bluuebunny/crossref_metadata_2025 huggingface dataset:
Out of the Antilles: Fossil phylogenies support reverse colonization of bats to South America
Authors: Tavares Valéria da C. , Warsi Omar M. , Balseiro Fernando , Mancina Carlos A. , Dávalos Liliana M.
Published: January 2018

Aim

Previous phylogenies of extant short‐faced bats (Chiroptera: Stenodermatina) supported either two colonization events from the mainland to the Antilles, or reverse colonization, but lacked both fossil data and statistical modelling of biogeography. Recent multi‐locus phylogenies of noctilionoid bats and likelihood modelling of ancestral ranges support a continental origin for the clade. We include all known extinct and extant stenodermatina species and apply statistical modelling to test competing biogeographical hypotheses.

Location

The Neotropics, including the Antilles.

Methods

We combined mitochondrial and nuclear sequences with 302 new morphological characters to infer phylogenies. Bayesian tip‐dating analyses applied codon models to protein‐coding genes, with relaxed molecular clocks fitting a compound Poisson process. The combined maximum clade credibility tree was used in comparisons of alternative biogeographical models.

Results

The new phylogenies support the fossil Cubanycteris silvai as sister to all extant species of short‐faced bats. Among Artibeus (the sister group to short‐faced bats), the Antillean fossil A. anthonyi has distinctive characters and is nested within the subgenus Artibeus. The common ancestor of all short‐faced bats is inferred to be Antillean, as a mainland origin is unlikely. Founder‐event speciation is the most probable process explaining the distribution of these highly divergent fossil lineages.

Main conclusions

Dated, character‐based phylogenies of fossil species are indispensable for biogeographical inference: without fossils, biogeographical analyses find a mainland origin for short‐faced bats. The rate of founder speciation in this clade is twice as high as the estimate from noctilionoids in general, highlighting the role of founder events in the diversification of island taxa. Although rare, reverse colonization contributes key species to continental communities. Short‐faced bats, including Cubanycteris, share biomechanical adaptations for a strong bite conferring access to harder figs. We hypothesize these adaptations and characters related to roosting ecology enabled ancestral lineages to successfully establish and diversify on the mainland.
Multimodal teaching analytics: Automated extraction of orchestration graphs from wearable sensor data
Authors: Prieto L.P. , Sharma K. , Kidzinski Ł. , Rodríguez‐Triana M.J. , Dillenbourg P.
Published: January 2018

The pedagogical modelling of everyday classroom practice is an interesting kind of evidence, both for educational research and teachers' own professional development. This paper explores the usage of wearable sensors and machine learning techniques to automatically extract orchestration graphs (teaching activities and their social plane over time) on a dataset of 12 classroom sessions enacted by two different teachers in different classroom settings. The dataset included mobile eye‐tracking as well as audiovisual and accelerometry data from sensors worn by the teacher. We evaluated both time‐independent and time‐aware models, achieving median F1 scores of about 0.7–0.8 on leave‐one‐session‐out k‐fold cross‐validation. Although these results show the feasibility of this approach, they also highlight the need for larger datasets, recorded in a wider variety of classroom settings, to provide automated tagging of classroom practice that can be used in everyday practice across multiple teachers.
Ipragliflozin improves mitochondrial abnormalities in renal tubules induced by a high‐fat diet
Authors: Takagi Susumu , Li Jinpeng , Takagaki Yuta , Kitada Munehiro , Nitta Kyoko , Takasu Toshiyuki , Kanasaki Keizo , Koya Daisuke
Published: January 2018

Aims/Introduction

Complete mechanisms of renoprotective effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors have not been elucidated yet. Mitochondrial biogenesis is regulated by membrane GTPases, such as optic atrophy factor 1 and mitofusion 2. Here, we investigated whether SGLT2 inhibition in mice fed with a high‐fat diet (HFD) improved mitochondrial morphology and restored mitochondrial biogenesis‐related molecules.

Materials and Methods

Mice were fed a control diet or HFD with or without ipragliflozin treatment. After 16 weeks, the kidneys were taken out and utilized for the analysis.

Results

HFD‐fed mice treated with ipragliflozin showed increased caloric intake and ate more food than the control HFD‐fed mice. Body and kidney weights, and blood glucose levels were not altered by ipragliflozin treatment in HFD‐fed mice. Histological analysis showed that, compared with control mice, HFD‐fed mice displayed tubular vacuolation, dilatation and epithelial cell detachment; ipragliflozin ameliorated these alterations. Furthermore, ultrastructural analysis showed that the tubule mitochondria of HFD‐fed mice exhibited significant damage. Again, ipragliflozin reversed the damage to a normal state, and restored optic atrophy factor 1 and mitofusion 2 levels in HFD‐fed mice. Increased urine 8‐hydroxydeoxyguanosine levels in HFD‐fed mice were suppressed by ipragliflozin as well. In vitro experiments using HK‐2 cells revealed that either high glucose or high palmitate suppressed optic atrophy factor 1 and mitofusion 2 levels. Suppression of SGLT2 by a specific small interfering ribonucleic acid or ipragliflozin restored these GTPase levels to their normal values.

