bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute intrarenal angiotensin (1‐7) infusion decreases diabetes‐induced glomerular hyperfiltration but increases kidney oxygen consumption in the rat
Authors: Persson Patrik , Fasching Angelica , Palm Fredrik
Published: January 2019

Aim

Common kidney alterations early after the onset of insulinopenic diabetes include glomerular hyperfiltration, increased oxygen consumption and tissue hypoxia. Increased activity of the renin‐angiotensin‐aldosterone system (RAAS) has been implicated in most of these early alterations. The RAAS peptide angiotensin (1‐7) has the potential to modulate RAAS‐mediated alterations in kidney function. Thus, the aim of the present study was to determine the acute effects of angiotensin (1‐7) in the kidney of insulinopenic type 1 diabetic rat and the results compared to that of normoglycaemic controls.

Methods

Renal haemodynamics and oxygen homeostasis were measured 3 weeks after administration of streptozotocin before and after acute intrarenal infusion of angiotensin (1‐7) at a dose of 400 ng min−1.

Results

Arterial pressure and renal blood flow were similar between groups and not affected by exogenous angiotensin (1‐7). Diabetics presented with glomerular hyperfiltration, increased urinary sodium excretion and elevated kidney oxygen consumption. Angiotensin (1‐7) infusion normalized glomerular filtration, increased urinary sodium excretion, decreased proximal tubular reabsorption, and elevated kidney oxygen consumption even further. The latter resulting in tubular electrolyte transport inefficiency. Angiotensin (1‐7) did not affect tissue oxygen tension and had no significant effects in controls on any of the measured parameters.

Conclusion

Diabetes results in increased responsiveness to elevated levels of angiotensin (1‐7) which is manifested as inhibition of tubular sodium transport and normalization of glomerular filtration. Furthermore, elevated angiotensin (1‐7) levels increase kidney oxygen consumption in the diabetic kidney even further which affects tubular electrolyte transport efficiency negatively.
Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats
Authors: Laouafa Sofien , Roussel Damien , Marcouiller François , Soliz Jorge , Gozal David , Bairam Aida , Joseph Vincent
Published: January 2019

Aim

Chronic intermittent hypoxia (CIH) induces systemic (hypertension) and central alterations (mitochondrial dysfunction underlying cognitive deficits). We hypothesized that agonists of oestradiol receptors (ER) α and β prevent CIH‐induced hypertension and brain mitochondrial dysfunction.

Methods

Ovariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh), the ERα agonist propylpyraoletriol (PPT — 30 μg/kg/day) or the ERβ agonist diarylpropionitril (DPN — 100 μg/kg/day). Animals were exposed to CIH (21%‐10% FIO2 — 10 cycles/hour – 8 hours/day – 7 days) or normoxia. Arterial blood pressure was measured after CIH or normoxia exposures. Mitochondrial respiration and H2O2 production were measured in brain cortex with high‐resolution respirometry, as well as activity of complex I and IV of the electron transport chain, citrate synthase, pyruvate, and lactate dehydrogenase (PDH and LDH).

Results

Propylpyraoletriol but not DPN prevented the rise of arterial pressure induced by CIH. CIH exposures decreased O2 consumption, complex I activity, and increased H2O2 production. CIH had no effect on citrate synthase activity, but decreased PDH activity and increased LDH activity indicating higher anaerobic glycolysis. Propylpyraoletriol and DPN treatments prevented all these alterations.

Conclusions

We conclude that in OVX female rats, the ERα agonist prevents from CIH‐induced hypertension while both ERα and ERβ agonists prevent the brain mitochondrial dysfunction and metabolic switch induced by CIH. These findings may have implications for menopausal women suffering of sleep apnoea regarding hormonal therapy.
Don't forget astrocytes when targeting Alzheimer's disease
Authors: Sadick Jessica S. , Liddelow Shane A.
Published: January 2019

Astrocytes are essential for CNS health, regulating homeostasis, metabolism, and synaptic transmission. In addition to these and many other physiological roles, the pathological impact of astrocytes (“reactive astrocytes”) in acute trauma and chronic disease like Alzheimer's disease (AD) is well established. Growing evidence supports a fundamental and active role of astrocytes in multiple neurodegenerative diseases. With a growing interest in normal astrocyte biology, and countless studies on changes in astrocyte function in the context of disease, it may be a surprise that no therapies exist incorporating astrocytes as key targets. Here, we examine unintentional effects of current AD therapies on astrocyte function and theorize how astrocytes may be intentionally targeted for more efficacious therapeutic outcomes. Given their integral role in normal neuronal functioning, incorporating astrocytes as key criteria for AD drug development can only lead to more effective therapies for the millions of AD sufferers worldwide.

