bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiobjective approach for detecting communities in heterogeneous networks
Authors: Karimi‐Majd Amir‐Mohsen , Fathian Mohammad
Published: August 2017

Online social networks have a strong potential to be divided into a number of dense substructures, called communities. In such heterogeneous networks, the communities refer not only to dense parts of links but also to clusters present among other dimensions such as users' profiles, comments, and information flows. To find communities in these networks, researchers have developed a number of methods; however, to the best of the authors' knowledge, these methods are limited in taking only 2 dimensions into account, and they are also not able to give a sense of how users behave in their communities. To deal with these issues, this paper proposes a multiobjective optimization model in which a specific objective function has been used for each considered dimension in a given network. Because of the NP‐hardness of the studied problem, an efficient and effective multiobjective metaheuristic algorithm has been developed. By juxtaposing the nondominated solutions obtained, the proposed algorithm can demonstrate how users behave in their communities. To illustrate the effectiveness of the algorithm, a set of experiments with a comprehensive evaluation method is provided. The results show the superiority and the stability of the proposed algorithm.
Favorable results in ABO‐incompatible renal transplantation without B cell‐targeted therapy: Advantages and disadvantages of rituximab pretreatment
Authors: Okada Manabu , Watarai Yoshihiko , Iwasaki Kenta , Murotani Kenta , Futamura Kenta , Yamamoto Takayuki , Hiramitsu Takahisa , Tsujita Makoto , Goto Norihiko , Narumi Shunji , Takeda Asami , Morozumi Kunio , Uchida Kazuharu , Kobayashi Takaaki
Published: August 2017

The effectiveness of desensitization with rituximab in ABO‐incompatible renal transplantation (ABO‐I) has been widely reported. However, ABO‐I outcomes are still worse than those of ABO‐identical or ABO‐compatible renal transplantation (ABO‐Id/C). We retrospectively examined the outcomes in consecutive living donor ABO‐Id/C (n = 412) and ABO‐I (n = 205) cases to elucidate the causes of inferiority in ABO‐I. ABO‐I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti‐A/B antibody titers (NoR/S, n = 53). Graft survival, infection, and de novo HLA antibody production were compared for ABO‐I and ABO‐Id/C, followed by stratification into RIT and NoR/S groups. Propensity score‐based methods were employed to limit selection bias and potential confounders. Overall graft survival for ABO‐I was significantly lower than that for ABO‐Id/C (92.8% vs 97.2% after 5 years, P = .0037). Graft loss due to infection with ABO‐I was significantly more frequent than that with ABO‐Id/C, whereas acute antibody‐mediated rejection (AMR) caused no graft failure in ABO‐I recipients. Stratified analysis demonstrated significantly higher infection risk with RIT than with NoR/S. Safe reduction or avoidance of rituximab in desensitization protocols might contribute to further improvement of ABO‐I outcome.
Individual variation in body color in the field cricket Teleogryllus occipitalis (Orthoptera: Gryllidae)
Authors: Nagai Taiki , Kuriwada Takashi
Published: August 2017

Body color of animals may affect individual fitness through direct effects on various processes, such as predatory avoidance, thermoregulation, UV resistance, and mating behavior. Body color variation of the field cricket Teleogryllus occipitalis (Audinet‐Serville) (Orthoptera: Gryllidae) is often observed. We quantified the individual variation in body color of this species by measuring the luminance of hind leg femur. Thereafter, we examined whether the body color was a heritable trait or not using parent–offspring analysis. In addition, the effect of body color of both parents on body size, sex ratio, and survival rate of progeny was investigated. The results showed that maternal body color was not heritable, whereas paternal body color was correlated with the body color of the progeny. Body size and sex ratio were not correlated with body color of parents. Although paternal body color did not affect the survival rate of the progeny beyond the stage of final instar nymph, progeny survival rate significantly increased with darkness of maternal body.
Digital workflow in full‐arch implant rehabilitation with segmented minimally veneered monolithic zirconia fixed dental prostheses: 2‐year clinical follow‐up
Authors: Papaspyridakos Panos , Kang Kiho , DeFuria Catherine , Amin Sarah , Kudara Yukio , Weber Hans‐Peter
Published: August 2017

Objective

To illustrate a digital workflow in full‐arch implant rehabilitation with minimally veneered monolithic zirconia and to report the outcomes including technical complications.

Clinical Considerations

Three patients (5 edentulous arches) received full‐arch fixed implant rehabilitation with monolithic zirconia and mild facial porcelain veneering involving a digital workflow. The incisal edges and occluding surface areas were milled out of monolithic zirconia to reduce the possibility of chipping. Porcelain veneering was applied on the facial aspect to improve the esthetic result. Outcomes and technical complications are reported after 2 years of clinical and radiographic follow‐up.

Conclusion

Implant and prosthesis survival rates were 100% after a short‐term follow‐up of 2 years. Technical complications were encountered in one patient. They did not adversely affect prosthesis survival or patient satisfaction and were easily addressed. A digital workflow for the design and fabrication of full‐arch monolithic zirconia implant fixed implant prostheses has benefits, but caution is necessary during CAD planning of the prosthesis to ensure a successful outcome. Long‐term clinical studies are needed to corroborate the findings discussed in this report.

