bluuebunny/crossref_metadata_2025 huggingface dataset:
High blood lead concentrations in captive Tasmanian devils (Sarcophilus harrisii): a threat to the conservation of the species?
Authors: Hivert LG , Clarke JR , Peck SJ , Lawrence C , Brown WE , Huxtable SJ , Schaap D , Pemberton D , Grueber CE
Published: October 2018

Background

The Tasmanian devil (Sarcophilus harrisii) is the world’s largest extant marsupial carnivore. Since the emergence of devil facial tumour disease in 1996, the species has undergone a severe population decline. The insurance population (IP) was established in 2006 to build a disease‐free captive population to maintain 95% of the wild Tasmanian devil genetic diversity for 50 years. Captive and semi‐wild Tasmanian devils are fed with possum and wallaby meat provided by local hunters, who use lead ammunition. Lead ingestion can cause acute toxicity, including ataxia, coma and death, or chronic subclinical deleterious effects including decreased fertility.

Methods

We determined blood lead concentrations in 26 captive and 133 wild Tasmanian devils from various sites across Tasmania.

Results

Captive Tasmanian devils showed significantly higher blood lead concentrations than their conspecifics in the wild. In captivity, older animals had higher blood lead concentrations than young animals, which suggested regular exposure, as lead can accumulate in a living organism in the blood, soft tissues and bones. After a response measure was implemented by removing the heads and wounds containing lead from the diet, blood concentrations significantly decreased in animals at one of the captive study sites, supporting the suspicion of food as the source of lead.

Conclusion

This study highlights the need to ensure meat fed to captive carnivores is not contaminated by lead, especially in the context of a conservation program breeding individuals in captivity, as for Tasmanian devils.
Kidney function estimates using cystatin C versus creatinine: Impact on medication prescribing in acutely hospitalized elderly patients
Authors: Iversen Esben , Bodilsen Ann Christine , Klausen Henrik Hedegaard , Treldal Charlotte , Andersen Ove , Houlind Morten Baltzer , Petersen Janne
Published: October 2018

Background

Medication errors due to inaccurate measures of kidney function are common among elderly patients. We investigated differences between estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C and how these differences would affect prescribing recommendations among acutely hospitalized elderly patients. We also identified factors associated with discrepancies between estimates.

Methods

Estimated glomerular filtration rate and chronic kidney disease (CKD) classifications were determined for 338 acutely hospitalized elderly patients using equations from Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI), Berlin Initiative Study (BIS) and Cockcroft‐Gault (CG). Prescribed renal risk medications were compared with dosing guidelines in Renbase®. Linear regression models were used to identify explanatory variables for eGFR discrepancies between equations. Muscle weakness was assessed by handgrip strength; inflammation was assessed by smoking status, serum C‐reactive protein (CRP), soluble urokinase plasminogen activator receptor (suPAR) and neutrophil gelatinase‐associated lipocalin (NGAL); and organ dysfunction was assessed by thyroid‐stimulating hormone (TSH) and FI‐OutRef.

Results

Median eGFR values were 65.5, 60.7, 54.1, 57.1, 55.1 and 57.6 mL/min/1.73m2 according to CKD‐EPICr, CKD‐EPIComb, CKD‐EPICys, BISCr, BISComb and CGCr, respectively. Depending on choice of equation, renal risk medications were prescribed at higher than recommended dose in 13.6% to 22.5% of patients using normalized GFR units and 9.9% to 19.1% of patients using absolute units. Age, handgrip strength, CRP, suPAR, NGAL and smoking status had significant association with eGFR discrepancies between creatinine‐ and cystatin C‐based equations.

Conclusions

Significant discrepancies in eGFR and CKD classification were observed when switching between eGFR equations in acutely hospitalized elderly patients. Switching from a creatinine‐based equation to its corresponding cystatin C‐based equation resulted in lower GFR estimates, and these differences were larger than in community‐dwelling older populations. Switching between CKD‐EPICr, CGCr and the alternative equations would result in clinically relevant changes to medication prescribing. Discrepancies between equations were associated with high age, muscle weakness and inflammation.
The predictive value of scores based on peripheral complete blood cell count for long‐term neurological outcome in acute carbon monoxide intoxication
Authors: Moon Jeong Mi , Chun Byeong Jo , Cho Yong Soo
Published: October 2018

Growing evidence indicates that inflammation is associated with neurological sequelae after CO poisoning. Several scores incorporating the peripheral complete blood cell (CBC) count have been introduced as indicators of systemic inflammation. This study investigated whether these scores can improve the predictive accuracy for long‐term neurological outcome of acute carbon monoxide (CO) poisoning. Two hundred seventy‐nine patients who suffered from acute CO poisoning were included. Data on the demographic details, serial peripheral CBC counts and scores based on peripheral CBC counts (neutrophil‐lymphocyte ratio (NLR), monocyte‐lymphocyte ratio (MLR), platelet‐lymphocyte ratio (PLR), systemic immune inflammation index [SII]) over the first 12 hours after presentation together with the clinical course during hospitalization and long‐term neurological outcome were collected. Both a multivariate logistic regression model with only significant univariate predictors and a model with univariate predictors plus each score for long‐term neurological outcome were constructed. Patients with a poor long‐term neurological outcome had higher neutrophil and monocyte counts and lower lymphocyte counts over the first 12 hours after admission than patients with a good outcome. The diagnostic performance of the NLR, MLR and SII over the first 12 hours for predicting long‐term neurological outcome was acceptable. These scores at presentation were independently associated with the long‐term neurological outcome. Among these scores, only the SII at presentation significantly improved the predictive accuracy of the model when combined with clinical parameters (AUC 0.949, 95% CI 0.916‐0.972 vs AUC 0.923, 95% CI 0.884‐0.952 for the model with clinical parameters only, P = 0.0476). The optimal cut‐off value for SII at presentation was 1012.2, resulting in a sensitivity of 97% (84.2%‐99.9%) and specificity of 64.6% (58.2%‐70.6%). The SII at presentation could significantly improve the prognostic accuracy for predicting the long‐term neurological outcome in patients with acute CO poisoning. Because the SII is an inexpensive and easily measurable parameter, it might be used as a prognostic tool in clinical fields.
Penile cancer information on the internet: a needle in a haystack
Authors: Teh Jiasian , Op't Hoog Stephanie , Nzenza Tatenda , Duncan Catriona , Wang Judy , Radojcic Matija , Feng Cheng , Lawrentschuk Nathan
Published: October 2018