Linked Articles

This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc
Betulinic acid alleviates endoplasmic reticulum stress‐mediated nonalcoholic fatty liver disease through activation of farnesoid X receptors in mice
Authors: Gu Ming , Zhao Ping , Zhang Shiying , Fan Shengjie , Yang Li , Tong Qingchun , Ji Guang , Huang Cheng
Published: January 2019

Background and Purpose

The molecular mechanism for the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains elusive. Both farnesoid X receptor (FXR) signalling and endoplasmic reticulum (ER) stress contribute to the progression of NAFLD; however, it is not clear whether the actions of these two pathways are dependent on each other. Moreover, the pharmacological benefits and mechanism of betulinic acid (BA) in controlling metabolic syndrome and NAFLD are largely unknown.

Experimental Approach

A reporter assay and a time‐resolved FRET assay were used to identify BA as an agonist of the FXR. NAFLD was induced by a methionine and choline‐deficient L‐amino acid diet (MCD) and high‐fat diet (HFD). The pharmacological effects of BA (100 mg·kg−1·day−1) and potential interactions between hepatic FXR activation and ER stress pathways were evaluated by FXR silencing, Western blot and RT‐PCR analyses using control and FXR−/− mice.

Key Results

Activation of the FXR inhibited intracellular PERK/EIF2α/ATF4 and CHOP signalling, thereby alleviating hepatic ER stress, whereas FXR silencing resulted in an opposite effect. Furthermore, we identified BA as an FXR agonist that effectively attenuated the progression of NAFLD and metabolic disorders in both HFD‐ and MCD diet‐fed mice and restored the hepatocellular ER homeostasis by stimulating the FXR signalling pathway and blocking PERK/EIF2α signalling. In contrast, the effects of BA were attenuated in FXR−/− mice.

Conclusions and Implications

Our data demonstrate that pharmacological activation of the FXR by BA reduces hepatocellular ER stress and attenuates NAFLD in an animal model of hepatic steatosis.
Design and antimicrobial activities of LL‐37 derivatives inhibiting the formation of Streptococcus mutans biofilm
Authors: Chen Zhao , Yang Guang , Lu Shengsheng , Chen Daiwei , Fan Sheng , Xu Junyang , Wu Buling , He Jian
Published: January 2019

Dental plaque is closely related to the occurrence of dental caries, of which the main causative bacterium is Streptococcus mutans (S. mutans). In this study, to create potent antibiofilm agents, we chose a human antimicrobial peptide LL‐37 as our starting material and modified it by cutting it shorter and varying its charge and hydrophobicity. The results of anti‐S. mutans as well as biofilm inhibitory activity tests indicated that two derivatives, IG‐13‐1 and IG‐13‐2, were the most potent one toward both planktonic and biofilm S. mutans cells with the minimal inhibitory concentration of 5.0 μM and minimal biofilm inhibitory concentrations of 5.91 ± 0.91 μM and 7.58 ± 0.23 μM, respectively. The modes of action study showed that IG‐13‐1 and IG‐13‐2 were functioned by disrupting the bacterial membrane, causing the leakage of inner contents, thereby leading to the death of bacterial cells eventually. In addition, IG‐13‐1 and IG‐13‐2 were able to suppress the expression of proinflammatory cytokine of TNF‐α and reduce the level of nuclear transcription factor‐κB, which indicated the potential anti‐inflammatory activity of these peptides. Conclusively, this study indicated that IG‐13‐1 and IG‐13‐2 are potent peptides in both anti‐S. mutans and anti‐inflammatory activities, therefore, showing a potential application for the prevention and treatment of dental caries.
Connecting the Dots Between Past and Future: Constraints in Episodic Future Thinking in Early Childhood
Authors: Prabhakar Janani , Ghetti Simona
Published: January 2019

