimens collected in PreservCyt medium (Hologic, Inc.) and the indicating FTA elute cartridge were compared in an area where transportation and storage may affect the performance of the test. Cervical cells from 319 young adult women enrolled in the Costa Rica Vaccine Trial were collected by a nurse using a Cervex brush (Roberts), which was placed on the FTA cartridge and subsequently rinsed in 20 ml of PreservCyt medium. Two 0.5-ml PreservCyt aliquots were frozen for HPV-PCR testing; the FTA cartridges were kept at room temperature. HPV-DNA detection and typing was performed using SPF
10
PCR/DEIA (DNA enzyme immunoassay detection of amplimers)/LiPA
25
system. The percent agreement, agreement among positives, and kappas were estimated. Positivity was higher for FTA compared to PreservCyt specimens (54.5% versus 45.8%,
P
< 0.001). For oncogenic types, the overall agreement was 0.92, the agreement between positives was 0.74, and the kappa was 0.79. For individual HPV types, the overall agreement ranged from 0.97 to 1.00. We did not observe reduced cytology adequacy when specimen collection for cytology was preceded by FTA collection for HPV testing. HPV-DNA detection from FTA cartridges is broadly comparable to detection from PC medium. The higher HPV detection observed for FTA-collected specimens should be explored further. FTA cartridges could provide a simpler and more cost-effective method for cervical cell collection, storage, and transportation for HPV-DNA detection in research settings in developing countries.
NS5A Sequence Heterogeneity of Hepatitis C Virus Genotype 4a Predicts Clinical Outcome of Pegylated-Interferon–Ribavirin Therapy in Egyptian Patients
Authors: El-Shamy Ahmed , Shoji Ikuo , El-Akel Wafaa , Bilasy Shymaa E. , Deng Lin , El-Raziky Maissa , Jiang Da-peng , Esmat Gamal , Hotta Hak
Published: September 2012

Hepatitis C virus genotype 4 (HCV-4) is the cause of approximately 20% of the 180 million cases of chronic hepatitis C in the world. HCV-4 infection is common in the Middle East and Africa, with an extraordinarily high prevalence in Egypt. Viral genetic polymorphisms, especially within core and NS5A regions, have been implicated in influencing the response to pegylated-interferon and ribavirin (PEG-IFN/RBV) combination therapy in HCV-1 infection. However, this has not been confirmed in HCV-4 infection. Here, we investigated the impact of heterogeneity of NS5A and core proteins of HCV-4, mostly subtype HCV-4a, on the clinical outcomes of 43 Egyptian patients treated with PEG-IFN/RBV. Sliding window analysis over the carboxy terminus of NS5A protein identified the IFN/RBV resistance-determining region (IRRDR) as the most prominent region associated with sustained virological response (SVR). Indeed, 21 (84%) of 25 patients with SVR, but only 5 (28%) of 18 patients with non-SVR, were infected with HCV having IRRDR with 4 or more mutations (IRRDR ≥ 4) (
P
= 0.0004). Multivariate analysis identified IRRDR ≥ 4 as an independent SVR predictor. The positive predictive value of IRRDR ≥ 4 for SVR was 81% (21/26;
P
= 0.002), while its negative predictive value for non-SVR was 76% (13/17;
P
= 0.02). On the other hand, there was no significant correlation between core protein polymorphisms, either at residue 70 or at residue 91, and treatment outcome. In conclusion, the present results demonstrate for the first time that IRRDR ≥ 4, a viral genetic heterogeneity, would be a useful predictive marker for SVR in HCV-4 infection when treated with PEG-IFN/RBV.
A Herpes Simplex Virus 2 Glycoprotein D Mutant Generated by Bacterial Artificial Chromosome Mutagenesis Is Severely Impaired for Infecting Neuronal Cells and Infects Only Vero Cells Expressing Exogenous HVEM
Authors: Wang Kening , Kappel Justin D. , Canders Caleb , Davila Wilmer F. , Sayre Dean , Chavez Mayra , Pesnicak Lesley , Cohen Jeffrey I.
Published: September 2012

