bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of physical activity on cardiovascular status in obesity
Authors: Lind Lars , Carlsson Axel C. , Siegbahn Agneta , Sundström Johan , Ärnlöv Johan
Published: December 2016

Background

We have recently shown that being physically active (PA) counteracts, but not eliminates the increased risk of future cardiovascular disease in overweight and obese subjects. To investigate this further, we studied the impact of being normal weight, overweight and obese on multiple markers of subclinical cardiovascular disease in relation to physical activity.

Materials and methods

At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Being PA was defined as performing regular heavy exercise (self‐reported). According to body mass index (BMI)/PA groups, the participants were categorized as PA/normal weight (BMI < 25 kg/m2, n = 104), non‐PA/normal weight (n = 234), PA/overweight (BMI 25–29·9 kg/m2, n = 133), non‐PA/overweight (n = 295), PA/obese (BMI ≥ 30 kg/m2, n = 54) and non‐PA/obese (n = 169). Several different measurements of endothelial reactivity and arterial compliance (plethysmography and ultrasound), cartotid artery atherosclerosis and echocardiography were performed, and seven markers of coagulation/fibrinolysis were measured.

Results

Physically active subjects with obesity showed impaired vasoreactivity in the forearm resistance vessels, increased left ventricular mass and impaired left ventricular systolic and diastolic functions, together with impaired coagulation/fibrinolysis when compared to PA/normal‐weight subjects (P < 0·05 to <0·001). The majority of these disturbances were seen also in PA/overweight subjects when compared to PA/normal‐weight subjects (P < 0·05 to <0·001).

Conclusions

Our data provide additional support for the notion that an increased level of self‐reported physical activity does not fully eliminate the deleterious cardiovascular consequences associated with overweight and obesity.
Prognostic impact of CD5 expression in diffuse large B‐cell lymphoma in patients treated with rituximab‐EPOCH
Authors: Thakral Beenu , Medeiros L. Jeffrey , Desai Parth , Lin Pei , Yin C. Cameron , Tang Guilin , Khoury Joseph D. , Hu Shimin , Xu Jie , Loghavi Sanam , Hu Bei , Oki Yasuhiro , Li Shaoying
Published: December 2016

Objectives

CD5‐positive (CD5+) diffuse large B‐cell lymphoma (DLBCL) represents 5%‐10% of all DLBCL cases, which has been associated with a poorer prognosis in patients treated with R‐CHOP. Prognostic impact of CD5 expression in patients with DLBCL treated with R‐EPOCH has not been evaluated.

Methods

We studied 130 patients with de novo DLBCL who received frontline R‐EPOCH therapy. The clinicopathologic features and overall survival (OS) were compared between patients with CD5+ and CD5‐ DLBCL. MYC, BCL2, and BCL6 rearrangements were examined by fluorescent in situ hybridization.

Results

Sixteen (12.3%) of 130 DLBCLs were CD5+. Most clinicopathologic features including cell of origin and frequency of MYC, BCL2, and BCL6 rearrangements were similar between CD5+ and CD5− groups. Patients with CD5+ DLBCL, however, showed higher rate of central nervous system relapse (33.3% vs 15.6%; P<.01) and a higher Ki67 proliferative index compared with CD5‐ patients. The median OS was significantly worse in CD5+ than CD5‐ patients (28.13 months vs not reached, P=.006). CD5 expression was an independent prognostic factor for OS in multivariate analysis.

Conclusions

R‐EPOCH therapy does not seem to impact the known poorer prognosis of patients with de novo CD5+ DLBCL, and CD5 expression was still an independent prognostic factor in R‐EPOCH‐treated patients with DLBCL.
Global synthesis of the temperature sensitivity of leaf litter breakdown in streams and rivers
Authors: Follstad Shah Jennifer J. , Kominoski John S. , Ardón Marcelo , Dodds Walter K. , Gessner Mark O. , Griffiths Natalie A. , Hawkins Charles P. , Johnson Sherri L. , Lecerf Antoine , LeRoy Carri J. , Manning David W. P. , Rosemond Amy D. , Sinsabaugh Robert L. , Swan Christopher M. , Webster Jackson R. , Zeglin Lydia H.
Published: December 2016

