bluuebunny/crossref_metadata_2025 huggingface dataset:
Does dual‐energy computed tomography pulmonary angiography (CTPA) have improved image quality over routine single‐energy CTPA?
Authors: Chen Tony , Xiao Hao
Published: December 2018

Introduction

The aim of this study is to compare the diagnostic sensitivity between dual‐energy computed tomography pulmonary angiography (CTPA) studies and routine single‐energy CTPA studies.

Methods

A total of 117 patients with clinically suspected pulmonary embolism were examined with dual‐energy CTPA (DECT) and reformatted single‐energy multidetector CTPA (MDCT) studies. Two independent radiologists assessed the image quality of the CTPAs with objective and subjective parameters, including by assigning an image quality score out of 10 for each study. Dose length product and effective dose were also calculated and compared.

Results

The subjective image quality score for DECT and MDCT studies was 9.19 and 7.88, respectively; however, the increased level of detail in DECT may not be clinically applicable. Pulmonary artery filling defects were found in 12 patients, with no subjective diagnostic differences between dual‐energy or single‐energy studies with either radiologist. The effective dose for DECT ranged from 1.8 to 7.8 mSv. The effective dose for MDCT ranged from 1.2 to 6.4 mSv.

Conclusions

Radiologists are trained to look at routine MDCTs with high specificity and sensitivity. DECTs do not appear to offer trained radiologists improved detection of clinically relevant pulmonary emboli.
Can spectral computed tomography imaging improve the differentiation between malignant and benign pulmonary lesions manifesting as solitary pure ground glass, mixed ground glass, and solid nodules?
Authors: Chen Mai‐Lin , Li Xiao‐Ting , Wei Yi‐Yuan , Qi Li‐Ping , Sun Ying‐Shi
Published: December 2018

Background

This study quantitatively assessed the efficacy of spectral computed tomography (CT) imaging parameters for differentiating the malignancy and benignity of solitary pulmonary nodules (SPNs) manifesting as ground glass nodules (GGNs) and solid nodules (SNs).

Methods

The study included 114 patients with SPNs (61 GGNs, and 53 SNs) who underwent CT plain and enhanced scans in the arterial (a) and venous (v) phases using the spectral imaging mode. The spectral CT imaging parameters included: iodine concentrations (IC) of lesions in the arterial (ICLa) and venous (ICLv) phases; normalized IC (NICa/NICv, normalized to the IC in the aorta); the slope of the spectral Hounsfield unit (HU) curve (λHUa/λHUv); and monochromatic CT number (CT40keVa/v, CT70keVa/v) enhancement on 40 and 70 keV images. The two‐sample Mann–Whitney U test was used to compare quantitative parameters between malignant and benign SPNs, SNs, and GGNs.

Results

Pathology revealed 75 lung cancer cases, 3 metastatic nodules, 14 benign nodules, and 22 inflammatory nodules. Among the 53 SNs there were 37 malignant and 16 benign nodules. Among the 61 GGNs there were 41 malignant and 20 benign nodules. Overall, the CT40keVa, λHUa, CT40keVv, λHUv, and ICLv of benign SPNs were all greater than those of malignant SPNs (all P < 0.05). For GGNs, CT40keVa/v, CT70keVa/v, λHUa/λHUv, and ICLv of malignant GGNs were all lower than those of benign GGNs.

Conclusion

Spectral CT imaging is a more promising method for distinguishing malignant from benign nodules, especially in nodules manifesting as GGNs in contrast‐enhanced scanning.
Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study
Authors: Soda Hiroshi , Ogawara Daiki , Fukuda Yuichi , Tomono Hiromi , Okuno Daisuke , Koga Seiko , Taniguchi Hirokazu , Yoshida Masataka , Harada Tatsuhiko , Umemura Asuka , Yamaguchi Hiroyuki , Mukae Hiroshi
Published: December 2018

Several recent studies have shown that salvage chemotherapy following PD‐1 blockade produces high antitumor activity in some patients with non‐small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil‐to‐lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid‐derived suppressor cells and tumor‐associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time‐series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non‐responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non‐responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD‐1 blockade and chemotherapy.
How to choose an antidepressant medication
Authors: Bayes A. , Parker G.
Published: December 2018

Objective

We consider how to choose an antidepressant (AD) medication for the treatment of clinical depression.

Method

A narrative review was undertaken addressing antidepressant ‘choice’ considering a range of parameters either weighted by patients and clinicians or suggested in the scientific literature. Findings were synthesised and incorporated with clinical experience into a model to assist AD choice.

Results

Efficacy studies comparing ADs offer indicative guidance, while precision psychiatry prediction based on genetics, developmental trauma, neuroimaging, behavioural and cognitive biomarkers, currently has limited clinical utility. Our model offers guidance for AD choice by assessing first for the presence of a depressive subtype or symptom cluster and matching choice of AD class accordingly. Failing this, an AD can be chosen based on depression severity. Within‐class choice can be determined by reference to personality style, patient preference, medical or psychiatric comorbidities and side‐effect profile.