Introduction

Penile cancer is a disease with high morbidity and mortality and is rare in developed countries. In the developing world, the incidence is significantly higher, and accounts for 1–2% of malignant disease in men. Penile cancer is associated with delayed diagnosis, often due to psychological factors. Web based resources are especially important when obtaining information from health professionals is challenging, such as when symptoms are embarrassing or stigmatised.

Objective

To assess the quality of information about penile cancer on the internet and to compare the quality of information from developed countries with developing countries.

Method

Health on the Net (HON) principles were applied to websites using the Google search engine imbedded with HON toolbar. This was used to assess 750 websites in English, French, German, Spanish and Portuguese by two independent examiners using the key word ‘penile cancer’ in all languages. The first 150 websites in each language were analysed. Further analysis was completed comparing results between languages and site sponsors.

Results

Of the 750 websites analysed, 10.4% were HON accredited. There were significantly more HON accredited websites in English and French compared with Portuguese (P = 0.009 and P = 0.0007). A total of 45% of websites were sponsored by Commercial enterprise and 27% were sponsored by Government organisations.

Conclusion

A lack of validation of penile cancer internet resources should be appreciated by clinicians. Additionally, there is a discrepancy in the quality of websites between languages, with significantly more resources available in the developed world. Limited available web resources in Spanish and Portuguese contribute to disparities in information access and disease outcomes.
Synthesis of 99mTc‐roxithromycin: A novel diagnostic agent to discriminate between septic and aseptic inflammation
Authors: Rizvi Syed Faheem Askari , Tariq Saleha , Mehdi Muhammad , Hassan Ahmad Junaid
Published: October 2018

Roxithromycin is a second‐generation macrolide antibiotic derived from erythromycin. In the current study, roxithromycin (ROX) was successfully labeled with technetium‐99m for early diagnosis of bacterial infection and discrimination between septic and aseptic inflammation. The highest radiochemical purity of ≥95% was achieved by investigating different labeling parameters such as pH, ligand/reducing agent concentration, temperature, and amount of stabilizing agent. For this purpose, 0.3–0.5 mg ligand, 2–6 μg SnCl2·2H2O as a reducing agent at basic pH (8–10 pH) and 2 mg mannitol used as a stabilizing agent, in the end, 370 MBq 99mTc added into the reaction vials and incubated for a wide range of temperature (−4 to 65°C). The percent radiochemical purity of 99mTc‐roxithromycin was assessed with the help of the radio‐thin‐layer chromatography technique. The characterization studies were carried out using electrophoresis and Radio‐HPLC techniques as well as saline stability and serum stability studies were also performed. Furthermore, biodistribution study was also performed in an inflamed animal model to discriminate between septic (heat‐killed Staphylococcus aureus) and aseptic (turpentine oil) inflammatory lesions. The results were elaborated that 99mTc‐roxithromycin (99mTc‐ROX) was clearly bounded at the septic inflammation site (T/NT ratio of 7.08 ± 1.14) at 30 min postadministration, and maximum accumulation was seen in heart, lungs, liver, stomach, kidneys, and intestine. The results were suggested that 99mTc‐ROX might be used to discriminate between septic and aseptic inflammatory lesions at an early stage.
Development of an artificial intelligence system to classify pathology and clinical features on retinal fundus images
Authors: Stevenson Clark H. , Hong Sheng Chiong , Ogbuehi Kelechi C.
Published: October 2018

Importance

Artificial intelligence (AI) algorithms are under development for use in diabetic retinopathy photo screening pathways. To be clinically acceptable, such systems must also be able to classify other fundus abnormalities and clinical features at the point of care.

Background

We aimed to develop an AI system that can detect several fundus pathologies and report relevant clinical features.

Design

Convolutional neural network training with retrospective data set.

Participants

Colour fundus photos were obtained from publicly available fundus image databases.

Methods

Images were uploaded to a web‐based AI platform for training and validation of AI classifiers. Separate classifiers were created for each fundus pathology and clinical feature.

Main Outcome Measures

Accuracy, sensitivity, specificity and area under receiver operating characteristic curve (AUC) for each classifier.

Results

We obtained 4435 images from publicly available fundus image databases. AI classifiers were developed for each disease state above. Although statistical performance was limited by the small sample size, average accuracy was 89%, average sensitivity was 75%, average specificity was 89% and average AUC was 0.58.

