bluuebunny/crossref_metadata_2025 huggingface dataset:
Arcuate nucleus neuropeptide coexpression and connections to gonadotrophin‐releasing hormone neurones in the female rhesus macaque
Authors: True C. , Takahashi D. , Kirigiti M. , Lindsley S. R. , Moctezuma C. , Arik A. , Smith M. S. , Kievit P. , Grove K. L.
Published: May 2017

The underlying hypothalamic neurocircuitry by which metabolism and feeding regulates reproductive function has been well‐studied in the rodent; however, recent data have demonstrated significant neuroanatomical differences in the human brain. The present study had three objectives, centred on arcuate nucleus neuropeptides regulating feeding and reproduction: (i) to characterise coexpression patterns in the female nonhuman primate; (ii) to establish whether these neuronal populations make potential contacts with gonadotophin‐releasing hormone (GnRH) neurones; and (iii) to determine whether these contacts differ between the low and high GnRH‐releasing states of pre‐puberty and adulthood, respectively. Female nonhuman primates have several coexpression patterns of hypothalamic neuropeptides that differ from those reported in rodents. Cocaine‐ and amphetamine‐regulated transcript (CART) is not coexpressed with pro‐opiomelanocortin but instead with neuropeptide Y (NPY). CART is also expressed in a subpopulation of kisspeptin cells in the nonhuman primate, similar to observations in humans but diverging from findings in rodents. Very few GnRH‐expressing neurones received close appositions from double‐labelled kisspeptin/CART fibres; however, both single‐labelled kisspeptin and CART fibres were in frequent apposition with GnRH neurones, with no differences between prepubertal and adult animals. NPY/agouti‐related peptide (AgRP) coexpressing fibres contacted significantly more GnRH neurones in prepubertal animals than adults, consistent with increased NPY and AgRP mRNA observed in prepubertal animals. The findings of the present study detail significant differences in arcuate nucleus neuropeptide coexpression in the monkey compared to the rodent and are consistent with the hypothesis that arcuate nucleus NPY/AgRP neurones play an inhibitory role in controlling GnRH neuronal regulation in the prepubertal primate.
Factors Influencing Resilience of Burn Patients in South Korea
Authors: Jang Mi Heui , Park Jongui , Chong Mi Kyong , Sok Sohyune R.
Published: May 2017

Purpose

To examine and identify the factors influencing the degree of resilience among Korean burn patients.

Design

A cross‐sectional descriptive design was employed.

Methods

The study sample consisted of 138 burn patients recovering from the acute phase in H hospital, Seoul. The male patient participants numbered 93 (67.4%) and the female participants numbered 45 (32.6%). The average age of the participants was 46.79 years. Measures used were the Beck Depression Inventory, State Trait Anxiety Inventory, self‐esteem scale, family support scale, and resilience scale.

Findings

The analyses showed that the prediction model for resilience among burn patients was significant (F = 33.94, p < .001). The value of the adjusted R2 was 0.492, which corresponds to the explanatory power of 49.2%. The factor that was found to have the most influence on resilience among burn patients was self‐esteem (β = .35), followed by family support (β = .29).

Conclusions

This study provides preliminary evidence that self‐esteem is a major and primary predictor of resilience among burn patients, next followed by family support.

Clinical Relevance

In the nursing practice, nurses need to pay attention to the burn patient's self‐esteem and family support. Concrete interventions and strategies to improve the resilience of burn patients are needed.
Statistical shape modelling of hip and lumbar spine morphology and their relationship in the MRC National Survey of Health and Development
Authors: Pavlova Anastasia V. , Saunders Fiona R. , Muthuri Stella G. , Gregory Jennifer S. , Barr Rebecca J. , Martin Kathryn R. , Hardy Rebecca J. , Cooper Rachel , Adams Judith E. , Kuh Diana , Aspden Richard M.
Published: May 2017

The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition statistics to describe and quantify such shapes from images; it uses principal components analysis to generate modes of variation describing each image in terms of a set of numerical scores after removing global size variation. We used SSM to quantify the shapes of the hip and the lumbar spine in dual‐energy x‐ray absorptiometry (DXA) images from 1511 individuals in the MRC National Survey of Health and Development at ages 60–64 years. We compared shapes of both joints in men and women and hypothesised that hip and spine shape would be strongly correlated. We also investigated associations with height, weight, body mass index (BMI) and local (hip or lumber spine) bone mineral density. In the hip, all except one of the first 10 modes differed between men and women. Men had a wider femoral neck, smaller neck‐shaft angle, increased presence of osteophytes and a loss of the femoral head/neck curvature compared with women. Women presented with a flattening of the femoral head and greater acetabular coverage of the femoral head. Greater weight was associated with a shorter, wider femoral neck and larger greater and lesser trochanters. Taller height was accompanied by a flattening of the curve between superior head and neck and a larger lesser trochanter. Four of the first eight modes describing lumbar spine shape differed between men and women. Women tended to have a more lordotic spine than men with relatively smaller but caudally increasing anterior‐posterior (a‐p) vertebral diameters. Men were more likely to have a straighter spine with larger vertebral a‐p diameters relative to vertebral height than women, increasing cranially. A weak correlation was found between body weight and a‐p vertebral diameter. No correlations were found between shape modes and height in men, whereas in women there was a weak positive correlation between height and evenness of spinal curvature. Linear relationships between hip and spine shapes were weak and inconsistent in both sexes, thereby offering little support for our hypothesis.