We constructed a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) clone, bHSV2-BAC38, which contains full-length HSV-2 inserted into a BAC vector. Unlike previously reported HSV-2 BAC clones, the virus genome inserted into this BAC clone has no known gene disruptions. Virus derived from the BAC clone had a wild-type phenotype for growth
in vitro
and for acute infection, latency, and reactivation in mice. HVEM, expressed on epithelial cells and lymphocytes, and nectin-1, expressed on neurons and epithelial cells, are the two principal receptors used by HSV to enter cells. We used the HSV-2 BAC clone to construct an HSV-2 glycoprotein D mutant (HSV2-gD27) with point mutations in amino acids 215, 222, and 223, which are critical for the interaction of gD with nectin-1. HSV2-gD27 infected cells expressing HVEM, including a human epithelial cell line. However, the virus lost the ability to infect cells expressing only nectin-1, including neuronal cell lines, and did not infect ganglia in mice. Surprisingly, we found that HSV2-gD27 could not infect Vero cells unless we transduced the cells with a retrovirus expressing HVEM. High-level expression of HVEM in Vero cells also resulted in increased syncytia and enhanced cell-to-cell spread in cells infected with wild-type HSV-2. The inability of the HSV2-gD27 mutant to infect neuronal cells
in vitro
or sensory ganglia in mice after intramuscular inoculation suggests that this HSV-2 mutant might be an attractive candidate for a live attenuated HSV-2 vaccine.
Complete Genome Sequence of Two Variant Porcine Reproductive and Respiratory Syndrome Viruses Isolated from Vaccinated Piglets
Authors: Zhang Guanqun , Lu Wenhui , Chen Yanshan , Zhu Ling , Wei Zhongyan , Li Zhili , Sun Baoli , Xie Qingmei , Bi Yingzuo , Ma Jingyun
Published: September 2012

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to affect the Chinese swine industry. Since 2006, variant PRRSV strains sharing two unique discontinuous deletions of 30 amino acids in the nonstructural protein Nsp2 have become dominant in Chinese swine herds and have caused huge economic losses to the swine industry in China. Here we report the complete genome sequence of two novel PRRSV variants isolated from vaccinated piglets with additional amino acid deletions in Nsp2.
Complete Genome Sequence of a Novel Newcastle Disease Virus Strain Isolated from a Chicken in West Africa
Authors: Kim Shin-Hee , Nayak Subhashree , Paldurai Anandan , Nayak Baibaswata , Samuel Arthur , Aplogan Gilbert L. , Awoume Kodzo A. , Webby Richard J. , Ducatez Mariette F. , Collins Peter L. , Samal Siba K.
Published: September 2012

The complete genome sequence of an African Newcastle disease virus (NDV) strain isolated from a chicken in Togo in 2009 was determined. The genome is 15,198 nucleotides (nt) in length and is classified in genotype VII in the class II cluster. Compared to common vaccine strains, the African strain contains a previously described 6-nt insert in the downstream untranslated region of the N gene and a novel 6-nt insert in the HN-L intergenic region. Genome length differences are a marker of the natural history of NDV. This is the first description of a class II NDV strain with a genome of 15,198 nt and a 6-nt insert in the HN-L intergenic region. Sequence divergence relative to vaccine strains was substantial, likely contributes to outbreaks, and illustrates the continued evolution of new NDV strains in West Africa.
Regulation of Paramyxovirus Fusion Activation: the Hemagglutinin-Neuraminidase Protein Stabilizes the Fusion Protein in a Pretriggered State
Authors: Porotto Matteo , Salah Zuhair W. , Gui Long , DeVito Ilaria , Jurgens Eric M. , Lu Hong , Yokoyama Christine C. , Palermo Laura M. , Lee Kelly K. , Moscona Anne
Published: September 2012