Conclusion

Clarification of AD choice would occur if medications are trialled in specific depressive subtypes rather than using the generic diagnosis of major depressive disorder (MDD). Such ‘top‐down’ methods could be enhanced by ‘bottom‐up’ studies to classify individuals according to symptom clusters and biomarkers with AD efficacy tested in these categories. Both methods could be utilised for personalised AD choice.
Children aged 0–16 admitted to Swedish intensive care units and paediatric intensive care units showed low mortality rates
Authors: Larsson Viksten Jessica , Engerström Lars , Steinvall Ingrid , Samuelsson Anders , Fredrikson Mats , Walther Sten , Sjöberg Folke B.
Published: December 2018

Aim

This study described the basic characteristics of children aged 0–16 years who were treated in intensive care units (ICUs) and paediatric ICUs (PICUs), compared their outcomes and examined any causes of death.

Methods

This was a retrospective cohort study of admissions to 74 ICUs and three PICUs in Sweden that were recorded in the Swedish Intensive Care Registry from January 1, 2008 to December 31, 2012.

Results

We retrieved data on 12 756 children who were admitted 17 003 times. The case mix differed between the ICUs, which were mainly admissions for injuries, accidents and observation, and PICUs, which were mainly admissions for malformations, genetic abnormalities and respiratory problems (p < 0.001). The median stays in the ICUs and PICUs were 1.4 and 3.5 days (p < 0.001), respectively. The respective crude mortality rates were 1.1% and 2.0, and the Paediatric Index of Mortality version 2 standardised mortality ratios were 0.43 and 0.50. None of these differences were significant. Most deaths were within 24 hours: About 57% in the ICUs, mainly from brain anomalies, and 13% in the PICUs, mainly from circulatory problems.

Conclusion

Sweden had a low mortality rate in both ICUs and PICUs and the children admitted to these two types of unit differed.
27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice
Authors: Zhang Xiaona , Xi Yuandi , Yu Huiyan , An Yu , Wang Ying , Tao Lingwei , Wang Yushan , Liu Wen , Wang Tao , Xiao Rong
Published: December 2018

The oxysterol 27‐hydroxycholesterol (27‐OHC) has been considered to play a key role in the pathogenesis of Alzheimer’s disease (AD). Because β‐amyloid peptide (Aβ) is the pathological hallmark of AD, the aim of this study is to verify whether 27‐OHC could lead to cognitive impairment through modulating Aβ accumulation and deposition. Regulation of Aβ metabolism was explored as the pathogenic mechanism of 27‐OHC. Furthermore, microRNAs (miRNAs) and their relations with 27‐OHC were also detected. In present study, matched case‐control study and APP/PS1 transgenic mice research were conducted. The results showed that the 27‐OHC and Aβ in plasma were increased in mild cognitive impairment patients, and a slight correlation was found between 27‐OHC and Aβ1‐40. This relationship was also proved by the research of APP/PS1 mice. More severe learning and memory impairment and higher Aβ1‐40 expression in brain and plasma were detected in the APP/PS1 mice of 27‐OHC treatment group. In addition, increased amyloid plaques were also found in the hippocampus of 27‐OHC‐treated mice. In order to find out the mechanism of 27‐OHC on regulating Aβ metabolism, the factors of Aβ production (APP, BACE1 and ADAM10), transport (LRP1 and RAGE) and elimination (NEP and IDE) were tested respectively. The gene and protein expressions of APP, BACE1 and RAGE were increased while LRP1 and IDE were decreased in the brain of 27‐OHC‐treated mice. At last, down‐regulated expression of miRNA let‐7g‐5p was found after 27‐OHC treatment. In conclusion, these findings suggested that excessive 27‐OHC could enhance the accumulation and deposition of Aβ both in brain and blood, resulting in a severe impairment of cognition, especially in the modulation of Aβ1‐40. The mechanism might be associated with the regulation of Aβ metabolism, and miRNA let‐7g‐5p was likely to play a vital role in this pathological process induced by 27‐OHC.
Oxaprozin: A new hope in the modulation of matrix metalloproteinase 9 activity
Authors: Ianni Andrea , Celenza Giuseppe , Franceschini Nicola
Published: December 2018

Oxaprozin (4,5‐diphenyl‐2‐oxazolepropionic acid) is a non‐steroidal, analgesic and antipyretic propionic acid derivative, whose activity in treating inflammatory disorders is well known. The aim of this study was to investigate the ability of oxaprozin to modulate the activity of matrix metalloproteinase 9 (MMP‐9), a zinc‐dependent endopeptidase involved in a wide range of physiological and pathological events associated with extracellular matrix (ECM) remodelling. The interaction between oxaprozin and MMP‐9 was firstly investigated in silico by molecular docking and analysis with LIGPLOT software. Subsequently, the potential inhibitory activity of oxaprozin against MMP‐9 and the possible mechanism of the ligand–enzyme interaction were investigated in vitro. Taking into account the in silico findings, MMP‐9 can be considered a potential target of oxaprozin, which seems to be able to chelate the catalytic zinc ion through the nitrogen of the oxazole ring and the carboxylate moiety. Moreover, one of the phenyl rings interact with the S1′ inhibitor‐binding pocket through hydrophobic interaction. Gelatin zymography and enzymatic inhibition assay confirmed the potential role of oxaprozin as a competitive inhibitor of MMP‐9. These observations sound particularly interesting if we consider the pathological role of MMP‐9, especially evident in inflammatory conditions and cancer. This work may represent a starting point to improve the understanding of the role of oxaprozin, as well as its structural analogues, in modulating the MMP‐9 function.
Insight into the selective mechanism of phosphoinositide 3‐kinase γ with benzothiazole and thiazolopiperidine γ‐specific inhibitors by in silico approaches
Authors: Zhu Jingyu , Li Kan , Xu Lei , Jin Jian
Published: December 2018