Conclusion and Relevance

This study is a proof‐of‐concept AI system that could be implemented within a diabetic photo‐screening pathway. Performance was promising but not yet at the level that would be required for clinical application. We have shown that it is possible for clinicians to develop AI classifiers with no previous programming or AI knowledge, using standard laptop computers.
A nomogram prediction of peri‐implantitis in treated severe periodontitis patients: A 1–5‐year prospective cohort study
Authors: Zhang Haidong , Li Wenjing , Zhang Li , Yan Xia , Shi Dong , Meng Huanxin
Published: October 2018

Background

No nomogram of peri‐implantitis was reported before which is valuable for risk‐estimating, clinical decision‐making, and better‐patients‐communicating.

Purpose

To identify the risk indicators and develop a nomogram prediction model of peri‐implantitis in treated severe periodontitis patients.

Materials and Methods

A prospective study was conducted on 100 patients with 214 implants. Periodontal and peri‐implant parameters were evaluated at implant surgery procedure (T1), and at follow‐up (T2). Risk factors were analyzed by logistic regression analyses with generalized estimating equations. Nomogram was developed and the discriminatory ability of the model was analyzed.

Results

The incidence of peri‐implantitis at patient‐level and implant level were 16% and 11.2% respectively, with no implant lost. The variables associated with peri‐implantitis were the PDT1 ≥ 6 mm (%) > 10%, the implant position, length, and diameter after adjusting for covariates. A nomogram prediction model of peri‐implantitis were developed with factors of PD T1 ≥ 6 mm (%) > 10% and implant placed in posterior. The area under the ROC curves of stepwise model was 0.794.

Conclusions

The residual pockets and implants position were identified as predictors for the peri‐implantitis. The nomogram can be used to estimate the risk of peri‐implantitis in treated severe periodontitis patients.
Cutaneous localization of angioimmunoblastic T‐cell lymphoma may masquerade as B‐cell lymphoma or classical Hodgkin lymphoma: A histologic diagnostic pitfall
Authors: Szablewski Vanessa , Dereure Olivier , René Céline , Tempier Ariane , Durand Luc , Alame Melissa , Cacheux Valère , Costes‐Martineau Valérie
Published: October 2018

Background

We report the cases of three patients presenting skin lesions whose biopsies showed nodular polymorphic infiltrates consisting of lymphocytes, plasma cells, histiocytes, eosinophils, B blasts, and Hodgkin Reed‐Sternberg (HRS)‐like cells. Two of them were initially diagnosed as classical Hodgkin lymphoma (cHL), on the other hand, the last one as a B‐cell lymphoma. All patients have been treated for angioimmunoblastic T‐cell lymphoma (AITL).

Methods

We performed a second review of the skin biopsies with further immunophenotypic molecular analyses. Scrupulous observation revealed, in the background of the three cases, atypical small to medium‐sized lymphocytes carrying a CD3+, CD4+ T‐cell phenotype and expressing PD1 and CXCL13 follicular helper T‐cell markers. The two lesions initially diagnosed as cHL showed scattered HRS‐like cells with CD30+, CD15+, PAX5+, CD20−, Epstein Barr Virus (EBV) + classical phenotype. The case initially diagnosed as B‐cell lymphoma showed a diffuse B‐cell proliferation associated with small B‐cell and medium to large‐sized B blasts that were positive for EBV.

Conclusion

Those cases highlighted that atypical T‐cells may be obscured by B‐cell proliferation mimicking cHL or B‐cell lymphoma in cutaneous localization of AITL and confirmed the requirement of collecting clinical information before performing a diagnosis.
Outpatient appointment non‐attendance and unplanned health care for children and young people with neurological conditions: a retrospective cohort study
Authors: Jarvis Stuart , Livingston John , Childs Anne‐Marie , Fraser Lorna
Published: October 2018

Aim

To test the hypothesis that children and young people with neurological conditions who missed outpatient appointments have more emergency inpatient admissions and Accident and Emergency centre (A&E) visits than those who missed none.

Method

Retrospective cohort of individuals aged up to 19 years with neurological conditions, identified from routine hospital data in England, UK from April 1st, 2003 to March 31st, 2015 using an International Statistical Classification of Diseases and Related Health Problems, coding framework. Counts of emergency inpatient admissions and A&E visits per person per year were modelled (random intercept negative binomial regression) with outpatient attendance the independent variable of interest.

Results

The cohort numbered 524 613 individuals. Those who missed outpatient appointments had 19 per cent (95% confidence interval [CI] 18–19) more emergency inpatient admissions and 16 per cent (95% CI 15–17) more A&E visits per year than those who missed none. ‘Did not attends’ had a larger increase in unplanned health care than patient or provider cancellations. If no appointments were missed, the models predict there would have been 107 000 fewer A&E visits from 2007/2008 to 2014/2015 and 104 000 fewer emergency inpatient admissions from 2003/2004 to 2014/2015.

Interpretation

Missed outpatient appointments were associated with increased unplanned health care. Improving outpatient attendance may have the potential to reduce emergency inpatient admissions and A&E visits.

What this paper adds

Missed outpatient appointments by children and young people with neurological conditions are associated with increased unplanned health care.

Both emergency inpatient admissions and Accident and Emergency centre visits are increased.