Preschoolers have limited capacity to use past experiences to prepare for the future. Two experiments sought to further understand these limitations. Experiment 1 (N = 42) showed that 3‐ to 4‐year olds’ difficulty performing anticipated future actions was constrained by their memory for relevant past actions, especially those including temporal information. Experiment 2 (N = 94) sought to determine whether preschoolers fail to see that past experiences can inform future‐oriented actions. When the connection between the past and future was experimentally heightened, future thinking accuracy improved, but only if preschoolers remembered past experiences. The results indicate that past recall is a prerequisite for future thinking but failure to bridge past and future further accounts for observed limitations in future thinking in early childhood.
Vasoactive intestinal peptide is required in the maintenance of immune regulatory competency of immune regulatory monocytes
Authors: Guan L , Yu D , Wu G-H , Ning H-J , He S-D , Li S-S , Hu T-Y , Yang G , Liu Z-Q , Yu H-Q , Sun X-Z , Liu Z-G , Yang P-C
Published: January 2019

Dysfunction of the immune regulatory system plays an important role in the pathogenesis of rheumatoid arthritis (RA). Vasoactive intestinal peptide (VIP) has multiple bioactivities. This study aims to investigate the role of VIP in the maintenance of the immune regulatory capacity of monocytes (Mos). Human peripheral blood samples were collected from RA patients and healthy control (HC) subjects. Mos and CD14+ CD71–CD73+CD25+ regulatory Mos (RegMos) were isolated from the blood samples and characterized by flow cytometry. A rat RA model was developed to test the role of VIP in the maintenance of the immune regulatory function of Mos. The results showed that RegMos of HC subjects had immune suppressive functions. RegMos of RA patients expressed less interleukin (IL)-10 and showed an incompetent immune regulatory capacity. Serum levels of VIP were lower in RA patients, which were positively correlated with the expression of IL-10 in RegMos. In-vitro experiments showed that the IL-10 mRNA decayed spontaneously in RegMos, which could be prevented by the presence of VIP in the culture. VIP suppressed the effects of tristetraprolin (TTP) on inducing IL-10 mRNA decay in RegMos. Administration of VIP inhibited experimental RA in rats through restoring the IL-10 expression in RegMos. RegMos have immune suppressive functions. VIP is required in maintaining IL-10 expression in RegMos. The data suggest that VIP has translational potential in the treatment of immune disorders such as RA.
Peri‐implantitis and its prevention
Authors: Berglundh Tord , Jepsen Søren , Stadlinger Bernd , Terheyden Hendrik
Published: January 2019

This perspective article on peri‐implantitis and its prevention was produced as a supplement to a 3‐D, computer‐animated film aiming at presenting key characteristics of peri‐implant health, the build‐up of a biofilm and the ensuing host‐response resulting in peri‐implant mucositis and, subsequently, peri‐implantitis. Treatment concepts for peri‐implantitis were briefly reviewed, and prevention of the condition was brought to attention as a priority in implant dentistry. The overview also highlighted the 2017 World Workshop on Classification of Periodontal and Peri‐implant diseases and Conditions, in which new disease definitions and case definitions were presented for peri‐implant health, peri‐implant mucositis, and peri‐implantitis.
Evaluation of Wearable Digital Devices in a Phase I Clinical Trial
Authors: Izmailova Elena S. , McLean Ian L. , Bhatia Gaurav , Hather Greg , Cantor Matthew , Merberg David , Perakslis Eric D. , Benko Christopher , Wagner John A.
Published: January 2019

We assessed the performance of two US Food and Drug Administration (FDA) 510(k)‐cleared wearable digital devices and the operational feasibility of deploying them to augment data collection in a 10‐day residential phase I clinical trial. The Phillips Actiwatch Spectrum Pro (Actiwatch) was used to assess mobility and sleep, and the Vitalconnect HealthPatch MD (HealthPatch) was used for monitoring heart rate (HR), respiratory rate (RR), and surface skin temperature (ST). We measured data collection rates, compared device readouts with anticipated readings and conventional in‐clinic measures, investigated data limitations, and assessed user acceptability. Six of nine study participants consented; completeness of data collection was adequate (> 90% for four of six subjects). A good correlation was observed between the HealthPatch device derived and in‐clinic measures for HR (Pearson r = 0.71; P = 2.2e‐16) but this was poor for RR (r = 0.08; P = 0.44) and ST (r = 0.14; P = 0.14). Manual review of electrocardiogram strips recorded during reported episodes of tachycardia > 180 beats/min showed that these were artefacts. The HealthPatch was judged to be not fit‐for‐purpose because of artefacts and the need for time‐consuming manual review. The Actiwatch device was suitable for monitoring mobility, collecting derived sleep data, and facilitating the interpretation of vital sign data. These results suggest the need for fit‐for‐purpose evaluation of wearable devices prior to their deployment in drug development studies.
Hypocellular medallion‐like dermal dendrocyte hamartoma on the abdomen of a 25 year old male
Authors: Porubsky Caitlin F. , Combs Angela , Buckley Christopher , Goodman Marcus B.
Published: January 2019