The phosphoinositide 3‐kinase γ (PI3Kγ) has been verified to be a potential drug target for the treatments of various human physical disorders. Although received lots of attention, the development of PI3Kγ‐selective inhibitors is still a challenging subject because of its unique protein structural features. Aiming to uncover the interaction mechanism between the selective inhibitors and PI3Kγ, a series of benzothiazole and thiazolopiperidine PI3Kγ isoform‐selective inhibitors were studied with an integrated in silico strategy by combining molecular docking, molecular dynamic simulations, binding free energy calculations, and decomposition analysis. Firstly, three molecular docking models, including rigid receptor docking, induced fit docking (IFD), and quantum mechanical‐polarized ligand docking, were respectively, built, and the IFD preliminarily predicted the docking poses of all studied inhibitors and roughly analyzed the binding mechanism. Secondly, four binding complexes with representative inhibitors were selected to perform molecular dynamic simulations and free energy calculations. The predicted binding energies were consistent with the experimental bioactivities and different binding patterns between potent and weak inhibitors were uncovered. Finally, through the Molecular Mechanics/Generalized Born Surface Area binding free energy decomposition, residue–inhibitor interactions spectra were obtained and several key residues contributing to favorable binding were highlighted, which provides valuable information for rational PI3Kγ inhibitor design and modification.
Neuroblastoma‐like schwannoma with giant rosette: A potential diagnostic pitfall for hyalinizing spindle cell tumor
Authors: Koubaa Mahjoub Wafa , Jouini Raja , Khanchel Fatma , Ben Brahim Ehsen , Llamas‐Velasco Mar , Helel Imen , Khayat Olfa , Chadli Aschraf , Badri Talel , Mentzel Thomas
Published: December 2018

Neuroblastoma‐like schwannoma (NLS) is a rare variant of a common tumor. The aim of this study is to discuss, through a literature review, the differential diagnoses of NLS while emphasizing the importance of ancillary studies.

So far, 24 cases have been reported. We describe an additional case in a 64‐year‐old woman who had a 3‐cm subcutaneous tumor on her flank. The histological examination showed an encapsulated neoplasm. Most of the tumor was made of giant rosettes. These rosettes had several sizes reaching 2.6 mm. They showed a palisade of rounded cells. Nuclei were hyperchromatic but bland. The center was made of eosinophilic cores of collagenous radiating fibrils. Neoplastic cells stained strongly for S‐100 protein. In the capsule, perineural cells stained for epithelial membrane antigen (EMA). No expression of Mucin 4 (MUC4) was present. This was consistent with NLS. The same peculiar appearance of giant rosettes has been described in hyalinizing spindle cell tumor with giant rosettes (HSCT). We propose the term “neuroblastoma‐like schwannoma” when there are small rosettes, “HSCT‐like schwannoma” for tumors with giant rosettes and “collagen‐rich schwannoma” when there are “ill‐defined” structures reminiscent of rosettes. Immunohistochemical panel containing S100, EMA, and MUC4, as well as molecular testing when needed should be performed.
Pilomatrical carcinosarcoma of the temple: A case report
Authors: Mori Daisuke
Published: December 2018

Pilomatrical carcinosarcoma is a very rare entity, with only six cases reported until now. This report describes the case of a 100‐year‐old woman with a mass on the left temple that had existed for several decades but had recently grown in size. Histology showed an asymmetric lesion composed of basaloid cells, spindle cells, and “shadow” or “ghost” cells. Cells had atypical hyperchromatic nuclei with prominent nucleoli, high mitotic activity, and atypical mitosis. In the central area, an epidermal cyst‐like structure was seen. The diagnosis of pilomatrical carcinosarcoma was rendered. This case appeared to have arisen from malignant transformation of a pilomatricoma because of the long clinical history and existence of a benign epidermal cyst‐like structure. In addition, the observation that the basaloid cells and spindle cells showed a gradual transition from one to the other and that both types were positive for β‐catenin would seem to support a common clonal origin for the carcinomatous and sarcomatous components.
Morphological awareness predicts the growth rate of Chinese character reading
Authors: Lin Dan , Sun Huilin , McBride Catherine
Published: December 2018

In this longitudinal study, we assessed 88 Hong Kong Chinese typically developing kindergarteners' Chinese character reading accuracy four times with 6‐month intervals over 1.5 years with the first testing point in the fall of the second year of kindergarten (K2), during which morphological awareness, phonological awareness, orthographic awareness, visual–spatial relationships, and nonverbal IQ were tested (Time 1). The latent growth curve modeling showed that reading development in Chinese of typically developing kindergarteners followed a cumulative linear trajectory, suggesting that children with higher initial reading ability develop reading ability at a faster rate. Additionally, morphological awareness at K2 positively and uniquely predicted a linear growth pattern of character reading between K2 and K3 over 1.5 years, a period in which formal teaching and learning Chinese takes place in Hong Kong. Contributing to the literature, these findings highlighted the unique significance of morphological awareness in the growth rate of reading: Typically developing children with better early morphological awareness tend to have a higher initial point of reading ability and, more importantly, a faster growth rate, resulting in a wider discrepancy of developmental outcomes between low‐ and high‐ performers. The results suggest that greater attention should be focused on the development of morphological awareness in early readers, given its salient role in Chinese reading development.
Long‐term cannabidiol treatment in patients with Dravet syndrome: An open‐label extension trial
Authors: Devinsky Orrin , Nabbout Rima , Miller Ian , Laux Linda , Zolnowska Marta , Wright Stephen , Roberts Claire
Published: December 2018

Objective

Add‐on cannabidiol (CBD) significantly reduced seizures associated with Dravet syndrome (DS) in a randomized, double‐blind, placebo‐controlled trial: GWPCARE1 Part B (NCT02091375). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or a second placebo‐controlled trial, GWPCARE2 (NCT02224703), were invited to enroll in a long‐term open‐label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient‐reported outcomes from GWPCARE5.

