bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotype‐temperature interactions on larval performance shape population structure in hybridogenetic water frogs (Pelophylax esculentuscomplex)
Authors: Pruvost Nicolas B. M. , Hollinger Daniel , Reyer Heinz‐Ulrich
Published: January 2013

The evolutionary potential and ecological importance of interspecific hybrids continues to be a controversial issue. Traditionally, hybridization – often associated with polyploidy and clonal reproduction – was considered an important mechanism for speciation in plants, but not in animals. More recently, investigations have shifted to the question: Under which genetic and ecological conditions do hybrid taxa and different ploidies arise and succeed, and when and where do they fail? Finding answers to this question is aggravated by the fact that suitable taxa for such studies are often far apart on the phylogenetic tree. Hence, results are influenced by many confounding variables.

In this study, we reduce this problem by investigating the fitness within a complex of three closely related water frog taxa consisting of the two sexually reproducing parental speciesPelophylax lessonae(genotypeLL) andP. ridibundus(RR) plus their interspecific hybridP. esculentuswhich comes in three ploidy types (LR,LLRandLRR), as well as with sexual and hemiclonal reproduction. Offspring of all five genotypes were produced by artificially crossing adults sampled from populations in Slovakia, Germany and Switzerland. This created genetic variation. They were then raised at two temperature levels: 18 and 24 °C. This created ecological variation. Larval performance under the two temperature regimes was analysed with respect to three fitness‐related parameters: survival rate, days to metamorphosis and weight at tail resorption.

Survival rate was significantly higher for offspring of the three hybrid types (LR,LLRandLRR) compared with those of the parental species (LL,RR), at both rearing temperatures. For days to metamorphosis and weight at metamorphosis, we found an interaction between offspring type and temperature. In both cases, performance of hybrid and parental offspring did not differ at 24 °C, but at 18 °C hybrids metamorphosed faster and at a lower weight than parentals.

We discuss these results in relation to those from other studies and conclude that under cold conditions hybrids (especially the two triploid types) have higher fitness than both parental species. This genotype × environment interaction could be one reason why all‐hybrid populations mainly occur at the cooler northern range of the water frog distribution.
Ontogeny of constitutive immunity: maternal vs. endogenous influences
Authors: Arriero Elena , Majewska Ania , Martin Thomas E.
Published: January 2013

Variation in ontogeny and strength of immune defence mechanisms can be integrally related to variation in life‐history strategies and determined by trade‐offs during development. However, little is known about the ontogeny of immune function in wild birds, especially in altricial birds and in a comparative context across altricial species with diverse life‐history strategies.

In this study, we examined the ontogeny of constitutive immunity in a group of 22 passerine species sampled in tropicalVenezuela and north temperateArizona.

Our results show activity of constitutive components of the immune defence at 1–3 days posthatching and an increase in immune activity with age. Interspecific variation in immune activity at hatching was mainly explained by extrinsic factors mediated by the mother (egg size and egg temperature), suggesting an important role of maternal effects on offspring immunity at hatching. In contrast, the increase in agglutination activity with age suggests that immune function in older nestlings reflects intrinsic development. The increase in immune activity was greater in species that hatched with lower initial levels, and was somewhat negatively related to growth rate across species.

Our results suggest slower intrinsic development of immune function may be compensated by larger maternal contributions. Slower intrinsic development of immune function, in turn, may reflect a trade‐off with faster somatic growth. Our study highlights the importance of both maternal (extrinsic) and endogenous (intrinsic) contributions to variation in immune function across altricial species that may reflect an important axis of developmental strategies.
Does community‐level floral abundance affect the pollination success of a rewardless orchid, Calanthe reflexaMaxim.?
Authors: Sakata Yuzu , Sakaguchi Shota , Yamasaki Michimasa
Published: January 2013

Decreases in pollinator abundance may particularly constrain plants that lack floral rewards, since they are poor competitors for pollinators in the plant community. Here, we documented the pollination ecology of a rewardless orchid, Calanthe reflexa Maxim., and examined effects of forest understory degradation by deer browsing on pollination success of the species in the light of a change in the abundance of neighboring flowering plants in 2010 and 2011. Bombus species were the only pollinators at each site and the flowering phenology of C. reflexa did not overlap with that of other rewarding plants. Pollinator visit rates (assessed by time‐lapse photography), and pollinia removal rate were higher in the undegraded understory site than the degraded site in both years, while the fruit set ratio did not differ between the sites in 2011. Coverage by neighboring flowering plants was extremely low in the degraded site. Our results suggest that, although its flowering phenology and consequently lower interspecific competition of C. reflexa with rewarding plants for attracting bumblebees, neighboring flowering plants may play an important role for maintaining the visitation frequency of bumblebees of C. reflexa and contribute to its pollination success.
The Impact of Profitability of Hospital Admissions on Mortality
Authors: Lindrooth Richard C. , Konetzka R. Tamara , Navathe Amol S. , Zhu Jingsan , Chen Wei , Volpp Kevin
Published: January 2013

Background

Fiscal constraints faced by Medicare are leading to policies designed to reduce expenditures. Evidence of the effect of reduced reimbursement on the mortality of Medicare patients discharged from all major hospital service lines is limited.