‘Did not attends’ are more strongly associated with unplanned health care than cancellations.
Both local presence and regional distribution of predator cues modulate prey colonisation in pond landscapes
Authors: Trekels Hendrik , Vanschoenwinkel Bram
Published: October 2018

Recent work on habitat selection has shown that the perceived quality of habitat patches may depend on the quality of adjacent patches. However, it is still unclear how local habitat selection cues can alter distribution patterns in metacommunities at a larger (regional) scale. We studied mosquito oviposition in pond landscapes that differed in the proportion of bad patches with fish predation risk. Our experiment provided conclusive evidence for two local and two regional types of habitat selection. Good patches near bad patches were avoided (local risk contagion) while more distant good patches experienced increased oviposition (regional compression). Oviposition in bad patches increased when located next to good patches (reward contagion) or when there were no good patches regionally present (regional compromise). This complex colonisation behaviour involving compromises at different spatial scales forces experimenters to reconsider the independence of spatial replicates and challenges available theories to predict species distribution patterns.
Translating olfactomes into attractants: shared volatiles provide attractive bridges for polyphagy in fruit flies
Authors: Biasazin Tibebe Dejene , Larsson Herrera Sebastian , Kimbokota Fikira , Dekker Teun
Published: October 2018

Tephritid flies are serious fruit pests. Despite clear niche differences, many species show considerable overlap in fruit preferences, of which we here analysed the olfactory correlate. Using the volatiles of four unrelated fruit species, antennal responses were quantified to construct a fruit‐odour response database for four tephritid species. Although responses were distinct with a significant niche‐correlated bias, the analyses show that the probability of detection of a volatile strongly increased with its sharedness across fruits. This also held for the unrelated fruit fly Drosophila melanogaster (DoOR repository‐based analyses). We conjectured that shared volatiles signify ‘host’ to the fly ‘nose’ and induce attraction. Indeed, blends of volatiles shared by fruit and detected by all four species were very attractive for tephritid species, more than fruits. Quantitative whole antennal recordings en lieu of, or complementing bottom‐up molecular neurogenetic approaches, enables comparative olfactomics in non‐model species, and facilitate interpretation of olfaction in evolutionary, ecological, and applied contexts.
Imaging biomarkers of behavioral impairments: A pilot micro–positron emission tomographic study in a rat electrical post–status epilepticus model
Authors: van Dijk R. Maarten , Di Liberto Valentina , Brendel Matthias , Waldron Ann Marie , Möller Christina , Gildehaus Franz Josef , von Ungern‐Sternberg Barbara , Lindner Magdalena , Ziegler Sibylle , Hellweg Rainer , Gass Peter , Bartenstein Peter , Potschka Heidrun
Published: October 2018

Objective

In patients with epilepsy, psychiatric comorbidities can significantly affect the disease course and quality of life. Detecting and recognizing these comorbidities is central in determining an optimal treatment plan. One promising tool in detecting biomarkers for psychiatric comorbidities in epilepsy is positron emission tomography (PET).

Methods

Behavioral and biochemical variables were cross‐correlated with the results from two μPET scans using the tracers [18F]fluoro‐2‐deoxy‐D‐glucose ([18F]FDG) and 2′‐methoxyphenyl‐(N‐2′‐pyridinyl)‐p‐18F‐fluoro‐benzamidoethylpiperazine ([18F]MPPF) to explore potential biomarkers for neurobehavioral comorbidities in an electrically induced post–status epilepticus rat model of epilepsy.

Results

In rats with epilepsy, μPET analysis revealed a local reduction in hippocampal [18F]FDG uptake, and a local increase in [18F]MPPF binding. These changes exhibited a correlation with burrowing as a “luxury” behavior, social interaction, and anxiety‐associated behavioral patterns. Interestingly, hippocampal [18F]FDG uptake did not correlate with spontaneous recurrent seizure activity.

Significance

In the electrically induced post–status epilepticus rat model, we demonstrated hippocampal hypometabolism and its correlation with a range of neurobehavioral alterations. These findings require further confirmation in other preclinical models and patients with epilepsy and psychiatric disorders to address the value of [18F]FDG uptake as an imaging biomarker candidate for psychiatric comorbidities in patients as well as for severity assessment in rodent epilepsy models.
Traumatic Home: Argentinian Victimhood and the Everyday Moral Comfort of Trauma
Authors: van Roekel Eva
Published: October 2018

The renewed anthropological debate on morality has invoked the idea that local moralities can be analyzed through the phenomenological arrangement of moral breakdown, which is followed by a liminal period of performing ethics that reinstates the unreflective moral disposition (i.e., home) of everyday life. The ethnographic example of the heterogeneous group of Argentinian victims of the last military dictatorship (1976–83) illustrates how ongoing ethical performance about trauma produces a reflective way of engaging with and in the world. These ongoing ethical performances are coined as “traumatic home” and constitute an everydayreflectivemoral disposition. From this local perspective, trauma is an intrinsic aspect of being alive that needs ongoing verbalization and reflection. The enduring traumas become expressible and meaningful by means of ongoing, shared practices of truth telling and informal therapies. Thus, by ongoing expression, trauma also becomes an influential source for everyday moral comfort.
Effects of mesenchymal stem cell therapy on alopecia areata in cellular and hair follicle organ culture models
Authors: Kim Jung Eun , Oh Jee Hye , Woo Young Jun , Jung Ji Hee , Jeong Kwan Ho , Kang Hoon
Published: October 2018