Conclusions

SGLT2 inhibition might act directly on tubular cells and protect kidney tubular cells from mitochondrial damage by metabolic insults regardless of blood glucose levels or improvement in bodyweight reduction.
Inferring climatic controls of rice stem borers’ spatial distributions using maximum entropy modelling
Authors: Jalaeian M. , Golizadeh A. , Sarafrazi A. , Naimi B.
Published: January 2018

Accurate assessment of pest potential distributions is needed to identify their establishment risks that play a key role in pest management in agricultural ecosystems. We used a correlative niche modelling method (Maxent) to predict and map the spatial distributions of two important rice stem borers, Chilo suppressalis and Sesamia cretica, in paddy fields of Iran. In total, 195 presence occurrence records (101 records for C. suppressalis and 94 records for S. cretica) were compiled. A set of environmental and topographic variables, with the highest effects on the species distributions and the lowest correlations among themselves, were used. The results showed that mainly the northern parts of Iran were the most suitable areas for C. suppressalis, and north, north‐east and south‐west of Iran as the most suitable areas for S. cretica. Both models performed well, with an area under the receiver operating characteristic curve (AUC) of 0.983 and 0.786 for C. suppressalis and S. cretica, respectively. The Maxent models showed higher accuracy for predicting the distribution of the specialist pest with the small range sizes compared to the generalist species. Assessing the importance of environmental variables, which were derived from the jackknife test, showed the precipitation as the variable with the highest contribution (66%) in explaining the spatial distribution of C. suppressalis compared to the other variables. The distribution of S. cretica was influenced by a set of variables derived from both the precipitation and temperature. The Maxent predictions were useful to map the geographical distributions of the risk for both rice stem borers that is needed to develop effective management strategies.
Carers' preferences for the delivery of therapy services for people with disability in rural Australia: evidence from a discrete choice experiment
Authors: Gallego G. , Dew A. , Lincoln M. , Bundy A. , Bulkeley K. , Brentnall J. , Veitch C.
Published: January 2018

Background

The implementation of the Australian National Disability Insurance Scheme is expected to generate a responsive, person‐centred system that will empower people with disability to choose the services and support they receive. However, little attention has been paid to examine how users of the National Disability Insurance Scheme will choose and spend their individual budgets. This study aimed to determine quantitatively the relative importance that carers of people with a disability living in rural Australia place on different therapy service delivery characteristics.

Methods

A stated preference discrete choice experiment was incorporated into a survey of carers of people with disability living in rural Australia. Carers chose between therapy delivery services differing in attributes such as travel time to receive therapy, sector providing the service (i.e. Government, not‐for‐profit and private), out‐of‐pocket costs, person who delivers the therapy (therapist or other staff) and waiting time.

Results

A total of 133 carers completed the discrete choice experiment. The majority of respondents cared for a child with a disability (84%); the average age of the person they cared for was 17 years (SD 14.25). Participants expressed strong preferences for a short waiting time (0–3 months) to receive therapy services; services delivered by a therapist, no out‐of‐pocket cost and travelling up to 4 h to receive a therapy session (P < 0.05). Sector providing the service was not statistically significant.

Conclusion

Carers of people with a disability in rural Australia exhibited strongest preferences for short waiting times (0–3 months). Therapy services that are delivered by therapy assistants or support workers will require careful introduction to achieve uptake and acceptability.
Childbirth Fear: Relation to Birth and Care Provider Preferences
Authors: Stoll Kathrin , Fairbrother Nichole , Thordarson Dana S.
Published: January 2018

Introduction

The purpose of this study was to assess how preferences for place of birth and mode of birth relate to different dimensions of childbirth fear and whether there is an association between Canadian women's prenatal fear of childbirth and the type and quality of prenatal care they received.

Methods

A link to an online survey was posted on Canadian pregnancy and birth websites; 409 women completed the survey that included sociodemographic questions, questions about the current pregnancy and previous pregnancy experiences (if applicable), and the Childbirth Fear Questionnaire, a validated 40‐item scale that measures 9 dimensions of childbirth fear.

Results

Women under physician care and those with a preference for cesarean birth were generally more fearful of pain associated with vaginal birth, fear of loss of sexual pleasure and attractiveness, and fear of harm to themselves or their infant. Conversely, women under the care of midwives and women who preferred to give birth vaginally were more fearful of interventions. Women who preferred a cesarean birth were significantly more likely to report that fear of childbirth interfered with daily functioning, compared to women who preferred a vaginal birth. Satisfaction with care was associated with lower scores on the Childbirth Fear Questionnaire full and subscales, especially among midwifery clients.