Streams and rivers are important conduits of terrestrially derived carbon (C) to atmospheric and marine reservoirs. Leaf litter breakdown rates are expected to increase as water temperatures rise in response to climate change. The magnitude of increase in breakdown rates is uncertain, given differences in litter quality and microbial and detritivore community responses to temperature, factors that can influence the apparent temperature sensitivity of breakdown and the relative proportion of C lost to the atmosphere vs. stored or transported downstream. Here, we synthesized 1025 records of litter breakdown in streams and rivers to quantify its temperature sensitivity, as measured by the activation energy (Ea, in eV). Temperature sensitivity of litter breakdown varied among twelve plant genera for which Ea could be calculated. Higher values of Ea were correlated with lower‐quality litter, but these correlations were influenced by a single, N‐fixing genus (Alnus). Ea values converged when genera were classified into three breakdown rate categories, potentially due to continual water availability in streams and rivers modulating the influence of leaf chemistry on breakdown. Across all data representing 85 plant genera, the Ea was 0.34 ± 0.04 eV, or approximately half the value (0.65 eV) predicted by metabolic theory. Our results indicate that average breakdown rates may increase by 5–21% with a 1–4 °C rise in water temperature, rather than a 10–45% increase expected, according to metabolic theory. Differential warming of tropical and temperate biomes could result in a similar proportional increase in breakdown rates, despite variation in Ea values for these regions (0.75 ± 0.13 eV and 0.27 ± 0.05 eV, respectively). The relative proportions of gaseous C loss and organic matter transport downstream should not change with rising temperature given that Ea values for breakdown mediated by microbes alone and microbes plus detritivores were similar at the global scale.
Development of polymorphic microsatellite markers and their use in collections of Erianthus arundinaceus in China
Authors: Zhang Jian‐Bo , Yan Jia‐Jun , Shen Xiao‐Yun , Bai Shi‐Qie , Li Da‐Xun , Zhang Yu , You Ming‐Hong , Zhang Yu
Published: December 2016

Erianthus arundinaceus (Retz.) Jeswiet is not only a candidate plant for sugarcane breeding programs, but also a potential bioenergy grass. However, there are no simple sequence repeat (SSR) markers for E. arundinaceus, and information on genetic structure essential in genetics based on Chinese wild germplasm is limited. Therefore, in this study, 15 polymorphic microsatellite markers for E. arundinaceus were developed, and genetic variation and genetic structure of Chinese wild E. arundinaceus was studied. Genetic variation of 164 individuals of 18 populations collected from natural habitats in six Chinese provinces was analyzed using developed SSR markers, which generated 105 polymorphic bands. The numbers of alleles per locus ranged from 6 to 11 with a mean of 9. Among and within the populations, the percentage of polymorphic bands was 91.18% and 46.45%, effective number of alleles was 1.63 and 1.30, Shannon's information index was 0.52 and 0.25, respectively. The populations were clustered into seven groups exhibiting a high level of genetic differentiation, which was highly associated with geographic origins of respective germplasm populations, and was significantly associated with geographic distances between the populations. The developed SSR markers had advantages in revealing genetic diversity and the variance among populations of Chinese E. arundinaceus. Large genetic variation among Chinese E. arundinaceus germplasm and the genetic structure of E. arundinaceus populations effected by geographic landforms and environments were revealed, which will be highly valuable in genetic improvement and the genetics research.
Sex allocation and sex‐specific parental investment in an endangered seabird
Authors: Spelt Anouk , Pichegru Lorien
Published: December 2016

Biased offspring sex ratio is relatively rare in birds and sex allocation can vary with environmental conditions, with the larger and more costly sex, which can be either the male or female depending on species, favoured during high food availability. Sex‐specific parental investment may lead to biased mortality and, coupled with unequal production of one sex, may result in biased adult sex ratio, with potential grave consequences on population stability. The African Penguin Spheniscus demersus, endemic to southern Africa, is an endangered monogamous seabird with bi‐parental care. Female adult African Penguins are smaller, have a higher foraging effort when breeding and higher mortality compared with adult males. In 2015, a year in which environmental conditions were favourable for breeding, African Penguin chick production on Bird Island, Algoa Bay, South Africa, was skewed towards males (1.5 males to 1 female). Males also had higher growth rates and fledging mass than females, with potentially higher post‐fledging survival. Female, but not male, parents had higher foraging effort and lower body condition with increasing number of male chicks in their brood, thereby revealing flexibility in their parental strategy, but also the costs of their investment in their current brood. The combination of male‐biased chick production and higher female mortality, possibly at the juvenile stage as a result of lower parental investment in female chicks, and/or at the adult stage as a result of higher parental investment, may contribute to a biased adult sex ratio (ASR) in this species. While further research during years of contrasting food availability is needed to confirm this trend, populations with male‐skewed ASRs have higher extinction risks and conservation strategies aiming to benefit female African Penguin might need to be developed.
Structure and electrical properties of perovskite layer (1−x)Sr2Nb2O7‐x(Na0.5Bi0.5)TiO3 high‐temperature piezoceramics
Authors: Chen Tao , Liang Ruihong , Li Yuchen , Zhou Zhiyong , Dong Xianlin
Published: December 2016

The structure and electrical properties of perovskite layer structured (PLS) (1−x)Sr2Nb2O7‐x(Na0.5Bi0.5)TiO3 (SNO‐NBT) prepared by solid‐state reaction method are investigated. The addition of NBT is beneficial to speed up mass transfer and particle rearrangement during sintering, leading to better sinterability and higher bulk density up to 96.8%. The solid solution limit x in the SNO‐NBT system is below 0.03, over which Ti4+ is preferable to aggregate and results in the generation of secondary phase. After the modification by NBT, all SNO‐NBT ceramics have a Curie temperature Tc up to over 1300°C and piezoelectric constant d33 about 1.0 pC/N. The breakthrough of piezoelectricity can mainly be attributed to rotation and distortion of oxygen octahedron as well as higher poling electric field resulting from the improved bulk density. This study not only demonstrates how to improve piezoelectricity by NBT addition, but also opens up a new direction to design PLS piezoceramics by introducing appropriate second phase.
Accurate determination of fiber strength distributions
Authors: Callaway Evan Benjamin , Zok Frank W.
Published: December 2016

