bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 objectivesTo investigate experienced symptoms of parastomal bulging in relation to an ileostomy or colostomy.BackgroundParastomal 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 methodA 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.FindingsThe 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.ConclusionsVarious 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 practiceThe 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

AbstractCircadian 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

AbstractColonization 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

AbstractSocial 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

SummaryBacterial 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

SummaryQuinone‐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

SummaryBackgroundSun 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.MethodsTo 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.ResultsGERg3 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.ConclusionGERg3 had antiphotoaging effects in UV‐ or IR‐exposed human dermal fibroblasts and normal human 3D skin model.
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.
AbstractShort‐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.
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

ABSTRACT

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 methodsData 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.ResultsLongitudinal 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).ConclusionsEthnic 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

ObjectiveWe aimed to determine if abnormal laboratory values which may indicate volume depletion are associated with increased odds of experiencing a hospital-acquired fall.DesignMatched case–control study.SettingFour hospitals located in the Southeast USA.ParticipantsData 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 measuresThe 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.ResultsSerum 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.)ConclusionsLaboratory 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.