Discussion

At present there are no guidelines in Canada or the United States for the treatment and/or referral of pregnant women who suffer from childbirth fear. Until such guidelines are developed, findings from the current study can help maternity care providers identify and address specific fears among women in their care and understand how different fear domains relate to care provider choice, satisfaction with care, and women's preferences for place and mode of birth.
Melatonin ameliorates Aβ42‐induced alteration of βAPP‐processing secretases via the melatonin receptor through the Pin1/GSK3β/NF‐κB pathway in SH‐SY5Y cells
Authors: Chinchalongporn Vorapin , Shukla Mayuri , Govitrapong Piyarat
Published: January 2018

Melatonin is involved in the physiological regulation of the β‐amyloid precursor protein (βAPP)‐cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42‐induced downregulation of a disintegrin and metalloproteinase domain‐containing protein 10 (ADAM10) as well as upregulation of β‐site APP‐cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH‐SY5Y cell cultures. We also demonstrate that the intrinsic mechanisms of the observed effects occurred via regulation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) and glycogen synthase kinase (GSK)‐3β as melatonin reversed Aβ42‐induced upregulation and nuclear translocation of NF‐κBp65 as well as activation of GSK3β via its receptor activation. Furthermore, specific blocking of the NF‐κB and GSK3β pathways partially abrogated the Aβ42‐induced reduction in the BACE1 and PS1 levels. In addition, GSK3β blockage affected α‐secretase cleavage and modulated nuclear translocation of NF‐κB. Importantly, our study for the first time shows that peptidyl‐prolyl cis‐trans isomerase NIMA‐interacting 1 (Pin1) is a crucial target of melatonin. The compromised levels and/or genetic variation of Pin1 are associated with age‐dependent tau and Aβ pathologies and neuronal degeneration. Interestingly, melatonin alleviated the Aβ42‐induced reduction of nuclear Pin1 levels and preserved the functional integrity of this isomerase. Our findings illustrate that melatonin attenuates Aβ42‐induced alterations of βAPP‐cleaving secretases possibly via the Pin1/GSK3β/NF‐κB pathway.
The effects of late gestation nutrient restriction of dams on beef heifer intake, metabolites and hormones during an ad libitum feeding trial
Authors: Tipton J. E. , Ricks R. E. , LeMaster C. T. , Long N. M.
Published: January 2018

This study's objective was to determine if nutrient restriction during late gestation affected beef heifer feed intake, body weight (BW) gain and endocrine regulation during a 10‐week feeding trial. During the last 100 days of gestation, control (CON) dams were fed to increase body condition score (BCS). Whereas, nutrient‐restricted dams (NR) and NR dams protein supplemented 3 days/week (NRS) were fed to decrease BCS by 1.2. After parturition, all cow‐calf pairs were moved to a common pasture and fed in excess of requirements until weaning. At 15 months of age, heifers were randomly sorted into two pens and adjusted to a commercial total mixed ration over a 2‐week period. Blood samples and BW were taken at the initiation of feeding and on a biweekly basis for the duration of the feeding trial. Feed intake was monitored for 10 weeks using a GrowSafe System. After 10 weeks, an intravenous glucose tolerance test (IVGTT) was performed on 21 randomly subsampled heifers. During the feeding trial, NR heifers consumed more feed than CON and NRS heifers. Heifers from NR dams tended to increase BW compared to NRS and CON heifers when adjusted for initial BW. Heifers from NR and NRS dams had a greater increase in BCS compared to heifers from CON dams. Plasma glucose and insulin concentrations during the feeding trial increased in NR heifers compared to the other groups beginning at 2 and 4 weeks respectively. Plasma leptin concentrations were increased in the NR and NRS heifers compared to the CON heifers beginning at week 4 of feeding. During the IVGTT at the conclusion of the feeding challenge, plasma glucose and insulin were increased in NR heifers compared to other treatment groups. These results show that nutrient restriction during late gestation alters appetite and endocrine regulation in heifer offspring.
Redox potential: An intrinsic parameter of the rumen environment
Authors: Huang Y. , Marden J. P. , Julien C. , Bayourthe C.
Published: January 2018

The ruminal ecosystem is a fermentative milieu which is interesting to discuss in terms of its redox status as a reflection of an intense bacterial activity. The objective of this systematic literature review is to quantitatively analyze data collected on redox potential (Eh) in the rumen and to explore relationship between ruminal Eh, nature of the diet fed to ruminants, and ruminal fermentation parameters. Data obtained from 15 studies comprising 24 different diets was used in the analysis. Studies included in the data file were selected based on the criteria of: (i) the nature of the reference electrode was specified, (ii) the ruminal Ehwas recorded simultaneously topH, (iii) animal body weight (BW) and dry matter intake (DMI) were reported and (iv) the composition of the diet was precisely described. Results showed a high variability in ruminal Ehvalues. However, all recorded values are markedly negative reflecting the absence of oxygen and the strong reducing power of the rumen environment. The main factors contributing to the variation were the method of Ehmeasurement and the nature of the diet fed to ruminants. Redox potential was positively correlated withDMIand proportion of concentrate in the diet, and tended to be positively correlated with soluble carbohydrates content. In contrast, it was negatively correlated with neutral detergent fibre from forages. The hierarchical ascendant classification discriminated two groups of diets leading to significant change in ruminal Ehlevel. Ruminal Ehwas negatively correlated withpH, total volatile fatty acids produced and proportion of acetate, and positively correlated with proportion of propionate. This review revealed Ehto be dependent on the diet composition andDMI, at least within the range of diets included in the database.
Effect of dietary manipulation and vaccination of turkey breeder hens on immunoglobulin levels of yolk, yolk sac and neonate poults
Authors: Bhattacharyya A. , Majumdar S. , Bhanja S. K. , Mandal A. B. , Dash B. B.
Published: January 2018