Tensile strengths of small‐diameter ceramic fibers are commonly obtained from measured fracture loads on individual fibers and the average cross‐sectional area of the entire fiber population. The goal of the present article is to provide a critical assessment of the consequences of using the average fiber area in the inferred strength distribution. The issues are addressed through established theorems in convolution and uncertainty propagation as well as Monte Carlo simulations. Systematic errors introduced by using the average area are well‐represented by simple analytical formulae. The formulae are couched in terms of the coefficient of variation in fiber area and the dispersion in fiber strengths, characterized by the Weibull modulus. In turn, the formulae are used to determine the true values of Weibull modulus and reference strength from their nominal values. Random uncertainties associated with a finite number of tests decay slowly with number, in accordance with an inverse root scaling. When systematic errors are conflated with random uncertainties, accurate determination of the true Weibull modulus becomes increasingly challenging, even for seemingly large numbers of strength measurements. The results are used to assess the fidelity of previously‐reported experimental results based on nominal strength data.
Influence of A‐site nonstoichiometry on the electrical properties of BT‐BMT
Authors: Muhammad Raz , Khesro Amir
Published: December 2016

A stoichiometric and 2 mol% Ba deficient samples in the formulation 0.5BaTiO3‐0.5BiMg1/2Ti1/2O3 (BT‐BMT) were processed via a mixed oxide solid‐state route. The deficient sample exhibited a high relative permittivity (2100±15%) over the temperature range 90‐450°C and a low dielectric loss (tanδ < 0.01), maintained up to high temperature (430°C). The samples exhibited intrinsic conduction mechanism and showed an n‐type character. By introducing 2 mol% Ba vacancies, a dramatic influence on the dielectric loss was observed which was mainly associated with the trapping of electrons by barium‐oxygen vacancy pair associated with the intentionally produced cation vacancies. Thus, control of composition by creating deficiency allows fine tuning of the dielectric properties of BT‐BMT ceramics for applications in high‐temperature multilayered ceramic capacitors.
Effect of point defects on Curie temperature of lithium niobate
Authors: Koyama Chihiro , Nozawa Jun , Fujiwara Kozo , Uda Satoshi
Published: December 2016

The effect of point defects on the Curie temperature (Tc) of LiNbO3 (LN) was investigated by combining Tc measurements with an analysis of the defect structures of LN doped with impurities having various valences. The data show that Tc of congruent LN increases with the impurity concentration up to around 3 and 2 mol% for divalent and trivalent impurities, respectively, whereas it decreases continuously with increased concentrations of tetravalent impurities. These Tc variations were examined with respect to the defect structures of impurity‐doped LN, which are expressed in the form chemical formulae using Kröger‐Vink notation. The defect structures of divalent and trivalent impurity‐doped LN are and , respectively (NbLi: Nb at Li sites; VLi: vacancies at Li sites, MLi: impurities at Li sites, and Li/Nb = the congruent ratio). The defect structure in the case of tetravalent impurities is . Analyses of the defect structures indicated that the NbLi concentration decreases with divalent or trivalent impurity doping, which increases Tc. In contrast, the NbLi concentration increases with tetravalent impurity doping, which decreases Tc. In addition, the divalent or trivalent impurity concentrations at which the NbLi concentration becomes zero were found to correspond to the concentrations at which Tc is maximized, suggesting that Tc of LN depends on the NbLi concentration.
Use of Oral Anticoagulant Therapy in Older Adults with Atrial Fibrillation After Acute Ischemic Stroke
Authors: McGrath Emer R. , Go Alan S. , Chang Yuchiao , Borowsky Leila H. , Fang Margaret C. , Reynolds Kristi , Singer Daniel E.
Published: December 2016

Objectives

To explore barriers to anticoagulation in older adults with atrial fibrillation (AF) at high risk of stroke and to identify opportunities for interventions that might increase use of oral anticoagulants (OACs).

Design

Retrospective cohort study.

Setting

Two large community‐based AF cohorts.

Participants

Individuals with ischemic stroke surviving hospitalization (N = 1,405, mean age 79).

Measurements

Using structured chart review, reasons for nonuse of OAC were identified, and 1‐year poststroke survival was assessed. Logistic regression was used to identify correlates of OAC nonuse.

Results

Median CHA2DS2‐VASc score was 5, yet 44% of participants were not prescribed an OAC at discharge. The most‐frequent (nonmutually exclusive) physician reasons for not prescribing OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), participant or family refusal (14.9%), older age (11.0%), and dementia (9.4%). Older age (odds ratio (OR) = 8.96, 95% confidence interval (CI) = 5.01–16.04 for aged ≥85 vs <65) and disability (OR = 12.58, 95% CI = 5.82–27.21 for severe vs no deficit) were the most‐important independent predictors of nonuse of OACs. By 1 year, 42.5% of those not receiving an OAC at discharge had died, versus 19.1% of those receiving an OAC (P < .001), far higher than recurrent stroke rates.