Medallion‐like dermal dendrocyte hamartoma is a rare congenital lesion that is more commonly seen in females. It often presents at birth on the neck or upper trunk as a well‐circumscribed, atrophic patch with wrinkling of the overlying skin. Clinically, the differential diagnosis includes atrophoderma, anetoderma, and congenital atrophic dermatofibrosarcoma protuberans. Histologic findings show epidermal atrophy and dermal spindle cell proliferation that is CD34 positive, along with Factor XIIIa in the original reports. Due to this CD34 positivity, another name for the lesion is plaque‐like CD34+ dermal fibroma. We present a unique patient case as he is male and the lesion is located on his abdomen. Further reports and studies need to be done for thorough understanding of this neoplasm.
1‐(2‐Hydroxyethyl)‐2‐imidazolidinone, a heparanase and matrix metalloproteinase inhibitor, improves epidermal basement membrane structure and epidermal barrier function
Authors: Iriyama Shunsuke , Yamanishi Haruyo , Kunizawa Naomi , Hirao Tetsuji , Amano Satoshi
Published: January 2019

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.
ITGB4 deficiency induces senescence of airway epithelial cells through p53 activation
Authors: Yuan Lin , Du Xizi , Tang Sha , Wu Shuangyan , Wang Leyuan , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Liu Chi
Published: January 2019

Aging is characterized by a progressive loss of physiological integrity, leading to impaired organ function and, ultimately, increased vulnerability to death. Many complex diseases are related to aging, including asthma. In the lung, the airway epithelium serves as the first barrier to prevent the access of inspired external stimuli and dictates the initial stress responses. Notably, in the airway mucosa of asthma patients, an increase in senescent airway epithelial cells has been detected. Although it has been speculated that the senescence of airway epithelial cells could increase asthma susceptibility and aggravate asthma severity, the role of cell senescence in the development of asthma remains unclear. Integrin β4 (ITGB4) is a structural adhesion molecule with complex physiological functions that is downregulated in airway epithelial cells of asthma patients. This study demonstrates that the expression of ITGB4 in airway epithelial cells is downregulated significantly under oxidative stress or upon inflammatory stimulation. Moreover, we show that ITGB4 deficiency induces the senescence of airway epithelial cells through the activation of the p53 pathway both in vitro and in vivo. Together, our results demonstrate that airway epithelial senescence induced by ITGB4 deficiency after oxidative stress or inflammatory stimulation may be involved in the pathogenesis of asthma. Understanding the contribution of ITGB4 deficiency to the senescence of airway epithelial cells in asthma patients may provide new therapeutic approaches for the treatment of asthma.
Structural and functional characterization of a frataxin from a thermophilic organism
Authors: Rasheed Masooma , Jamshidiha Mostafa , Puglisi Rita , Yan Robert , Cota Ernesto , Pastore Annalisa
Published: January 2019