Two hundred turkey breeder hens and 24 viable toms of 30–35 weeks age of small white variety were distributed into two treatment groups having four replicates of 25 hens and three toms in each treatment. First four replicates were offered a turkey breeder diet (Diet A) (Nutrient requirements of poultry, 1994, National Academic Press, Washington, DC) and the rest four replicates were maintained on a higher plane of nutrition (Diet B) for 8‐week duration. After 6 weeks of experimental feeding, two replicates from each treatment groups were vaccinated with ND (R2B) vaccine. Yolk sac of embryo from birds fed Diet B had a significantly higher (p < .05) IgG, IgM level and HI titre (log 2) than those fed Diet A. HI titre values of embryonic yolk sac from the vaccinated birds fed Diet B were significantly higher (p < .05) than that of the control groups. In addition, HI titre values were significantly higher (p < .05) in the day‐old poults of the birds fed Diet B than that of those fed Diet A. There was significantly (p < .01) positive correlation between serum IgG and IgM of the breeder birds and day‐old chicks. Similarly, there was significantly (p < .05) positive correlation between yolk IgG and IgM after 1‐month experimental feeding and yolk sac IgG and IgM. Positive correlation (p < .05) also existed between yolk sac IgM and day‐old chick serum IgM. Furthermore, the HI titres of breeder birds' serum at 14 days post‐vaccination were positively correlated with their egg yolk after 10 and 15 days post‐vaccination, yolk sac and day‐old chicks. Thus, the study envisaged that a higher immunity in neonate poults from turkey breeders maintained on a higher plane of nutrition may be elicited as there was maternal transfer of antibodies from the serum of breeder birds to their offsprings through their yolk sac.
Clinical and microbiological evaluation of the effect of Lactobacillus reuteri in the treatment of mucositis and peri‐implantitis: A triple‐blind randomized clinical trial
Authors: Galofré M. , Palao D. , Vicario M. , Nart J. , Violant D.
Published: January 2018

Background and Objective

Oral probiotics appear to improve the treatment of periodontal diseases but there is limited evidence on their efficacy in the treatment of peri‐implant diseases. The objective of the present study was to evaluate, clinically and microbiologically, the effect of the oral probiotic, Lactobacillus reuteri Prodentis, as adjuvant to non‐surgical mechanical therapy in implants with mucositis or peri‐implantitis, placed in patients with a history of periodontal disease.

Material and Methods

A randomized, controlled, parallel‐design, triple‐blind prospective clinical study was designed. Patients included in the study were partially edentulous and had implants with mucositis or peri‐implantitis. Implants with radiographic bone loss of ≥5 mm and/or ≥50% of the implant length were excluded, and only one implant per patient was included. After non‐surgical mechanical therapy, subjects were randomly assigned to take either 1 probiotic lozenge or 1 placebo lozenge every day for 30 days. Clinical measurements were taken in the whole mouth (general plaque index and general bleeding on probing) and at the implant site (probing pocket depth, plaque index and bleeding on probing) at baseline and 30 and 90 days Microbiological examination (to identify Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Peptostreptococcus micros, Fusobacterium nucleatum, Campylobacter rectus and Eikenella corrodens) was performed at the same study time points that clinical measurements were made.

Results

A total of 44 patients – 22 with mucositis and 22 with peri‐implantitis – randomly received treatment with either probiotic or placebo. The probiotic L. reuteri, together with mechanical therapy, produced an additional improvement over treatment with mechanical therapy alone, both in the general clinical parameters of patients with mucositis (bleeding on probing) and at the level of implants with mucositis (probing pocket depth) or peri‐implantitis (bleeding on probing and probing pocket depth). However, L. reuteri had a very limited effect on the peri‐implant microbiota because the only parameter in which a significant decrease was found was the bacterial load of P. gingivalis in implants with mucositis (P = .031).

