bluuebunny/crossref_metadata_2025 huggingface dataset:
Good + Bad = ? Developmental Differences in Balancing Gains and Losses in Value‐Based Decisions From Memory
Authors: Horn Sebastian S. , Mata Rui , Pachur Thorsten
Published: January 2019

Value‐based decisions often involve comparisons between benefits and costs that must be retrieved from memory. To investigate the development of value‐based decisions, 9‐ to 10‐year olds (N = 30), 11‐ to 12‐year olds (N = 30), and young adults (N = 30) first learned to associate gain and loss magnitudes with symbols. In a subsequent decision task, participants rapidly evaluated objects that consisted of combinations of these symbols. All age groups achieved high decision performance and were sensitive to gain–loss magnitudes, suggesting that required core cognitive abilities are developed early. A cognitive‐modeling analysis of performance revealed that children were less efficient in object evaluation (drift rate) and had longer nondecision times than adults. Developmental differences, which emerged particularly for objects of high positive net value, were linked to mnemonic and numerical abilities.
Exploration of the role of anti‐Mullerian hormone and LH/FSH ratio in diagnosis of polycystic ovary syndrome
Authors: Le Minh Tam , Le Viet Nguyen Sa , Le Dinh Duong , Nguyen Vu Quoc Huy , Chen Chen , Cao Ngoc Thanh
Published: January 2019

Objective

This study explores the role of anti‐Mullerian hormone (AMH) and LH/FSH ratio in diagnosis of polycystic ovary syndrome (PCOS).

Methods

In this multicentre cross‐sectional descriptive study, a total of 863 infertile women between 18 and 45 years were evaluated at three infertility centres in Vietnam and were recruited from June 2016 to June 2017. The patients were classified into two groups: Group I included 441 patients with PCOS (based on Rotterdam criteria consensus) and Group II included 422 non‐PCOS women. Diagnosis of PCOS was established based on Rotterdam 2003 consensus, and exclusion criteria were ovarian disease (ovary cyst/tumour), history of ovarian surgery and ovarian failure.

Results

At an optimum cut‐off level of 32.79 pmol/L, AMH showed sensitivity and specificity of 78.50% and 75.83%, respectively, with the AUC 0.852 (95% CI: 0.826‐0.875). The LH/FSH ratio had a similar AUC at the optimum cut‐off of 1.33 (AUC = 0.867, 95% CI 0.842‐0.889), which demonstrated a similar diagnosis value to AMH (P = 0.340). By using multiple logistic regression analysis, 1 ng/mL increase in AMH levels was associated with an increased risk of PCOS (OR = 1.63, 95% CI: 1.506‐1.764; P < 0.001). Similarly, one unit increase in LH/FSH ratio was associated with 14.433 times increased (95% CI: 9.302‐22.395; P < 0.001) risk of PCOS. There were no significant differences between values of AMH and LH/FSH ratio in PCOS diagnosis, as the difference between the two AUCs was 0.013, 95% CI: −0.024 to 0.028 and P = 0.897.

Conclusion

The value of serum AMH concentration has been found not significantly superior to LH/FSH ratio in PCOS diagnosis. Although these biomarkers separately are not adequate for PCOS diagnosis based on their own value, the combination of different endocrine factors including AMH, LH and LH/FSH ratio together with BMI and other anthropometric and clinical characteristics may offer extra value to establish the diagnosis of PCOS.
Priority areas for conservation of Old World vultures
Authors: Santangeli Andrea , Girardello Marco , Buechley Evan , Botha Andre , Minin Enrico Di , Moilanen Atte
Published: January 2019

The prosperity and well‐being of human societies relies on healthy ecosystems and the services they provide. However, the biodiversity crisis is undermining ecosystems services and functions. Vultures are among the most imperiled taxonomic groups on Earth, yet they have a fundamental ecosystem function. These obligate scavengers rapidly consume large amounts of carrion and human waste, a service that may aid in both disease prevention and control of mammalian scavengers, including feral dogs, which in turn threaten humans. We combined information about the distribution of all 15 vulture species found in Europe, Asia, and Africa with their threats and used detailed expert knowledge on threat intensity to prioritize critical areas for conserving vultures in Africa and Eurasia. Threats we identified included poisoning, mortality due to collision with wind energy infrastructures, and other anthropogenic activities related to human land use and influence. Areas important for vulture conservation were concentrated in southern and eastern Africa, South Asia, and the Iberian Peninsula, and over 80% of these areas were unprotected. Some vulture species required larger areas for protection than others. Finally, countries that had the largest share of all identified important priority areas for vulture conservation were those with the largest expenditures related to rabies burden (e.g., India, China, and Myanmar). Vulture populations have declined markedly in most of these countries. Restoring healthy vulture populations through targeted actions in the priority areas we identified may help restore the ecosystem services vultures provide, including sanitation and potentially prevention of diseases, such as rabies, a heavy burden afflicting fragile societies. Our findings may guide stakeholders to prioritize actions where they are needed most in order to achieve international goals for biodiversity conservation and sustainable development.
Serum cardiac troponin elevation predicts mortality in patients with pulmonary hypertension: A meta‐analysis of eight cohort studies
Authors: Xu Shuang‐Lan , Yang Jiao , Zhang Chun‐Fang , Xu Shuang‐Yan , Zhao Fang‐Yun , Liu Li‐Qiong , Xie Chun‐Lin , Xing Xi‐Qian , Zhu Yun
Published: January 2019

Objective

To determine the association of serum cardiac troponin (cTn) with the mortality of pulmonary hypertension (PH) patients via a meta‐analysis.