In conclusion, men and women entering their seventh decade have small but statistically significant differences in the shapes of their hips and their spines. Associations with height, weight, BMI and BMD are small and correspond to subtle variations whose anatomical significance is not yet clear. Correlations between hip and spine shapes are small.
Retracted: Oral misoprostol alone versus oral misoprostol and Foley's catheter for induction of labor: A randomized controlled trial
Authors: Husain Samia , Husain Sonia , Izhar Rubina
Published: May 2017

Aim

The aim of this study was to evaluate the efficacy of oral misoprostol and Foley's catheter versus oral misoprostol alone for induction of labor.

Methods

This open‐label randomized controlled trial included 335 women requiring induction of labor. A total of 166 women were randomly allocated to induction with oral misoprostol alone and 169 women were assigned for induction with Foley's balloon catheter and oral misoprostol using a computer‐generated allocation sequence. The primary outcome was rate of failure to achieve vaginal delivery within 24 h of induction.

Results

The proportion of women failing to achieve vaginal delivery within 24 h in the combination group was lower (11.8% vs 28.7%, P = 0.001). When the two groups were stratified according to parity, the difference remained statistically significant only for parous women. The median induction‐to‐delivery interval (13.0 h vs 19 h, P = 0.000) and the median number of doses of misoprostol used (2 vs 3, P = 0.000) were lower in the combination group. The number of women who delivered vaginally in the combination group was significantly higher (91% vs 79%, P = 0.001). More neonates born to women in the misoprostol group had Apgar scores < 7 and were admitted to the neonatal intensive care unit (P = 0.016 and P = 0.007, respectively).

Conclusion

The rate of failure to achieve vaginal delivery within 24 h was lower with Foley's balloon and oral misoprostol as compared to oral misoprostol alone.
Combined impact of healthy lifestyle factors on lifespan: two prospective cohorts
Authors: Larsson S. C. , Kaluza J. , Wolk A.
Published: May 2017

Background

The impact of multiple healthy lifestyle factors on survival time is unclear.

Objective

The aim of this study was to examine differences in survival time associated with a healthy lifestyle versus a less healthy lifestyle.

Methods

This study consisted of 33 454 men (Cohort of Swedish Men) and 30 639 women (Swedish Mammography Cohort) aged 45–83 years and free of cancer and cardiovascular disease at baseline. The healthy lifestyle factors included the following: (i) nonsmoking; (ii) physical activity at least 150 min per week; (iii) alcohol consumption of 0–14 drinks per week; (iv) and healthy diet defined as a modified Dietary Approaches to Stop Hypertension Diet score above the median. Cox proportional hazards regression models and Laplace regression were used to estimate, respectively, hazard ratios of all‐cause mortality and differences in survival time.

Results

During follow‐up from 1998 through 2014, 8630 deaths amongst men and 6730 deaths amongst women were ascertained through linkage to the Swedish Cause of Death Register. Each of the four healthy lifestyle factors was inversely associated with all‐cause mortality and increased survival time. Compared with individuals with no or one healthy lifestyle factor, the multivariable hazard ratios of all‐cause mortality for individuals with all four health behaviours were 0.47 (95% 95% confidence interval [CI]: 0.44–0.51) in men and 0.39 (95% CI: 0.35–0.44) in women. This corresponded to a difference in survival time of 4.1 (95% CI: 3.6–4.6) years in men and 4.9 (95% CI: 4.3–5.6) years in women.

Conclusion

Adopting healthy lifestyle behaviours may markedly increase lifespan.
Differences in Lip Support with and without Labial Flanges in a Maxillary Edentulous Population. Part 4: Patient‐Centered Analysis
Authors: Bidra Avinash S. , Touloumi Foteini , Wu Rong
Published: May 2017

Purpose

To study the subjective differences in facial esthetics evaluations and the ability to distinguish facial changes due to changes in lip support, when evaluated by patients themselves. An additional objective was to study the differences between patients’ self‐evaluation versus evaluation of other patients.

Materials and Methods

A total of 22 maxillary edentulous patients from the original sample of 31 patients described in Part 1 of the study, returned to participate in this part of the study. The 22 patients acted as judges for all images in this study, and were therefore un‐blinded to the objectives and details of the study. Patients first completed evaluation of facial esthetics on a visual analog scale (VAS). Four digital images per patient (total of 88 images) were evaluated in a random order, twice by all 22 patients. The mean scores from all judgments were used as the outcomes to be analyzed. All patients then took a discriminatory sensory analysis test (triangle test) where they were required to correctly identify the image with a flangeless denture out of a set of 3 images. Both the VAS and triangle test ratings were conducted twice in a random order, and mean ratings were used for all analyses.

Results

For VAS analysis, there were no statistically significant or clinically significant differences in facial esthetics ratings between flange and flangeless dentures (p < 0.05). This was true for both profile and frontal images, irrespective of self‐evaluation versus evaluation of other patients, years of patient edentulism, and judge (patient) gender. For the triangle test, frontal images had a correct identification rate of 50.2% and profile images of 50.4%, and the difference was not significant. There were no significant differences in triangle test results with respect to self‐evaluation versus evaluation of other patients and judge (patient) gender. For all patients, the likelihood of correctly identifying images with flangeless dentures was significantly greater than 1/3, which was the minimum chance for correct identification (p < 0.0001).