CLINICAL SIGNIFICANCE

This article presents an integrated digital workflow that was implemented for the implant‐prosthodontic rehabilitation of three edentulous patients with monolithic zirconia prostheses. Monolithic zirconia has been successfully incorporated in implant prosthodontics in an effort to reduce the technical complications associated with bilayered ceramics. This workflow simplifies design and fabrication of the zirconia prostheses. However, caution should be taken during CAD planning of the prosthesis to make sure the zirconia cylinder is sufficiently thick at the interface with the titanium insert. Additionally, when cutback is planned for facial porcelain veneering, the functional occluding cusps and incisal edges should be fabricated in monolithic zirconia to avoid chipping.
Apathy: Risk Factor for Mortality in Nursing Home Patients
Authors: Nijsten Johanna M. H. , Leontjevas Ruslan , Pat‐El Ron , Smalbrugge Martin , Koopmans Raymond T. C. M. , Gerritsen Debby L.
Published: August 2017

Objectives

To determine the prognostic value of apathy for mortality in patients of somatic (SC) and dementia special care (DSC) nursing home (NH) units.

Design

Longitudinal design, secondary analyses of a 2‐year, cluster‐randomized trial with six measurements, approximately 4 months in between.

Setting

SC and DSC‐units of Dutch NHs.

Participants

NH‐patients of seventeen SC‐units (n = 342) and sixteen DCS‐units (n = 371).

Measurements

Data were available for 713 NH‐patients, 266 of whom died during the study. Apathy was assessed using the 10‐item Apathy Evaluation Scale (AES‐10) and applied as categorical variable using known cut‐off scores as well as dimensional variable. Additionally, depressive symptoms were assessed using the Cornell Scale for Depression in Dementia.

Results

Mixed effects cox models using the coxme package in R revealed a higher risk of mortality between two measurements, if apathy was present (hazard ratio (HR) = 1.77; 95% confidence interval (CI] = 1.35–2.31, P < .001). Results remained significant (HR = 1.64; 95% CI = 1.23–2.19, P < .001) when controlled for depressive symptoms. DSC‐units and SC‐units did not differ (P > .05) in the effect of apathy on mortality. Male gender (HR = 1.67; 95% CI = 1.23–2.27, P < .001), and higher age in years (HR = 1.06; 95% CI = 1.04–1.08, P < .001) were also predictors of mortality. Regarding apathy as a dimensional construct, one standard deviation increase of AES‐10 scores was associated with a 62% increase of mortality risk (HR = 1.62, 95% CI = 1.40–1.88, P < .001).

Conclusions

Apathy was associated with mortality over a 4‐month period in NH patients, even when controlling for depression. These data suggest that screening and treatment strategies for apathy should be developed for this patient population.
The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation
Authors: McLaughlin Ian , Dani John A. , De Biasi Mariella
Published: August 2017

Abstinence from chronic use of addictive drugs triggers an aversive withdrawal syndrome that compels relapse and deters abstinence. Many features of this syndrome are common across multiple drugs, involving both affective and physical symptoms. Some of the network signaling underlying withdrawal symptoms overlaps with activity that is associated with aversive mood states, including anxiety and depression. Given these shared features, it is not surprising that a particular circuit, the dorsal diencephalic conduction system, and the medial habenula (MHb) and interpeduncular nucleus (IPN), in particular, have been identified as critical to the emergence of aversive states that arise both as a result and, independently, of drug addiction. As the features of this circuit continue to be characterized, the MHb‐IPN axis is emerging as a viable target for therapeutics to aid in the treatment of addiction to multiple drugs of abuse as well as mood‐associated disorders.

This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

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Ascending pathways that mediate cholinergic modulation of lumbar motor activity
Authors: Anglister Lili , Cherniak Meir , Lev‐Tov Aharon
Published: August 2017

Deciphering neuronal pathways that reactivate spinal central pattern generators (CPGs) and modulate the activity of spinal motoneurons in mammals in the absence of supraspinal control is important for understanding of neural control of movement and for developing novel therapeutic approaches to improve the mobility of spinal cord injury patients. Previously, we showed that the sacral and lumbar cholinergic system could potently modulate the locomotorCPGs in newborn rodents. Here, we review these and our more recent studies of sacral relay neurons with lumbar projections to the locomotorCPGs and to lumbar motoneurons and demonstrate that sacral and lumbar cholinergic components have the capacity to control the frequency of the locomotorCPGs and at the same time the motor output of the activated lumbar motoneurons during motor behavior. A model describing the suggested ascending sacro‐lumbar connectivity involved in modulation of the locomotor rhythm by sacral cholinergic components is proposed and discussed.