Date Source

We searched PubMed and EMBASE from inception to October 25, 2017.

Study Selection

The reference lists of the retrieved articles were also consulted. The Q test and I2 test were used for to assess heterogeneity. The relationship between cTn elevation and mortality was analysed. Studies were stratified according to type of troponin (cTnT vs cTnI), region (Europe vs America) and follow‐up length (≤3 years vs >3 years).

Results

Eight studies with 739 patients were included in the meta‐analysis. Cardiac troponin elevation ranged from 14.3% to 94.5%. Overall, 48.8% (39/80) of patients with elevated cTn died compared to 18.6% (45/242) of patients with normal cTn levels. These findings showed cTn elevation was significantly related to an increased mortality risk in PH patients [hazard ratio (HR) = 3.05, 95% confidence interval (95% CI) = 2.16‐4.32, I2 = 24.9%]. cTnI was better at predicting mortality than cTnT (HR = 3.37, 95%CI = 2.05‐5.55 vs HR = 2.80, 95%CI = 1.97‐3.98, respectively). American populations had increased mortality compared to European populations (HR = 4.23, 95%CI = 2.29‐7.80 vs HR = 2.70, 95% CI = 1.95‐3.74, respectively). This finding was independent of the follow‐up length of the studies (≤3 years: HR = 2.36, 95%CI = 1.65‐3.38; >3 years: HR = 4.55, 95%CI = 2.80‐7.39).

Conclusions

Although different studies detected the expression cTnT or cTnI by various methods, the mortality in the cTn‐positive group was higher than that in the cTn‐negative group. Serum cTn elevation emerged as an independent predictor of increased risk of mortality in PH patients.
Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women
Authors: Chen Peizhu , Hou Xuhong , Wei Li , Feng Liang , Zhong Lichang , Jiao Lei , Wang Hongmei , Bao Yuqian , Jia Weiping
Published: January 2019

Background

The association between nonalcoholic fatty liver disease (NAFLD) and free triiodothyronine (FT3) in euthyroid subjects was in dispute. We aimed to investigate this issue in a population‐based cohort study.

Materials and methods

A total of 3144 euthyroid subjects at baseline from the Shanghai Nicheng Atherosclerosis Study were selected for the cross‐sectional analysis, and 2089 subjects being followed up after 2.2 years were selected for the longitudinal analysis. NAFLD was diagnosed by ultrasound. The cut‐off point of elevated alanine aminotransferase (ALT) level was 40 U/L. The FIB‐4 index was used to assess the risk of advanced liver fibrosis.

Results

Age‐adjusted mean levels of FT3 and FT3/free thyroxine (FT4) ratio were higher in subjects with NAFLD than those without NAFLD and linearly increased with a higher risk of NAFLD progression (assessed by levels of ALT and FIB‐4 index) in euthyroid women but not in men. After adjustment for confounding variables, FT3 levels significantly increased with the presence of NAFLD (β = 0.1, P < 0.001) and linearly increased with a higher risk of NAFLD progression in euthyroid women. After a 2.2‐year follow‐up, FT3 levels increased with the occurrence of NAFLD (mean change percentage: 1.4%) and decreased with the remission of NAFLD (mean change percentage: −2.7%) in euthyroid women.

Conclusions

There are positive associations of FT3 levels with NAFLD and the risk of NAFLD progression in euthyroid women. The changes in FT3 levels with the alteration of NAFLD status may be an adaptive response to maintain energy and metabolic homeostasis.
High prevalence of metabolic alterations in Latin American patients at initial stages of psychosis
Authors: Iruretagoyena Barbara , Castañeda Carmen P. , Undurraga Juan , Nachar Rubén , Mena Cristian , Gallardo Carlos , Crossley Nicolas A. , Gonzalez‐Valderrama Alfonso
Published: January 2019

Aim

Studies conducted in the United States have highlighted a higher prevalence of metabolic alterations (MA) in Latino population and Latino psychotic patients. Metabolic risk in psychosis is known to be present from initial stages of the disease. To better characterize this population, we explored the prevalence of MA and metabolic syndrome (MS) in early psychosis patients in a Latin American country.

Methods

Transversal, observational study comparing the prevalence of MA and MS in patients with early psychosis from an outpatient program in Chile (n = 148) with a community representative sample from the 2009‐2010 National Health Survey (n = 568). ANOVA and regression analysis were performed obtaining odds ratio for MA and MS.

Results

The prevalence of MS was 44.7% in patients compared to 11.4% in the community sample (odds ratio [OR] 5.28, confidence interval [CI] 95% 3.07‐9.08; P‐value <0.001). There was no effect of gender. Subgroup analyses showed no significant association of MS with clozapine/olanzapine use, treatment duration or tobacco use. There was an association between treatment duration and hypertriglyceridemia (P = 0.024; OR 1.02, CI 95% 1.00‐1.04) and obesity (P = 0.007; OR 5.93, CI 95% 1.82‐20.22). Clozapine/olanzapine use was associated with hyperglycaemia (P = 0.007; OR 6.04, CI 95% 1.63‐22.38) and high low density lipoprotein (P = 0.033 ANOVA; OR 5.28, CI 95% 1.14‐24.37).