Mesenchymal stem cell therapy (MSCT) has been suggested as a new therapeutic strategy for immunological disorders. There have been only a few attempts to treat alopecia areata (AA) with MSCT. MSCT efficacy and mechanism of action in treating AA are not known. We sought to investigate the effect of human hematopoietic mesenchymal stem cells (hHMSCs) on an in vitro model of AA and to explore relevant mechanisms that regulate efficacy. An AA‐like environment was induced by pretreatment of human dermal papilla cells (hDPCs) with interferon gamma (IFN‐γ). hHMSCs were administered to the hDPCs, and cell viability was determined. Similar studies were also conducted with human hair follicles (HFs) in culture. The change in expression of the Wnt/β‐catenin pathway and JAK/STAT pathway‐related molecules and growth factors in hHMSC‐treated hDPCs was also examined by reverse transcription‐PCR, Western blot assay and growth factor array. Immune privilege–related molecules were examined by immunohistochemistry in HF culture models. hHMSCs enhanced the cell viability of the hDPCs. hHMSCs activated several molecules in the Wnt/β‐catenin signalling pathway, including ß‐catenin and phosphorylated GSK3b, and decreased IFN‐γ‐induced expression of DKK1 in hDPCs. hHMSCs suppressed IFN‐γ‐induced expression of caspase‐1, caspase‐3 and IFN‐γ receptor. hHMSCs induced the phosphorylation of STAT1 and STAT3 compared to controls and IFN‐γ–pretreated hDPCs. hHMSC‐treated HFs enhanced several growth factor mRNAs. hHMSC pretreatment modulated IFN‐γ–induced expression of molecules related to HF immune privilege on HFs in organ culture. These data suggest MSCT may be a new potential therapeutic option in treating AA.
Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?
Authors: Zhang Hanqian , Ericsson Maja , Weström Simone , Vahlquist Anders , Virtanen Marie , Törmä Hans
Published: October 2018

Autosomal recessive congenital ichthyosis (ARCI) is a group of monogenic skin disorders caused by mutations in any of at least 12 different genes, many of which are involved in the epidermal synthesis of ω‐O‐acylceramides (acylCer). AcylCer are essential precursors of the corneocyte lipid envelope crosslinked by transglutaminase‐1 (TGm‐1), or a yet unidentified enzyme, for normal skin barrier formation. We hypothesized that inactivating TGM1 mutations will lead to a compensatory overexpression of the transcripts involved in skin barrier repair, including many other ARCI‐causing genes. Using microarray, we examined the global mRNA expression profile in skin biopsies from five ARCI patients with TGM1 mutations and four healthy controls. There were a total of 599 significantly differentially expressed genes (adjusted P < 0.05), out of which 272 showed more than 1.5 log2fold‐change (FC) up‐ or down‐regulation. Functional classification of the latter group of transcripts showed enrichment of mRNA encoding proteins mainly associated with biological pathways involved in keratinocyte differentiation and immune response. Moreover, the expression of seven out of twelve ARCI‐causing genes was significantly increased (FC = 0.98‐2.05). Also, many of the genes involved in keratinocyte differentiation (cornified envelope formation) and immune response (antimicrobial peptides and proinflammatory cytokines) were upregulated. The results from the microarray analysis were also verified for selected genes at the mRNA level by qPCR and at the protein level by semi‐quantitative immunofluorescence. The upregulation of these genes might reflect a compensatory induction of acylCer biosynthesis as a part of a global barrier repair response in the patient′s epidermis.
Senescent fibroblasts in melasma pathophysiology
Authors: Kim Misun , Kim So Min , Kwon Soohyun , Park Tae Jun , Kang Hee Young
Published: October 2018

It has been proposed that melasma is a photoageing skin disorder. The photoaged fibroblasts have been suggested as an important source of melanogenic factors which are involved in the regulation of pigmentation. To investigate whether melasma includes senescent cells, lesional and perilesional normal skin from 38 melasma patients was assessed using a cell senescence marker, p16INK4A. The results showed that lesional dermal skin had more p16INK4A‐positive senescent cells than perilesional skin. The impact of senescent fibroblasts was further investigated in a pilot study using radiofrequency (RF) intervention for melasma. It showed that the RF therapy decreased the number of senescent cells with increased expression of procollagen‐1, which were associated with reduced epidermal pigmentation. This leads us to the speculation that senescent fibroblasts may contribute to drive melasma and might be considered as a potential therapeutic target.
Soil water dynamics, herbage production and water use efficiency of three tropical grasses: Implications for use in a variable summer‐dominant rainfall environment, Australia
Authors: Murphy Sean R. , Boschma Suzanne P. , Harden Steven
Published: October 2018

In the moist mid‐latitudes of eastern Australia, soil water dynamics, herbage production and water use efficiency (WUE) were monitored during 2006–2008, for five perennial pastures: digit grass (Digitaria eriantha), Rhodes grass (Chloris gayana), forest bluegrass (Bothriochloa bladhii), native grass (Bothriochloa macra and Rytidosperma bipartita dominant), lucerne (Medicago sativa); and two forage crops: oat (Avena fatua) and sorghum (Sorghum bicolor). Ground cover formed more quickly in Rhodes grass and lucerne (>70% ground cover in 120 and 175 days after sowing [DAS] respectively) than in forest bluegrass and digit grass (245 and 365 DAS respectively). Values of maximum extractable water (MEW) for Rhodes grass and lucerne were similar (180–242 mm), while values for digit grass and forest bluegrass (129–175 mm) were equal to or greater than those for native grass, and two annual forage crops (77–144 mm). Lucerne expressed the maximum root depth (1.46 m), while values for the tropical grasses (0.96–1.39 m) were greater than native grasses and forage crops (0.87–0.96 m). Native grasses (6.5–12 t DM/ha) had the lowest herbage production, which resulted in values of WUE that were significantly less than most other treatments (16–21 vs. 23–43 kg DM ha−1 mm−1). Digit grass (33–34 kg DM ha−1 mm−1) had higher WUE compared with the other tropical grasses (20–27 kg DM ha−1 mm−1). The data collected here suggest that a forage system comprising digit grass, lucerne and forage oat would provide high production and WUE in this environment.
Historiography of heresy: The debate over “Catharism” in medieval Languedoc
Authors: Shulevitz Deborah
Published: October 2018