Conclusions

Flangeless dentures resulted in no differences in facial esthetics ratings for frontal and profile images, when evaluated by patients. When patients were forced to look for differences, flangeless dentures were detected in half of the image sets. These findings were similar for self‐evaluation versus evaluation of other patients and for both patient genders.
How people from Chinese backgrounds make sense of and respond to the experiences of mental distress: Thematic analysis
Authors: Yeung E. Y. W. , Irvine F. , Ng S. M. , Tsang K. M. S.
Published: May 2017

Accessible Summary

Rationale for the study

Many Chinese people do not contact mental health services when they first develop mental health problems. It is therefore important to find out reasons for low uptake of services so that strategies can be identified to promote early intervention.

What is already known about the topic?

Most Chinese people only come into contact with mental health services during crisis situations.

Language difference, lack of knowledge of mainstream services and stigma attached to mental health problems are barriers to access and utilize mental health services.

What the study adds to the international evidence?

Chinese people apply both Western medication and traditional healing to manage distress caused by mental health problems.

Because of the extreme stigma associated with mental health problems, Chinese people are reluctant to accept support from their own cultural groups outside their family. Family plays a major role in caring for relatives with mental health problems.

Families are prepared to travel across the world in search of folk healing if not available in Western societies.

What are the implications for practice?

It is important to recognize the different approaches to understanding and managing mental health problems among Chinese people, otherwise they will be dissuaded from engaging with mental health services if their beliefs are disregarded and invalidated.

Services that involve Chinese speaking mental health workers can address the issue of language differences and sensitive mental health issues within the Chinese community.

Introduction

Late presentation and low utilization of mental health services are common among Chinese populations. An understanding of their journey towards mental health care helps to identify timely and appropriate intervention.

Aim

We aimed to examine how Chinese populations make sense of the experiences of mental distress, and how this understanding influences their pathways to mental health care.

Method

We undertook in‐depth interviews with fourteen people with mental health problems (MHPs) and sixteen family members. Thematic analysis was used to analyse data.

Results/Discussions

Different conceptualization of mental distress and the stigma attached to MHPs explained why most participants accessed services at crisis points. Because of mental illness stigma, they were reluctant to seek help outside of the family. Participants used a pragmatic pluralistic approach to incorporate ritual healing and Western interventions to manage mental distress as they travelled further on the pathway journey. Families play a key role in the journey and are prepared to visit different parts of the world to seek traditional healers.

Implications for practice

Mental health nurses need to adopt a transcultural working approach to address mental health issues so that family will get the support needed to continue their caring role.
Moving Fourier Analysis for Locally Stationary Processes with the Bootstrap in View
Authors: Häfner Franziska , Kirch Claudia
Published: May 2017

We introduce a moving Fourier transformation for locally stationary time series, which captures the time‐varying spectral density in a similar manner as the classical Fourier transform does for stationary time series. In particular, the resulting Fourier coefficients as well as moving local periodograms are shown to be (almost all) asymptotically uncorrelated. The moving local periodogram is obtained by thinning the local periodogram to avoid multiple information present at different but close points in time. We obtain consistent estimators for the local spectral density at each point in time by smoothing the moving local periodogram. Furthermore, the moving Fourier coefficients, respectively periodograms, are well suited to adapt stationary frequency domain bootstrap methods to the locally stationary case. For the wild time frequency toggle bootstrap, it is shown that the corresponding bootstrap covariance of a global locally stationary bootstrap samples captures the time‐varying covariance structure of the underlying locally stationary time series correctly. Furthermore, this bootstrap in addition to adaptations of other frequency domain bootstrap methods is used in a simulation study to obtain uniform confidence bands for the time‐varying autocorrelation at lag 1. Finally, this methodology is applied to a wind data set.
Stable isotope and DNA analyses reveal the spatial distribution of crop‐foraging brown bears
Authors: Hata A. , Takada M. B. , Nakashita R. , Fukasawa K. , Oshida T. , Ishibashi Y. , Sato Y.
Published: May 2017

We investigated maize (Zea mays) consumption by brown bears (Ursus arctos) in a subpopulation of eastern Hokkaido, Japan, using carbon stable isotope analysis of hair samples to better understand the pattern and scale of movement of the bears’ crop‐foraging behavior. We identified a total of 30 individuals (19 males and 11 females) using DNA analysis of the hair samples. Stable isotope analysis suggested that female bears that were more likely to consume maize lived closer to agricultural crop fields. Our statistical model also estimated that the relative maize consumption of female bears decreased rapidly as the distance to crop fields increased to 3–4 km, similar to the radius of the annual home range of female bears. In contrast, male bears that were more likely to consume maize lived both in forested areas and near crop fields. Even if male bears live in a forested area except during the maize harvest period, they appeared to be at risk of being killed by lethal control because they can move from forested areas to crop fields during the maize harvest period. Collecting hair samples of many bears in the population over several years may allow the effect of lethal control on population viability to be estimated non‐invasively.
Disciplinary literacy and multimodal text design in physical education
Authors: Chandler‐Olcott Kelly
Published: May 2017