Methods

We modeled risk‐adjusted 30‐day mortality of patients discharged from 21 hospital service lines as a function of service line profitability, service line time trends, and hospital service line and year‐fixed effects. We simulated the effect of alternative revenue‐neutral reimbursement policies on mortality. Our sample included all Medicare discharges from PPS‐eligible hospitals (1997, 2001, and 2005).

Results

The results reveal a statistically significant inverse relationship between changes in profitability and mortality. A $0.19 average reduction in profit per $1.00 of costs led to a 0.010–0.020 percentage‐point increase in mortality rates (p < .001). Mortality in newly unprofitable service lines is significantly more sensitive to reduced payment generosity than in service lines that remain profitable. Policy simulations that target service line inequities in payment generosity result in lower mortality rates, roughly 700–13,000 fewer deaths nationally.

Conclusions

The policy simulations raise questions about the trade‐offs implicit in universal reductions in reimbursement. The effect of reduced payment generosity on mortality could be mitigated by targeting highly profitable services only for lower reimbursement.
Resource Use Trajectories for Aged Medicare Beneficiaries with Complex Coronary Conditions
Authors: Federspiel Jerome J. , Stearns Sally C. , D'Arcy Laura P. , Geissler Kimberley H. , Beadles Christopher A. , Crespin Daniel J. , Carey Timothy S. , Rossi Joseph S. , Sheridan Brett C.
Published: January 2013

Objective

To use coronary revascularization choice to illustrate the application of a method simulating a treatment's effect on subsequent resource use.

Data Sources

Medicare inpatient and outpatient claims from 2002 to 2008 for patients receiving multivessel revascularization for symptomatic coronary disease in 2003–2004.

Study Design

This retrospective cohort study of 102,877 beneficiaries assessed survival, days in institutional settings, and Medicare payments for up to 6 years following receipt of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

Methods

A three‐part estimator designed to provide robust estimates of a treatment's effect in the setting of mortality and censored follow‐up was used. The estimator decomposes the treatment effect into effects attributable to survival differences versus treatment‐related intensity of resource use.

Principal Findings

After adjustment, on averageCABGrecipients survived 23 days longer, spent an 11 additional days in institutional settings, and had cumulative Medicare payments that were $12,834 higher thanPCIrecipients. The majority of the differences in institutional days and payments were due to intensity rather than survival effects.

Conclusions

In this example, the survival benefit fromCABGwas modest and the resource implications were substantial, although further adjustments for treatment selection are needed.
Genetic diversity in morphological characters and phenolic acids content resulting from an interspecific cross between eggplant, Solanum melongena, and its wild ancestor (S. incanum)
Authors: Prohens J. , Whitaker B.D. , Plazas M. , Vilanova S. , Hurtado M. , Blasco M. , Gramazio P. , Stommel J.R.
Published: January 2013

Solanum incanum, the wild ancestor of eggplant, Solanum melongena, has been considered as a source of variation for high content of phenolic acid conjugates in breeding programmes aimed at improving the functional quality of eggplant. We have evaluated the morphological and phenolic acids content in an interspecific family including S. incanum (P1), S. melongena (P2), their interspecific hybrid (F1), progeny from the selfing of the F1 (F2) and the backcross of the F1 to P2 (BC1P2). Many morphological differences were found between parents, while the F1 was intermediate for most traits. However, F1 plants were taller and pricklier and presented higher fruit flesh browning than any of the parents. F2 and BC1P2 were morphologically highly variable and the results obtained suggest that a rapid recovery of the characteristic combination of S. melongena traits can be achieved in a few backcross generations. Segregation for prickliness was found to be compatible with simple genetic control, prickliness being dominant over non‐prickliness. A total of 16 phenolic acid conjugates were studied, of which chlorogenic acid (5‐O‐(E)‐caffeoylquinic acid) was the most common compound in all samples, averaging 77.8% of all hydroxycinnamic acid derivatives. Contents of total phenolic acid conjugates were much higher in S. incanum than in S. melongena fruit flesh, and no major differences were found in the profile of phenolic acids among parents. The interspecific hybrid (F1) was intermediate between the two parents in phenolic acids content. Non‐segregating generations presented considerable variation in phenolic acids content, but the range of variation was wider in segregating F2 and BC1P2 generations. Additive genetic effects were the most important in explaining the results obtained for the phenolic acids content. A number of BC1P2 plants presented a good combination of phenolic acids content and fruit weight or flesh browning. Overall, the results demonstrate that improvement of functional quality in S. melongena can be obtained using S. incanum as a donor of alleles for high phenolic acids content.
Increased frequency of skin-infiltrating FoxP3+ regulatory T cells as a diagnostic indicator of severe atopic dermatitis from cutaneous T cell lymphoma
Authors: Hanafusa T , Matsui S , Murota H , Tani M , Igawa K , Katayama I
Published: January 2013