Whether or not a dualist Cathar heresy existed in medieval Europe has been widely debated among medieval historians over the past twenty years. Historians taking the traditional view hold that reports of a dualist heresy in various places and at different times during the High Middle Ages evidence a pan‐European, institutional, counter‐church. This church, many have argued, was influenced by dualism emanating from the Balkans and possibly reaching back to Late Antiquity. A recent generation of skeptics challenges this story, claiming that what was perceived as a dualist heresy was actually a manifestation of dissidence arising out of local conditions and, in any case, tied to anticlericalism and the enthusiasms of the Gregorian reform. The alleged dualism, they argue, derives from contemporary critics' readings of the patristic sources they consulted in attempting to understand dissidence. These two historiographical camps do not agree on the facts, the terminology, or the proper interpretation of sources, making it very difficult to discuss medieval heresy. This paper seeks to familiarize historians with the state of the debate over heresy in medieval Languedoc by describing and critiquing the positions of the two sides and suggests that the controversy provides an important lesson to students of history.
1H NMR and Raman spectroscopy of oils and extracts obtained from organic and conventional goji berries: yield, fatty acids, carotenoids and biological activities
Authors: Pedro Alessandra Cristina , Bach Fabiane , Stafussa Ana Paula , Menezes Leociley Rocha Alencar , Barison Andersson , Maciel Giselle Maria , Haminiuk Charles Windson Isidoro
Published: October 2018

The yields of extraction, fatty acid and carotenoid compositions, antioxidant and antimicrobial activities of organic and conventional Lycium barbarum oils and extracts were investigated. Different methods were used in the extraction: Soxhlet, maceration and Bligh & Dyer. Sample characterization was performed by proton nuclear magnetic resonance and Raman spectroscopy. Soxhlet presented a higher yield for organic (4.58%) and conventional (2.83%) fruit. The Goji samples showed a high content of unsaturated fatty acids (UFA) for organic (78.29–84.72%) and conventional (70.74–80.20%) fruit. The main phytochemicals identified in the samples were linoleic acid and zeaxanthin dipalmitate. The maceration method was the most efficient in the extraction of carotenoids with high antioxidant (2.23–40.94 mmolTE 100 g−1) and antimicrobial (3.12–200 mg mL−1) activities. The organic goji samples showed higher yield, UFA, carotenoids and biological activities and these results indicate that this fruit is suitable for cosmetic, pharmaceutical and food applications.
Recent advances in upper tract urothelial carcinomas: From bench to clinics
Authors: Shao I‐Hung , Chang Ying‐Hsu , Pang See‐Tong
Published: October 2018

Urothelial carcinoma in the upper tract is rare and often discussed separately. Many established risk factors were identified for the disease, including genetic and external risk factors. Radiographic survey, endoscopic examination and urine cytology remained the most important diagnostic modalities. In localized upper tract urothelial carcinomas, radical nephroureterectomy with bladder cuff excision are the gold standard for large, high‐grade and suspected invasive tumors of the renal pelvis and proximal ureter, whereas kidney‐sparing surgeries should be considered in patients with low‐risk disease. Advances in technology have given endoscopic surgery an important role, not only in diagnosis, but also in treatment. Although platinum‐based combination chemotherapy is efficacious in advanced or metastatic disease, current established chemotherapy regimens are toxic and lack a sustained response. Immune checkpoint inhibitors have led to a new era of treatment for advanced or metastatic urothelial carcinomas. The remarkable results achieved thus far show that immunotherapy will likely be the future treatment paradigm. The combination of immune checkpoint inhibitors and other agents is another inspiring avenue to explore that could benefit even more patients. With respect to the high incidence rate and different clinical appearance of upper tract urothelial carcinomas in Taiwan, a possible correlation exists between exposure to certain external risk factors, such as arsenic in drinking water and aristolochic acid in Chinese herbal medicine. As more gene sequencing differences between upper tract urothelial carcinomas and various disease causes are detailed, this has warranted the era of individualized screening and treatment for the disease.
The effect of TiO2 additions on CaO–MgO–Al2O3–SiO2 (CMAS) crystallization behavior from the melt
Authors: Webster Rebekah I. , Opila Elizabeth J.
Published: October 2018

Titania (TiO2) was introduced into a model calcium‐magnesium aluminosilicate (CMAS) glass in additions of 5‐20 wt%. The crystallization behavior of the mixtures was characterized over a series of temperature profiles and compared to that of CMAS alone. X‐ray diffraction, differential scanning calorimetry, light and scanning electron microscopy, and energy dispersive spectroscopy were used to characterize glass and crystalline products. Titania additions in the amount of approximately 12.5‐20 wt% aided in the formation of CaTiO3 from melts equilibrated at either 1300 or 1500°C and cooled at 10°C/min. Holding CMAS + TiO2 (TiO2 ≥ 10 wt%) at 900°C after cooling from 1300/1500°C resulted in the formation of additional crystalline phases including melilite, paqueite, and diopside. Implications for CMAS interactions with thermal and environmental barrier coatings are discussed.
3‐Cl‐AHPC inhibits pro‐HGF maturation by inducing matriptase/HAI‐1 complex formation
Authors: Ye Fang , Chen Shuang , Liu Xingxing , Ye Xiaohong , Wang Keqi , Zeng Zhiping , Su Ying , Zhang Xiao‐kun , Zhou Hu
Published: October 2018