This article argues that scholarship on literacy in and across the disciplines has disproportionately focused on the core subjects of English, Mathematics, Science, and Social Studies rather than on “specialist” subjects such as Physical Education. This disparity in emphasis has provided little guidance to specialist teachers seeking to understand and address the literacy demands of subject areas that often privilege an expanded conception of literacy. To illustrate the affordances of such analysis for PE teachers as well as their literacy colleagues, the reading demands of a particular multimodal text from PE—a three‐part basketball play—are presented in light of key themes from the US Common Core State Standards for English Language Arts and Literacy. Complexities related to collective, embodied, and sequential meaning construction are explored. Recommendations for instruction and professional collaboration are shared.
Children's and parents' opinions on the sport‐related food environment: a systematic review
Authors: Smith M. , Signal L. , Edwards R. , Hoek J.
Published: May 2017

Sport is a key setting for interventions to address child obesity given its obesogenic nature. Understanding children's and parents' opinions on the sport‐related food environment is critical in developing effective programmes and policies to improve children's health. This systematic review synthesizes quantitative and qualitative research examining children's and parents' opinions on the sport‐related food environment. During July 2016, a range of electronic databases of academic and grey literature were searched. Thirty‐two publications (11 including children, 17 parents and 4 both) were included for review. The publications were assessed using the Analysis Grid for Environments Linked to Obesity framework to categorize the sport‐related food environment into the physical, sociocultural, economic and political environments. The literature available investigating children's and parents' opinions of the sport‐related food environment suggests that many children and parents consider the environment neither conducive to nor supportive of children's healthy food behaviours or wider health and well‐being. Both groups would likely support actions to change and improve it. This systematic review found that original research specifically investigating children's and parents' perspectives on almost all aspects of the sport‐related food environment is limited. Thus, there is scope for further investigation into this important part of children's food environments.
Pathogen‐inducible Ta‐Lr34res expression in heterologous barley confers disease resistance without negative pleiotropic effects
Authors: Boni Rainer , Chauhan Harsh , Hensel Goetz , Roulin Anne , Sucher Justine , Kumlehn Jochen , Brunner Susanne , Krattinger Simon G. , Keller Beat
Published: May 2017

Plant diseases are a serious threat to crop production. The informed use of naturally occurring disease resistance in plant breeding can greatly contribute to sustainably reduce yield losses caused by plant pathogens. The Ta‐Lr34res gene encodes an ABC transporter protein and confers partial, durable, and broad spectrum resistance against several fungal pathogens in wheat. Transgenic barley lines expressing Ta‐Lr34res showed enhanced resistance against powdery mildew and leaf rust of barley. While Ta‐Lr34res is only active at adult stage in wheat, Ta‐Lr34res was found to be highly expressed already at the seedling stage in transgenic barley resulting in severe negative effects on growth. Here, we expressed Ta‐Lr34res under the control of the pathogen‐inducible Hv‐Ger4c promoter in barley. Sixteen independent barley transformants showed strong resistance against leaf rust and powdery mildew. Infection assays and growth parameter measurements were performed under standard glasshouse and near‐field conditions using a convertible glasshouse. Two Hv‐Ger4c::Ta‐Lr34res transgenic events were analysed in detail. Plants of one transformation event had similar grain production compared to wild‐type under glasshouse and near‐field conditions. Our results showed that negative effects caused by constitutive high expression of Ta‐Lr34res driven by the endogenous wheat promoter in barley can be eliminated by inducible expression without compromising disease resistance. These data demonstrate that Ta‐Lr34res is agronomically useful in barley. We conclude that the generation of a large number of transformants in different barley cultivars followed by early field testing will allow identifying barley lines suitable for breeding.
Reproductive biology of Ferocactus recurvus (Mill.) Borg subsp. recurvus (Cactaceae) in the Tehuacán‐Cuicatlán Valley, Mexico
Authors: Córdova‐Acosta E. , Zavala‐Hurtado J. A. , Golubov J. , Casas A.
Published: May 2017

Mexico has one of the highest diversities of barrel cacti species worldwide; however, all are threatened and require conservation policies. Information on their reproductive biology is crucial, but few studies are available. Ferocactus recurvus subsp. recurvus is a barrel cactus endemic to the Tehuacán‐Cuicatlán Valley. Our research aimed to characterise its floral and pollination biology. We hypothesised bee pollination, as suggested by its floral morphology and behaviour, and self‐incompatibility, like most barrel cacti studied.

Three study sites were selected in the semiarid Zapotitlán Valley, Mexico. We examined 190 flowers from 180 plants to determine: morphometry and behaviour of flowers, flower visitors and probable pollinators, and breeding system.

Flowers showed diurnal anthesis, lasting 2–5 days, the stigma being receptive on day 2 or 3 after the start of anthesis. Flowers produced scarce/no nectar and main visitors were bees (Apidae), followed by flies (Muscidae), ants (Formicidae), thrips (Thripidae) and hummingbirds (Throchilidae); however, only native bees and occasionally wasps contacted the stigma and anthers. Pollination experiments revealed that this species is self‐incompatible and xenogamous. In natural conditions, fruit set was 60% and cross‐pollination fruit set was 100%. Percentage seed germination resulting from cross‐pollination was higher than in the control treatment.