Differential diagnosis of cutaneous T cell lymphoma (CTCL) and severe atopic dermatitis (AD) is often difficult because of the similarity in their skin manifestations. However, such differentiation is extremely important because of the differences in remedy and prognosis. The aim of this study was to investigate new, helpful diagnostic aids for distinguishing CTCL from AD. The frequency of forkhead box protein 3+ (FoxP3+) regulatory T cells (Tregs) in cutaneous lesions was evaluated among the three populations. Serum-soluble interleukin-2 receptor (sIL-2R), immunoglobulin (Ig)E-radioimmunosorbent test, lactate dehydrogenase (LDH) and blood eosinophil count were measured in 11 CTCL patients (including three CTCL patients misdiagnosed previously with intractable AD), 10 adult AD patients and nine psoriasis patients. The frequency of Tregs was increased significantly in cutaneous lesions of AD compared with those of CTCL. Serum IgE and LDH levels were also elevated significantly in AD compared with CTCL, whereas there were no significant differences in serum sIL-2R levels between CTCL and AD. In the three CTCL patients who were misdiagnosed with intractable AD, IgE and LDH levels were lower than in AD patients, whereas serum sIL-2R levels were as high as in AD patients and higher than in the other eight CTCL patients. The higher frequency of Tregs in the cutaneous lesions of patients with AD than in those with CTCL and higher serum IgE and LDH levels in patients with AD than in those with CTCL might be helpful reference values for the differential diagnosis of these two diseases.
The UK national evaluation of the development and impact of Early Intervention Services (the National EDEN studies): study rationale, design and baseline characteristics
Authors: Birchwood Max , Lester Helen , McCarthy Linda , Jones Peter , Fowler David , Amos Tim , Freemantle Nick , Sharma Vimal , Lavis Anna , Singh Swaran , Marshall Max
Published: January 2013

Aims

National EDEN aims to evaluate the implementation and impact on key outcomes of somewhat differently configured Early Intervention Services (EIS) across sites in England and to develop a model of variance in patient outcomes that includes key variables of duration of untreated psychosis (DUP), fidelity to the EIS model and service engagement. The cohort is being followed up for two further years as patients are discharged, to observe the stability of change and the impact of the discharge settings.

Methods

A longitudinal cohort study of patients with a first episode of a psychosis, managed by EIS in six services across England. Patients are followed up 12 months after inception, then up to 2 years following discharge. Measures of DUP, psychosis, social functioning and relapse were taken. User and carer experience of EIS were monitored over time; as was the fidelity of each EIS to national guidelines. Service use is costed for a health economic evaluation.

Results

1027 people consented to the study of which 75% were successfully followed up at 12 months, with almost 100% data on treatment, relapse and recovery and service use.

Conclusions

National EDEN is the largest cohort study of young people with psychosis receiving care under EIS. It will be able definitively to indicate whether this major investment in the United Kingdom in EI is achieving meaningful change for its users in practice and provide indications concerning who does well under this approach and who does not, and the long‐term stability of any improvements.
Help seeking by Aboriginal men who are mentally unwell: a pilot study
Authors: Isaacs Anton N. , Maybery Darryl , Gruis Hilton
Published: January 2013

Aims

Mental illness is widespread among Aboriginal men in Australia. However, they do not access mental health services in proportion to their need. Although several reports implicate cultural differences of mental health services as the cause of underutilization, very little is known about help seeking by Aboriginal men who are mentally unwell. This study explores the help‐seeking behaviour of Aboriginal men who are mentally unwell in a rural Victorian community.

Methods

The study was carried out using a combination of culturally appropriate research methodologies. Within a Qualitative Description design, semi‐structured interviews were conducted with a range of Aboriginal people including men, carers and those involved in service delivery. A total of 17 Aboriginal people were interviewed, of whom 15 were men. Data were analysed thematically.

Results

Four themes emerged from the data collected. They included ‘Difficulty in recognizing mental health problems’, ‘Barriers to disclosing one's problems’, ‘Reluctance to contact services’ and ‘Alternate coping strategies’.

Conclusions

These findings suggest that there is a need for programmes that aim to improve mental health literacy and promote help seeking among Aboriginal men who are mentally unwell. Such programmes need to be developed jointly by mental health services as well as Aboriginal stakeholders, and implemented in a culturally sensitive and acceptable way.
Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualising and manipulating neuronal circuits in vivo
Authors: Kim Ji‐Yoen , Ash Ryan T. , Ceballos‐Diaz Carolina , Levites Yona , Golde Todd E. , Smirnakis Stelios M. , Jankowsky Joanna L.
Published: January 2013

The neonatal intraventricular injection of adeno‐associated virus has been shown to transduce neurons widely throughout the brain, but its full potential for experimental neuroscience has not been adequately explored. We report a detailed analysis of the method's versatility with an emphasis on experimental applications where tools for genetic manipulation are currently lacking. Viral injection into the neonatal mouse brain is fast, easy, and accesses regions of the brain including the cerebellum and brainstem that have been difficult to target with other techniques such as electroporation. We show that viral transduction produces an inherently mosaic expression pattern that can be exploited by varying the titer to transduce isolated neurons or densely‐packed populations. We demonstrate that the expression of virally‐encoded proteins is active much sooner than previously believed, allowing genetic perturbation during critical periods of neuronal plasticity, but is also long‐lasting and stable, allowing chronic studies of aging. We harness these features to visualise and manipulate neurons in the hindbrain that have been recalcitrant to approaches commonly applied in the cortex. We show that viral labeling aids the analysis of postnatal dendritic maturation in cerebellar Purkinje neurons by allowing individual cells to be readily distinguished, and then demonstrate that the same sparse labeling allows live in vivo imaging of mature Purkinje neurons at a resolution sufficient for complete analytical reconstruction. Given the rising availability of viral constructs, packaging services, and genetically modified animals, these techniques should facilitate a wide range of experiments into brain development, function, and degeneration.
Alpine cushion plants inhibit the loss of phylogenetic diversity in severe environments
Authors: Butterfield B. J. , Cavieres L. A. , Callaway R. M. , Cook B. J. , Kikvidze Z. , Lortie C. J. , Michalet R. , Pugnaire F. I. , Schöb C. , Xiao S. , Zaitchek B. , Anthelme F. , Björk R. G. , Dickinson K. , Gavilán R. , Kanka R. , Maalouf J.‐P. , Noroozi J. , Parajuli R. , Phoenix G. K. , Reid A. , Ridenour W. , Rixen C. , Wipf S. , Zhao L. , Brooker R. W.
Published: January 2013