Matriptase is an epithelia‐specific membrane‐anchored serine protease, and its dysregulation is highly related to the progression of a variety of cancers. Hepatocyte growth factor activator inhibitor‐1 (HAI‐1) inhibits matriptase activity through forming complex with activated matriptase. The balance of matriptase activation and matriptase/HAI‐1 complex formation determines the intensity and duration of matriptase activity. 3‐Cl‐AHPC, 4‐[3‐(1‐adamantyl)‐4‐hydroxyphenyl]‐3‐chlorocinnamic acid, is an adamantly substituted retinoid‐related molecule and a ligand of retinoic acid receptor γ (RARγ). 3‐Cl‐AHPC is of strong anti‐cancer effect but with elusive mechanisms. In our current study, we show that 3‐Cl‐AHPC time‐ and dose‐ dependently induces matriptase/HAI‐1 complex formation, leading to the suppression of activated matriptase in cancer cells and tissues. Furthermore, 3‐Cl‐AHPC promotes matriptase shedding but without increasing the activity of shed matriptase. Moreover, 3‐Cl‐AHPC inhibits matriptase‐mediated cleavage of pro‐HGF through matriptase/HAI‐1 complex induction, resulting in the suppression of pro‐HGF‐stimulated signalling and cell scattering. Although 3‐Cl‐AHPC binds to RARγ, its induction of matriptase/HAI‐1 complex is not RARγ dependent. Together, our data demonstrates that 3‐Cl‐AHPC down‐regulates matriptase activity through induction of matriptase/HAI‐1 complex formation in a RARγ‐independent manner, providing a mechanism of 3‐Cl‐AHPC anti‐cancer activity and a new strategy to inhibit abnormal matriptase activity via matriptase/HAI‐1 complex induction using small molecules.
5‐Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy
Authors: Kornicka Katarzyna , Szłapka‐Kosarzewska Jolanta , Śmieszek Agnieszka , Marycz Krzysztof
Published: October 2018

Obesity and endocrine disorders have become prevalent issues in the field of both human and veterinary medicine. Equine metabolic syndrome is a complex disorder involving alternation in metabolism and chronic systemic inflammation. It has been shown that unfavourable microenvironment of inflamed adipose tissue negatively affects adipose stem cell population (ASC) residing within, markedly limiting their therapeutic potential. ASCsEMS are characterized by increased senescence apoptosis, excessive accumulation of reactive oxygen species (ROS), mitochondria deterioration and “autophagic flux.” The aim of the present study was to evaluate whether treatment of ASCsEMS with a combination of 5‐azacytydine (AZA) and resveratrol (RES) would reverse aged phenotype of these cells. For this reason, we performed the following analyzes: molecular biology (RT‐PCR), microscopic (immunofluorescence, TEM) and flow cytometry (JC‐1, ROS, Ki67). We evaluated the mitochondrial status, dynamics and clearance as well as autophagic pathways. Furthermore, we investigated epigenetic alternations in treated cells by measuring the expression of TET genes and analysis of DNA methylation status. We have demonstrated that AZA/RES treatment of ASCsEMS is able to rejuvenate these cells by modulating mitochondrial dynamics, in particular by promoting mitochondrial fusion over fission. After AZA/RES treatment, ASCsEMS were characterized by increased proliferation rate, decreased apoptosis and senescence and lower ROS accumulation. Our findings offer a novel approach and potential targets for the beneficial effects of AZA/RES in ameliorating stem cell dysfunctions.
Nupharidine enhances Aggregatibacter actinomycetemcomitans clearance by priming neutrophils and augmenting their effector functions
Authors: Levy Dan Henry , Chapple Iain L. C. , Shapira Lior , Golan‐Goldhirsh Avi , Gopas Jacob , Polak David
Published: October 2018

Objectives

Nupharidine (6,6′‐Dihydroxythiobinupharidine), purified from the aquatic plant Nuphar lutea leaves (Water lily) prompts antimicrobial activity of immune cells. The aim of the study was to test the effect of Nupharidine on neutrophil function against Aggregatibacter actinomycetemcomitans, JP2 clone (Aa‐JP2).

Methods

Neutrophils derived from the human cell line HL60 and human peripheral blood derived from aggressive periodontitis and periodontally healthy subjects were incubated with Nupharidine or vehicle and inoculated with JP2. Bacterial survival was tested using viable counts on blood agar (CFU's). Neutrophils’ necrosis/apoptosis, reactive oxygen species (ROS) production, phagocytosis and neutrophil extracellular traps (NET) production following infection were tested, as well as markers of neutrophil priming.

Results

Nupharidine had no direct bactericidal effect on JP2, but it enhanced Aa‐JP2 clearance by neutrophils. Nupharidine enhanced neutrophil phagocytosis, ROS production and NET formation during JP2 infection. Furthermore, Nupharidine enhanced the expression of certain markers of neutrophils priming, specifically iCAM1, DECTIN‐2 and intracellular IL‐1β.