Conclusion

Latino psychotic patients have a high risk of MA and MS at initial stages of the disease which is not entirely explained by the higher risk in the whole Latino population, is irrespective of gender, and does not seem to be entirely a response to atypical antipsychotic use.
Blood markers of cardiac stress after generalized convulsive seizures
Authors: Nass Robert D. , Motloch Lukas J. , Paar Vera , Lichtenauer Michael , Baumann Jan , Zur Berndt , Hoppe Uta C. , Holdenrieder Stefan , Elger Christian E. , Surges Rainer
Published: January 2019

Objective

Generalized convulsive seizures (GCS) are associated with high demands on the cardiovascular system, thereby facilitating cardiac complications. To investigate occurrence, influencing factors, and extent of cardiac stress or injury, the alterations and time course of the latest generation of cardiac blood markers were investigated after documented GCS.

Methods

Adult patients with refractory epilepsy who underwent video–electroencephalography (EEG) monitoring along with simultaneous one‐lead electrocardiography (ECG) recordings were included. Cardiac biomarkers (cardiac troponin I [cTNI]; high‐sensitive troponin T [hsTNT]; N‐terminal prohormone of brain natriuretic peptide [NT‐proBNP]; copeptin; suppression of tumorigenicity‐2 [SST‐2]; growth differentiation factor 15, [GDF‐15]; soluble urokinase plasminogen activator receptor [suPAR]; and heart‐type fatty acid binding protein [HFABP]) and catecholamines were measured at inclusion and at different time points after GCS. Periictal cardiac properties were assessed by analyzing heart rate (HR), HR variability (HRV), and corrected QT intervals(QTc).

Results

Thirty‐six GCS (6 generalized‐onset tonic–clonic seizures and 30 focal to bilateral tonic–clonic seizures) were recorded in 30 patients without a history of cardiac or renal disease. Postictal catecholamine levels were elevated more than twofold. A concomitant increase in HR and QTc, as well as a decrease in HRV, was observed. Elevations of cTNI and hsTNT were found in 3 of 30 patients (10%) and 6 of 23 patients (26%), respectively, which were associated with higher dopamine levels. Copeptin was increased considerably after most GCS, whereas SST‐2, HFABP, and GDF‐15 displayed only subtle variations, and suPAR was unaltered in the postictal period. Cardiac symptoms did not occur in any patient.

Significance

The use of more sensitive biomarkers such as hsTNT suggests that signs of cardiac stress occur in about 25% of the patients with GCS without apparent clinical symptoms. SuPAR may indicate clinically relevant troponin elevations. Copeptin could help to diagnose GCS, but specificity needs to be tested.
Searching for serum protein markers of equine squamous gastric disease using gel electrophoresis and mass spectrometry
Authors: Tesena P. , Yingchutrakul Y. , Roytrakul S. , Taylor J. , Angkanaporn K. , Wongtawan T.
Published: January 2019

Background

Equine squamous gastric disease (ESGD) is a very common disorder but an accurate and practical screening technique for detecting ESGD is currently lacking.

Objectives

To identify serum protein markers to detect ESGD using electrophoresis and mass spectrometry.

Study design

Proteomic analysis and bioinformatics.

Methods

ESGD was diagnosed using gastroscopy in 30 horses. Gastric ulceration was categorised into three groups: normal, mild/moderate and severe ESGD. Pooled sera from each group were compared using 1D electrophoresis and mass spectrometry. The candidate proteins for ESGD markers were selected based on their specifically high expression in nonglandular stomach, and their association with gastric ulceration using public gene and protein databases.

Results

The prevalence of ESGD in this study was 43% (with mild/moderate ESGD at 33% and severe ESGD at 10%). The proteomic study revealed that the identified serum protein markers for normal equine stomach were B4GALNT2 and XDH. The marker for mild/moderate EGSD was KRT10, while the marker for severe ESGD was KLK13. Furthermore, markers for both ulcer types were SLC4A7, PPARG, FCGBP, PKP1, ASPRV1 and KRT5‐like proteins.

Main limitations

The functions of the identified proteins are not well characterised in horse. Proteomics is a tool for screening protein markers, but confirmation of putative protein markers with specific antibodies is required.

Conclusions

In total, 10 serum proteins found in this study may be used as putative markers for ESGD. However, confirmation of candidate proteins with specific antibodies in a larger study cohort is necessary before it can be used in the veterinary clinic or on horse farms.

The Summary is available in Portuguese – see Supporting Information
Continuous digital hypothermia prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp model of equine laminitis
Authors: Stokes S. M. , Belknap J. K. , Engiles J. B. , Stefanovski D. , Bertin F. R. , Medina‐Torres C. E. , Horn R. , van Eps A. W.
Published: January 2019

Background

Continuous digital hypothermia can prevent the development and progression of laminitis associated with sepsis but its effects on laminitis due to hyperinsulinaemia are unknown.

Objectives

To determine the effects of continuous digital hypothermia on laminitis development in the euglycaemic hyperinsulinaemic clamp model.

Study design

Randomised, controlled (within subject), blinded, experiment.

Methods

Eight clinically normal Standardbred horses underwent laminitis induction using the euglycaemic hyperinsulinaemic clamp model (EHC). At initiation of the EHC, one forelimb was continuously cooled (ICE), with the other maintained at ambient temperature (AMB). Dorsal lamellar sections (proximal, middle, distal) were harvested 48 h after initiation of the EHC and were analysed using histological scoring (0–3) and histomorphometry. Cellular proliferation was quantified by counting epidermal cell nuclei staining positive with an immunohistochemical proliferation marker (TPX2).