Our results provide ecological information for conservation programmes to ensure a high probability of breeding and seed production in natural populations of F. recurvus.
Radiographic assessment of pulmonary fluid clearance and lung aeration in newborn calves delivered by elective Caesarean section
Authors: Abdelmegeid MK , Kutasi O , Nassiff MN , Wirth K , Bodai E , Farrag F , Molnár L , Szenci O
Published: May 2017

Contents

The aim of this study was to develop a radiographic standard for the assessment of pulmonary fluid clearance and lung aeration in newborn calves. Caesarean‐delivered mature calves (n = 9) underwent lung assessment by thoracic radiography as well as arterial and venous blood gas analysis within the first 30 min, 1, 2, 3, 6, 12 and 24 hr after birth. The results indicated that newborn calves delivered by elective Caesarean section suffered from a physiological combined respiratory and metabolic acidosis with the dominance of respiratory acidosis, and an improvement in these conditions was recorded within 24 hr after birth. Concerning the radiographic results, clear lung fields, improvement in lung expansion, air content of the lung and absence of lung opacification occurred within 24 hr of birth. Furthermore, the ventral lung quadrant showed an improvement in radiographic opacification and lung expansion earlier than the dorsal lung regions. The findings of this study support the potential role of thoracic radiography in the assessment of pulmonary fluid clearance and lung aeration in newborn calves.
Urban and rural river restoration in France: a typology
Authors: Zingraff‐Hamed Aude , Greulich Sabine , Pauleit Stephan , Wantzen Karl M.
Published: May 2017

River restoration (RR) is widely practiced in both rural and urban contexts by combining various goals and measures. The theoretical discourse on RR not yet adequately reflects this breadth of restoration practice. In this study, we investigated 110 French RR projects implemented between 1980 and 2015. We analyzed projects considering eight key design features, main project motivation, restoration goals, project dates, costs, size, funding, river annual discharge, and implemented evaluation procedures. The study (1) provides a detailed account of the French RR effort, (2) compares restoration efforts in urban and rural contexts, and (3) establishes a RR project typology. The results also show that urban RR comprises a wider range of goals and measures than its rural counterpart, includes restoration of riparian habitats, and integrates ecological and social goals. A hierarchical multiple factor analysis yielded five types of projects, Fish RR (14% of the urban and 53% of the rural projects), Blue RR (4%, 7%), Water Framework Directive RR (36%, 40%), Flood protection RR (14%, 0%), and Human RR (32%, 0%). We suggest that the restoration community needs databases that use a project typology as developed in this study. This approach would take into account the multiple facets of RR projects, enabling more transparency into their communication and allow more suitable project comparisons.
Anti‐FcγRIIB (CD32) Antibodies Differentially Modulate Murine FVIII‐Specific Recall Response in vitro
Authors: Vollack N. , Friese J. , Bergmann S. , Cragg M. S. , Tiede A. , Werwitzke S.
Published: May 2017

Fc gamma receptors (FcγRs) for IgG regulate adaptive immune responses by modulating activating and inhibitory signalling pathways within immune cells. Data from a haemophilia A mouse model demonstrate that genetic deletion or blockade of the inhibitory FcγR (CD32) suppresses the formation of antibody‐secreting cells (ASCs) in vitro. Mechanisms preventing the FVIII‐specific recall response, however, remain unclear. Here, the potential role of CD32 inhibition was studied by differentially modulating receptor activity with selected anti‐CD32 monoclonal antibodies (mAbs). Splenocytes from immunized FVIII‐/‐ mice were restimulated with FVIII in the absence or presence of different anti‐CD32 mAbs over 6 days. At day 6, cytokine release was quantified from cell culture supernatant and the formation of FVIII‐specific ASCs assessed. Binding of FVIII‐containing immune complexes (F8‐ICs) to bone marrow‐derived dendritic cells (BMdDCs) was also investigated. The antagonistic CD32 mAb AT128 suppressed the formation of FVIII‐specific ASCs and reduced secretion of IFN‐γ and IL‐10. In contrast, the agonistic mAbs AT130‐2 and AT130‐5, and their F(ab’)2 fragments, allowed the formation of FVIII‐specific ASCs, even though the full IgG of AT130‐2 reduced binding of F8‐ICs to CD32. Data suggest that an inhibitory signal is transmitted when F8‐ICs bind to CD32 and that this signal is required during memory B cell (MBC) activation to support formation of FVIII‐specific ASCs. If the inhibitory signal is lacking due to CD32 deletion or blockade with antagonistic anti‐CD32 mAbs, FVIII‐specific T cell stimulation and ASC formation are suppressed, whereas agonistic stimulation of CD32 restores T cell stimulation and ASC formation.
Two easy ways to cheat
Authors: Meyer Joerg M.
Published: May 2017

Different groupings of data may lead to quite different conclusions, even to contradictory ones.
Epidemiology of bloodstream infections after myeloablative and non‐myeloablative allogeneic hematopoietic stem cell transplantation: A single‐center cohort study
Authors: Gjærde Lars I. , Moser Claus , Sengeløv Henrik
Published: May 2017

Background

Patients who undergo allogeneic hematopoietic stem cell transplantation (allo‐HSCT) often develop bloodstream infections (BSI). We aimed to describe the etiologies and antibiotic resistance patterns of BSI after allo‐HSCT, and, as knowledge about the impact of conditioning regimen is limited, we looked at the incidence, timing, risk factors, and mortality of BSI separately for myeloablative (MA)‐ and non‐myeloablative (NMA)‐conditioned patients.