Conclusion

Nupharidine was shown to promote neutrophil effector bactericidal functions, boosting Aa‐JP2 clearance. The results point to the potential of Nupharidine as an adjunctive agent in the treatment of Aa‐JP2 periodontitis, but this should be tested initially using pre‐clinical and clinical studies.
Nature of aflatoxins: Their extraction, analysis, and control
Authors: Tahir Nasir Ishaque , Hussain Shabbir , Javed Mohsin , Rehman Hajira , Shahzady Tanzeela Gulab , Parveen Bushra , Ali Kalsoom Ghulam
Published: October 2018

Aflatoxins gain entry into food products when proper drying, storage, and transport conditions are not applied. They comprise of closely related compounds for example, aflatoxins B1, B2, G1, G2, M1, and M2. The order of toxicity among aflatoxis is B1 > G1 > B2 > G2. In developing countries, the serious illness and deaths are common due to acute aflatoxicosis and human children are more prone to their attack. Chronic aflatoxicosis affects on animal nutrition status. Aflatoxins are commonly extracted from foodstuffs by liquid–liquid extraction, supercritical fluid extraction, and solid phase extraction. They are analyzed by thin layer chromatography, high‐performance liquid chromatography (HPLC), HPLC‐mass spectrometry and UV‐Visible spectroscopy. They demonstrate high stability within food or feed stuffs and can be removed by physical, chemical, and biological means. Physical approaches use heat, sunlight, UV light, gamma rays, or adsorption phenomenon while chemical methods involve various fungicides, herbal plant extracts, oxidizing/hydrolytic/chlorinating agents, or clay. Biological approaches involve either probiotic and yeast mixtures or atoxigenic fungi. A proper detoxification procedure ensures the nutritional value of food/feed stuffs and does not generate new carcinogenic, mutagenic, or toxic substances. Consideration of hygienic precautions and technical assistance, implementation of regulatory initiatives, and stricter quality control measures are all important for their control.

Practical applications

Aflatoxins are toxic metablotics produced primarily by means of fungal species. Cereals, spices, nuts, grapes, apples, dried fruit, dried vegetables (peas, beans), oil seeds, teas, cocoa, and coffees are commonly infected aflatoxins. Their presence in an animal diet severely affects the kidneys, liver, rate of growth and reproduction, serious illness, and even death. The aflatoxin problem is more common in developing countries. The present work highlights the physical and chemical nature of aflatoxins, various types of aflatoxicosis, and the strategies used for their control; their control methods have been correlated with the environmental conditions. Attempts have also been made to discuss the techniques used for their detection, extraction, identification, analysis, and characterization.
Grey matter differences associated with age and sex hormone levels between premenopausal and perimenopausal women: A voxel‐based morphometry study
Authors: Lu Weizhao , Guo Wei , Hou Kun , Zhao Huihui , Shi Liting , Dong Kejiang , Qiu Jianfeng
Published: October 2018

The present study aimed to explore brain morphological alterations associated with age and sex hormone levels between premenopausal and perimenopausal women using magnetic resonance imaging (MRI) T1‐weighted structural images. Thirty‐two premenopausal women aged (mean ± SD) 47.75 ± 1.55 years and twenty‐five recently perimenopausal women aged 51.60 ± 1.63 years were evaluated for sex hormone levels, including prolactin, follicle‐stimulating hormone, luteinising hormone, oestradiol, free testosterone and progesterone. A 3.0‐Tesla MRI scanner was utilised to acquire T1 images. Voxel‐based morphometry (VBM) was used to evaluate changes in grey matter volume between the two groups. The general linear model was applied with false discovery rate correction for between group voxel‐wise statistics. Spearman partial correlation analyses were conducted between age, sex hormone levels and regions of grey matter volume showing significant differences between the two groups. The VBM analysis revealed that age and menopause per se lead to grey matter volume reduction in certain brain structures. These structural changes might be potential causes of sexual dysfunction, nervous system degeneration and depression, which need to be examined in future studies. Our findings might provide evidence and guide future research in understanding the menopausal transition.
Melatonin‐mediated downregulation of ZNF746 suppresses bladder tumorigenesis mainly through inhibiting the AKT‐MMP‐9 signaling pathway
Authors: Chen Yen‐Ta , Yang Chih‐Chao , Shao Pei‐Lin , Huang Chi‐Ruei , Yip Hon‐Kan
Published: October 2018

There still lacking effective treatment for bladder cancer. This study investigated whether melatonin (Mel) can suppress the growth and invasion of bladder cancer cells. Male C57B/L6 mice were categorized into control group (ie, subcutaneous injection of HT1197 bladder cancer cell line at the back] and treatment group [subcutaneous HT1197 cells + intraperitoneal Mel (100 mg/kg/d) from day 8 to day 21 after tumor cell injection]. In vitro Mel suppressed cell growth of four bladder cancer cell lines (ie, T24, RT4, HT1197, HT1376), cell migration in HT1197/HT1376, mitochondrial membrane potential (MMP) in T24 and colony formation in RT4 cells as well as arrested the cell cycle at G0 phase and inhibited the mitotic phase of T24 cells (all P < 0.0001). Protein expression of ZNF746 in RT4/T24 cells and protein expression phosphorylated (p)‐AKT/MMP‐2/MMP‐9 in HT1197/HT1376 cells were reduced following Mel treatment (all P < 0.001). Transfection of T24 cells with plasmid‐based shRNA (ie, ZNF746‐silencing) downregulated the protein expression of MMP‐9, cell growth, and invasion and attachment to endothelial cells but upregulated the colony formation (all P < 0.001). Mel suppressed oxidative stress and MMP but upregulated mitochondria mass in ZNF746‐silenced T24 cells, whereas these parameters exhibited a similar patter to Mel treatment in ZNF746‐silenced T24 cells (all P < 0.0001). In vivo study demonstrated that Mel treatment significantly suppressed cellular expressions of MMP‐9/MMP‐2, protein expressions of ZNF746/p‐AKT, and tumor size (all P < 0.001). Mel treatment suppressed the growth, migration, and invasion of bladder carcinoma cells through downregulating ZNF746‐regulated MMP‐9/MMP‐2 signaling.