Results

Severe elongation and disruption of SEL with dermo‐epidermal separation (score of 3) was observed in all AMB feet at one or more section locations, but was not observed in any ICE sections. Overall 92% of the AMB sections received the most severe histological score (grade 3) and 8% were grade 2, whereas ICE sections were classified as either grade 1 (50%) or grade 2 (50%). Relative to AMB feet, ICE sections were 98% less likely to exhibit grades 2 or 3 (OR: 0.02, 95% CI 0.001, 0.365; P<0.01). Histomorphometry measurements of total and nonkeratinised primary epidermal lamellar length were significantly increased (P<0.01) in AMB limbs compared with ICE. TPX2 positive cell counts were significantly increased (P<0.01) in AMB limbs compared with ICE.

Main limitations

Continuous digital hypothermia was initiated before recognition of laminitis and therefore the clinical applicability requires further investigation.

Conclusions

Continuous digital hypothermia reduced the severity of laminitis in the EHC model and prevented histological lesions compatible with lamellar structural failure.
Utility of ultrasound‐guided liver tumor biopsy for next‐generation sequencing‐based clinical sequencing
Authors: Eso Yuji , Kou Tadayuki , Nagai Hiroki , Kim Young Hak , Kanai Masashi , Matsumoto Shigemi , Mishima Masako , Arasawa Soichi , Iguchi Eriko , Nakamura Fumiyasu , Takeda Haruhiko , Takai Atsushi , Takahashi Ken , Ueda Yoshihide , Muto Manabu , Seno Hiroshi
Published: January 2019

Aim

Recent advances in next‐generation sequencing (NGS) technologies allow for evaluation of genetic alterations in various cancer‐related genes in daily clinical practice. Archival formalin‐fixed paraffin‐embedded (FFPE) tumor tissue is often used for NGS‐based clinical sequencing assays; however, the success rate of NGS assays using archival FFPE tumor tissue is reported to be lower than that using fresh tumor tissue. We aimed to evaluate the feasibility and safety of ultrasound (US)‐guided liver tumor biopsy for NGS‐based multiplex gene assays.

Methods

We compared the success rate of NGS assays between archival FFPE tumor tissues and US‐guided liver tumor biopsy tissues, and summarized the treatment progress of the patients.

Results

Next‐generation sequencing assays using US‐guided liver biopsy samples were successful in all patients (22/22), whereas the success rate with archival FFPE tumor tissue was 84.8% (151/178, P < 0.05). At least one potentially actionable genetic alteration was identified from the US‐guided liver biopsy samples in 20 of 22 patients. Among the 18 patients with actionable genetic alterations targetable with drugs approved by the US Food and Drug Administration, eight initiated mutation‐driven targeted therapies. Of these eight patients, four achieved partial response or stable disease for at least 4 months, and three were not assessable for response due to short exposure. There were no biopsy‐related complications requiring additional treatment.

Conclusion

Our findings suggest that US‐guided liver tumor biopsy is a useful and safe method for obtaining high‐quality samples for NGS‐based clinical sequencing. In cases with metastatic liver tumors, US‐guided biopsy should be considered to provide accurate and optimal sequencing results for patients.
Surgical breast cancer patient pathway: Experiences of patients and relatives and their unmet needs
Authors: Zøylner Ingrid Annette , Lomborg Kirsten , Christiansen Peer Michael , Kirkegaard Pia
Published: January 2019

Background and aim

Breast cancer is the most common cancer disease in women worldwide. In Denmark, the law prescribes cancer patient pathways (CPPs) in general and thus also for breast cancer. Although results from patient satisfaction surveys show overall satisfaction with the pathway, a call for improvement has been voiced for some areas. The aim of this study was to explore patients’ and relatives’ experiences with the surgical breast CPP and to identify any unmet needs.

Method

This study was based on focus groups with patients who had surgery for breast cancer, and their relatives. The settings were two Danish surgical breast cancer clinics.

Findings

Overall, patients and relatives found the structure of the surgical breast CPP satisfactory. The time in the surgical department was short, and most patients found it difficult to cope with the situation. Empathy and a supportive relationship between patients, relatives and health‐care professionals were of great importance. Five key points were identified in which some of the participants had unmet needs. Suggestions for change were related to information, communication, choice of treatment, flexibility in the pathway and easy access to the clinic after surgery.

Conclusion

Although patients and relatives found the CPP for breast cancer satisfactory and well planned, suggestions for change were made relating to unmet needs with respect to five key points in the pathway. Implementing findings from this study in clinical practice requires co‐operation between health‐care professionals and support from the leaders of the organization.
Advancing the science of unfinished nursing care: Exploring the benefits of cross‐disciplinary knowledge exchange, knowledge integration and transdisciplinarity
Authors: Jones Terry , Willis Eileen , Amorim‐Lopes Mário , Drach‐Zahavy Anat ,   On behalf of the RANCARE Consortium COST – CA 15208
Published: January 2019

Aims

The aims of this paper are to explore the role of cross‐disciplinary knowledge exchange and integration in advancing the science of unfinished nursing care and to offer preliminary guidance for theory development activities for this growing international community of scholars.

Background

Unfinished nursing care, also known as missed care or rationed care is a highly prevalent problem with negative consequences for patients, nurses and healthcare organizations around the world. It presents as a ‘wicked’ sustainability problem resulting from structural obstacles to effective resource allocation that have been resistant to conventional solutions. Research activity related to this problem is on the rise internationally but is hindered by inconsistencies in conceptualizations of the problem and lack of robust theory development around the phenomenon. A unified conceptual framework is needed to focus scholarly activities and facilitate advancement of a robust science of unfinished nursing care.

Design

Discussion paper.