This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

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Combining clinical practice and academic work in nursing: A qualitative study about perceived importance, facilitators and barriers regarding clinical academic careers for nurses in university hospitals
Authors: van Oostveen Catharina J. , Goedhart Nicole S. , Francke Anneke L. , Vermeulen Hester
Published: August 2017

Aims and objectives

To obtain in‐depth insight into the perceptions of nurse academics and other stakeholders regarding the importance, facilitators and barriers for nurses combining clinical and academic work in university hospitals.

Background

Combining clinical practice and academic work facilitates the use of research findings for high‐quality patient care. However, nurse academics move away from the bedside because clinical academic careers for nurses have not yet been established in the Netherlands.

Methods

This qualitative study was conducted in two Dutch university hospitals and their affiliated medical faculties and universities of applied sciences. Data were collected between May 2015 and August 2016. We used purposive sampling for 24 interviews. We asked 14 participants in two focus groups for their perceptions of importance, facilitators and barriers in nurses’ combined clinical and academic work in education and research. We audiotaped, transcribed and thematically analysed the interviews and focus groups.

Results

Three themes related to perceived importance, facilitators and barriers: culture, leadership and infrastructure. These themes represent deficiencies in facilitating clinical academic careers for nurses. The current nursing culture emphasises direct patient care, which is perceived as an academic misfit. Leadership is lacking at all levels, resulting in the underuse of nurse academics and the absence of supporting structures for nurses who combine clinical and academic work.

Conclusions

The present nursing culture appears to be the root cause of the dearth of academic positions and established clinical academic posts.

Relevance to clinical practice

A culture change would require a show of leadership that would promote and enable combined research, teaching and clinical practice and that would introduce clinical academic career pathways for nurses. Meanwhile, nurse academics should collaborate with established medical academics for whom combined roles are mainstream, and they should take advantage of their established infrastructure for success.
Individual and mutual predictors of marital satisfaction among prostate cancer patients and their spouses
Authors: Chien Ching‐Hui , Chuang Cheng‐Keng , Liu Kuan‐Lin , Huang Xuan‐Yi , Pang See‐Tong , Wu Chun‐Te , Chang Ying‐Hsu , Liu Hsueh‐Erh
Published: August 2017

Aims and objectives

To determine the individual and mutual predictors of the marital satisfaction of couples in which the husband experienced prostate cancer.

Background

Marital satisfaction of patients with prostate cancer has been insufficiently studied in Asian countries as compared with Western countries.

Design

This study used a prospective and repeated‐measures design.

Methods

Seventy Taiwanese couples in which the husband had prostate cancer completed measures at 6 and 12 months post‐treatment. Assessments of physical symptoms, marital satisfaction, coping behaviour and psychological distress were made. Multiple linear regression was used to analyse the data.

Results

The marital satisfaction of patients with prostate cancer and that of their spouses were significantly correlated. At 6 months, spouses’ marital satisfaction, patients’ appraisal of prostate cancer as a threat and patients’ serum prostate‐specific antigen levels were found to be the predictors of patients’ marital satisfaction. Furthermore, patients’ marital satisfaction and their spouses’ psychological distress were predictors of spouses’ marital satisfaction. At 12 months, spouses’ marital satisfaction and patients’ appraisal of prostate cancer as harm were predictors of patients’ marital satisfaction. Finally, spouses’ marital satisfaction (at 6 months) and appraisal of prostate cancer as a threat were predictors of spouses’ marital satisfaction.

Conclusions

At 6 months post‐treatment, patients’ and spouses’ marital satisfaction will influence each other. However, at 12 months, patients’ marital satisfaction exerts an insignificant effect on spouses’ marital satisfaction. Moreover, patients’ serum prostate‐specific antigen level or the negative appraisal of prostate cancer affects their marital satisfaction. Spouses’ marital satisfaction is affected by psychological distress and their negative appraisal of prostate cancer.

Relevance to clinical practice

The results can be used to develop interventions for prostate cancer couples. Such an intervention can be used to modify couples’ appraisal of prostate cancer by changing incorrect thinking or to ease the psychological distress to improve marital satisfaction.
The intersection of culture in the provision of dementia care: A systematic review
Authors: Brooke Joanne , Cronin Camille , Stiell Marlon , Ojo Omorogieva
Published: August 2017

Aims and objectives

To understand the intersection of healthcare professionals’ and care workers’ culture and their provision of person‐centred care for people with dementia.

Background

Due to the nature of global immigration and recruitment strategies, health care is provided by a culturally diverse workforce. Consequently, there is a need to understand healthcare professionals’ and care workers’ cultural values of illness, disease and dementia. Cultural values and beliefs regarding dementia and care of the older person differ, and currently, there is a lack of clarity regarding the intersection of culture in the provision of person‐centred dementia care.

Method

A search of the following databases was completed: Medline, CINAHL, Psychology and Behavioural Sciences, PsycINFO and PubMed for papers published from 1st January 2006 to 31st July 2016.