Conclusion

Despite very high stroke risk, more than 40% of participants were not discharged with an OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These individuals’ high 1‐year mortality rate confirmed their high level of comorbidity. To improve anticoagulation decisions and outcomes in this population, future research should focus on strategies to mitigate fall risk, improve assessment of risks and benefits of anticoagulation in individuals with AF, and determine whether newer anticoagulants are safer in complex elderly and frail individuals.
Effect of Resting Heart Rate on All‐Cause Mortality and Cardiovascular Events According to Age
Authors: Li Kuibao , Yao Chonghua , Yang Xinchun , Dong Lei
Published: December 2016

Objectives

To examine whether the association between resting heart rate (RHR) and all‐cause mortality and cardiovascular events differs according to age.

Design

Prospective cohort.

Setting

Community in Beijing, China.

Participants

Individuals aged 40 and older without cardiovascular disease at baseline (N = 6,209).

Measurements

Trained investigators interviewed participants using a standard questionnaire to obtain information on demographic characteristics, medical history and lifestyle risk factors in 1991. RHR was evaluated according to quartiles (<72, 72–76, 76–84, ≥84 beats/min). Cox regression models were used to assess the associations between RHR and all‐cause mortality and cardiovascular events.

Results

During a mean follow‐up of 8.3 years, 840 subjects died, and 676 experienced a cardiovascular event. Higher RHR was significantly associated with all‐cause mortality (P trend < .001) and cardiovascular events (P trend = .002) in older (≥60) but not younger (<60) participants (both P trend > .05). There were significant modifying effects of age on the association between RHR and all‐cause mortality (P interaction < .001) and cardiovascular events (P interaction =.002). Similar results were observed after exclusion of individuals who died (n = 100) or had a cardiovascular event (n = 45) during the first 2 years of follow‐up.

Conclusion

High RHR appears to be an independent determinant of all‐cause mortality and cardiovascular events in older but not younger individuals.
Pathway from Delirium to Death: Potential In‐Hospital Mediators of Excess Mortality
Authors: Dharmarajan Kumar , Swami Sunil , Gou Ray Y. , Jones Richard N. , Inouye Sharon K.
Published: December 2016

Objectives

(1) To determine the relationship of incident delirium during hospitalization with 90‐day mortality; (2) to identify potential in‐hospital mediators through which delirium increases 90‐day mortality.

Design

Analysis of data from Project Recovery, a controlled clinical trial of a delirium prevention intervention from 1995 to 1998 with follow‐up through 2000.

Setting

Large academic hospital.

Participants

Patients ≥70 years old without delirium at hospital admission who were at intermediate‐to‐high risk of developing delirium and received usual care only.

Measurements

(1) Incident delirium; (2) potential mediators of delirium on death including use of restraining devices (physical restraints, urinary catheters), development of hospital acquired conditions (HACs) (falls, pressure ulcers), and exposure to other noxious insults (sleep deprivation, acute malnutrition, dehydration, aspiration pneumonia); (3) death within 90 days of admission.

Results

Among 469 patients, 70 (15%) developed incident delirium. These patients were more likely to experience restraining devices (37% vs 16%, P < .001), HACs (37% vs 12%, P < .001), other noxious insults (63% vs 49%, P = .03), and 90‐day mortality (24% vs 6%, P < .001). The inverse probability weighted hazard of death due to delirium was 4.2 (95% CI = 2.8–6.3) in bivariable analyses, increased in a graded manner with additional exposures to restraining devices, HACs, and other noxious insults, and declined by 10.9% after addition of these potential mediator categories, providing evidence of mediation.

Conclusion

Restraining devices, HACs, and additional noxious insults were more frequent among patients with delirium, increased mortality in a graded manner, and were responsible for a significant percentage of the association of delirium with death. Additional efforts to prevent potential downstream mediators through which delirium increases mortality may help to improve outcomes among hospitalized older adults.
Unique Associations Between Big Five Personality Aspects and Multiple Dimensions of Well‐Being
Authors: Sun Jessie , Kaufman Scott Barry , Smillie Luke D.
Published: December 2016

Objective

Personality traits are associated with well‐being, but the precise correlates vary across well‐being dimensions and within each Big Five domain. This study is the first to examine the unique associations between the Big Five aspects (rather than facets) and multiple well‐being dimensions.

Method

Two samples of U.S. participants (total N = 706; Mage = 36.17; 54% female) recruited via Amazon's Mechanical Turk completed measures of the Big Five aspects and subjective, psychological, and PERMA well‐being.

Results

One aspect within each domain was more strongly associated with well‐being variables. Enthusiasm and Withdrawal were strongly associated with a broad range of well‐being variables, but other aspects of personality also had idiosyncratic associations with distinct forms of positive functioning (e.g., Compassion with positive relationships, Industriousness with accomplishment, and Intellect with personal growth).