Data Sources

This discussion paper is based on our own experiences in international and interdisciplinary research partnerships related to unfinished nursing care. These experiences are placed in the context of both classic and current literature related to the evolution of scientific knowledge.

Implications for Nursing

The problem of unfinished nursing care crosses multiple scientific disciplines. It is imperative that the community of scholars interested in solving this wicked problem engage in meaningful cross‐disciplinary knowledge integration and move towards transdisciplinarity.

Conclusion

Metatheorizing guided by structuration theory should be considered as a strategy to promote transdiciplinarity around the problem of unfinished nursing care.
Does late 10K filing impact companies’ financial reporting strategy? Evidence from discretionary accruals and real transaction management
Authors: Mitra Santanu , Al‐Hayale Talal , Hossain Mahmud
Published: January 2019

The study investigates how late 10K filers adapt their financial reporting strategy in the post‐late filing period in their response to bad publicity, negative market sentiment, and higher stakeholders’ scrutiny resulting from reporting delays. Both the level and change regressions show that late 10K filers significantly reduce the use of discretionary accruals from pre‐ to post‐late filing year. However, they simultaneously increase real transaction management over the same time period. The trade‐offs between the two earnings management techniques are more prominent when the late filers have a strong incentive to meet or beat earnings benchmarks. Our primary results are robust when late filings are caused by accounting, auditing, and internal control issues, and when the late filers cited no meaningful reason for late 10K filings. It is further evident that late filers with material internal control weaknesses and late filers that subsequently restate their financial statements make relatively higher trade‐offs than the matched non‐late filers. Finally, the trade‐offs between reduced accruals and increased real transaction management are stronger for the accelerated filers, and for the late filers audited by Big 4 auditors.
TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal
Authors: Li Puma Simone , Landini Lorenzo , Macedo Sergio J. , Seravalli Viola , Marone Ilaria M. , Coppi Elisabetta , Patacchini Riccardo , Geppetti Pierangelo , Materazzi Serena , Nassini Romina , De Logu Francesco
Published: January 2019

Safranal, contained in Crocus sativus L., exerts anti‐inflammatory and analgesic effects. However, the underlying mechanisms for such effects are poorly understood. We explored whether safranal targets the transient receptor potential ankyrin 1 (TRPA1) channel, which in nociceptors mediates pain signals. Safranal by binding to specific cysteine/lysine residues, stimulates TRPA1, but not the TRP vanilloid 1 and 4 channels (TRPV1 and TRPV4), evoking calcium responses and currents in human cells and rat and mouse dorsal root ganglion (DRG) neurons. Genetic deletion or pharmacological blockade of TRPA1 attenuated safranal‐evoked release of calcitonin gene‐related peptide (CGRP) from rat and mouse dorsal spinal cord, and acute nociception in mice. Safranal contracted rat urinary bladder isolated strips in a TRPA1‐dependent manner, behaving as a partial agonist. After exposure to safranal the ability of allyl isothiocyanate (TRPA1 agonist), but not that of capsaicin (TRPV1 agonist) or GSK1016790A (TRPV4 agonist), to evoke currents in DRG neurons, contraction of urinary bladder strips and CGRP release from spinal cord slices in rats, and acute nociception in mice underwent desensitization. As previously shown for other herbal extracts, including petasites or parthenolide, safranal might exert analgesic properties by partial agonism and selective desensitization of the TRPA1 channel.
Inhibition of Ctsk alleviates periodontitis and comorbid rheumatoid arthritis via downregulation of the TLR9 signalling pathway
Authors: Pan Weiyi , Yin Wuwei , Yang Li , Xue Lili , Ren Jie , Wei Wei , Lu Qiuyu , Ding Handong , Liu Zhaohui , Nabar Neel R. , Wang Min , Hao Liang
Published: January 2019

Aim

In this study, we investigate the mechanistic link between rheumatoid arthritis (RA) and periodontitis to identify a novel target (cathepsin K; Ctsk) for the treatment of comorbid periodontitis and RA.

Methods

An experimental model of periodontitis with arthritis was established in DBA/1 mice. We then tested the effect of BML‐244, a specific inhibitor of Ctsk, by quantifying several inflammatory markers of TLR9 signalling both in vivo and in vitro.

Results

Our results showed that periodontitis–rheumatoid arthritis comorbidity causes severer periodontal bone and joint cartilage destruction than either disease alone. Inhibition of Ctsk reduced infiltration by dendritic cells and T cells and inflammatory cytokine production; these improvements alleviated the hard‐tissue erosion in periodontitis and RA as measured by bone erosion in periodontal lesions and cartilage destruction in knee joints. Inhibition of Ctsk also decreased the expression of TLR4 and TLR9 in vivo, whereas in vitro experiments indicated that Ctsk is involved specifically in the production of cytokines in response to TLR9 engagement.

Conclusion

Our data reveal that periodontitis and RA may have additive pathological effects through dysregulation of the TLR9 pathway and that Ctsk is a critical mediator of this pathway and contributes to the pathogenesis of RA and periodontitis.
New insights in the link between malocclusion and periodontal disease
Authors: Bernhardt Olaf , Krey Karl‐Friedrich , Daboul Amro , Völzke Henry , Kindler Stefan , Kocher Thomas , Schwahn Christian
Published: January 2019

Aim

We aimed to investigate associations between malocclusions and periodontal disease by comparing it to that of smoking in subjects recruited from the population‐based cross‐sectional study “Study of Health in Pomerania.”