Results

A total of seven qualitative studies met the inclusion and exclusion criteria, all explored the impact of healthcare professionals’ and care workers’ culture in relation to their provision of person‐centred dementia care. A meta‐synthesis of the data from these studies identified four themes: cultural perceptions of dementia, illness and older people; impact of cultural perceptions on service use; acculturation of the workforce; and cross‐cultural communication.

Conclusion

Limited evidence was found on the impact of healthcare professionals’ and care workers’ culture on their provision of person‐centred dementia care. The intersection of culture and dementia included the understanding of dementia, care and family roles. Acculturation of migrant healthcare workers to the culture of the host country, workplace, and support with the communication was identified as necessary for the provision of person‐centred dementia care.

Relevance to clinical practice

Open access education and training to support communication is required, alongside the development of robust interventions to support the process of acculturation of migrant healthcare professionals and care workers to provide culturally competent person‐centred dementia care.
Mental health work in school health services and school nurses’ involvement and attitudes, in a Norwegian context
Authors: Skundberg‐Kletthagen Hege , Moen Øyfrid Larsen
Published: August 2017

Aims and objectives

To explore school nurses’ experiences with and attitudes towards working with young people with mental health problem in the school health services.

Background

Worldwide, 10%–20% of children and adolescents are affected by mental health problems. When these occur during youth, they constitute a considerable burden and are one of the main causes of disability among adolescents. School nurses are at the forefront of care for children and adolescents, identifying pupils struggling with physical, mental, psychosocial or emotional issues.

Design

A qualitative, explorative study was performed based on open‐ended questions in a cross‐sectional study of 284 school nurses in Norway. Inclusion criteria were as follows: working as a school nurse in the school health services with children and adolescents between the ages of 11–18 years. A qualitative inductive content analysis was conducted.

Results

Three generic categories emerged: perception of their role and experiences with mental health: the school nurses acknowledge their important role in work with adolescents focusing on their mental health. Perception of their professional competence: the school nurses described a lack of confidence and unmet training needs concerning mental health problems. Experiences with collaboration: the school nurses requested more knowledge about inter‐ and multidisciplinary cooperation regarding follow‐up of pupils with mental health problems.

Conclusions

The school nurses lacked knowledge and confidence in respect of working with children and adolescents suffering from mental health problems. This may be a barrier to giving pupils adequate aid.

Relevance to clinical practice

Nurses need to acquire more knowledge about mental health problems among children and adolescents as this is a growing public health issue. Educational programmes for school nurses need to be revised to achieve this.
Living with a parastomal bulge ‐ patients’ experiences of symptoms
Authors: Krogsgaard Marianne , Thomsen Thordis , Vinther Anders , Gögenur Ismail , Kaldan Gudrun , Danielsen Anne Kjærgaard
Published: August 2017

Aims and objectives

To investigate experienced symptoms of parastomal bulging in relation to an ileostomy or colostomy.

Background

Parastomal bulging is a common complication of stoma formation that can affect patients’ physical, psychological and social function. Symptom burdens reported by health professionals vary from asymptomatic to high symptom load; however, patients’ experiences of symptoms are lacking.

Design and method

A qualitative design with focus group interviews was chosen for data collection. Twenty patients participated in five semi‐structured interviews. Analysis was performed using a phenomenological‐hermeneutic approach.

Findings

The bulge caused different unfamiliar bodily sensations that interacted with patients’ everyday lives. Some but not all of these sensations were modifiable. As the bulge and the ostomy changed size and shape, patients had to adjust and readjust stoma care continuously. The physical change called for patients’ awareness and posed a threat to patients’ control of the ostomy and challenged stoma self‐care. The bulge caused a bodily asymmetry that deformed the patients’ bodies in a way that exceeded the perceived alteration already caused by the stoma. To cover the physical disfigurement, new clothing solutions, garment wear and creativity were essential in everyday life. Patients gradually adapted to the bulge over time. Easy access to professional help was crucial in order to find the best appliance and garment solution in relation to the bulge.

Conclusions

Various symptoms related to the parastomal bulge affected patients’ everyday lives in different ways and underpinned that an individualised approach is important when addressing patients’ problems and complaints. Research into nonsurgical treatments and patient perspectives is limited and highly warranted to improve clinical outcome.

Relevance to clinical practice

The ever‐changing bulge posed a threat to patients′ control of the ostomy and required specific care from the stoma therapist. Needs‐based access to counselling, advice and supplementary materials is important.
Circadian rhythms vary over the growing season and correlate with fitness components
Authors: Rubin Matthew J. , Brock Marcus T. , Davis Amanda M. , German Zachary M. , Knapp Mary , Welch Stephen M. , Harmer Stacey L. , Maloof Julin N. , Davis Seth J. , Weinig Cynthia
Published: August 2017