Biotic interactions can shape phylogenetic community structure (PCS). However, we do not know how the asymmetric effects of foundation species on communities extend to effects on PCS. We assessed PCS of alpine plant communities around the world, both within cushion plant foundation species and adjacent open ground, and compared the effects of foundation species and climate on alpha (within‐microsite), beta (between open and cushion) and gamma (open and cushion combined) PCS. In the open, alpha PCS shifted from highly related to distantly related with increasing potential productivity. However, we found no relationship between gamma PCS and climate, due to divergence in phylogenetic composition between cushion and open sub‐communities in severe environments, as demonstrated by increasing phylo‐beta diversity. Thus, foundation species functioned as micro‐refugia by facilitating less stress‐tolerant lineages in severe environments, erasing a global productivity – phylogenetic diversity relationship that would go undetected without accounting for this important biotic interaction.
Health‐related quality of life as an independent predictor of long‐term disability for patients with relapsing–remitting multiple sclerosis
Authors: Baumstarck K. , Pelletier J. , Butzkueven H. , Fernández O. , Flachenecker P. , Idiman E. , Stecchi S. , Boucekine M. , Auquier P. ,   for the MusiQoL study group
Published: January 2013

Background and purpose

Predictive factors of long‐term disability in patients with relapsing–remitting multiple sclerosis (RR‐MS) are well known, but the weight of these factors does not explain the entire change of disability. Few studies have examined the predictive value of quality of life (QoL).

Objectives

To determine the value of the initial level of QoL to predict changes in the disability status of patients with MS and to determine if specific‐MS questionnaires predict more accuracy in these changes than generic questionnaires.

Methods

Design: multicenter, multi‐regional, and longitudinal study. Main inclusion criteria: patients with RR‐MS subtype and an Expanded Disability Status Scale (EDSS) score lower than 7.0. Sociodemographic and clinical data were recorded at baseline. Every 6 months up to month 24, QoL (MusiQoL and SF‐36) was recorded. At 24 months, individuals were defined into two ‘disability change’ groups: the worsened and not worsened patients.

Results

Five‐hundred and twenty‐six patients were enrolled: 386 (83.7%) not worsened and 75 (16.3%) worsened patients at 24 months. The activity of daily living and the relationship with healthcare workers dimensions of MusiQoL questionnaire were independent predictors of change in the EDSS score after 24 months. The physical‐functioning dimension of the SF‐36 questionnaire predicted independently disability change after 24 months.

Conclusions

Patient‐reported baseline QoL levels provide additional prognostic information on MS disability beyond traditional clinical or sociodemographic factors. These findings reinforce the importance of incorporating a patient's evaluation of their own QoL level during patient monitoring and the assessment of treatment effects.
Investigating the Social Aspects Early Medieval Mortuary Practice
Authors: Sayer Duncan
Published: January 2013

Pre‐Christian early medieval cemeteries are rich archaeological sites; they contained burials with weapons, jewellery and pottery vessels. These sites also show some structured organisation – clusters of rich inhumations, rows of graves or differently oriented burials positioned adjacent to earlier features. But the interpretation of these sites has not always been holistic; archaeologists across Europe have developed different theoretical traditions and emphasised different types of evidence. This paper will describe some of these traditions as they relate to social interpretations while emphasising the multi‐scaled nature of early medieval culture. Indeed individuals, sites and regional level interpretations are all important ways to understand the social aspects of mortuary practice and it is by combining evidence and learning from different traditions that it might be possible to understand the human experience of the ancient past.
Accounting for data heterogeneity in patterns of biodiversity: an application of linear mixed effect models to the oceanic island biogeography of spore‐producing plants
Authors: Patiño Jairo , Guilhaumon François , Whittaker Robert J. , Triantis Kostas A. , Gradstein S. Robbert , Hedenäs Lars , González‐Mancebo Juana M. , Vanderpoorten Alain
Published: January 2013