Methods

Patients received a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2‐week period, with their existing medications. Based on response and tolerance, CBD could be reduced or increased up to 30 mg/kg/d.

Results

By November 2016, a total of 278 patients had completed the original randomized trials, and 264 (95%) enrolled in this open‐label extension. Median treatment duration was 274 days (range 1‐512) with a mean modal dose of 21 mg/kg/d, and patients received a median of 3 concomitant antiepileptic medications. Adverse events (AEs) occurred in 93.2% of patients and were mostly mild (36.7%) or moderate (39.0%). Commonly reported AEs were diarrhea (34.5%), pyrexia (27.3%), decreased appetite (25.4%), and somnolence (24.6%). Seventeen patients (6.4%) discontinued due to AEs. Twenty‐two of the 128 patients from GWPCARE1 (17.2%), all taking valproic acid, had liver transaminase elevations ≥3 times the upper limit of normal. In patients from GWPCARE1 Part B, the median reduction from baseline in monthly seizure frequency assessed in 12‐week periods up to week 48 ranged from 38% to 44% for convulsive seizures and 39% to 51% for total seizures. After 48 weeks of treatment, 85% of patients/caregivers reported improvement in the patient's overall condition on the Subject/Caregiver Global Impression of Change scale.

Significance

This trial shows that long‐term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment‐resistant DS.
Comment on: Mass Fractions of Forty‐Six Major and Trace Elements, Including Rare Earth Elements, in Sediment and Soil Reference Materials Used in Environmental Studies. Fiket et al. (2017), Geostandards and Geoanalytical Research, 41, 123–135
Authors: Roje Vibor
Published: December 2018

This paper is intended to be a constructive discussion of Fiket et al. (2017, Geostandards and Geoanalytical Research, 41, 123–135), who dealt with the determination of major, trace and rare earth elements in several sediment and soil certified reference materials. In the present author's view, the paper by Fiket et al. (2017) suffers from a lack of reference to several publications in which somewhat similar results had already been reported. The present contribution therefore provides a comparison of previously published results with those of Fiket et al. for the CRMs soil NCS DC 77302 (GBW 07410), stream sediment NCS DC 73309 (GBW 07311), marine sediments MESS‐3 and NCS DC 75301 (GBW 07314) and estuarine sediment IAEA‐405. It is argued that this fuller consideration (a) allows critical evaluation of the quality of the results presented by Fiket et al. and (b) highlights the advantages of their work. Finally, attention is drawn to the (possible or real) problems that can arise during simultaneous determination of multiple trace elements.
Surface Water‐Groundwater Interaction in the Guanzhong Section of the Weihe River Basin, China
Authors: Kong Feihe , Song Jinxi , Zhang Yan , Fu Guobin , Cheng Dandong , Zhang Guotao , Xue Ying
Published: December 2018

As a crucial agricultural and economic development zone since the Qin Dynasty (221 to 206 BC), the Guanzhong section of the Weihe River basin is facing serious water resource shortages due to population growth and regional development. Its water resource amount per capita is only 361 m3, about 1/6 of the average in China and less than 1/20 of the average in the world. Surface water and groundwater (SW‐GW) interaction, having a significant influence on the spatiotemporal distribution of water resources, was qualitatively and quantitatively investigated during a wet year based on stable isotopes and hydrochemistry. The results show that the recharge pattern in the north part varies with season, that is, 40% of the surface water recharge comes from groundwater in the dry season, but 93% of the groundwater recharge comes from surface water in the rainy season. In the south part, groundwater is always recharged by surface water, with contributions of 47% and 61% in the rainy and dry seasons, respectively. For the main stream, the recharge pattern is complicated and varies with season and site. This study will provide useful information about SW‐GW interaction at basin scale. Integrated management of groundwater and surface water could improve the efficiency of regional water resources utilization and promote accurate and sustainable water management in the semi‐arid basin.
Dental condition and salivary characteristics in Vietnamese patients with chronic kidney disease
Authors: Pham Thuy A. V. , Le Dinh D.
Published: December 2018

Objectives

To determine the dental status and salivary characteristics and to analyse the correlation between creatinine clearance with DMFT index and salivary flow rate in Vietnamese patients with chronic kidney disease (CKD).

Methods

This study was conducted on 111 CKD and 109 non‐CKD patients. The socio‐demographic characteristics associated with dental habits and xerostomia status were recorded from a self‐administered questionnaire. Dental status (DT, MT, FT) and salivary characteristics (flow rate; pH; buffering capacity; urea and creatinine concentrations) were examined. The multivariate regression models were used to assess the correlation of creatinine clearance with DMFT index and salivary flow rate with adjustment for confounders.