Methods

All 460 patients (207 MA‐ and 253 NMA‐conditioned) who underwent their first allo‐HSCT at our center from 2008 to 2013 were included in a historical cohort. BSI were registered from initiation of conditioning to day 360 after transplantation.

Results

BSI occurred in 34% (95% confidence interval [CI]: 28%, 41%) of MA‐conditioned patients and in 17% (95% CI: 12%, 22%) of NMA‐conditioned patients. Of all isolates, 68% were gram‐positive bacteria (GPB), 23% gram‐negative bacteria (GNB), and 9% fungi. The GPB/GNB ratio declined from 2008 to 2014 (P for trend <.01). Of all GNB, 47% were multidrug resistant (MDR), but the proportion declined over the study period. In a multivariate Cox regression model, only acute graft‐versus‐host disease was associated with a higher hazard of first BSI (hazard ratio 2.50, 95% CI: 1.48, 4.21). Overall 30‐day survival after a BSI was higher for MA‐conditioned patients than for NMA‐conditioned patients (89% vs 74%, P=.04).

Conclusion

MA‐conditioned patients experience BSI more often than NMA‐conditioned patients in the year after allo‐HSCT. While BSI are increasingly caused by GNB, the rate of MDR GNB is declining.
Reversible and cachexia‐associated feline skin fragility syndrome in three cats
Authors: Furiani Nicla , Porcellato Ilaria , Brachelente Chiara
Published: May 2017

Background

Feline skin fragility syndrome (FSFS) is an acquired disorder characterized by altered collagen production resulting in an extremely thin and fragile skin. FSFS is associated with diseases characterized by excessive steroidal hormones that can inhibit collagen synthesis. It is also described concomitantly with severe inflammatory, infectious or neoplastic conditions where the pathogenesis remains largely unknown.

Objectives

To describe three cases of FSFS in cats that become cachectic secondary to different causes without glucocorticoid involvement. To describe the histopathological features of connective tissue for both fragile skin and the skin after healing.

Results

All cats developed cachexia in less than two months (body condition score ranging from 1–1.5). Concomitant diseases were diagnosed in Case 1 (aspiration pneumonia due to mega‐oesophagus) and Case 2 (feline immunodeficiency virus (FIV)). In Case 3, malnutrition was suspected as a primary cause. The main histological feature of fragile skin was an atrophic dermis with pale eosinophilic, thin and irregular collagen fibres with numerous red cores observed with Masson's stain. Elastic fibres were normal. Postrecovery histopathological findings at 11 (Case 1) and six months (Case 3) after diagnosis, indicated normalization of the collagen and of the whole skin as compared with controls.

Conclusions and clinical importance

To the best of the authors’ knowledge, this is the first report describing a reversible, nonsteroid‐induced FSFS, associated with rapidly developing cachexia in cats.
Oral antiplatelet therapy: impact for transfusion medicine
Authors: Gremmel T. , Panzer S.
Published: May 2017

Patients on antiplatelet therapy, be it aspirin only, or aspirin in combination with oral adenosine diphosphate (ADP) receptor inhibitors like clopidogrel, prasugrel and ticagrelor, or the protease‐activated receptor‐1 inhibitor vorapaxar, may develop bleeding or need transient reversal of platelet blockade for acute interventions. In this review, we summarize reports on patients with antiplatelet therapy receiving platelet concentrates due to bleeding, and in vitro experiments estimating the feasibility to restore platelet function by spiking blood from healthy individuals or patients on antiplatelet treatment with noninhibited platelets. So far, all clinical data were gained from patients on aspirin with or without ADP P2Y12 receptor inhibitors. Platelet inhibition due to clopidogrel, and to some extent also prasugrel may be overcome by platelet transfusion, but clinical data on massive platelet transfusion in these patients are lacking. Platelet transfusion may even be associated with worse outcomes. Ticagrelor‐mediated platelet inhibition remains a challenge, as case reports show that platelet transfusion did not restore haemostasis. Prescription of the latter therefore demands a particular stringent indication.
Ubiquitin immobilized on mesoporous MCM41 silica surfaces – Analysis by solid-state NMR with biophysical and surface characterization
Authors: Adiram-Filiba Nurit , Schremer Avital , Ohaion Eli , Nadav-Tsubery Merav , Lublin-Tennenbaum Tammi , Keinan-Adamsky Keren , Goobes Gil
Published: May 2017

Deriving the conformation of adsorbed proteins is important in the assessment of their functional activity when immobilized. This has particularly important bearings on the design of contemporary and new encapsulated enzyme-based drugs, biosensors, and other bioanalytical devices. Solid-state nuclear magnetic resonance (NMR) measurements can expand our molecular view of proteins in this state and of the molecular interactions governing protein immobilization on popular biocompatible surfaces such as silica. Here, the authors study the immobilization of ubiquitin on the mesoporous silica MCM41 by NMR and other techniques. Protein molecules are shown to bind efficiently at pH 5 through electrostatic interactions to individual MCM41 particles, causing their agglutination. The strong attraction of ubiquitin to MCM41 surface is given molecular context through evidence of proximity of basic, carbonyl and polar groups on the protein to groups on the silica surface using NMR measurements. The immobilized protein exhibits broad peaks in two-dimensional 13C dipolar-assisted rotational resonance spectra, an indication of structural multiplicity. At the same time, cross-peaks related to Tyr and Phe sidechains are missing due to motional averaging. Overall, the favorable adsorption of ubiquitin to MCM41 is accompanied by conformational heterogeneity and by a major loss of motional degrees of freedom as inferred from the marked entropy decrease. Nevertheless, local motions of the aromatic rings are retained in the immobilized state.
Review Article: Reactions of fluorine atoms with silicon, revisited, again
Authors: Donnelly Vincent M.
Published: May 2017