The general dynamic model of oceanic island biogeography describes the evolution of species diversity properties, including species richness (SR), through time. We investigate the hypothesis that SR in organisms with high dispersal capacities is better predicted by island area and elevation (as a surrogate of habitat diversity) than by time elapsed since island emergence and geographic isolation. Linear mixed effect models (LMMs) subjected to information theoretic model selection were employed to describe moss and liverwort SR patterns from 67 oceanic islands across 12 archipelagos. Random effects, which are used to modulate model parameters to take differences among archipelagos into account, included only a random intercept in the best‐fit model for liverworts and in one of the two best‐fit models for mosses. In this case, the other coefficients are constant across archipelagos, and we interpret the intercept as a measure of the intrinsic carrying capacity of islands within each archipelago, independently of their size, age, elevation and geographic isolation. The contribution of area and elevation to the models was substantially higher than that of time, with the least contribution made by measures of geographic isolation. This reinforces the idea that oceanic barriers are not a major impediment for migration in bryophytes and, together with the almost complete absence of in situ insular diversification, explains the comparatively limited importance of time in the models. We hence suggest that time per se has little independent role in explaining bryophyte SR and principally features as a variable accounting for the changing area and topographic complexity during the life‐cycle of oceanic islands. Simple area models reflecting habitat availability and diversity might hence prevail over more complex temporal models reflecting in‐situ speciation and dispersal (time, geographic connectivity) in explaining patterns of biodiversity for exceptionally mobile organisms.
Controls over reproductive phenology among ungulates: allometry and tropical‐temperate contrasts
Authors: Owen‐Smith Norman , Ogutu Joseph O.
Published: January 2013

Ungulates inhabiting high latitudes schedule the timing of conceptions so that offspring are born during the most favourable nutritional conditions for reproductive success. The optimal period for births is less reliably predictable in tropical and subtropical savanna environments where plant growth is governed by rainfall, suggesting that reproductive phenology could be influenced more proximately by resources affecting the body condition of females around the time of conceptions. To assess how these controls operate, we compared the timing of births and conceptions among tropical and subtropical savanna ungulates with the patterns shown by ungulates in northern temperate or subarctic latitudes. The association between the timing of births and the onset of plant growth early in the growing season is less consistent among tropical savanna ungulates than among ungulates inhabiting northern temperate environments, and apparently subject to other influences affecting vegetation phenology. Nevertheless, birth peaks seem to coincide with the time of the year when forage quality is expected to be best for offspring survival and growth for most tropical or subtropical ungulates with gestation periods shorter than a year. When gestation time exceeds one year, proximal effects of nutritional conditions around the time of conceptions apparently become overriding and birth synchrony with early season plant growth is no longer effective. Proximate nutritional influences on conceptions may also govern the somewhat diffuse spread of births shown by ungulate populations in equatorial latitudes where photoperiod cues controlling oestrus and mating cannot be used to schedule the later timing of births.
Complex Müllerian malformation without any present classification: Unilateral ovarian and tubal absence with an arcuate uterus
Authors: Tanaka Yusuke , Koyama Shinsuke , Kobayashi Masaki , Kubota Satoshi , Nakamura Ryo , Isobe Masanori , Shiki Yasuhiko
Published: January 2013

Müllerian duct anomalies are known to cause infertility and reproductive problems. The true incidence of such abnormalities is not well defined. The most widely accepted method of classification for a Müllerian duct anomaly is the American Society of Reproductive Medicine classification (1988). However, there are some rare anomalies inconsistent with the current classification.

Herein, we report a rare case of Müllerian duct anomaly, unilateral ovarian and tubal absence with an arcuate uterus. The failure of the Müllerian ducts to canalize can also lead to the development of a unicornuate uterus and adnexal agenesis. An arcuate uterus indicates incomplete septal absorption after normal fusion of the Müllerian ducts. Therefore, its coexistence with adnexal absence and an arcuate uterus is considered to be extremely unlikely.
State Policies About Physical Activity Minutes in Physical Education or During School
Authors: Carlson Jordan A. , Sallis James F. , Chriqui Jamie F. , Schneider Linda , McDermid Lindsey C. , Agron Peggy
Published: January 2013

ABSTRACT

BACKGROUND

School policies can change practices on a relatively permanent basis. This study investigated adoption and implementation of state‐level policies specifying minutes (or percent) of physical activity in physical education (PE) or during school.

METHODS

Policies were identified from existing databases and rated as having weak, moderate, or strong wording. Interviews with state‐level PE coordinators were conducted to investigate the level of implementation, monitoring, and enforcement of the identified policies.

RESULTS

Sixteen states had a policy that met inclusion criteria (19 policies total); 11 states had a policy addressing minutes of physical activity during school, 2 had a policy addressing percent of PE time to be spent in physical activity, and 3 had policies addressing both. None of the 19 policies were rated as having strong wording and 5 were rated as having moderate wording. The range in minutes of physical activity per week addressed in the policies was 60 to 300. Four of the 5 (elementary) and 5 of 5 (middle) policies addressing percent of PE spent physically active specified 50%. The only monitoring efforts reported consisted of schools self‐reporting progress to the state.

CONCLUSIONS

More states need to adopt school physical activity policies and policy language needs to be more specific to prevent potential loopholes. Monitoring and evaluation strategies, beyond school self‐report, are likely needed for these policies to lead to increases in physical activity.
Assessment of the Efficacy of Combination Therapy with Folic Acid and Tadalafil for the Management of Erectile Dysfunction in Men with Type 2 Diabetes Mellitus
Authors: Hamidi Madani Ali , Asadolahzade Ahmad , Mokhtari Gholamreza , Shahrokhi Damavand Reza , Farzan Alireza , Esmaeili Samaneh
Published: January 2013

Introduction

Phosphodiesterase type 5 inhibitors PDE5Is are less effective in diabetic men with erectile dysfunction (ED); however, the effect of combination therapy with folic acid and PDE5Is in these patients has not been investigated.

Aim

To evaluate the efficacy and safety of combination therapy with folic acid and tadalafil for the management of ED in men with type 2 diabetes mellitus.