Results

Patients with CKD made MT and DMFT indices significantly higher than non‐CKD subjects. Chronic kidney disease patients had reduced salivary flow rate; but higher xerostomia level, salivary pH and buffering capacity than those in non‐CKD subjects. Results of multivariate regression models showed that with lower creatinine clearance 1 mL/min, DMF index was higher 0.02 teeth, and salivary flow rate lower 0.003 mL/min.

Conclusions

There were no differences in dental status between patients with CKD and those without CKD, except that poor renal function is directly related with a higher DMFT index and lower salivary flow rate. Dental professionals should pay greater attention to oral problems during the progression of CKD to prevent deterioration of oral health.
Treatment of peri‐implant mucositis with a chitosan brush—A pilot randomized clinical trial
Authors: Wohlfahrt Johan Caspar , Aass Anne M. , Koldsland Odd C.
Published: December 2018

Objective

This aim of this study was to evaluate a chitosan brush for the treatment of peri‐implant mucositis.

Materials and methods

A total of 11 patients with a combined total of 24 dental implants and who were diagnosed with peri‐implant mucositis were included in this 6‐month, split mouth, pilot clinical trial. Implants were randomly assigned to either treatment with a chitosan brush using an oscillating dental hand piece or treatment with titanium curettes. Supportive treatment was provided at 3 months. Two calibrated periodontists, blinded to treatment group, performed all examinations, including probing pocket depths (PPD) and bleeding on probing (mBoP). The changes in clinical parameters were compared between groups at 2 weeks, 4 weeks and 6 months. A Mann‐Whitney U test with an alpha level of 0.05 was used for the statistical analyses.

Results

Both groups demonstrated significant reductions in mBoP between baseline and 6 months. The test implants treated with the chitosan brush had a better improvement in mBoP at 2 weeks and 4 weeks compared to the implants treated with the titanium curettes. The reduction in PPD was significantly better in the test group at 4 weeks. All implants had stable bone levels, as seen on radiographs between baseline and 6 months.

Conclusion

Reduced signs of inflammation were seen in both groups 6 months after the baseline treatment and 3 months after maintenance. A chitosan brush seems to be a safe and efficient device for debridement of dental implants.
Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67high) thymocytes
Authors: Ghosh Sayan , Choudhury Sreetama , Mukherjee Sudeshna , Gupta Payal , Chowdhury Olivia , Baral Rathindranath , Chattopadhyay Sreya
Published: December 2018

Inappropriate functioning of the immune system is observed during sustained systemic inflammation, which might lead to immune deficiencies, autoimmune disorders and cancer. Primary lymphoid organs may progress to a deregulated proliferative state in response to inflammatory signals in order to intensify host defense mechanisms and exacerbate an inflammatory niche. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been projected as an anti‐inflammatory agent. This study had been designed to evaluate the potential novel role of fluoxetine in reversing inflammation‐induced immune dysfunction. Lipopolysaccharide (LPS) administration in Swiss albino mice potentiated a systemic inflammatory response, along with increased proliferation of thymocytes and peripheral blood mononuclear cells, as evident from increased Ki‐67 expression. The proliferative changes in the immune system were mainly associated with increased phosphorylation of PI3k, AKT and IκB along with elevated NFκB‐p65 nuclear translocation. The Ki‐67high thymocytes obtained from LPS administered mice demonstrated significantly low p53 nuclear activity, which was established to be mediated by NFκB through reduced nuclear translocation of p53 during LPS‐induced proliferative conditions, thereby blocking p53‐dependent apoptosis. Fluoxetine supplementation not only reversed the proinflammatory condition, but also induced selective apoptosis in the proliferation‐dictated Ki‐67high thymocytes possibly by modulating the hypothalamus–pituitary–adrenal axis and inducing glucocorticoid receptor activation and apoptosis in these proliferation‐biased immune cells, authenticating a novel antiproliferative role of an established drug.
Association between socioeconomic status and incident atrial fibrillation
Authors: Ramkumar Satish , Ochi Ayame , Yang Hong , Nerlekar Nitesh , D’Elia Nicholas , Potter Elizabeth L. , Murray Isabella C. , Nattraj Nishee , Wang Ying , Marwick Thomas H.
Published: December 2018

Background

Low socioeconomic status is associated with cardiovascular diseases, and an association with atrial fibrillation (AF) could guide screening.

Aim

To investigate if indices of advantage/disadvantage (IAD), index of education/occupation (IEO) and index of economic resources were associated with incident AF, independent of risk factors and cardiac function.

Methods

We studied community‐based participants aged ≥65 years with AF risk factors (n = 379, age 70 ± 4 years, 45% men). The CHARGE‐AF score (a well validated AF risk score) was used to assess 5‐year risk of developing AF. Participants also had baseline echocardiograms. IAD, IEO and index of economic resources were obtained from the 2011 Socio‐Economic Indexes for Areas score, in which higher decile ranks indicate more advantaged areas. Patients were followed up for incident AF (median 21 (range 5–31) months), with AF diagnosed by clinical review, including 12‐lead electrocardiogram (ECG), as well as single‐lead portable ECG monitoring used to record 60 s ECG tracings five times/day for 1 week. Cox proportional hazards models were used to assess the association between socioeconomic status and incident AF.

Results

Subjects with AF (n = 50, 13%) were more likely to be male (64 vs 42%, P = 0.003) and had higher CHARGE‐AF score (median 7.1% (5.2–12.8%) vs 5.3% (3.3–8.6%), P < 0.001). Areas with lower socioeconomic status (IAD and IEO) had a higher risk of incident AF independent of LV function and CHARGE‐AF score (hazard ratio for IAD 1.16, 95% confidence interval 1.05–1.29, P = 0.005 and hazard ratio for IEO 1.18, 95% confidence interval 1.07–1.30, P = 0.001).