Chemical etching of silicon by fluorine atoms in the absence of ion bombardment is reviewed. Controversies on the identity of etching products and reaction probabilities are discussed. Attempts are made to explain the apparent presence of SiF2 as a primary product in many studies, dating back to 1980, but not in others, including those of Harold Winters from as early as 1979. Reported estimates of reaction probabilities (here defined as the probability of removing a Si atom from the substrate per incident F atom) vary by a factor of 2000. When these values, with some corrections and reasonable adjustments, are plotted as a function of F atom flux, most of them fall on a “universal curve” that reveals a large (∼30-fold) decrease in the reaction probability with increasing F flux, from 0.03 at a F flux 1012 cm−2 s−1 to 0.001 at a flux of 1020 cm−2 s−1. These values were extracted from beam experiments with F atoms generated from cracking of F2, including those by Harold Winters, from isotropic etching in plasma experiments (both in-plasma and downstream) with F2, CF4/10%O2, and NF3 feed gases, as well as from molecular dynamics simulations. Reaction coefficients derived from chemical etching rates in SF6 plasmas do not follow this trend, however, suggesting a large enhancement in the F reaction probability (∼20 to 100-fold at F fluxes of 1018–1019 cm−2 s−1), due to the presence of sulfur.
Comparison of permeation of atmospheric gases through Viton O-ring gaskets for different initial conditions
Authors: Sefa Makfir , Setina Janez
Published: May 2017

Viton O-ring gaskets are frequently used in high vacuum for demountable flange and vacuum valve seals. Atmospheric gases, particularly water vapor from humid air, permeate through Viton gaskets and thus limit the lowest attainable pressure level in vacuum systems. In this work, a comparison of a vacuum degassed Viton O-ring gasket and a gasket fully saturated with atmospheric gases was performed. A reference measurement with an alternative soft metal gasket for Klein Flange type flanges was also made. The permeation rate of each individual gas from the atmosphere (water vapor, N2, O2, Ar, and CO2) through the Viton O-ring was measured using quadrupole mass spectrometry. The partial gas flow curves Q(t) were also modeled using finite difference modeling (FDM). Using FDM, one can determine the diffusion constant, permeability, and solubility of the gas in the material.
Efficacy of Rhesus Theta-Defensin-1 in Experimental Models of Pseudomonas aeruginosa Lung Infection and Inflammation
Authors: Bensman Timothy J. , Jayne Jordanna G. , Sun Meiling , Kimura Elza , Meinert Joshua , Wang Joshua C. , Schaal Justin B. , Tran Dat , Rao Adupa P. , Akbari Omid , Selsted Michael E. , Beringer Paul M.
Published: May 2017

Chronic airway infection and inflammation contribute to the progressive loss of lung function and shortened survival of patients with cystic fibrosis (CF). Rhesus theta defensin-1 (RTD-1) is a macrocyclic host defense peptide with antimicrobial and immunomodulatory activities. Combined with favorable preclinical safety and peptide stability data, RTD-1 warrants investigation to determine its therapeutic potential for treatment of CF lung disease. We sought to evaluate the therapeutic potential of RTD-1 for CF airway infection and inflammation using
in vitro
,
ex vivo
, and
in vivo
models. We evaluated RTD-1's effects on basal and
Pseudomonas aeruginosa-
induced inflammation in CF sputum leukocytes and CF bronchial epithelial cells. Peptide stability was evaluated by incubation with CF sputum. Airway pharmacokinetics, safety, and tolerance studies were performed in naive mice. Aerosolized RTD-1 treatment effects were assessed by analyzing lung bacterial burdens and airway inflammation using an established model of chronic
P. aeruginosa
endobronchial infection in CF (ΔF508) mice. RTD-1 directly reduces metalloprotease activity, as well as inflammatory cytokine secretion from CF airway leukocyte and bronchial epithelial cells. Intrapulmonary safety, tolerability, and stability data support the aerosol administration route. RTD-1 reduced the bacterial lung burden, airway neutrophils, and inflammatory cytokines in CF mice with chronic
P. aeruginosa
lung infection. Collectively, these studies support further development of RTD-1 for treatment of CF airway disease.
An Effective Antiviral Approach Targeting Hepatitis B Virus with NJK14047, a Novel and Selective Biphenyl Amide p38 Mitogen-Activated Protein Kinase Inhibitor
Authors: Kim So-Young , Kim Hong , Kim Sang-Won , Lee Na-Rae , Yi Chae-Min , Heo Jinyuk , Kim Bum-Joon , Kim Nam-Jung , Inn Kyung-Soo
Published: May 2017