Materials and Methods

Sagittal intermaxillary relationship, variables of malocclusion and socio‐demographic parameters of 1,202 dentate subjects, 20–39 years of age, were selected. Probing depth (PD) and attachment loss (AL) were assessed at four sites by tooth in a half‐mouth design. Analyses were performed with multilevel models on subject, jaw and tooth level.

Results

Distal occlusion determined in the canine region, ectopic position of canines, anterior spacing, deep anterior overbite and increased sagittal overjet were associated with AL (p‐value <0.05). Associations between malocclusions and PD: deep anterior overbite with gingival contact (odds ratio [OR] = 1.40, 95% CI: 1.08–1.82;p‐value = 0.0101) and anterior crossbite (OR = 1.75, 95% CI: 1.29–2.38;p‐value = 0.0003). Regarding crowding, only severe anterior crowding was compatible with a moderate to large association with PD (OR = 1.93, 95% CI: 0.89–4.20). Compared to smoking, the overall effect of malocclusions was about one half for AL and one‐third for PD.

Conclusion

Malocclusions or morphologic parameters were associated with periodontal disease.
The Effect of a Geriatric Oncology Clinic on Treatment Decisions in Mexican Older Adults With Cancer
Authors: Verduzco‐Aguirre Haydeé C. , Navarrete‐Reyes Ana P. , Chavarri‐Guerra Yanin , Ávila‐Funes José A. , Soto‐Perez‐de‐Celis Enrique
Published: January 2019

OBJECTIVES

Geriatric assessment and interventions improve the care of older adults with cancer, but their effect on treatment decision making in resource‐limited settings is unknown. We studied the effect of recommendations made by a consultative geriatric oncology clinic on treatment decision making by oncologists in Mexico.

DESIGN, SETTING, AND PARTICIPANTS

Retrospective chart review of 173 consecutive patients with solid tumors referred before treatment initiation to the geriatric oncology clinic at a third‐level public hospital in Mexico City between March 2015 and October 2017. Patients were evaluated by a multidisciplinary geriatric oncology clinic, and treatment recommendations were issued to treating oncologists.

MEASUREMENTS

We determined the overall proportion of agreement between geriatric oncology recommendations and oncologists' treatment decisions. We assessed whether agreement increased when geriatric oncology recommendations were acknowledged in the treating oncologist's clinic note. The homogeneity of agreement was tested using the Stuart‐Maxwell test.

RESULTS

Median age was 79 years (range = 64‐97 years). “Standard treatment” was recommended in 48% of cases, followed by “less intensive treatment” in 32%, and “best supportive care” in 20%. The overall proportion of agreement for the entire population was 80% (κ = 0.69), although agreement was heterogeneous (X2 = 8.16, P = .02). Geriatric oncology recommendations were acknowledged in the treating oncologists' notes in 62% of cases. Overall agreement was higher when the evaluation was acknowledged (83%, κ = 0.74) than when it was not acknowledged (74%, κ = 0.60). Agreement was homogeneous only when recommendations were acknowledged in the oncologist's note (X2 = 3.0, P = .22).

CONCLUSIONS

The overall proportion of agreement between geriatric oncology recommendations and final treatment decisions was high, particularly when recommendations were acknowledged in the treating oncologists' note. Including geriatric oncology evaluations in everyday clinical practice and fostering interdisciplinary communication between geriatric oncology and treating oncologists may provide valuable guidance for physicians caring for older patients with cancer in resource‐limited settings. J Am Geriatr Soc 67:992–997, 2019.
Doppler and oscillometric mean blood pressure best represent direct blood pressure measurements in anesthetized rhesus macaques (Macaca mulatta)
Authors: Kang Stacey Carol , Jampachaisri Katechan , Pacharinsak Cholawat
Published: January 2019

Background

Indirect blood pressure measurements are often used to guide clinical decisions, but few studies have verified their agreement with direct arterial blood pressure in nonhuman primates. Here, the accuracy and precision of Doppler (DOP) and oscillometric (OS) [systolic (OSsys), mean (OSmean), and diastolic (OSdias)] blood pressure readings were assessed in rhesus macaques.

Methods

DOP and OS were utilized to measure blood pressure values in nine anesthetized rhesus macaques, which were compared to direct measurements via a saphenous arterial catheter. All measurements were taken simultaneously every 5 min for 60‐240 min.

Results

DOP and OSsys underestimated direct systolic arterial pressure with a bias ± precision of 10.21 ± 6.37 mmHg and 11.67 ± 11.55 mmHg, respectively. OSmean correlated well with direct mean arterial pressure with a bias ± precision of 7.25 ± 7.35 mmHg.

Conclusions

DOP provided the better representation of systolic blood pressure, and OSmean provided a useful representation of mean arterial pressure in anesthetized rhesus macaques.
Clinical efficacy of herbal extract cream on the skin hydration, elasticity, thickness, and dermis density for aged skin: A randomized controlled double‐blind study
Authors: Roh Seok Seon , Choi Inhwa , Kim Hyung‐Min , Lee Myeong Soo , Jin Mu‐Hyun , Kim Byung Hyun , Hwang Seung‐Jin , Kim Min Hee
Published: January 2019

Background

Traditional medicine herbal prescriptions used for the treatment of skin disease have been developed into cosmetics. Sang‐Hyul‐Yun‐Boo‐Em (SHYBE) is a mixed herbal formula prescribed for patients with yin or blood deficiency patterns of skin disease. A previous study reported that SHYBE exercises anti‐allergic and anti‐inflammatory effects. To date, no study has reported the efficacy of cosmetics containing the SHYBE extract.

Aims

To observe the efficacy of SHYBE extract cream on hydration, elasticity, thickness, and dermis density in aged skin.