Conclusions

An aspect‐level analysis provides an optimal (i.e., parsimonious yet sufficiently comprehensive) framework for describing the relation between personality traits and multiple ways of thriving in life.
Infection Process of Burkholderia glumae in Rice Spikelets
Authors: Li Lu , Wang Ling , Liu Lian Meng , Hou Yu Xuan , Huang Shi Wen , Li Qi Qin
Published: December 2016

Burkholderia glumae, which causes bacterial panicle blight of rice (BPBR), is a well‐known pathogen. The pathogen‐induced symptoms include seedling rot, grain rot and leaf‐sheath browning in rice plants. B. glumae can incubate in rice plants as endophytes before booting stage of rice. In this study, we constructed a gfp‐labelled system of B. glumae LMG 2196 and used SEM to clarify the colonization course of B. glumae at the heading stage. New locations of B. glumae were found. The pathogens initially distributed on the surface of the glumes and colonized in the glume hairs and cells of the edge of sterile lemma, palea and lemma. The base of glume hairs was the initial position for colonization. Bacterial population raised around glume hairs, penetrated into the inner surface of the palea and lemma, and spread on the gynoecium and stamens through contact. The spreading of B. glumae among the panicles mainly occurred through the contact or friction among glumes or leaf sheaths, but the inner spread of the stamens mainly occurred through the connective tissue of anther. We also detected the differences of bacterial content in stamens, gynoecia and glumes. The growing stage of B. glumae in spikelets could be divided into two sections. The biomass of all parts continued to increase to nearly 108 CFU/g at 10 DAI. This caused wilt symptoms and stopped the pollination. This work showed that glume hairs played an important role in the initial colonization of B. glumae, and provides a foundation for further studies of the infection manner of B. glumae and other pathogenic bacteria.
Utilization of teledentistry as a tool to screen for dental caries among 12‐year‐old school children in a rural region of India
Authors: Purohit Bharathi M. , Singh Abhinav , Dwivedi Ashish
Published: December 2016

Objective

The study aims to assess the reliability of video‐graphic method as a tool to screen the dental caries among 12‐year‐old school children in a rural region of India.

Methods

A total of 139 school children participated in the study. Visual tactile examinations were conducted using the Decayed, Missing, and Filled Teeth (DMFT) index. Simultaneously, standardized video recording of the oral cavity was performed. Sensitivity and specificity values were calculated for video‐graphic assessment of dental caries. Bland–Altman plot was used to assess agreement between the two methods of caries assessment. Likelihood ratio (LR) and receiver‐operating characteristic (ROC) curve were used to assess the predictive accuracy of the video‐graphic method.

Results

Mean DMFT for the study population was 2.47 ± 2.01 and 2.46 ± 1.91 by visual tactile and video‐graphic assessment (P = 0.76; > 0.05). Sensitivity and specificity values of 0.86 and 0.58 were established for video‐graphic assessment. A fair degree of agreement was noted between the two methods with Intraclass correlation coefficient (ICC) value of 0.56. LR for video‐graphic assessment was 2.05. Bland–Altman plot confirmed the level of agreement between the two assessment methods. The area under curve was 0.69 (CI 0.57, 0.80, P = 0.001).

Conclusion

Teledentistry examination is comparable to clinical examination when screening for dental caries among school children. This study provides evidence that teledentistry may be used as an alternative screening tool for assessment of dental caries and is viable for remote consultation and treatment planning. Teledentistry offers to change the dynamics of dental care delivery and may effectively bridge the rural–urban oral health divide.
Metformin-loaded alginate nanoparticles as an effective antidiabetic agent for controlled drug release
Authors: Kumar Sandeep , Bhanjana Gaurav , Verma Ritesh Kumar , Dhingra Dinesh , Dilbaghi Neeraj , Kim Ki-Hyun
Published: December 2016

Objectives

Present modalities for the diagnosis and treatment of diabetes still suffer from certain limitations such as erratic absorption, need of high dose, poor sensitivity or specificity, resistance, substantial morbidity and mortality, long-term complications, and patient-to-patient variability with lifetime treatment.

Methods

This study focused on the development of a water-in-oil-in-water metformin nanoemulsion as an effective method in diabetes treatment. As a Biopharmaceutics Classification System (BCS) class III drug, metformin is hydrophilic in nature with high solubility and poor absorption characteristics. To simultaneously facilitate gastrointestinal absorption and intestinal permeability, metformin was loaded into alginate nanocapsules prepared by an emulsion cross-linking technology.

Key findings

These prepared metformin-loaded alginate nanoparticles (MLANs) were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and photon correlation spectroscopy (PCS)-based particle size analysis.

Conclusions

The drug loading and encapsulation efficiency in MLANs were 3.12 mg (the amount of metformin added in 100 mg of nanoparticles) and 78%, respectively. The results of in-vitro drug release studies and in-vivo efficacy tests (using animal models) demonstrated enhanced efficiency and response of MLANs relative to pure metformin. The efficacy of MLANs (46.8 mg/kg) was overall about three times higher than that of pure metformin150 mg/kg.
Bacteriophage formulated into a range of semisolid and solid dosage forms maintain lytic capacity against isolated cutaneous and opportunistic oral bacteria
Authors: Brown Teagan L , Thomas Tereen , Odgers Jessica , Petrovski Steve , Spark Marion Joy , Tucci Joseph
Published: December 2016

Background

Resistance of bacteria to antimicrobial agents is of grave concern. Further research into the development of bacteriophage as therapeutic agents against bacterial infections may help alleviate this problem.