Conclusion

The administration of a daily lozenge of L. reuteri for 30 days, together with mechanical debridement of the whole mouth, improved the clinical parameters of implants with mucositis or peri‐implantitis over a period of at least 90 days, but the microbiological effect was much more limited. Probiotics provide an alternative therapeutic approach to consider in the prevention and treatment of peri‐implant diseases, but further long‐term prospective studies with standardized variables are needed.
Efficacy of local phytotherapy in the nonsurgical treatment of periodontal disease: A systematic review
Authors: Moro M. G. , Silveira Souto M. L. , Franco G. C. N. , Holzhausen M. , Pannuti C. M.
Published: January 2018

Herbal drugs are commonly used in the treatment of several diseases, including periodontitis. So far, no systematic review had evaluated the evidence regarding the efficacy of these agents in the treatment of periodontal disease. Therefore, the purpose of this review was to evaluate the effect of local application of phytotherapic agents as adjuncts to scaling and root planing (SRP), compared to SRP alone, on clinical parameters of chronic periodontal patients. Only randomized controlled trials of at least 3 months follow‐up, of SRP alone in association with local phytotherapic agents were included. MEDLINE (PubMed), Google Scholar and LILACS databases were searched for articles published up to October 2016. Random‐effects meta‐analyses were conducted for clinical attachment level and probing pocket depth (PPD) change after treatment. Of 1861 papers potentially relevant, 7 were included. All studies showed that periodontal treatment in association with local phytotherapic delivery promotes a significant PPD reduction and the majority of them showed clinical attachment level gain. The local use of phytotherapy as an adjunct to SRP may promote additional benefits in PPD reduction and clinical attachment level gain. However, these results must be interpreted with caution due to the small sample size, high risk of bias and heterogeneity of the studies.
The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats
Authors: Pasloske K. , Ranasinghe M. G. , Sauer S. , Hare J.
Published: January 2018

To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single‐dose, randomized, two‐period, two‐sequence, cross‐over bioequivalence study with a 7‐day washout period between treatments. Twenty‐four (12 neutered males and 12 intact females), healthy, adult cats weighing 4.1±0.9 kg. Cats were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using a randomized cross‐over design. One‐milliliter venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time. Alfaxalone concentrations were determined by a validated analytical testing method using HPLC‐MS/MS. Plasma profiles of alfaxalone concentration against time were analyzed by noncompartmental analysis. The pivotal variables for bioequivalence were AUClast and Cmax. Equivalence was achieved if the 90% confidence interval for AUClast and Cmax fell into the asymmetric ±20% interval (0.80–1.25). Physiological variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX was used for nonnormally distributed data. VAS scores were analyzed as for blood bioequivalence data. Variables were evaluated for safety and assessed at alpha = 0.10. Cmax and AUClast for Reference and Test Products were statistically bioequivalent. No physiological variables except for a drug by time interaction for respiratory rate differed between treatment groups, and this difference was not clinically relevant. No anesthetic event times or VAS scores for quality of anesthesia were different between treatment groups. Neither formulation caused pain upon injection. The Reference and Test Products are pharmaceutically bioequivalent formulations when administered as a single intravenous administration for the purpose of induction of anesthesia in cats.
The impact ofMK‐467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal
Authors: Adam M. , Raekallio M. R. , Keskitalo T. , Honkavaara J. M. , Scheinin M. , Kajula M. , Mölsä S. , Vainio O. M.
Published: January 2018

The effect ofMK‐467, a peripheral α2‐adrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2‐week washout periods. Medetomidine (MED) 30 μg/kg alone or combined in the same syringe withMK‐467 300 μg/kg (MMK) was injected intramuscular, followed byATI150 μg/kg (MED + ATIandMMK + ATI) or saline intramuscular 30 min later. Plasma was analysed for drug concentrations, and sedation was subjectively assessed with a visual analogue scale. Systemic haemodynamics and blood gases were measured before treatments and at intervals thereafter. WithMK‐467, medetomidine plasma concentrations were threefold higher prior toATI, which was associated with more profound sedation and shorter onset. No significant differences were observed in early cardiopulmonary changes between treatments. Atipamezole reversed the medetomidine‐related cardiopulmonary changes after both treatments. Sedation scores decreased more rapidly whenMK‐467 was included. In this study,MK‐467 appeared to have a pronounced effect on the plasma concentration and central effects of medetomidine, with minor cardiopulmonary improvement.
Pharmacokinetics of single‐dose sildenafil administered orally in clinically healthy dogs: Effect of feeding and dose proportionality
Authors: Akabane R. , Sato T. , Sakatani A. , Miyagawa Y. , Tazaki H. , Takemura N.
Published: January 2018

Basic information related to the pharmacokinetics of sildenafil in dogs is scarce. This study aimed to describe the pharmacokinetic properties of oral sildenafil and determine the effect of feeding and dose proportionality. The effect of feeding on pharmacokinetics of sildenafil (1 mg/kg) was investigated using a crossover study with six dogs. In addition, the dose proportionality of sildenafil ranging 1–4 mg/kg was evaluated using five dogs in the fasted states. The plasma concentrations of sildenafil were determined using high‐performance liquid chromatography, and pharmacokinetic parameters were calculated using a noncompartmental analysis. Sildenafil administrations were well tolerated in all studies. Feeding reduced the area under the curve extrapolated to infinity (AUCinf) and the maximum plasma concentration (Cmax) significantly. The elimination half‐life (T1/2) did not differ between the fasted and the fed states. For dose proportionality, nonproportional increases in AUCinf and Cmax at 1–4 mg/kg doses were detected by a power model analysis.
Individual species–area relationships in temperate coniferous forests
Authors: Das Adrian J. , Larson Andrew J. , Lutz James A.
Published: January 2018

Questions

What drives individual species–area relationships in temperate coniferous forests?