Frataxins form an interesting family of iron‐binding proteins with an almost unique fold and are highly conserved from bacteria to primates. They have a pivotal role in iron–sulfur cluster biogenesis as regulators of the rates of cluster formation, as it is testified by the fact that frataxin absence is incompatible with life and reduced levels of the protein lead to the recessive neurodegenerative disease Friedreich's ataxia. Despite its importance, the structure of frataxin has been solved only from relatively few species. Here, we discuss the X‐ray structure of frataxin from the thermophilic fungus Chaetomium thermophilum, and the characterization of its interactions and dynamics in solution. We show that this eukaryotic frataxin has an unusual variation in the classical frataxin fold: the last helix is shorter than in other frataxins which results in a less symmetrical and compact structure. The stability of this protein is comparable to that of human frataxin, currently the most stable among the frataxin orthologues. We also characterized the iron‐binding mode of Ct frataxin and demonstrated that it binds it through a semiconserved negatively charged ridge on the first helix and beta‐strand. Moreover, this frataxin is also able to bind the bacterial ortholog of the desulfurase, which is central in iron–sulfur cluster synthesis, and act as its inhibitor.
Four decades of plant community change along a continental gradient of warming
Authors: Becker‐Scarpitta Antoine , Vissault Steve , Vellend Mark
Published: January 2019

Many studies of individual sites have revealed biotic changes consistent with climate warming (e.g., upward elevational distribution shifts), but our understanding of the tremendous variation among studies in the magnitude of such biotic changes is minimal. In this study, we resurveyed forest vegetation plots 40 years after the initial surveys in three protected areas along a west‐to‐east gradient of increasingly steep recent warming trends in eastern Canada (Québec). Consistent with the hypothesis that climate warming has been an important driver of vegetation change, we found an increasing magnitude of changes in species richness and composition from west to east among the three parks. For the two mountainous parks, we found no significant changes in elevational species’ distributions in the easternmost park (raw mean = +11.4 m at Forillon Park) where warming has been minimal, and significant upward distribution shifts in the centrally located park (+38.9 m at Mont‐Mégantic), where the recent warming trend has been marked. Community Temperature Indices (CTI), reflecting the average affinities of locally co‐occurring species to temperature conditions across their geographic ranges (“Species Temperature Indices”), did not change over time as predicted. However, close examination of the underpinnings of CTI values suggested a high sensitivity to uncertainty in individual species’ temperature indices, and so a potentially limited responsiveness to warming. Overall, by testing a priori predictions concerning variation among parks in the direction and magnitude of vegetation changes, we have provided stronger evidence for a link between climate warming and biotic responses than otherwise possible and provided a potential explanation for large variation among studies in warming‐related biotic changes.
Headache Attributed to Aeroplane Travel: An Historical Outline
Authors: Mainardi Federico , Maggioni Ferdinando , Zanchin Giorgio
Published: January 2019

Introduction

Headache attributed to aeroplane travel (AH) is one of the new nosological entries in the International Classification of Headache Disorders (ICHD) 3 beta.

Materials and Methods

This study retraces the history of headache related to flight, from the initial description to the modern reports, on the basis of original sources.

Results

Head pain related to flight has been reported since the beginning of flight era. However, most of those early cases are easily recognized as secondary to an exceptional barotrauma and/or a sinusitis concomitant with the flight. Instead, contemporary research identified a new nosological entity, AH, which by definition occurs in normal flying conditions and in absence of any sinus pathology. Moreover, we identified recently similar forms of headache, triggered by sudden changes of external pressure (rapid descent from mountain, mountain descent headache, MDH); and ascent from diving, diving ascent headache (DAH).

Conclusion

Head pain related to flight has been reported since the origin of aviation, but it was caused by an exceptional barotrauma or a respiratory infection. Instead, AH occurs in normal flying conditions. Two newly identified conditions, MDH and DAH, appear to share a common pathogenetic mechanism with AH: namely the imbalance between intrasinusal and external air pressure. Therefore, we assert that an expansion of this entity of AH is something that should be considered in the next ICHD.
Sphenopalatine Neuralgia: An Independent Neuralgia Entity. Pooled Analysis of a Case Series and Literature Review
Authors: He Wei , Zhang Yixin , Long Ting , Pan Qi , Zhang Shanshan , Zhou Jiying
Published: January 2019

Background

Structural damage or demyelization of the sphenopalatine ganglion may cause sphenopalatine neuralgia (SN). The current International Classification of Headache Disorders, third edition (ICHD‐3) regards SN as a phenotype of cluster headache. Whether SN is an independent neuralgia entity has been debated for years.

Methods

This article presents a case series of SN, a review of all published cases, and a pooled data analysis of the identified cases.