The hemagglutinin (HA)-neuraminidase protein (HN) of paramyxoviruses carries out three discrete activities, each of which affects the ability of HN to promote viral fusion and entry: receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein. Binding of HN to its sialic acid receptor on a target cell triggers its activation of the fusion protein (F), which then inserts into the target cell and mediates the membrane fusion that initiates infection. We provide new evidence for a fourth function of HN: stabilization of the F protein in its pretriggered state before activation. Influenza virus hemagglutinin protein (uncleaved HA) was used as a nonspecific binding protein to tether F-expressing cells to target cells, and heat was used to activate F, indicating that the prefusion state of F can be triggered to initiate structural rearrangement and fusion by temperature. HN expression along with uncleaved HA and F enhances the F activation if HN is permitted to engage the receptor. However, if HN is prevented from engaging the receptor by the use of a small compound, temperature-induced F activation is curtailed. The results indicate that HN helps stabilize the prefusion state of F, and analysis of a stalk domain mutant HN reveals that the stalk domain of HN mediates the F-stabilization effect.
Complete Genome Sequence of a Novel Pestivirus from Sheep
Authors: Becher Paul , Schmeiser Stefanie , Oguzoglu Tuba Cigdem , Postel Alexander
Published: September 2012

We report here the complete genome sequence of pestivirus strain Aydin/04-TR, which is the prototype of a group of similar viruses currently present in sheep and goats in Turkey. Sequence data from this virus showed that it clusters separately from the established and previously proposed tentative pestivirus species.
Contribution of NS1 Effector Domain Dimerization to Influenza A Virus Replication and Virulence
Authors: Ayllon Juan , Russell Rupert J. , García-Sastre Adolfo , Hale Benjamin G.
Published: September 2012

Conserved tryptophan-187 facilitates homodimerization of the influenza A virus NS1 protein effector domain. We generated a mutant influenza virus strain expressing NS1-W187R to destabilize this self-interaction. NS1-W187R protein exhibited lower double-stranded RNA (dsRNA)-binding activity, showed a temporal redistribution during infection, and was minimally compromised for interferon antagonism. The mutant virus replicated similarly to the wild type
in vitro
, but it was slightly attenuated for replication in mice, causing notably reduced morbidity and mortality. These data suggest biological relevance for the W187-mediated homotypic interaction of NS1.
MAGIC NUCLEI IN SUPERHEAVY VALLEY
Authors: BHUYAN M. , PATRA S. K.
Published: September 2012

An extensive theoretical search for the proton magic number in the superheavy valley beyond Z = 82 and the corresponding neutron magic number after N = 126 is carried out. For this we scanned a wide range of elements Z = 112–130 and their isotopes. The well-established non-relativistic Skryme–Hartree–Fock and Relativistic Mean Field formalisms with various force parameters are used. Based on the calculated systematics of pairing gap, two-neutron separation energy and the shell correction energy for these nuclei, we find Z = 120 as the next proton magic and N = 172, 182/184, 208 and 258 the subsequent neutron magic numbers.
SPINOR PARTICLES IN THE SPACETIMES OF VACUUMLESS DEFECTS
Authors: FERNANDES SANDRO G. , MARQUES GEUSA DE A. , BEZERRA V. B.
Published: September 2012

We obtain approximate solutions of the Dirac equation in the gravitational fields of vacuumless defects. In all obtained solutions we show the role played by the presence of these defects.
SPECIFIC ANGULAR MOMENTUM DISTRIBUTION FOR SOLAR ANALOGS AND TWINS: WHERE IS THE SUN MISSING HIS ANGULAR MOMENTUM?
Authors: DA COSTA J. S. , DO NASCIMENTO J. D.
Published: September 2012

It is well established that there is a breakdown in the curve of specific angular momentum as a function of mass for stars on the main sequence Ref. 5. Stars earlier than F5 and more massive than the sun, rotate rapidly over a large mass range. For spectral type F5 and later, including the Sun, much smaller rotational velocities are found. We revisit this question from a new sample to shed a light on the basis of a sample solar twins and analogs recently observed by interferometric measurements of stellar radius. Our results clearly show that, as the Sun, the solar twins present similar global behavior from their specific angular momentum. 18 Sco and HIP 100963 have a specific angular momentum one order higher than the solar value, and HIP 55459 and HIP 56948 have a specific angular momentum one order lower than the solar value.
ON THE GEOMETRICAL CONFINEMENT OF FERMIONS
Authors: FORMIGA J. B. , ROMERO C.
Published: September 2012