Methods

Eighty-three patients with type 2 diabetes mellitus and ED were included in this randomized double-blind clinical trial. They were randomly divided into two groups. Group A was treated with tadalafil 10 mg every other day plus folic acid 5 mg daily and group B received tadalafil 10 mg every other day plus placebo daily for 3 months. The mean International Index of Erectile Function (IIEF) scores before and after treatment in each groups were recorded. Men with diagnosis of psychological ED, spinal cord injury, or who used folic acid in the past 3 months and patients with any contradiction for use of PDE5Is were excluded.

Main Outcomes Measures

The cross tabulation and independent t-test were used to evaluate the difference between baseline characteristic of the patients in the two groups. Wilcoxon signed-ranks test and Mann–Whitney U-test were used to evaluate the IIEF score and also its changes before and after treatment in the two groups.

Results

The mean IIEF scores before and after treatment were 11.65 ± 2.67 and 16.80 ± 4.03 in group A (P < 0.001) and 12.70 ± 2.31 and 14.37 ± 2.17 in group B (P < 0.001), respectively. The difference of mean IIEF score after treatment between the two groups was significant (16.80 ± 4.03 vs. 14.37 ± 2.17 in groups A and B, respectively) (P = 0.002). Also, the mean IIEF score was significantly increased in group A as compared with group B (5.14 ± 3.84 vs. 1.68 ± 0.99 in groups A and B, respectively) (P < 0.001). Both folic acid and tadalafil were well tolerated by all the patients.

Conclusion

Sexual function in diabetic patients with ED treated with the combination of tadalafil and folic acid improved significantly as compared with the placebo group. The use of folic acid and tadalafil is safe.
Inhibition of Phosphodiesterase 4 Enhances Clitoral and Vaginal Blood Flow Responses to Dorsal Clitoral Nerve Stimulation or PGE1 in Anesthetized Female Rats
Authors: Castiglione Fabio , Bergamini Alice , Russo Andrea , La Croce Giovanni , Castagna Giulia , Colciago Giorgia , Salonia Andrea , Rigatti Patrizio , Montorsi Francesco , Hedlund Petter
Published: January 2013

Introduction

Cyclic adenosine 3′5′ monophosphate (cAMP) is produced by adenylate cyclase after activation by, e.g., vasoactive intestinal polypeptide or prostaglandin E1 (PGE1). The cAMP-degrading phosphodiesterase 4 (PDE4) is expressed in the vagina and clitoris, but no information is available on the functional role for PDE4-related signals in the female neurovascular genital response.

Aim

The aim of this study is to study the effect of inhibition of PDE4 with rolipram on nerve- and PGE1-induced vaginal and clitoral blood flow responses of rat.

Methods

Measure of clitoral and vaginal blood flow and blood pressure in anesthetized rats during activation of the dorsal clitoral nerve (DCN) before and after intraperitoneal administration of rolipram or sildenafil (phosphodiesterase type 5 inhibitors [PDE5]) and nitro-L-arginine (L-NNA) (nitric oxide synthase inhibitor). Effect by topical administration of PGE1 on genital blood flow was also evaluated.

Main Outcome Measure

Blood flow was recorded as tissue perfusion units (TPU) by a Laser Doppler Flowmeter. Mean arterial blood pressure (MAP) was recorded (cmH2O) in the carotid artery. Blood flow responses are expressed as TPU/MAP. Unpaired t-test and an analysis of variance were used.

Results

Compared with control stimulations, rolipram (0.3 mg/kg) caused a twofold increase in peak blood flow (P < 0.05) and fourfold increase of the rate of clitoral blood flow during activation of the DCN (P < 0.05). Simultaneously, a twofold increase in peak blood flow and threefold increase in rate of blood flow were noted in the vagina (P < 0.05). Similar effects were noted for sildenafil (0.2 mg/kg) (P < 0.05). Inhibitory effects by L-NNA (60 mg/kg) on blood flow responses to DCN activation were significantly lower for rats treated with rolipram than with sildenafil (P < 0.05). PGE1-induced (10 μg) blood flow responses were significantly higher (P < 0.05) in rats treated with rolipram than with sildenafil.

Conclusions

These findings suggest that the cAMP/PDE4 system may be of similar functional importance as the nitric oxide/cyclic guanosine monophosphate/PDE5 pathway for neurovascular genital responses of the female rat.
Superoxide Anion Production by NADPH Oxidase Plays a Major Role in Erectile Dysfunction in Middle-Aged Rats: Prevention by Antioxidant Therapy
Authors: Silva Fábio H. , Mónica Fabíola Z. , Báu Fernando R. , Brugnerotto Ana F. , Priviero Fernanda B.M. , Toque Haroldo A. , Antunes Edson
Published: January 2013

Introduction

Prevalence of erectile dysfunction (ED) increases progressively with aging, but the ED pathophysiology at its early stages is still poorly investigated.

Aim

This study aimed to evaluate the functional and molecular alterations of erectile function at middle age, focusing on the contribution of oxidative stress in erectile tissue for the ED.

Methods

Young (3.5-month) and middle-aged (10-month) male Wistar rats were used. Rat corpus cavernosum (RCC) was dissected free and mounted in 10-mL organ baths containing Krebs solution. Intracavernosal pressure (ICP) in anesthetized rats was evaluated.