Circadian clocks have evolved independently in all three domains of life, suggesting that internal mechanisms of time‐keeping are adaptive in contemporary populations. However, the performance consequences of either discrete or quantitative clock variation have rarely been tested in field settings. Clock sensitivity of diverse segregating lines to the environment remains uncharacterized as do the statistical genetic parameters that determine evolutionary potential. In field studies with Arabidopsis thaliana, we found that major perturbations to circadian cycle length (referred to as clock period) via mutation reduce both survival and fecundity. Subtler adjustments via genomic introgression of naturally occurring alleles indicated that clock periods slightly >24 hr were adaptive, consistent with prior models describing how well the timing of biological processes is adjusted within a diurnal cycle (referred to as phase). In segregating recombinant inbred lines (RILs), circadian phase varied up to 2 hr across months of the growing season, and both period and phase expressed significant genetic variances. Performance metrics including developmental rate, size and fruit set were described by principal components (PC) analyses and circadian parameters correlated with the first PC, such that period lengths slightly >24 hr were associated with improved performance in multiple RIL sets. These experiments translate functional analyses of clock behaviour performed in controlled settings to natural ones, demonstrating that quantitative variation in circadian phase is highly responsive to seasonally variable abiotic factors. The results expand upon prior studies in controlled settings, showing that discrete and quantitative variation in clock phenotypes correlates with performance in nature.
Rapid adaptation to a novel light environment: The importance of ontogeny and phenotypic plasticity in shaping the visual system of Nicaraguan Midas cichlid fish (Amphilophus citrinellus spp.)
Authors: Härer Andreas , Torres‐Dowdall Julián , Meyer Axel
Published: August 2017

Colonization of novel habitats is typically challenging to organisms. In the initial stage after colonization, approximation to fitness optima in the new environment can occur by selection acting on standing genetic variation, modification of developmental patterns or phenotypic plasticity. Midas cichlids have recently colonized crater Lake Apoyo from great Lake Nicaragua. The photic environment of crater Lake Apoyo is shifted towards shorter wavelengths compared to great Lake Nicaragua and Midas cichlids from both lakes differ in visual sensitivity. We investigated the contribution of ontogeny and phenotypic plasticity in shaping the visual system of Midas cichlids after colonizing this novel photic environment. To this end, we measured cone opsin expression both during development and after experimental exposure to different light treatments. Midas cichlids from both lakes undergo ontogenetic changes in cone opsin expression, but visual sensitivity is consistently shifted towards shorter wavelengths in crater lake fish, which leads to a paedomorphic retention of their visual phenotype. This shift might be mediated by lower levels of thyroid hormone in crater lake Midas cichlids (measured indirectly as dio2 and dio3 gene expression). Exposing fish to different light treatments revealed that cone opsin expression is phenotypically plastic in both species during early development, with short and long wavelength light slowing or accelerating ontogenetic changes, respectively. Notably, this plastic response was maintained into adulthood only in the derived crater lake Midas cichlids. We conclude that the rapid evolution of Midas cichlids’ visual system after colonizing crater Lake Apoyo was mediated by a shift in visual sensitivity during ontogeny and was further aided by phenotypic plasticity during development.
Social and spatial effects on genetic variation between foraging flocks in a wild bird population
Authors: Radersma Reinder , Garroway Colin J. , Santure Anna W. , de Cauwer Isabelle , Farine Damien R. , Slate Jon , Sheldon Ben C.
Published: August 2017

Social interactions are rarely random. In some instances, animals exhibit homophily or heterophily, the tendency to interact with similar or dissimilar conspecifics, respectively. Genetic homophily and heterophily influence the evolutionary dynamics of populations, because they potentially affect sexual and social selection. Here, we investigate the link between social interactions and allele frequencies in foraging flocks of great tits (Parus major) over three consecutive years. We constructed co‐occurrence networks which explicitly described the splitting and merging of 85,602 flocks through time (fission–fusion dynamics), at 60 feeding sites. Of the 1,711 birds in those flocks, we genotyped 962 individuals at 4,701 autosomal single nucleotide polymorphisms (SNPs). By combining genomewide genotyping with repeated field observations of the same individuals, we were able to investigate links between social structure and allele frequencies at a much finer scale than was previously possible. We explicitly accounted for potential spatial effects underlying genetic structure at the population level. We modelled social structure and spatial configuration of great tit fission–fusion dynamics with eigenvector maps. Variance partitioning revealed that allele frequencies were strongly affected by group fidelity (explaining 27%–45% of variance) as individuals tended to maintain associations with the same conspecifics. These conspecifics were genetically more dissimilar than expected, shown by genomewide heterophily for pure social (i.e., space‐independent) grouping preferences. Genomewide homophily was linked to spatial configuration, indicating spatial segregation of genotypes. We did not find evidence for homophily or heterophily for putative socially relevant candidate genes or any otherSNPmarkers. Together, these results demonstrate the importance of distinguishing social and spatial processes in determining population structure.
Functional redundancy of division specific penicillin‐binding proteins in Bacillus subtilis
Authors: Sassine Jad , Xu Meizhu , Sidiq Karzan R. , Emmins Robyn , Errington Jeff , Daniel Richard A.
Published: August 2017