Location

Two 25.6‐ha forest plots on the Pacific Slope of North America, one in California, and one in Washington State.

Methods

We mapped all trees ≥1 cm in diameter and examined tree species diversity of their local neighbourhoods by calculating the individual species–area relationship for each species and for each of three diameter classes (saplings, mature trees and large‐diameter trees).

Results

In the California plot, small trees in four of the five major species occurred in neighbourhoods with higher levels of diversity than would be expected at random. In the Washington plot, small trees for four of five abundant species had neighbourhoods with lower than expected diversity at distances ≤5 m for small trees. However, at distances >5 m, all five species showed higher than expected diversity in their neighbourhoods. Larger trees at both plots tended to occur in neighbourhoods with lower than expected diversity, and no large‐diameter focal species had neighbourhoods with higher than expected diversity.

Conclusion

Diversity and co‐existence in temperate conifer‐dominated forests do not appear to be the result of random processes. Competitive interactions appear to dominate for the largest trees of most species, resulting in neighbourhoods with lower diversity. For smaller trees, we suggest that a positive response to environmental heterogeneity is the likely driver of neighbourhoods with higher than expected diversity, although we cannot rule out the possibility that facilitation or conspecific negative density dependence (CNDD) also play a role.
Effect of metabolites on stress, adaptation and longevity in laboratory populations of Drosophila flies
Authors: Yadav J. P. , Singh P.
Published: January 2018

Metabolites like lipid and carbohydrate have significant roles on starvation, desiccation and longevity and differ in natural and laboratory populations of Drosophila. Five laboratory populations of Drosophila ananassae have been subjected to paraquat‐induced mortality and longevity, desiccation resistance, body size and ovariole number and tested for different metabolites (lipid, carbohydrate and water), fecundity and polymorphic chromosome inversions in each sex. Paraquat dose–response has clinal variation and means that paraquat mortality at different concentrations is significantly altered among males only. The overall mean ovariole number varies significantly (P ≪ 0.001) among different populations and one‐way ANOVA suggests significant variations (P ≪ 0.001) with mean fecundity and latitude. Only female longevity varies significantly among five different populations (P ≪ 0.001). Fecundity shows positive correlations with the longevity and suggests a possible role of different metabolites in keeping the cost effect. Two‐way ANOVA among mean water, lipid and carbohydrate contents in both sexes of different populations suggest significant differences among metabolites (P ≪ 0.001), between males and females (P ≪ 0.001, d.f. = 1) and for their interactions with each other (P ≪ 0.001) also. Significant differences are found for mean longevity, lipid and carbohydrate contents in both sexes of different populations in a two‐way ANOVA analysis (P ≪ 0.001), which suggests possible roles in their utilization at different levels during adaptation and stress. Longevity is affected significantly (P ≪ 0.001) by desiccation resistance also. Different chromosome inversions and their combinations show significant variations and sexual dimorphism with latitude and thorax length (P ≪ 0.001) and their roles are discussed in achieving adaptation, stress resistance and longevity.
Negative supercoiling of DNA by gyrase is inhibited in Salmonella enterica serovar Typhimurium during adaptation to acid stress
Authors: Colgan Aoife M. , Quinn Heather J. , Kary Stefani C. , Mitchenall Lesley A. , Maxwell Anthony , Cameron Andrew D.S. , Dorman Charles J.
Published: January 2018

DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during growth in the acidified (pH 4–5) macrophage vacuole and DNA relaxation correlates with the upregulation of Salmonella genes involved in adaptation to the macrophage environment. Bacterial ATP levels did not increase during adaptation to acid pH unless the bacterium was deficient in MgtC, a cytoplasmic‐membrane‐located inhibitor of proton‐driven F1F0 ATP synthase activity. Inhibiting ATP binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH on DNA relaxation. Bacteria expressing novobiocin‐resistant (NovR) derivatives of gyrase or topo IV also exhibited DNA relaxation at acid pH, although further relaxation with novobiocin was not seen in the strain with NovR gyrase. Thus, inhibition of the negative supercoiling activity of gyrase was the primary cause of enhanced DNA relaxation in drug‐treated bacteria. The Salmonella cytosol reaches pH 5–6 in response to an external pH of 4–5: the ATP‐dependent DNA supercoiling activity of purified gyrase was progressively inhibited by lowering the pH in this range, as was the ATP‐dependent DNA relaxation activity of topo IV. We propose that DNA relaxation in Salmonella within macrophage is due to acid‐mediated impairment of the negative supercoiling activity of gyrase.
Positive autoregulation and repression of transactivation are key regulatory features of the Candida glabrata Pdr1 transcription factor
Authors: Khakhina Svetlana , Simonicova Lucia , Moye‐Rowley W. Scott
Published: January 2018