Main Outcome Measures

Concentration–response curves to endothelium-dependent and endothelium-independent agents, as well as to electrical field stimulation (EFS), were obtained in RCC strips. Measurement of cyclic guanosine monophosphate (cGMP) and expressions of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS), gp91phox and superoxide dismutase-1 (SOD-1) expressions in RCC were evaluated.

Results

ICP was significantly reduced in middle-aged compared with young rats. RCC relaxations to acetylcholine (10−8 to 10−2 M), sodium nitroprusside (10−8 to 10−2 M), sildenafil (10−9 to 10−5 M), BAY 41-2272 (10−9 to 10−5 M), and EFS (4–32 Hz) were decreased in middle-aged group, which were nearly normalized by apocynin (NADPH oxidase inhibitor; 10−4 M) or SOD (75 U/mL). Prolonged treatment with apocynin (85 mg/rat/day, 4 weeks) also restored the impaired relaxations in middle-aged rats. Relaxations to 8-bromoguanosine 3′,5′-cyclic monophosphate sodium salt (8-Br-cGMP; 10−8 to 3 × 10−4 M) remained unchanged between groups. Basal and stimulated cGMP production were lower in middle-aged group, an effect fully restored by apocynin and SOD. Protein expression of nNOS and phosphorylated eNOS (p-eNOS) (Ser-1177) reduced, whereas gp91phox mRNA expression increased in RCC from middle-aged rats.

Conclusions

ED in middle-aged rats is associated with decreased NO bioavailability in erectile tissue due to upregulation of NADPH oxidase subunit gp91phox and downregulation of nNOS/p-eNOS. Antioxidant therapies may be a good pharmacological approach to prevent ED at its early stages.
Female Sexual Dysfunction and Diabetes: A Systematic Review and Meta-Analysis
Authors: Pontiroli Antonio E. , Cortelazzi Donatella , Morabito Alberto
Published: January 2013

Introduction

Sexual dysfunction is reported in diabetic women (female sexual dysfunction [FSD]).

Aim

To examine the frequency of FSD in diabetic women, and its clinical or metabolic correlates, through meta-analysis of available studies.

Methods

We searched in MEDLINE, EMBASE, Cochrane Library, and in reference lists of articles and systematic reviews; we considered human clinical studies published as full articles reporting on FSD in diabetic and control women. In total, we considered 26 studies, including 3,168 diabetic and 2,823 control women.

Main Outcome Measures

Frequency of FSD and score of Female Sexual Function Index (FSFI) as a function of study size, patient details (age, body mass index [BMI], duration of diabetes, metabolic control [HbA1c], chronic complications, Beck Depression Inventory [BDI] score).

Results

Frequency of FSD was higher in type 1 (OR [95%CI] 2.27 [1.23, 4.16]), in type 2 diabetes (2.49 [1.55, 3.99]), and in “any diabetes” (type 1 and 2) women (2.02 [1.49, 2.72]) than in controls for any duration of diabetes. FSFI was lower in type 1 (−0.27 [−0.41, −0.12]), in type 2 diabetes (−0.65 [−0.75, −0.54]), and in “any diabetes” women (−0.80 [−0.88, −0.71]) than in controls. Depression was significantly more frequent in diabetic than in control women. At meta-regression only BMI was significantly associated with effect size (P = 0.005). At weighed regression, the only significant association was found between age and FSFI (P = 0.059). The limitations were as follows: only studies of observational nature were available, and heterogeneity was seen among studies.

Conclusions

FSD is more frequent in diabetic than in control women, but it is still poorly understood; low FSFI is associated with high BMI. Further studies are necessary to better understand risk factors for FSD in diabetic women.
The Identification of Prediabetes Condition with ARIC Algorithm Predicts Long-Term CV Events in Patients with Erectile Dysfunction
Authors: Corona Giovanni , Rastrelli Giulia , Silverii Antonio , Monami Matteo , Sforza Alessandra , Forti Gianni , Mannucci Edoardo , Maggi Mario
Published: January 2013

Introduction

The Atherosclerosis Risk in Communities (ARIC) algorithm is one of the most efficient instruments for the prediction of incident type 2 diabetes. Recently, it has been shown to predict another relevant cardiovascular (CV) risk factor, such as chronic kidney disease.

Aim

To verify whether, in patients with erectile dysfunction (ED), the use of ARIC diabetes risk score might improve the efficacy in predicting major CV events of other CV risk algorithms specifically developed for the assessment of CV risk.

Methods

A consecutive series of 2,437 men (mean age 52.5 ± 12.9 years) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of this sample (N = 1,687) was enrolled in a longitudinal study (mean follow-up of 4.3 ± 2.6 years).

Main Outcome Measures

The assessment of metabolic risk was evaluated with the ARIC algorithm. The assessment of CV risk was evaluated using the Progetto Cuore risk engine.

Results

In the cross-sectional study, ARIC score was inversely related with testosterone levels, sexual functioning, and penile blood flow. When longitudinal sample was analyzed, higher baseline ARIC score significantly predicted major adverse cardiovascular event (MACE) even when subjects with diabetes mellitus at baseline were excluded from the analysis (hazard ratio = 1.522 [1.086–2.135]; P = 0.015 for trend). In addition, among subjects classified as “low risk” (CV risk <20% at 10 years corresponding to <9% at 4.3 years) by Progetto Cuore, a receiving operating curve (ROC) analysis for ARIC (vs. MACE) allowed the identification of a threshold of 0.22, which had a positive predictive value for 4.3-year MACE of 9%. Applying the ARIC score (with a threshold of 0.22) to Progetto Cuore “low-risk” subjects, we could classify as “at high risk” 89.8% of subjects with incident MACE vs. 79.6% with Progetto Cuore only.