Bacterial cell division involves the dynamic assembly of a diverse set of proteins that coordinate the invagination of the cell membrane and synthesis of cell wall material to create the new cell poles of the separated daughter cells. Penicillin‐binding protein PBP 2B is a key cell division protein in Bacillus subtilis proposed to have a specific catalytic role in septal wall synthesis. Unexpectedly, we find that a catalytically inactive mutant of PBP 2B supports cell division, but in this background the normally dispensable PBP 3 becomes essential. Phenotypic analysis of pbpC mutants (encoding PBP 3) shows that PBP 2B has a crucial structural role in assembly of the division complex, independent of catalysis, and that its biochemical activity in septum formation can be provided by PBP 3. Bioinformatic analysis revealed a close sequence relationship between PBP 3 and Staphylococcus aureus PBP 2A, which is responsible for methicillin resistance. These findings suggest that mechanisms for rescuing cell division when the biochemical activity of PBP 2B is perturbed evolved prior to the clinical use of β‐lactams.
Distinct activation mechanisms trigger the trypanocidal activity of DNA damaging prodrugs
Authors: Meredith Emma Louise , Kumar Ambika , Konno Aya , Szular Joanna , Alsford Sam , Seifert Karin , Horn David , Wilkinson Shane R.
Published: August 2017

Quinone‐based compounds have been exploited to treat infectious diseases and cancer, with such chemicals often functioning as inhibitors of key metabolic pathways or as prodrugs. Here, we screened an aziridinyl 1,4‐benzoquinone (ABQ) library against the causative agents of trypanosomiasis, and cutaneous leishmaniasis, identifying several potent structures that exhibited EC50 values of <100 nM. However, these compounds also displayed significant toxicity towards mammalian cells indicating that they are not suitable therapies for systemic infections. Using anti‐T. brucei ABQs as chemical probes, we demonstrated that these exhibit different trypanocidal modes of action. Many functioned as type I nitroreductase (TbNTR) or cytochrome P450 reductase (TbCPR) dependent prodrugs that, following activation, generate metabolites which promote DNA damage, specifically interstrand crosslinks (ICLs). Trypanosomes lacking TbSNM1, a nuclease that specifically repairs ICLs, are hypersensitive to most ABQ prodrugs, a phenotype exacerbated in cells also engineered to express elevated levels of TbNTR or TbCPR. In contrast, ABQs that contain substituent groups on the biologically active aziridine do not function as TbNTR or TbCPR‐activated prodrugs and do not promote DNA damage. By unravelling how ABQs mediate their activities, features that facilitate the desired anti‐parasitic growth inhibitory effects could be incorporated into new, safer compounds targeting these neglected tropical diseases.
Ultraviolet‐ and infrared‐induced 11 beta‐hydroxysteroid dehydrogenase type 1 activating skin photoaging is inhibited by red ginseng extract containing high concentration of ginsenoside Rg3(S)
Authors: Nam Jin‐Ju , Min Ji‐Eun , Son Min‐Ho , Oh Jin‐Hwan , Kang Seunghyun
Published: August 2017

Background

Sun irradiation is one of major extrinsic stressors responsible for premature skin aging through activation and expression of 11 beta‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), which converts inactive cortisone to active cortisol. The aim of this study was to evaluate the inhibitory effects of red ginseng extract containing high concentrations of ginsenoside Rg3 (S) (GERg3) on 11β‐HSD1‐induced skin photoaging.

Methods

To evaluate the inhibitory effects of GERg3 on ultraviolet‐ (UV) or infrared (IR)‐induced skin photoaging, human dermal fibroblasts or a normal human 3D skin model was exposed to UV or an IR. RT‐PCR, ELISA, Western blot, and H&E staining were used for evaluations. GERg3 was isolated from crude red ginseng.

Results

GERg3 inhibited the increased expressions of 11β‐HSD1, interleukin (IL)‐6, and matrix metalloproteinase‐1 (MMP‐1) in UVB‐ or IR‐exposed Hs68 cells. Additionally, the increased cortisol, IL‐6, and MMP‐1 expressions were effectively reduced by GERg3 in UVA‐exposed 3D skin models. The photoinduced decrease in type 1 procollagen also recovered as a result of GERg3 treatment in Hs68 cells and the 3D skin model. In addition, the UVA‐exposed dermal thickness was decreased in comparison with the UVA‐protected 3D skin model, recovered with GERg3 treatment.

Conclusion

GERg3 had antiphotoaging effects in UV‐ or IR‐exposed human dermal fibroblasts and normal human 3D skin model.
The Law: The Unitary Executive Theory and President Donald J. Trump
Authors: Crouch Jeffrey , Rozell Mark J. , Sollenberger Mitchel A.
Published: August 2017

The unitary executive theory first went mainstream during the George W. Bush administration as the president's justification for exercising broad executive powers. Barack Obama did not explicitly embrace the unitary executive theory, but he followed in Bush's footsteps by expanding and augmenting presidential power in new and questionable ways. President Donald J. Trump's campaign rhetoric, coupled with an early, controversial executive order on immigration, suggest the possibility of continued expansions of executive power. Thus, the time is right to examine the unitary executive theory anew. Here, we define the theory as understood by its advocates and then offer a critique. Finally, we highlight the theory's impact on the evolution of presidential powers over the past 16 years and set the stage for evaluating what may come next.
The relationship between military expenditure and certain growth and development related variables in transition economies: A panel data analysis
Authors: Bellos Sotirios K.
Published: August 2017