To show the important role that geometry may play in the problem of confining particles to our four-dimensional spacetime, we consider a five-dimensional model where fermions are confined in a hypersurface due to an interaction with geometric fields. We use two different fields which appear in non-Riemannian geometries, namely, the Weyl one-form and the torsion two-form. We show that for suitable choices of these fields one manages to confine fermions in our brane (our four-dimensional world). It turns out that this confinement is independent of the energy and the mass of the fermions.
Red Turpentine Beetle: Innocuous Native Becomes Invasive Tree Killer in China
Authors: Sun Jianghua , Lu Min , Gillette Nancy E. , Wingfield Michael J.
Published: September 2012

The red turpentine beetle (RTB), Dendroctonus valens LeConte (Coleoptera: Curculionidae: Scolytinae), is a secondary pest of pines in its native range in North and Central America. Outbreaks and tree mortality attributed to RTB alone are rare in its native range. RTB was introduced into China in the early 1980s and spread rapidly from Shanxi Province to four adjacent provinces; it has infested over 500,000 ha of pine forest and has caused extensive tree mortality since 1999. We provide a historical background on RTB outbreaks, explanations for its invasive success, management options, and economic impacts of RTB in China. Genetic variation in RTB fungal associates, interactions between RTB and its associated fungi, behavioral differences in Chinese RTB, and other factors favoring RTB outbreaks are considered in an effort to explain the invasiveness of RTB in China. The promise of semiochemicals as a management tool is also discussed.
Efficient Markets and the Law: A Predictable Past and an Uncertain Future
Authors: Hu Henry T.C.
Published: September 2012

This article analyzes the manifold situations in which the efficient-market hypothesis (EMH) has influenced—or has failed to influence—federal securities regulation and state corporate law, and the prospective roles for the EMH in these contexts. In federal securities regulation, the EMH has offered a theoretical construct to accompany the general belief in the value of accurate and complete information that has animated the US Securities and Exchange Commission (SEC) since its creation. Specific applications of the EMH have been straightforward and predictable: For instance, its tenets as to market processing of public information helped motivate the streamlining of procedural requirements as to corporate disclosures and, more controversially, as to private securities class action lawsuits. In state corporate law, the EMH has influenced developments as to takeovers and the corporate objective. In contrast, the EMH and related learning have failed to sufficiently inform governmental actions to address financial illiteracy. Belief in the EMH and the value of efficient markets has weakened in the face of recent market anomalies and stress. The May 2010 flash crash is not easily reconciled with the EMH, and related phenomena such as high frequency trading involve an equity market microstructure far different from the microstructure at the time the EMH emerged. Actions motivated by the global financial crisis (GFC), such as the SEC short-selling ban in September 2008, arguably suggest a greater willingness to subordinate market efficiency in favor of other governmental goals. A range of important EMH-related issues loom beyond those associated with financial illiteracy, the equity market microstructure, and governmental goals. Foremost are those relating to the informational predicate on which market efficiency rests. One key aspect of the informational predicate relates to the disclosure challenges associated with financial innovations (such as asset-backed securities) and business entities heavily involved in financial innovation activities (such as certain money center banks). The “intermediary depiction model” that the SEC has always used is inadequate in financial innovation–related contexts. Another key aspect relates to the massive amounts of information that the Dodd-Frank Act requires to be provided to governmental bodies.
Bacterial Persistence and Toxin-Antitoxin Loci
Authors: Gerdes Kenn , Maisonneuve Etienne
Published: September 2012