Conclusions

In patients with ED, identifying prediabetes, even with algorithms, predicts long-term CV events.
Health status and preventative behaviors of immigrants by gender and origin: A Portuguese cross‐sectional study
Authors: Dias Sónia , Gama Ana , Martins Maria O.
Published: January 2013

Migration has been associated with a greater vulnerability in health. Migrants, especially women, go through several experiences during the migration process and in the host countries that ultimately put their health at risk. This study examines self‐reported health status and preventive behaviors among female and male immigrants in Portugal, and identifies sociodemographic and behavioral factors underlying gender differences. A sample of 1375 immigrants (51.1% women) was studied. Data were analyzed through logistic regression. Good health status was reported by 66.7% of men and by 56.6% of women (P < 0.001). Gender differences were also found across preventative behaviors. Among women and men, reported good health was associated with younger age, African and Brazilian origin (compared to Eastern European), secondary/higher education, no chronic disease, and concern about eating habits. Among women, good health was also associated with perceived sufficient income, no experience of mental illness, and regular physical exercise. When developing health programs to improve immigrants’ health, special attention must be given to existing gender inequalities, and socioeconomic and cultural context, in accordance with their experience of living in the host country over time.
After theDoctorate: A qualitative study investigating nursing research career development inJordan
Authors: Al‐Nawafleh Ahmed , Zeilani Ruqayya S. , Evans Catrin
Published: January 2013

There is a dearth of research exploring the development of postdoctoral nursing research careers in non‐Western contexts. This paper reports on a qualitative study ofJordanian graduates ofUK PhDprograms. Interviews were held with 16 graduates who worked in the nursing faculty of seven different universities inJordan. Participants reported that their doctoral degree had equipped them with confidence and enthusiasm for developing a research career. Mentorship, leadership, and peer support were identified as essential to supporting ongoing research activity. Access to these sources of support was variable and participants also described a range of institutional and organizational structures that directly or indirectly discouraged them from developing research productivity. This research suggests that support for postdoctoral novice researchers is an important area for further attention – forJordanian universities, forUK PhDsupervisors (and their associated academic departments), and for the wider nursing community.
New β‐lactam–β‐lactamase inhibitor combinations in clinical development
Authors: Shlaes David M.
Published: January 2013

Tazobactam was the most recent β‐lactamase inhibitor to be approved in 1993. Since the approval of piperacillin–tazobactam, the complexity of β‐lactamase–mediated resistance among Gram‐negative bacilli has increased enormously. After more than 20 years since the first such combination, amoxicillin–clavulanic acid, was approved, several new β‐lactam–β‐lactamase inhibitor combinations have reached late‐stage (phase II and beyond) clinical trials. These include ceftolozane–tazobactam (2:1, ratios of β‐lactam to β‐lactamase inhibitor in parentheses), ceftazidime–avibactam (4:1), ceftaroline–avibactam (1:1), and imipenem–cilastatin–MK‐7655 (2:2:1 and 4:4:1). Avibactam and MK‐7655 are diazabicyclooctane (DABCO) inhibitors and thus not β‐lactams themselves; they include class A carbapenemases and class C enzymes within their spectra of activity. Ceftolozane is an antipseudomonal cephalosporin, and tazobactam is used to protect it against extended spectrum β‐lactamases to which it is labile. Additional novel combinations are in preclinical development. This review will focus on the biochemistry, antimicrobial activity, pharmacodynamics, and clinical development of these novel combinations.
Low/negative expression of DDX3 might predict poor prognosis in non‐smoker patients with oral cancer
Authors: Lee C‐H , Lin S‐H , Yang S‐F , Yang S‐M , Chen M‐K , Lee H , Ko J‐L , Chen C‐J , Yeh K‐T
Published: January 2013

Objective

DDX3 has diverse biological functions in translation control, cell growth regulation, and tumor progression. Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide with a poor clinical prognosis. The impact of DDX3 expression in OSCC is seldom discussed.

Materials and Methods

Tumor tissues and adjacent normal tissues were obtained from 324 patients with OSCC. In this study, we used immunohistochemical staining methods to investigate the associations between DDX3 expression and the clinicopathological characteristics of OSCC.

Results

Low/negative DDX3 expression in tumor cells was significantly associated OSCC patient characteristics including male gender (P < 0.001), smoking (P < 0.001), alcohol consumption (P < 0.001), betel quid chewing (P = 0.002), poor relapse‐free survival (P = 0.001), and poor overall survival (OS) (P = 0.001). Patients with low/negative DDX3 expression, and particularly non‐smoker OSCC patients, had significantly worse OS as defined by the log‐rank test (P = 0.020 for all cases; P = 0.008 for non‐smoker patients). In non‐smoker patients with OSCC, low/negative DDX3 expression in tumor cells was associated with poor prognosis (P = 0.024) and a 3.802‐fold higher death risk, as determined by Cox regression.

Conclusions

Low/negative DDX3 expression in tumor cells was significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in non‐smoker patients with OSCC.