The paper examines the relation between military expenditure and three growth and development related variables (GDP growth, GDP per capita and Industry Value Added) in 31 transition economies during the 1989-2014 period. The empirical results reflect a positive association between military expenditure and the examined growth and development variables. The causality analysis shows though that the causality direction runs from the examined growth and development related variables towards military expenditure in all cases. This in turn reveals a common tendency in the studied economies, which is related to the tensions and developments in the wider studied area.
Examining Students’ Opinions about STEAM Activities
Authors: Ozkan Gulbin , Topsakal Unsal Umdu
Published: August 2017

The purpose of this study is to determine the opinions of students about STEAM activities. This qualitative study was conducted on the with 7th grade students (n=37) who are studying at a public school in Istanbul. A purposeful sampling was used in this study. Nine STEAM activities were used while teaching Force and Energy unit. An evaluation form which is composed of open-ended questions was used as a data collection instrument at the end of the teaching process. The responses provided by students for the evaluation form were analysed qualitatively to determine the opinions of students about the activities. The study was structured as qualitative research and content analysis technique was used to evaluate the obtained data. The findings revealed that a relatively positive attitude about STEAM activities and the contribution that the approach had on students. It was therefore concluded that students have few negative opinions about STEAM activities.
Distinct temporal filters in mitral cells and external tufted cells of the olfactory bulb
Authors: Vaaga Christopher E. , Westbrook Gary L.
Published: August 2017

Key points

The release probability of the odorant receptor neuron (ORN) is reportedly one of the highest in the brain and is predicted to impose a transient temporal filter on postsynaptic cells.

Mitral cells responded to high frequency ORN stimulation with sustained transmission, whereas external tufted cells responded transiently.

The release probability of ORNs (0.7) was equivalent across mitral and external tufted cells and could be explained by a single pool of slowly recycling vesicles.

The sustained response in mitral cells resulted from dendrodendritic amplification in mitral cells, which was blocked by NMDA and mGluR1 receptor antagonists, converting mitral cell responses to transient response profiles.

Our results suggest that although the afferent ORN synapse shows strong synaptic depression, dendrodendritic circuitry in mitral cells produces robust amplification of brief afferent input, and thus the relative strength of axodendritic and dendrodendritic input determines the postsynaptic response profile.

Short‐term synaptic plasticity is a critical regulator of neural circuits, and largely determines how information is temporally processed. In the olfactory bulb, afferent olfactory receptor neurons respond to increasing concentrations of odorants with barrages of action potentials, and their terminals have an extraordinarily high release probability. These features suggest that during naturalistic stimuli, afferent input to the olfactory bulb is subject to strong synaptic depression, presumably truncating the postsynaptic response to afferent stimuli. To examine this issue, we used single glomerular stimulation in mouse olfactory bulb slices to measure the synaptic dynamics of afferent‐evoked input at physiological stimulus frequencies. In cell‐attached recordings, mitral cells responded to high frequency stimulation with sustained responses, whereas external tufted cells responded transiently. Consistent with previous reports, olfactory nerve terminals onto both cell types had a high release probability (0.7), from a single pool of slowly recycling vesicles, indicating that the distinct responses of mitral and external tufted cells to high frequency stimulation did not originate presyaptically. Rather, distinct temporal response profiles in mitral cells and external tufted cells could be attributed to slow dendrodendritic responses in mitral cells, as blocking this slow current in mitral cells converted mitral cell responses to a transient response profile, typical of external tufted cells. Our results suggest that despite strong axodendritic synaptic depression, the balance of axodendritic and dendrodendritic circuitry in external tufted cells and mitral cells, respectively, tunes the postsynaptic responses to high frequency, naturalistic stimulation.
Preventing chemotherapy-induced myelosuppression by repurposing the FLT3 inhibitor quizartinib
Authors: Taylor Samuel J. , Duyvestyn Johanna M. , Dagger Samantha A. , Dishington Emma J. , Rinaldi Catherine A. , Dovey Oliver M. , Vassiliou George S. , Grove Carolyn S. , Langdon Wallace Y.
Published: August 2017

A small-molecule tyrosine kinase inhibitor protects the bone marrow from chemotherapy.
The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome
Authors: Johnson Timothy A. , Looft Torey , Severin Andrew J. , Bayles Darrell O. , Nasko Daniel J. , Wommack K. Eric , Howe Adina , Allen Heather K.
Published: August 2017

Carbadox is a quinoxaline-di-
N
-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction
in vitro
; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the
in vivo
longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (
n
= 66) related to microbial respiration, carbohydrate utilization, and RNA metabolism (
q
< 0.1), suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (
q
≤0.07), suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration.