Objectives

To formulate bacteriophage into a range of semisolid and solid dosage forms and investigate the capacity of these preparations to kill bacteria under laboratory conditions.

Methods

Bacteriophage suspensions were incorporated into dosage forms such as creams, ointments, pastes, pessaries and troches. These were applied to bacterial lawns in order to ascertain lytic capacity. Stability of these formulations containing phage was tested under various storage conditions.

Key findings

A range of creams and ointments were able to support phage lytic activity against Propionibacterium acnes. Assessment of the stability of these formulations showed that storage at 4 °C in light-protected containers resulted in optimal phage viability after 90 days. Pessaries/suppositories and troches were able to support phage lytic activity against Rhodococcus equi.

Conclusions

We report here the in-vitro testing of semisolid and solid formulations of bacteriophage lytic against a range of bacteria known to contribute to infections of the epithelia. This study provides a basis for the future formulation of diverse phage against a range of bacteria that infect epithelial tissues.
Impact of treatment on hepatitis C virus transmission and incidence in Egypt: A case for treatment as prevention
Authors: Ayoub H. H. , Abu‐Raddad L. J.
Published: December 2016

Egypt has launched a hepatitis C virus (HCV) treatment programme using direct‐acting antivirals (DAAs). Our aim was to assess the impact of five plausible programme scale‐up and sustainability scenarios for HCV treatment as prevention in Egypt. We developed and analysed a mathematical model to assess programme impact using epidemiologic, programming and health economics measures. The model was parametrized with current and representative natural history, HCV prevalence and programme data. HCV incidence in Egypt is declining, but will persist at a considerable level for decades unless controlled by interventions. Across the five programme scenarios, 1.75‐5.60 million treatments were administered by 2030. Reduction in incidence (annual number of new infections) by 2030 ranged between 29% and 99%, programme‐attributed reduction in incidence rate (new infections per susceptible person per year) ranged between 18% and 99%, number of infections averted ranged between 42 393 and 469 599, and chronic infection prevalence reached as low as 2.8%‐0.1%. Reduction in incidence rate year by year hovered around 7%‐15% in the first decade of the programme in most scenarios. Treatment coverage in 2030 ranged between 24.9% and 98.8%, and number of treatments required to avert one new infection ranged between 9.5 and 12.1. Stipulated targets for HCV by 2030 could not be achieved without scaling‐up treatment to 365 000 per year and sustaining it for a decade. In conclusion, DAA scale‐up will have an immense and immediate impact on HCV incidence in Egypt. Elimination by 2030 is feasible if sufficient resources are committed to programme scale‐up and sustainability. HCV treatment as prevention is a potent and effective prevention approach.
Plasticity paves the way in an adaptive radiation
Authors: Sikkink Kristin L. , Snell‐Rood Emilie C.
Published: December 2016

Phenotypic plasticity has been hypothesized to play a central role in the evolution of phenotypic diversity across species (West‐Eberhard ). Through ‘genetic assimilation’, phenotypes that are initially environmentally induced within species become genetically fixed over evolutionary time. While genetic assimilation has been shown to occur in both the laboratory and the field (Waddington ; Aubret & Shine ), it remains to be shown whether it can account for broad patterns of phenotypic diversity across entire adaptive radiations. Furthermore, our ignorance of the underlying molecular mechanisms has hampered our ability to incorporate phenotypic plasticity into models of evolutionary processes. In this issue of Molecular Ecology, Parsons et al. () take a significant step in filling these conceptual gaps making use of cichlid fishes as a powerful study system. Cichlid jaw and skull morphology show adaptive, plastic changes in response to early dietary experiences (Fig. 1). In this research, Parsons et al. () first show that the direction of phenotypic plasticity aligns with the major axis of phenotypic divergence across species. They then dissect the underlying genetic architecture of this plasticity, showing that it is specific to the developmental environment and implicating the patched locus in genetic assimilation (i.e. a reduction in the environmental sensitivity of that locus in the derived species).
Ageing causes prominent neurovascular dysfunction associated with loss of astrocytic contacts and gliosis
Authors: Duncombe J. , Lennen R. J. , Jansen M. A. , Marshall I. , Wardlaw J. M. , Horsburgh K.
Published: December 2016

Aims

Normal neurovascular coupling, mediated by the fine interplay and communication of cells within the neurovascular unit, is critical for maintaining normal brain activity and cognitive function. This study investigated whether, with advancing age there is disruption of neurovascular coupling and specific cellular components of the neurovascular unit, and whether the effects of increasing amyloid (a key feature of Alzheimer's disease) would exacerbate these changes.

Methods

Wild‐type mice, in which amyloid deposition is absent, were compared to transgenic amyloid precursor protein (APP) littermates (TgSwDI) which develop age‐dependent increases in amyloid. Baseline cerebral blood flow and responses to whisker stimulation were measured. Components of the neurovascular unit (astrocytes, end‐feet, pericytes, microglia) were measured by immunohistochemistry.