Conclusion

Regional socioeconomic status is associated with risk of incident AF, independent of LV function and clinical risk. This association might permit better regional targeting of prevention.
Sustained fasting glucose oxidation and postprandial lipid oxidation associated with reduced insulin dose in type 2 diabetes with sodium–glucose cotransporter 2 inhibitor: A randomized, open‐label, prospective study
Authors: Kanazawa Ken , Uchino Hiroshi , Shigiyama Fumika , Igarashi Hiroyuki , Ikehara Kayoko , Yoshikawa Fukumi , Usui Shuki , Miyagi Masahiko , Yoshino Hiroshi , Ando Yasuyo , Kumashiro Naoki , Hirose Takahisa
Published: December 2018

Aims/Introduction

Hyperglycemia impairs energy substrate oxidation as a result of glucotoxicity. We examined whether the reduction of plasma glucose using a sodium–glucose cotransporter 2 inhibitor, in inpatient diabetes management, has any effect on: (i) treatment period and basal–bolus dosage of insulin that achieve euglycemia; (ii) fasting/postprandial energy expenditure (EE); and (iii) energy substrate oxidation.

Materials and Methods

This was a randomized, open‐label, 7‐day prospective study. Participants were type 2 diabetes patients with hyperglycemia, aged >20 years, with glycated hemoglobin >10%, daily mean preprandial blood glucose >11 mmol/L (200 mg/dL) and no previous antidiabetic medication. A total of 18 type 2 diabetes patients were randomized (1:1) to basal–bolus insulin titration algorithm (INS) alone or INS + dapagliflozin 5 mg/day (INS/DAPA). The main outcome measures were total daily insulin dose to achieve euglycemia, as well as EE and respiratory quotient during fasting and postprandial states, measured by indirect calorimetry.

Results

The rate of euglycemia was higher in the INS/DAPA compared with INS group (100 vs 55.6%, P = 0.04), whereas the total daily dose of insulin was 19% lower and was accompanied by a decreased basal–bolus ratio (P = 0.02). Fasting and postprandial EE elevation were similar in both groups. The post‐treatment fasting respiratory quotient significantly increased in the INS/DAPA group (0.72 ± 0.05 vs 0.79 ± 0.08, P = 0.04), and the postprandial respiratory quotient elevation was abolished; the opposite trend was observed in the INS group (P < 0.02).

Conclusions

INS/DAPA sustained fasting carbohydrate oxidation, postprandial lipid‐derived EE (failed to increase carbohydrate‐derived EE) and reduced basal insulin requirement might be related to further bodyweight loss.

Clinical Trial Registry

National University Hospital Medical Information Network UMIN000018997
An Exploratory Study of the Role of Infidelity Typologies in Predicting Attachment Anxiety and Avoidance
Authors: Girard Abby , Connor Jennifer J. , Woolley Scott R.
Published: December 2018

Extradyadic involvement (EDI) is one of the greatest challenges that couples and couples therapists face. Many clinicians and researchers attempt to understand motivations for EDI; however, there is a lack of theory‐driven research to support claims of infidelity typologies. The current study explored the relationship between adult attachment dimensions of avoidance and anxiety and the attachment‐based typology proposed by Woolley (2010). Results indicate significant differences in attachment anxiety in high anxiety affair types versus low anxiety affair types. Results confirmed significant differences in mean attachment anxiety for participants endorsing multiple affairs.
Prenatal programming of stress responsiveness and behaviours: Progress and perspectives
Authors: Hamada Hirotaka , Matthews Stephen G.
Published: December 2018

Parental exposure to stress or glucocorticoids either before or during pregnancy can have profound influences on neurodevelopment, neuroendocrine function and behaviours in offspring. Specific outcomes are dependent on the nature, intensity and timing of the exposure, as well as species, sex and age of the subject. Most recently, it has become evident that outcomes are not confined to first‐generation offspring and that there may be intergenerational and transgenerational transmission of effects. There has been intense focus on the mechanisms by which such early exposure leads to long‐term and potential transgenerational outcomes, and there is strong emerging evidence that epigenetic processes (histone modifications, DNA methylation, and small non‐coding RNAs) are involved. New knowledge in this area may allow the development of interventions that can prevent, ameliorate or reverse the long‐term negative outcomes associated with exposure to early adversity. This review will focus on the latest research, bridging human and pre‐clinical studies, and will highlight some of the limitations, challenges and gaps that exist in the field.
Tumour necrosis factor α induces neuroinflammation and insulin resistance in immortalised hypothalamic neurones through independent pathways
Authors: Clemenzi Matthew N. , Wellhauser Leigh , Aljghami Makram E. , Belsham Denise D.
Published: December 2018