IMPORTANCE
FDA regulations on agricultural antibiotic use have focused on antibiotics that are important for human medicine. Carbadox is an antibiotic not used in humans but frequently used on U.S. pig farms. It is important to study possible side effects of carbadox use because it has been shown to promote bacterial evolution, which could indirectly impact antibiotic resistance in bacteria of clinical importance. Interestingly, the present study shows greater prophage gene expression in feces from carbadox-fed animals than in feces from nonmedicated animals 2 days after the initiation of in-feed carbadox treatment. Importantly, the phage genetic material isolated in this study contained genes that could provide resistance to antibiotics that are important in human medicine, indicating that human-relevant antibiotic resistance genes are mobile between bacteria via phages. This study highlights the collateral effects of antibiotics and demonstrates the need to consider diverse antibiotic effects whenever antibiotics are being used or new regulations are considered.
Ethnic differences in early glycemic control in childhood-onset type 1 diabetes
Authors: Khanolkar Amal R , Amin Rakesh , Taylor-Robinson David , Viner Russell M , Warner Justin , Gevers Evelien F , Stephenson Terence
Published: August 2017

Some ethnic minorities with type 1 diabetes (T1D) have worse glycemic control (higher glycated hemoglobin (HbA1c)) and increased risk for vascular complications. There is limited evidence on the impact of ethnicity on early glycemic control when most patients experience transient remission postdiagnosis. We examined associations between ethnicity and longitudinal HbA1ctrajectories during the first 6 months postdiagnosis in a multiethnic cohort in East London.

Research design and methods

Data on 443 (50% female) children <19 years of age, with T1D and attending one of three clinics in East London between January 2005 and December 2015 were included. Linear mixed-effects modeling was used to assess ethnic differences in longitudinal HbA1ctrajectories during the first 6 months postdiagnosis (1,028 HbA1cdata points), adjusting for sex, age at diagnosis, socioeconomic status and pH at diagnosis. Growth curve modeling was used to plot discrete HbA1ctrajectories by ethnicity.

Results

Longitudinal modeling revealed that all ethnic minorities had higher mean HbA1cat diagnosis compared with White children and highest in Bangladeshi (9.7 mmol/mol, 95% CI 5.1 to 14.3), Asian-Other (5.8 mmol/mol, 95% CI 2.2 to 9.3) and Somali (5.2 mmol/mol, 95% CI 0.1 to 10.2) children, and these differences persisted over the 6-month period after diagnosis. During the first month, HbA1cdecreased on average by 19.6 mmol/mol (95% CI −21 to −18) for all children. Population averaged HbA1cdecreased between diagnosis and 4 months, followed by a gradual increase in HbA1clevels (mean difference of −30 mmol/mol between diagnosis and 6 months).

Conclusions

Ethnic minorities present with higher HbA1cat diagnosis, with the largest mean differences observed in Bangladeshi, Asian-Other and Somali children. These higher levels (indicating poorer glycemic control) track into the first 6 months postdiagnosis.
Associations between hyponatraemia, volume depletion and the risk of falls in US hospitalised patients: a case–control study
Authors: Fehlberg Elizabeth A , Lucero Robert J , Weaver Michael T , McDaniel Anna M , Chandler A Michelle , Richey Phyllis A , Mion Lorraine C , Shorr Ronald I
Published: August 2017

Objective

We aimed to determine if abnormal laboratory values which may indicate volume depletion are associated with increased odds of experiencing a hospital-acquired fall.

Design

Matched case–control study.

Setting

Four hospitals located in the Southeast USA.

Participants

Data from 699 adult fallers and 1189 matched controls (non-fallers) were collected via chart review from 2005 to 2010. Controls were matched to cases by nursing unit, time of fall and length of stay.

Outcome measures

The primary exposures included serum sodium, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio and haematocrit. Conditional logistic regression with m:n matching was used to determine adjusted and unadjusted ORs.

Results

Serum sodium levels were strongly associated with falls. In models controlling for demographic and other fall risk factors, patients with serum sodium levels of 125 mEq/L or less were associated with increased odds of experiencing a fall as compared with those with serum sodium levels of greater than 134 mEq/L (adjusted OR (aOR)=5.08, 95% CI 1.43 to 18.08). Conversely, elevated BUN, creatinine and elevated BUN/creatinine ratios were not associated with increased odds of experiencing a fall (aOR=0.64, 95% CI 0.49 to 0.84; aOR=0.70, 95% CI 0.54 to 0.92 and aOR=0.77, 95% CI 0.58 to 1.04, respectively.)

Conclusions

Laboratory indices that may indicate volume depletion appear to be unrelated to falls. However, hyponatraemia does appear to be a risk factor for falls, and those with serum sodium levels below 126 mEq/L are at especially high risk. It may be that other deficits associated with hyponatraemia, like altered mental status, are associated with risk of experiencing a hospital-acquired fall. These results indicate that abnormal laboratory values, like low sodium, can be useful for identifying hospitalised patients at risk of falling. Therefore, further investigation into abnormal laboratory values as predictors of hospital-acquired falls is warranted.