Methods

This was a double‐blind randomized placebo‐controlled parallel‐group trial. The trial consisted of an 8‐week topical application of the test or placebo products with two visits at 4‐week intervals. A total of 46 healthy Korean females, aged 40‐59, were enrolled in this study. Objective skin assessments for hydration, elasticity, thickness and dermis density, self‐assessment, and safety assessment were conducted.

Results

Sang‐Hyul‐Yun‐Boo‐Em extract cream improved skin hydration, elasticity, and dermal density in Asian middle‐aged females compared with placebo cream, which excluded SHYBE extract and contained other cosmetic materials.

Conclusions

Sang‐Hyul‐Yun‐Boo‐Em extract cream showed anti‐aging properties in middle‐aged women. It could be recommended for aging skin with dryness, and loss of elasticity and density.
Global periorbital skin rejuvenation by a topical eye cream containing low molecular weight heparan sulfate (LMW‐HS) and a blend of naturally derived extracts
Authors: Colvan Lora , Fleck Tina , Vega Virginia L.
Published: January 2019

Background

Maintaining a youthful appearance is a priority for many people. Global eye rejuvenation is sought more frequently and at a younger age than other treatments. Major concerns around the eye area are periorbital hyperpigmentation, puffiness, and lines and wrinkles. Glycosaminoglycans (GAGs) are complex carbohydrates that modulate skin health, repair and renew skin's appearance. Heparan sulfate (HS) is the most biologically active GAG, although it is too large and polar to penetrate the skin. Low Molecular Weight Heparan Sulfate (LMW‐HS) is a smaller version of HS designed for skin penetration while preserving its activity. In this study, we investigated the effects of a topical eye cream containing LMW‐HS and a blend of naturally derived extracts to address global periorbital rejuvenation.

Method

A single‐center, open‐label study including female and male subjects (n = 15) was conducted to evaluate the efficacy and tolerability of an eye cream containing LMW‐HS and a blend of naturally derived extracts applied twice daily for 12 weeks.

Results

Improvements in the appearance of periorbital hyperpigmentation and fine and coarse wrinkles were observed as early as week 2 with continuous improvement up to 12 weeks. Decrease in puffiness (73%) and dark circles (93%) were reported by subjects. The test product was highly rated by subjects on performance and attributes and was well tolerated by all the subjects in this study.

Conclusion

Results demonstrated that an eye cream containing LMW‐HS and a blend of naturally derived extracts achieved global skin rejuvenation by improving appearance of periorbital hyperpigmentation, puffiness, and fine and coarse wrinkles.
Effectiveness and safety of hyaluronic acid fillers used to enhance overall lip fullness: A systematic review of clinical studies
Authors: Stojanovič Larisa , Majdič Neža
Published: January 2019

Background

The majority of aesthetic treatments today are nonsurgical or minimally invasive aesthetic procedures. Soft‐tissue augmentation with hyaluronic acid (HA) is one of them. Lip fullness and definition are key aesthetic factors associated with attractiveness, which is the reason that lip augmentation with HA fillers has become so popular.

Objective

To provide a systematic review of published medical literature on the effectiveness and safety of different HA fillers used to enhance overall lip fullness.

Methods and materials

The literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Twenty‐two studies were included in the qualitative synthesis, 9 of them with level of evidence (LOE) 1b (randomized controlled trials), 1 with LOE 2b (individual cohort study), and 12 with LOE 4 (case series, poor‐quality cohort, and case‐control studies). A total number of subjects included in all studies were 3965.

Results

Hyaluronic acid fillers turned out to be an effective and safe treatment. The assessment methods (especially for efficacy) varied greatly from one study to another. Observed responses to the treatment in studies using different lip fullness scales varied between 71% and 93.2%. The most common adverse events were local reactions at the injection sites (swelling, contusion, bruising, pain, redness, and itching).

Conclusion

Based on the results of the studies included in this systematic review, HA fillers are effective and safe to use. The majority of included subjects were satisfied with the result and their looks.
Mon2 predicts poor outcome in ST‐elevation myocardial infarction
Authors: Shantsila E. , Ghattas A. , Griffiths H. R. , Lip G. Y. H.
Published: January 2019

Aims

There are limited data on the role of human monocyte subsets in ST‐elevation myocardial infarction (STEMI). The study aimed to establish the relationship between monocyte subsets, their phagocytic and nuclear factor κB (NFκB) activity and outcomes in STEMI.

Methods

Monocyte subsets and their phagocytic activity and intracellular levels of inhibitory κB kinase β (IKKβ, marker of NFκB activity) were measured by flow cytometry in 245 patients with STEMI, median follow‐up of 46 months.

Results

Mon2 (CD14++CD16+CCR2+) counts were independently predictive of major adverse cardiovascular events (MACE) [4th quartile HR 3.42 (95% CI 1.43–8.16), P = 0.006 and 3rd quartile HR 2.88 (95% CI 1.19–7.00), P = 0.02 vs. 1st quartile]. Mon2 subset was the only subset associated with higher occurrence of heart failure (4th quartile vs. 1st quartile, sevenfold, P = 0.001 on univariate analysis; fivefold, P = 0.04 on multivariable analysis). On receiver operating characteristic, analysis including of Mon2 improved prognostic value of troponin T and creatine kinase for MACE and heart failure (HF). Higher intracellular Mon2 IKKβ levels were associated with 10‐fold lower occurrence of HF on multivariable analysis (4th vs. 1st quartiles, P = 0.03). Abnormal Mon1 and Mon2 phagocytic capacities were related to HF development, but the association was dependent on the infarct size and other prognosticators. High Mon2 levels were associated with lower ejection fraction after STEMI onset (P = 0.001) and at 6‐month follow‐up (P < 0.001).