Results

Neurovascular coupling was progressively impaired with increasing age (starting at 12 months) but was not further altered in TgSwDI mice. Aged mice showed reduced vascular pericyte coverage relative to young but this was not related to neurovascular function. Aged mice displayed significant reductions in astrocytic end‐feet expression of aquaporin‐4 on blood vessels compared to young mice, and a prominent increase in microglial proliferation which correlated with neurovascular function.

Conclusions

Strategies aimed to restore the loss of astrocytic end feet contact and reduce gliosis may improve neurovascular coupling.
Time to onset of bisphosphonate‐related osteonecrosis of the jaws: a multicentre retrospective cohort study
Authors: Fung PPL , Bedogni G , Bedogni A , Petrie A , Porter S , Campisi G , Bagan J , Fusco V , Saia G , Acham S , Musto P , Petrucci MT , Diz P , Colella G , Mignogna MD , Pentenero M , Arduino P , Lodi G , Maiorana C , Manfredi M , Hallberg P , Wadelius M , Takaoka K , Leung YY , Bonacina R , Schiødt M , Lakatos P , Taylor T , De Riu G , Favini G , Rogers SN , Pirmohamed M , Nicoletti P ,   GENVABO Consortium, Fedele S
Published: December 2016

Objectives

Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP‐treated patients.

Subjects and Methods

Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP‐related ONJ between 2004 and 2012.

Results

The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate.

Conclusions

The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk‐reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.
Hospital staff experiences of their relationships with adults who self‐harm: A meta‐synthesis
Authors: O'Connor Sophie , Glover Lesley
Published: December 2016

Purpose

This review aimed to synthesize qualitative literature exploring inpatient hospital staff experiences of their relationships with people who self‐harm.

Methods

Nine studies were identified from a systematic search of five research databases. Papers included the experiences of physical health and mental health staff working in inpatient settings. The studies employed various qualitative research methods and were appraised using an adapted quality assessment tool (Tong, Sainsbury, & Craig, 2007). A meta‐synthesis was conducted using traditional qualitative analysis methods including coding and categorizing data into themes.

Results

Three main themes derived from the data. ‘The impact of the system’ influenced the extent to which staff were ‘Fearing the harm from self‐harm’, or were ‘Working alongside the whole person’. A fear‐based relationship occurred across mental health and physical health settings despite differences in training; however, ‘Working alongside the whole person’ primarily emerged from mental health staff experiences. Systemic factors provided either an inhibitory or facilitative influence on the relational process.

Conclusions

Staff experiences of their relationship with people who self‐harm were highlighted to have an important impact on the delivery and outcome of care. Increasing support for staff with a focus on distress tolerance, managing relational issues, and developing self‐awareness within the relationship may lead to a more mutually beneficial experience of care. Equally, structure, clarity, and support within inpatient systems may empower staff to feel more confident in utilizing their existing skills.

Practitioner points

Working with people who self‐harm can be emotionally challenging and how staff cope with this can significantly impact on the engagement of staff and patients.

Increasing the skills of staff in managing relational issues and tolerating distress, as well as providing support and reflective practice groups may be useful in managing emotional responses to working with people who self‐harm.

Refining the supportive, procedural, and environmental structures surrounding the caregiving relationship may help enable better integration of physical and mental health care.
The prediction of the level of personality organization on reduction of psychiatric symptoms and improvement of work ability in short‐ versus long‐term psychotherapies during a 5‐year follow‐up
Authors: Knekt Paul , Lindfors Olavi , Keinänen Matti , Heinonen Erkki , Virtala Esa , Härkänen Tommi
Published: December 2016

Objectives

How level of personality organization (LPO) predicts psychiatric symptoms and work ability in short‐ versus long‐term psychotherapies is poorly known. We investigated the importance of the LPO on the benefits of short‐term versus long‐term psychotherapies.

Design

A cohort study based on 326 outpatients with mood or anxiety disorder was allocated to long‐term (LPP) and short‐term (SPP) psychodynamic psychotherapy, and solution‐focused therapy (SFT).

Methods

The LPO was assessed by interview at baseline and categorized into neuroses and higher level borderline. Outcome was assessed at baseline and 4–9 times during a 5‐year follow‐up, using self‐report and interview‐based measures of symptoms and work ability.

Results

For patients receiving SPP, improvement in work ability, symptom reduction, and the remission rate were more considerable in patients with neuroses than in higher level borderline patients, whereas LPP or SFT showed no notable differences in effectiveness in the two LPO groups. In patients with neuroses, improvement was more considerable in the short‐term therapy groups during the first year of follow‐up, and in higher level borderline patients LPP was more effective after 3 years of follow‐up. The remission rate, defined as both symptom reduction and lack of auxiliary treatment, was higher in LPP than in SPP for both the LPO groups considered.

Conclusions

In neuroses, short‐term psychotherapy was associated with a more rapid reduction of symptoms and increase in work ability, whereas LPP was more effective for longer follow‐ups in both LPO groups. Further large‐scale studies are needed.

Practitioner points

Level of personality organization is relevant for selection between short‐ and long‐term psychotherapies.

Short‐term therapy gives faster benefits for neurotic patients but not for patients with higher level borderline personality organization.