Resistance to azole drugs, the major clinical antifungal compounds, is most commonly due to gain‐of‐function (GOF) substitution mutations in a gene called PDR1 in the fungal pathogen Candida glabrata. PDR1 encodes a zinc cluster‐containing transcription factor. GOF forms of Pdr1 drive high level expression of downstream target gene expression with accompanying azole resistance. PDR1 has two homologous genes in Saccharomyces cerevisiae, called ScPDR1 and ScPDR3. This study provides evidence that the PDR1 gene in C. glabrata represents a blend of the properties found in the two S. cerevisiae genes. We demonstrated that GOF Pdr1 derivatives are overproduced at the protein level and less stable than the wild‐type protein. Overproduction of wild‐type Pdr1 increased target gene expression but to a lesser extent than GOF derivatives. Site‐directed mutagenesis of Pdr1 binding sites in the PDR1 promoter provided clear demonstration that autoregulation of PDR1 is required for its normal function. An internal deletion mutant of Pdr1 lacking its central regulatory domain behaved as a hyperactive transcription factor that was lethal unless conditionally expressed. A full understanding of the regulation of Pdr1 will provide a new avenue of interfering with azole resistance in C. glabrata.
The common bean COK‐4 and the Arabidopsis FER kinase domain share similar functions in plant growth and defence
Authors: Azevedo Rafhael Felipin , Gonçalves‐Vidigal Maria Celeste , Oblessuc Paula Rodrigues , Melotto Maeli
Published: January 2018

Receptor‐like kinases are membrane proteins that can be shared by diverse signalling pathways. Among them, the Arabidopsis thaliana FERONIA (FER) plays a role in the balance between distinct signals to control growth and defence. We have found that COK‐4, a putative kinase encoded in the common bean anthracnose resistance locus Co‐4, which is transcriptionally regulated during the immune response, is highly similar to the kinase domain of FER. To assess whether COK‐4 is a functional orthologue of FER, we expressed COK‐4 in the wild‐type Col‐0 and the fer‐5 mutant of Arabidopsis and evaluated FER‐associated traits. We observed that fer‐5 plants show an enhanced apoplastic and stomatal defence against Pseudomonas syringae. In addition, the fer‐5 mutant shows reduced biomass, smaller guard cell size, greater number of stomata per leaf area, fewer leaves, faster transition to reproductive stage and lower seed weight per plant than the wild‐type Col‐0. Except for the stomatal complex length and number of stomata, COK‐4 expression in fer‐5 lines partially or completely rescued both defence and developmental defects of fer‐5 to the wild‐type level. Notably, COK‐4 may have an additive effect to FER, as the expression of COK‐4 in Col‐0 resulted in enhanced defence and growth phenotypes in comparison with wild‐type Col‐0 plants. Altogether, these findings indicate that the common bean COK‐4 shares at least some of the multiple functions of the Arabidopsis FER kinase domain, acting in both the induction of plant growth and regulation of plant defence.
Disruption of the methionine cycle and reduced cellular gluthathione levels underlie potex–potyvirus synergism in Nicotiana benthamiana
Authors: De Swarnalok , Chavez‐Calvillo Gabriela , Wahlsten Matti , Mäkinen Kristiina
Published: January 2018

Infection caused by the synergistic interaction of two plant viruses is typically manifested by severe symptoms and increased accumulation of either virus. In potex–potyviral synergism, the potyviral RNA silencing suppressor helper component proteinase (HCPro) is known to enhance the pathogenicity of the potexvirus counterpart. In line with this, Potato virus X (PVX; genus Potexvirus) genomic RNA (gRNA) accumulation and gene expression from subgenomic RNA (sgRNA) are increased in Nicotiana benthamiana by Potato virus A (PVA; genus Potyvirus) HCPro expression. Recently, we have demonstrated that PVA HCPro interferes with the host cell methionine cycle by interacting with its key enzymes S‐adenosyl‐l‐methionine synthetase (SAMS) and S‐adenosyl‐l‐homocysteine hydrolase (SAHH). To study the involvement of methionine cycle enzymes in PVX infection, we knocked down SAMS and SAHH. Increased PVX sgRNA expression between 3 and 9 days post‐infiltration (dpi) and upregulation of (–)‐strand gRNA accumulation at 9 dpi were observed in the SAHH‐silenced background. We found that SAMS and SAHH silencing also caused a significant reduction in glutathione (GSH) concentration, specifically in PVX‐infected plants between 2 and 9 dpi. Interestingly, HCPro expression in PVX‐infected plants caused an even stronger reduction in GSH levels than did SAMS + SAHH silencing and a similar level of reduction was also achieved by knocking down GSH synthetase. PVX sgRNA expression was increased in the GSH synthetase‐silenced background. GSH is a major antioxidant of plant cells and therefore GSH shortage may explain the strong oxidative stress and severe symptoms observed during potex–potyvirus mixed infection.
Mimicking Adie's pupils in the early phase of meningeal neurosyphilis
Authors: Seki Misa , Takeda Takahiro , Ito Eiichi , Iijima Mutsumi , Kitagawa Kazuo
Published: January 2018