The links between obesity, inflammation and insulin resistance, which are all key characteristics of type 2 diabetes mellitus, are yet to be delineated in the brain. One of the key neuroinflammatory proteins detected in the hypothalamus with over‐nutrition is tumour necrosis factor (TNF)α. Using immortalised embryonic rat and mouse hypothalamic cell lines (rHypoE‐7 and mHypoE‐46) that express orexigenic neuropeptide Y and agouti‐related peptide, we investigated changes in insulin signalling and inflammatory gene marker mRNA expression after TNFα exposure. A quantitative polymerase chain reaction array of 84 inflammatory markers (cytokines, chemokines and receptors) demonstrated an increase in the expression of multiple genes encoding inflammatory markers upon exposure to 100 ng mL‐1 TNFα for 4 hours. Furthermore, neurones pre‐exposed to TNFα (50 ng mL‐1) for 6 or 16 hours exhibited a significant reduction in phosphorylated Akt compared to control after insulin treatment, indicating the attenuation of insulin signalling. mRNA expression of insulin signalling‐related genes was also decreased with exposure to TNFα. TNFα significantly increased mRNA expression of IκBα, Tnfrsf1a and IL6 at 4 and 24 hours, activating a pro‐inflammatory state. An inhibitor study using an inhibitor of nuclear factor kappa B kinase subunit β (IKK‐β) inhibitor, PS1145, demonstrated that TNFα‐induced neuroinflammatory marker expression occurs through the IKK‐β/nuclear factor‐kappa B pathway, whereas oleate, a monounsaturated fatty acid, had no effect on inflammatory markers. To test the efficacy of anti‐inflammatory treatment to reverse insulin resistance, neurones were treated with TNFα and PS1145, which did not significantly restore the TNFα‐induced changes in cellular insulin sensitivity, indicating that an alternative pathway may be involved. In conclusion, exposure to the inflammatory cytokine TNFα causes cellular insulin resistance and inflammation marker expression in the rHypoE‐7 and mHypoE‐46 neurones, consistent with effects seen with TNFα in peripheral tissues. It also mimics insulin‐ and palmitate‐induced insulin resistance in hypothalamic neurones. The present study provides further evidence that altered central energy metabolism may be caused by obesity‐induced cytokine expression.
Gray vs. White Matter Segmentation of the Conus Medullaris: Reliability and Variability in Healthy Volunteers
Authors: Yiannakas Marios C. , Liechti Martina D. , Budtarad Nuttakarn , Cullinane Patrick , Yang Xixi , Toosy Ahmed T. , Panicker Jalesh N. , Gandini Wheeler‐Kingshott Claudia A. M.
Published: December 2018

BACKGROUND AND PURPOSE

Magnetic resonance imaging (MRI)‐derived spinal cord (SC) gray and white matter (GM/WM) volume are useful indirect measures of atrophy and neurodegeneration over time, typically obtained in the upper SC. Neuropathological evidence suggests that in certain neurological conditions, early degeneration may occur as low as the sacral SC. In this study, the feasibility of GM/WM segmentation of the conus medullaris (CM) was assessed in vivo.

METHODS

Twenty‐three healthy volunteers (11 female, mean age 47 years) underwent high‐resolution 3T MRI of the CM using a 3‐dimensional fast field echo sequence. Reproducibility of the volume measurements was assessed in 5 subjects (2 female, 25‐37 years) by one rater who repeated the analysis 3 times and also with 2 additional raters working independently in order to calculate the intra‐ and interrater coefficient of variation (COV), respectively. Furthermore, the influence of age, gender, spine and SC metrics on tissue‐specific measures of the CM was investigated.

RESULTS

Volumetric CM analyses (N = 23) for the SC, GM, and WM revealed a mean (SD) total volume of CM‐TV = 1746.9 (296.7) mm3, CM‐GM‐TV = 731.2 (106.0) mm3, and CM‐WM‐TV = 1014.6 (211.3) mm3, respectively. The intra‐rater COV for measuring the CM‐TV and CM‐GM‐TV was 3.38% and 7.42%, respectively; the interrater COV was 3.43% and 10.80%, respectively. Using age, gender, spine and SC metrics in regression models substantially reduced group variability for CM‐TV, CM‐WM‐TV, and CM‐GM‐TV by up to 39.2%, 42.7%, and 21.2%, respectively.

CONCLUSIONS

The results from this study demonstrate the feasibility of obtaining tissue‐specific volume measurements in the CM by means of MRI with good reproducibility and provide normative data for future applications in neurological diseases affecting the lower SC.
Reporting of Sample Size Parameters in Randomized Controlled Trials Published in Prosthodontic Journals
Authors: Dumbrigue Herman B. , Dumbrigue Ethan C. , Dumbrigue Derek C. , Chingbingyong Marianne I.
Published: December 2018

Purpose

An important consideration in the proper planning of randomized controlled trials (RCTs) is the determination of sample size. A study may fail to answer its research question if the sample size is inadequate, while a large enough sample size may be impractical to implement. The purpose of this study is to describe the reporting of sample size methodology and parameters used in RCTs published in prosthodontic journals.

Materials and Methods

A MEDLINE search for publications categorized as RCTs was conducted for articles in The Journal of Prosthodontics and The Journal of Prosthetic Dentistry published from 2008 to 2017. The Abstract and Methodology sections of RCTs identified were reviewed, and the following data recorded: reporting of method used to calculate sample size and reporting of parameters used for sample size calculation ‐ type I error (α), type II error (β) or power, minimal clinically relevant difference (MCRD), and variability.

Results

The search strategy retrieved 96 articles; 42 met inclusion criteria for RCTs and were reviewed. Fifty percent (21) of RCTs reported how sample size was determined, but only 17% (7) of RCTs reported all 4 parameters. Type I error (α) was reported in 90% (38) of RCTs, 38% (16) reported power, while only 26% (11) and 12% (5) reported MCRD and variability, respectively.