Bacterial persistence is caused by the presence of rare, slowly growing bacteria among populations of rapidly growing cells. The slowly growing bacteria are tolerant of antibiotics and other environmental insults, whereas their isogenic, rapidly growing siblings are sensitive. Recent research has shown that persistence of the model organism Escherichia coli depends on toxin-antitoxin (TA) loci. Deletion of type II TA loci reduces the level of persistence significantly. Lon protease but no other known ATP-dependent proteases is required for persistence. Polyphosphate and (p)ppGpp also are required for persistence. These observations led to the proposal of a simple and testable model that explains the persistence of E. coli. It is now important to challenge this model and to test whether the persistence of pathogenic bacteria also depends on TA loci.
Selective inhibition of phosphodiesterase 1 relaxes urinary bladder smooth muscle: role for ryanodine receptor-mediated BK channel activation
Authors: Xin Wenkuan , Soder Rupal P. , Cheng Qiuping , Rovner Eric S. , Petkov Georgi V.
Published: September 2012

The large conductance voltage- and Ca2+-activated K+ (BK) channel is a major regulator of detrusor smooth muscle (DSM) excitability and contractility. Recently, we showed that nonselective phosphodiesterase (PDE) inhibition reduces guinea pig DSM excitability and contractility by increasing BK channel activity. Here, we investigated how DSM excitability and contractility changes upon selective inhibition of PDE type 1 (PDE1) and the underlying cellular mechanism involving ryanodine receptors (RyRs) and BK channels. PDE1 inhibition with 8-methoxymethyl-3-isobutyl-1-methylxanthine (8MM-IBMX; 10 μM) increased the cAMP levels in guinea pig DSM cells. Patch-clamp experiments on freshly isolated DSM cells showed that 8MM-IBMX increased transient BK currents and the spontaneous transient hyperpolarization (STH) frequency by ∼2.5- and ∼1.8-fold, respectively. 8MM-IBMX hyperpolarized guinea pig and human DSM cell membrane potential and significantly decreased the intracellular Ca2+ levels in guinea pig DSM cells. Blocking BK channels with 1 μM paxilline or inhibiting RyRs with 30 μM ryanodine abolished the STHs and the 8MM-IBMX inhibitory effects on the DSM cell membrane potential. Isometric DSM tension recordings showed that 8MM-IBMX significantly reduced the spontaneous phasic contraction amplitude, muscle force integral, duration, frequency, and tone of DSM isolated strips. The electrical field stimulation-induced DSM contraction amplitude, muscle force integral, and duration were also attenuated by 10 μM 8MM-IBMX. Blocking BK channels with paxilline abolished the 8MM-IBMX effects on DSM contractions. Our data provide evidence that PDE1 inhibition relaxes DSM by raising cellular cAMP levels and subsequently stimulates RyRs, which leads to BK channel activation, membrane potential hyperpolarization, and decrease in intracellular Ca2+ levels.
In vivoDrosophiliagenetic model for calcium oxalate nephrolithiasis
Authors: Hirata Taku , Cabrero Pablo , Berkholz Donald S. , Bondeson Daniel P. , Ritman Erik L. , Thompson James R. , Dow Julian A. T. , Romero Michael F.
Published: September 2012

Nephrolithiasis is a major public health problem with a complex and varied etiology. Most stones are composed of calcium oxalate (CaOx), with dietary excess a risk factor. Because of complexity of mammalian system, the details of stone formation remain to be understood. Here we have developed a nephrolithiasis model using the genetic model Drosophila melanogaster, which has a simple, transparent kidney tubule. Drosophilia reliably develops CaOx stones upon dietary oxalate supplementation, and the nucleation and growth of microliths can be viewed in real time. The Slc26 anion transporter dPrestin (Slc26a5/6) is strongly expressed in Drosophilia kidney, and biophysical analysis shows that it is a potent oxalate transporter. When dPrestin is knocked down by RNAi in fly kidney, formation of microliths is reduced, identifying dPrestin as a key player in oxalate excretion. CaOx stone formation is an ancient conserved process across >400 My of divergent evolution (fly and human), and from this study we can conclude that the fly is a good genetic model of nephrolithiasis.