Conclusions

Abnormal Mon2 characteristics have a unique association with poor outcome in patients with STEMI. The relation of Mon2 with occurrence of HF is strongly and independently related to their functional status, which may have potential therapeutic implications.
MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma
Authors: Ivanidze Jana , Lum Mark , Pisapia David , Magge Rajiv , Ramakrishna Rohan , Kovanlikaya Ilhami , Fine Howard A. , Chiang Gloria C.
Published: January 2019

BACKGROUND AND PURPOSE

Telomerase reverse transcriptase (TERT) promoter mutations are associated with worse prognosis in glioblastoma. The purpose of this study was to evaluate whether TERT mutation status was associated with specific morphologic and quantitative imaging features.

METHODS

Twenty‐nine patients with isocitrate dehydrogenase 1/2‐wildtype glioblastoma (13 TERT‐wildtype, 16 TERT‐mutated), who underwent preoperative magnetic resonance (MR) imaging were included in this retrospective study. Qualitative imaging phenotypes were evaluated using the Visually Accessible Rembrandt Images (VASARIs) feature set. Histogram analysis of apparent diffusion coefficient (ADC) and dynamic contrast‐enhanced MR perfusion values were performed on enhancing tumor volumes‐of‐interest, and differences between TERT‐wildtype and TERT‐mutated tumors were assessed.

RESULTS

VASARI analysis demonstrated that the majority of morphologic features were not significantly different between TERT‐wildtype and TERT‐mutated tumors, although a higher proportion of TERT‐wildtype tumors featured nonenhancing tumor crossing midline (P = .014). TERT‐mutated tumors demonstrated lower median rate constant kep (.38 vs. .76, P = .03) and lower median volume transfer coefficient Ktrans (.13 vs. .31, P = .02). There was no significant difference in median plasma volume vp (P = .92) or ADC values (P = .66) between the two groups. We further found a significant interaction between median kep and Ktrans and TERT status, respectively, suggesting greater risk of death with increasing blood‐brain barrier dysfunction in TERT‐mutated but not in TERT‐wildtype tumors.

CONCLUSION

Our study demonstrates evidence of altered permeability metrics associated with TERT mutation in glioblastoma, laying the foundation for future prospective studies assessing implications for therapeutic management and clinical outcomes.
Treatment with direct‐acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma
Authors: Piñero Federico , Mendizabal Manuel , Ridruejo Ezequiel , Herz Wolff Fernando , Ameigeiras Beatriz , Anders Margarita , Schinoni María Isabel , Reggiardo Virginia , Palazzo Ana , Videla María , Alonso Cristina , Santos Luisa , Varón Adriana , Figueroa Sebastián , Vistarini Cecilia , Adrover Raúl , Fernández Nora , Perez Daniela , Tanno Federico , Hernández Nelia , Sixto Marcela , Borzi Silvia , Bruno Andres , Cocozzella Daniel , Soza Alejandro , Descalzi Valeria , Estepo Claudio , Zerega Alina , de Araujo Alexandre , Cheinquer Hugo , Silva Marcelo ,   LALREAN
Published: January 2019

Background & Aims

Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC.

Methods

This was a prospective multicentre cohort study from Latin America including 1400 F1‐F4‐treated patients with DAAs (F3‐F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out.

Results

During a median follow‐up of 16 months (IQR 8.9‐23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02‐0.05) at 12 months and 0.06 (CI 0.04‐0.08) at 24 months of follow‐up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non‐responder, Child‐Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%‐91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort.

Conclusions

Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.
How many came home? Evaluating ex situ conservation of green turtles in the Cayman Islands
Authors: Barbanti Anna , Martin Clara , Blumenthal Janice M. , Boyle Jack , Broderick Annette C. , Collyer Lucy , Ebanks‐Petrie Gina , Godley Brendan J. , Mustin Walter , Ordóñez Víctor , Pascual Marta , Carreras Carlos
Published: January 2019

Ex situ management is an important conservation tool that allows the preservation of biological diversity outside natural habitats while supporting survival in the wild. Captive breeding followed by re‐introduction is a possible approach for endangered species conservation and preservation of genetic variability. The Cayman Turtle Centre Ltd was established in 1968 to market green turtle (Chelonia mydas) meat and other products and replenish wild populations, thought to be locally extirpated, through captive breeding. We evaluated the effects of this re‐introduction programmme using molecular markers (13 microsatellites, 800‐bp D‐loop and simple tandem repeat mitochondrial DNA sequences) from captive breeders (N = 257) and wild nesting females (N = 57) (sampling period: 2013–2015). We divided the captive breeders into three groups: founders (from the original stock), and then two subdivisions of F1 individuals corresponding to two different management strategies, cohort 1995 (“C1995”) and multicohort F1 (“MCF1”). Loss of genetic variability and increased relatedness was observed in the captive stock over time. We found no significant differences in diversity among captive and wild groups, and similar or higher levels of haplotype variability when compared to other natural populations. Using parentage and sibship assignment, we determined that 90% of the wild individuals were related to the captive stock. Our results suggest a strong impact of the re‐introduction programmme on the present recovery of the wild green turtle population nesting in the Cayman Islands. Moreover, genetic relatedness analyses of captive populations are necessary to improve future management actions to maintain genetic diversity in the long term and avoid inbreeding depression.