Conclusion

Methodology and parameters used for sample size determination are inadequately reported in RCTs published in prosthodontic journals.
Influence of Primers and Additional Resin Layer on Zirconia Repair Bond Strength
Authors: Shafiei Fereshteh , Fattah Zahra , Kiomarsi Nazanin , Dashti Mohammad Hossein
Published: December 2018

Purpose

To evaluate the influence of alloy/zirconia primer and 10‐methacryloyloxydecyl dihydrogen phosphate (MDP)‐containing resin layer treatments on the shear bond strength (SBS) of composite resin to zirconia after aging.

Materials and Methods

Sixty zirconia (Y‐TZP) blocks were air‐abraded (35‐µm Al2O3) and divided into 6 experimental groups (n = 10) in terms of primer/resin layer as follows: (1) control, without any primer or resin; (2) AP, Alloy Primer; (3) ZPP, Z‐Prime Plus; (4) PL/ZPP, Z‐Prime Plus with light polymerization; (5) AP+SEB, Alloy Primer along with light‐cured bonding resin of a self‐etch adhesive system (SE Bond); and (6) ZPP+SEB, Z‐Prime Plus with SE Bond. After composite resin placement and light polymerization, the specimens were stored in distilled water (37°C for 4 months) and thermal‐cycled for 6000 cycles. The SBS was tested with a universal testing machine. Statistical analysis of the SBS data was performed with one‐way ANOVA, followed by HSD Tukey test (α = 0.05).

Results

There were significant differences between the groups (p < 0.001, F = 116.5). All the groups revealed significantly higher SBS than the control (p < 0.001). ZPP+SEB group exhibited the highest SBS (16.14 ± 2.52 MPa) and AP group the lowest SBS (7.00 ± 1.97 MPa) among experimental groups; both had significant differences with the other groups (p < 0.001). There were no significant differences between ZPP, PL/ZPP, and AP+SEB groups (p > 0.05).

Conclusions

The bond strength between zirconia ceramic and composite resin was affected by different primers/resin layer. Applying an MDP‐containing resin layer along with both primers resulted in significant enhancement of SBS. This improvement for Z‐Prime Plus was significantly higher than that of Alloy Primer.
A 30‐Year Follow‐Up of a Patient with Mandibular Complete‐Arch Fixed Implant‐Supported Prosthesis on 4 Implants: A Clinical Report
Authors: Balshi Thomas J. , Wolfinger Glenn J. , Balshi Stephen F. , Bidra Avinash S.
Published: December 2018

Mandibular complete‐arch fixed implant‐supported prostheses are recognized as one of the earliest and most popular prostheses in implant dentistry. This prosthesis was the main focus in the early era of osseointegration. Despite its widespread popularity, few clinical reports have described long‐term follow‐up greater than 10 years for this type of prosthesis. This report describes a 30‐year follow‐up of a patient who underwent treatment for a mandibular complete‐arch fixed implant‐supported prosthesis with 4 machined surfaced implants, opposing a maxillary complete denture. This report documents a variety of photographs and radiographs taken over a period of 30 years to compare bone levels at various stages of care and maintenance, including de novo bone formation underneath the distal cantilevers due to functional loading. The biologic and biomechanical response to this treatment protocol and long‐term clinical observations and prosthodontic outcome and maintenance needs are also addressed.
Distinct responses of terrestrial and epiphytic ferns and lycophytes along an elevational gradient in Southern Brazil
Authors: Nervo Michelle H. , Andrade Bianca O. , Tornquist Carlos G. , Mazurana Michael , Windisch Paulo G. , Overbeck Gerhard E.
Published: December 2018

Questions

What are the drivers that govern fern and lycophyte community composition across different elevation zones in the South Brazilian Atlantic Forest? Does explanatory power of the models increase when we consider substrate‐based life forms separately? Do terrestrial and epiphytic species respond similarly to environmental drivers?

Study site

Four distinct elevation zones of the Atlantic Rain Forest sensu stricto in northeastern Rio Grande do Sul, Brazil.

Method

Variation partitioning was used to investigate the role of climatic, edaphic and spatial variation on species composition at different spatial scales. We considered both the entire community and subsets with either only epiphytic or terrestrial species.

Results

On the broad scale, environmental variables were the most important in shaping the fern and lycophyte community composition. Edaphic filters had a more important role for the terrestrial community, and climatic filters for epiphytic species. Considering epiphytic and terrestrial species separately increased the explanatory power of the models.

Conclusions

Changes in community composition of ferns and lycophytes along an elevational gradient in the South Brazilian Atlantic Forest are primarily driven by niche processes. Ferns and lycophytes found on different substrates (epiphytic vs terrestrial species) show distinct responses to environmental factors and thus should be considered separately in ecological studies.
“FU”: One Response to the Liminal State Immigrant Youth Must Navigate
Authors: Rodriguez Darlene Xiomara , McDaniel Paul N. , Bisio Gianni
Published: December 2018

Undocumented youth experience partial integration in some institutional spaces but remain barred from others. Although they are permitted to attend and graduate from K–12 public schools, the geographic unevenness of immigration policy leads to inequitable access to higher education for undocumented youth. In this article, we examine undocumented higher education access and how an underground freedom school is providing an alternative. We apply the theoretical lens of spaces of care within the framework of geographies of care to understand the uneven legal geographies that exist and the structures that emerge to equip and empower youth to leverage their experiences with illegality.