Sustained remission from symptoms is more probable after long‐term than short‐term therapy.
The light response of mesophyll conductance is controlled by structure across leaf profiles
Authors: Théroux‐Rancourt Guillaume , Gilbert Matthew E.
Published: December 2016

Mesophyll conductance to CO2 (gm) may respond to light either through regulated dynamic mechanisms or due to anatomical and structural factors. At low light, some layers of cells in the leaf cross‐section approach photocompensation and contribute minimally to bulk leaf photosynthesis and little to whole leaf gm (gm,leaf). Thus, the bulk gm,leaf will appear to respond to light despite being based upon cells having an anatomically fixed mesophyll conductance. Such behaviour was observed in species with contrasting leaf structure using the variable J or stable isotope method of measuring gm,leaf. A species with bifacial structure, Arbutus × ‘Marina’, and an isobilateral species, Triticum durum L., had contrasting responses of gm,leaf upon varying adaxial or abaxial illumination. Anatomical observations, when coupled with the proposed model of gm,leaf to photosynthetic photon flux density (PPFD) response, successfully represented the observed gas exchange data. The theoretical and observed evidence that gm,leaf apparently responds to light has large implications for how gm,leaf values are interpreted, particularly limitation analyses, and indicates the importance of measuring gm under full light saturation. Responses of gm,leaf to the environment should be treated as an emergent property of a distributed 3D structure, and not solely a leaf area‐based phenomenon.
Living donor liver transplantation in a pediatric patient with preexisting yolk sac tumor
Authors: Wakiya Taiichi , Toyoki Yoshikazu , Ishido Keinosuke , Kudo Daisuke , Kimura Norihisa , Tsutsumi Shinji , Odagiri Tadashi , Suto Akiko , Uchida Chiaki , Hakamada Kenichi
Published: December 2016

There is ongoing discussion regarding the indications and timing of LT for patients with a preexisting extrahepatic malignancy. We herein report a pediatric case that underwent LDLT after therapy for YST. The patient, a 13‐year‐old female with biliary atresia, had undergone portoenterostomy at 2 months of age. She developed a left ovarian tumor with a high serum alpha‐fetoprotein concentration at 10 years of age. She underwent left oophorectomy and was diagnosed with ovarian YST (Stage I). After surgery, hepatopulmonary syndrome progressed gradually. She was examined carefully and exhibited no findings to suggest the recurrence of YST. We decided to perform LDLT at 3 years and 6 months of age after the surgery for YST. The patient is currently alive and doing well without recurrence of YST at approximately 2 years after transplantation. There is no significant difference between the recurrence rate of preexisting extrahepatic malignancy and the incidence of de novo malignancy if specific cases are selected. The indications and period from surgery for preexisting extrahepatic malignancy to LT should thus be determined according to the type and stage of cancer.
Longitudinal analysis of living donor kidney transplant rates in pediatric candidates in the United States
Authors: Keith Douglas S. , Vranic Gayle , Barcia John , Norwood Victoria , Nishio‐Lucar Angie
Published: December 2016

Among adults, living donor kidney transplant rates began declining in the United States after 2004 but whether a similar decline is occurring in the pediatric candidates has not been well studied. Share 35, a change in allocation rules implemented in October of 2005, may also have influenced rates of living donation. We sought to determine whether a decline in rates was occurring in pediatric candidates and whether the Share 35 program was the cause of the decline. All children listed for a kidney transplant or transplanted with a living donor without listing between 1996 and 2011 were identified in the United States (N=14 911) of which 6046 had received a living donor transplant during follow‐up. Kaplan‐Meier analysis showed a decline in living donor rates in candidates listed after 2001. Logistic regression analysis for living donor kidney transplantation confirmed the timing of the drop but also showed that changes in candidate demographics and center listing practices were impacting rates. A large drop in parental donation was the main cause for the drop. The rate of living donor transplant among pediatric candidates declined after 2001 predating by 4 years the implementation of Share 35, suggesting that factors other than changes in allocation rules are responsible for the decline.
Epstein‐Barr virus DNA monitoring in serum and whole blood in pediatric liver transplant recipients who do or do not discontinue immunosuppressive therapy
Authors: Kullberg‐Lindh C. , Saalman R. , Olausson M. , Herlenius G. , Lindh M.
Published: December 2016

The rate of PTLD can be reduced by weaned IS guided by monitoring of EBV DNA. In this single‐center retrospective case series study, we analyzed how reduction in IS influenced EBV DNA levels in whole blood and serum in 30 children during the first year after liver transplantation, and how these levels were related to symptoms putatively due to EBV. Primary and reactivated EBV infection was seen in 18 (60%) and eight patients (27%), respectively. Thirteen patients (42%) developed chronic high load the first year post‐transplant. IS was successfully discontinued in six patients the first year post‐transplant and in another two patients within 3 years. EBV DNA levels were reduced, but persisted long term in all the eight patients who had IS completely withdrawn. There was no case of PTLD. In summary, EBV DNAemia and chronic high load were very common after pediatric liver transplantation. Liver graft tolerance facilitates radical reduction in IS treatment, which may prevent PTLD, but EBV DNAemia may persist long term after discontinued IS.