We report on a patient who presented at our hospital with complaints of bilateral pupillary dilatation and abnormal ocular movement. These symptoms gradually worsened over a few months. After subsequent serological and CSF examinations, he was diagnosed with meningeal neurosyphilis. His pupillary abnormality was marked by deficits of the light reflex and accommodation reaction. Pilocarpine tests demonstrated less hypersensitivity in the bilateral pupils, which indicated preganglionic parasympathetic pupillary involvement. The symptoms improved with penicillin injection therapy. This case provides evidence of pupillary parasympathetic denervation associated with meningeal involvement in the early phase of neurosyphilis. It could be distinguished from a classical Adie's tonic pupil caused by postganglionic long‐standing denervation.
Self‐management for bipolar disorder and the construction of the ethical self
Authors: Wilson Lynere , Crowe Marie , Scott Anne , Lacey Cameron
Published: January 2018

The promotion of the self‐managing capacities of people has become a marker of contemporary mental health practice, yet self‐management remains a largely uncontested construct in mental health settings. This discourse analysis based upon the work of Foucault investigates self‐management practices for bipolar disorder and their action upon how a person with bipolar disorder comes to think of who they are and how they should live. Using Foucault's framework for exploring the ethical self and transcripts of interviews with people living with bipolar disorder, this discourse analysis finds that the discursive practices of self‐management for bipolar disorder are prescribing a restricted regime for living based upon the quintessential neo‐liberal subject using practices that are focused upon managing an unreliable and problematic self. The article concludes with the proposition that the problem of bipolar disorder (for which self‐management is an answer) is less about the object itself and more about how we construct the nature of the self. A Māori indigenous ontology is used here as an example of an alternative discursive resource through which people make sense of the self and which allows ways of thinking about self‐management that engage with ambivalence and ambiguity rather than restriction and regulation.
Successful hematopoietic cell transplantation following cardiac transplantation in two pediatric patients
Authors: Phelan Rachel , Smith Angela R. , Orchard Paul J. , Ameduri Rebecca K.
Published: January 2018

We report two patients who underwent cardiac transplantation at a young age and subsequently required a HCT for varied indications. Despite the challenges associated with HCT following cardiac transplant, including need for altered immunosuppression, toxicities related to chemotherapy exposure, and infection risks, both patients are currently alive and well. There is a paucity of such successful cases documented in the literature, and these cases highlight the critical importance of an experienced, multidisciplinary team when caring for this patient population.
Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non‐malignant diseases in children: A review
Authors: Guilcher Gregory M. T. , Shah Ravi , Shenoy Shalini
Published: January 2018

Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non‐malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable. In addition, the degree of immune suppression achieved with alemtuzumab has allowed for a reduction in the intensity of myeloablative cytotoxic agents included in some HCT conditioning regimens, allowing for fewer acute and late toxicities. This review paper will provide a comprehensive summary of the mechanism of action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in various allogeneic HCT protocols for non‐malignant conditions and a summary of the data regarding its use for GVHD therapy. The goal of this review was to provide an understanding as to how alemtuzumab might be safely incorporated into HCT conditioning regimens for children with non‐malignant disease, allowing for expanded access to curative HCT therapy.
Variability of pulsed energy outputs from three dermatology lasers during multiple simulated treatments
Authors: Britton Jason
Published: January 2018

Background

Dermatology laser treatments are undertaken at regional departments using lasers of different powers and wavelengths. In order to achieve good outcomes, there needs to be good consistency of laser output across different weeks as it is custom and practice to break down the treatments into individual fractions. Departments will also collect information from test patches to help decide on the most appropriate treatment parameters for individual patients.

Objectives

The objective of these experiments is to assess the variability of the energy outputs from a small number of lasers across multiple weeks at realistic parameters.

Methods

The energy outputs from 3 lasers were measured at realistic treatment parameters using a thermopile detector across a period of 6 weeks.

Results

All lasers fired in single‐pulse mode demonstrated good repeatability of energy output. In spite of one of the lasers being scheduled for a dye canister change in the next 2 weeks, there was good energy matching between the two devices with only a 4%‐5% variation in measured energies.

Conclusions

Based on the results presented, clinical outcomes should not be influenced by variability in the energy outputs of the dermatology lasers used as part of the treatment procedure.