Despite recent advances in therapeutic strategies against hepatitis B virus (HBV) infection, chronic hepatitis B remains a major global health burden. Recent studies have shown that targeting host factors instead of viral factors can be an effective antiviral strategy with low risk of the development of resistance. Efforts to identify host factors affecting viral replication have identified p38 mitogen-activated protein kinase (MAPK) as a possible target for antiviral strategies against various viruses, including HBV. Here, a series of biphenyl amides were synthesized as novel p38 MAPK selective inhibitors and assessed for their anti-HBV activities. The suppression of HBV surface antigen (HBsAg) production by these compounds was positively correlated with p38 MAPK-inhibitory activity. The selected compound NJK14047 displayed significant anti-HBV activity, as determined by HBsAg production, HBeAg secretion, and HBV production. NJK14047 efficiently suppressed the secretion of HBV antigens and HBV particles from HBV genome-transfected cells and HBV-infected sodium taurocholate cotransporting polypeptide-expressing human hepatoma cells. Furthermore, NJK14047 treatment resulted in a significant decrease of pregenomic RNA and covalently closed circular DNA (cccDNA) of HBV in HBV-harboring cells, indicating its ability to inhibit HBV replication. Considering that suppression of HBsAg secretion and elimination of cccDNA of HBV are the major aims of anti-HBV therapeutic strategies, the results suggested the potential use of these compounds as a novel class of anti-HBV agents targeting host factors critical for viral infection.
Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested
In Vitro
with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam
Authors: Zhang Yunliang , Kashikar Ankita , Brown C. Adam , Denys Gerald , Bush Karen
Published: May 2017

Carbapenemase-producing
Enterobacteriaceae
isolates (
n
= 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC
50
/MIC
90
values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftaroline-avibactam), and 0.25/0.5 μg/ml (aztreonam-avibactam.) A β-lactam MIC of 8 μg/ml was reported for the three combinations against one
Escherichia coli
isolate with an unusual TIPY insertion following Tyr344 in penicillin-binding protein 3 (PBP 3) as the result of gene duplication.
Mortality Associated with Bacteremia Due to Colistin-Resistant Klebsiella pneumoniae with High-Level Meropenem Resistance: Importance of Combination Therapy without Colistin and Carbapenems
Authors: Machuca Isabel , Gutiérrez-Gutiérrez Belén , Gracia-Ahufinger Irene , Rivera Espinar Francisco , Cano Ángela , Guzmán-Puche Julia , Pérez-Nadales Elena , Natera Clara , Rodríguez Marina , León Rafael , Castón Juan J. , Rodríguez-López Fernando , Rodríguez-Baño Jesús , Torre-Cisneros Julián
Published: May 2017

Combination therapy including colistin and a carbapenem has been found to be associated with lower mortality in the treatment of bloodstream infections (BSI) due to KPC-producing
Klebsiella pneumoniae
when the isolates show a meropenem or imipenem MIC of <16 mg/liter. However, the optimal treatment of BSI caused by colistin- and high-level carbapenem-resistant KPC-producing
K. pneumoniae
is unknown. A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/liter) KPC-producing
K. pneumoniae
diagnosed from July 2012 to February 2016 was performed. The impact of combination therapy on crude 30-day mortality was analyzed by Cox regression using a propensity score as a covariate to control for indication bias and in an inverse probability of treatment weighting (IPTW) cohort. The study sample comprised 104 patients, of which 32 (30.8%) received targeted monotherapy and 72 (69.2%) received targeted combination therapy; none of them received either colistin or a carbapenem. The 30-day crude mortality rate was 30.8% (43.8% in patients treated with monotherapy and 25% in patients receiving combination therapy). In the Cox regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (hazard ratio [HR], 6.03; 95% confidence interval [CI], 1.65 to 21.9;
P
= 0.006) and admission to the critical care unit (HR, 2.87; 95% CI, 0.99 to 8.27;
P
= 0.05). Targeted combination therapy was associated with lower mortality only in patients with septic shock (HR, 0.14; 95% CI, 0.03 to 0.67;
P
= 0.01). These results were confirmed in the Cox regression analysis of the IPTW cohort. Combination therapy is associated with reduced mortality in patients with bacteremia due to colistin-resistant KPC-producing
K. pneumoniae
with high-level carbapenem resistance in patients with septic shock.
Nucleotide Substrate Specificity of Anti-Hepatitis C Virus Nucleoside Analogs for Human Mitochondrial RNA Polymerase
Authors: Ehteshami Maryam , Zhou Longhu , Amiralaei Sheida , Shelton Jadd R. , Cho Jong Hyun , Zhang Hongwang , Li Hao , Lu Xiao , Ozturk Tugba , Stanton Richard , Amblard Franck , McBrayer Tamara R. , Coats Steven J. , Schinazi Raymond F.
Published: May 2017

Nucleoside analog inhibitors (NAIs) are an important class of antiviral agents. Although highly effective, some NAIs with activity against hepatitis C virus (HCV) can cause toxicity, presumably due to off-target inhibition of host mitochondrial RNA polymerase (POLRMT). The
in vitro
nucleotide substrate specificity of POLRMT was studied in order to explore structure-activity relationships that can facilitate the identification of nontoxic NAIs. These findings have important implications for the development of all anti-RNA virus NAIs.