Results

Seven patients were identified, with a median age at symptom onset of 59 years. Six cases were secondary to structural lesions surrounding the ipsilateral sphenopalatine ganglion, and all of them experienced significant clinical improvements after removing the primary causes. In the seventh patient, no evidence of underlying disease was found. The literature review showed that SN affected patients spanning a wide range of ages and both sexes. The clinical characteristics of SN might mimic cluster headache with the exception of cluster pattern and treatment response to oxygen. The typical duration of pain episodes in SN was several hours to several days; and in some cases, pain was persistent. Sixty‐seven percent (59/88) of patients with SN had structural lesions around the sphenopalatine ganglion.

Conclusion

SN could possibly be regarded as a different clinical entity from cluster headache. Based on our patients and literature review, SN can be categorized as idiopathic SN and secondary SN. Craniofacial structural lesions should be highly rating and taken into account when SN is suspected.
SMAD4 alteration associates with invasive‐front pathological markers and poor prognosis in colorectal cancer
Authors: Oyanagi Hidehito , Shimada Yoshifumi , Nagahashi Masayuki , Ichikawa Hiroshi , Tajima Yosuke , Abe Kaoru , Nakano Masato , Kameyama Hitoshi , Takii Yasumasa , Kawasaki Takashi , Homma Kei‐Ichi , Ling Yiwei , Okuda Shujiro , Takabe Kazuaki , Wakai Toshifumi
Published: January 2019

Aims

SMAD4 acts as a tumour suppressor, and the loss of SMAD4 is associated with poor prognosis in colorectal cancer (CRC) patients. Although next‐generation sequencing (NGS) enabled us to detect numerous genetic alterations in a single assay, the clinical significance of SMAD4 alteration detected with NGS has not been fully investigated. The aim of this study was to evaluate the clinicopathological characteristics and clinical significance of SMAD4 alteration detected with NGS in CRC.

Methods and results

We retrospectively investigated 201 patients with stage I–IV CRC, by using a 415‐gene panel. To analyse the relationship between SMAD4 alteration and other clinicopathological characteristics, we evaluated clinicopathological variables, including invasive‐front pathological markers: tumour budding, poorly differentiated cluster, and Crohn‐like lymphoid reaction. Fifty‐six patients (28%) had SMAD4 alteration: 24 and 32 patients had SMAD4 mutation and deletion, respectively. SMAD4 alteration was significantly associated with T category (P = 0.027), N category (P = 0.037), M category (P = 0.028), and invasive‐front pathological markers, such as poorly differentiated cluster grade 3 (P = 0.020) and absence of Crohn‐like lymphoid reaction (P = 0.004). Immunohistochemistry revealed that SMAD4 alteration was significantly associated with loss of SMAD4 (P = 0.023). In 90 patients with stage I–III disease, SMAD4 alteration was significantly associated with poor prognosis for relapse‐free and overall survival (P = 0.047; P = 0.022, respectively). Conversely, in 111 patients with stage IV disease, SMAD4 alteration was not significantly associated with overall survival.

Conclusion

SMAD4 alteration is associated with invasive‐front pathological markers and poor prognosis in stage I–III CRC patients.
C4d detection and histological patterns in the diagnosis of antibody‐mediated rejection after lung transplantation: a single‐centre study
Authors: Ngo Carine , Danel Claire , Duong‐Quy Sy , Dauriat Gaëlle , Castier Yves , Lortat‐Jacob Brice , Mal Hervé , Brugière Olivier , Cazes Aurélie
Published: January 2019

Aims

Antibody‐mediated rejection (AMR) is an emerging and challenging issue in transplantation. Endothelial deposition of C4d and microvascular inflammation (MI) are reliable markers of AMR in renal and cardiac transplantation, but remain controversial in the lung. Our aim was to assess C4d immunohistochemistry and histological patterns for the diagnosis of lung AMR.

Methods and results

We reviewed 158 transbronchial biopsies (TBBs) (n = 85 clinically indicated, and n = 73 surveillance TBBs) from 48 recipients, blinded to clinical and serological data. C4d was scored as 0, 1+ (<10%), 2+ (10–50%) or 3+ (>50%). TBBs were reassessed for MI and acute lung injury (ALI). Donor‐specific antibodies (DSAs), acute clinical graft dysfunction and chronic lung allograft graft dysfunction (CLAD) were recorded. C4d3+, C4d2+, C4d1+ and C4d0 occurred respectively in four (2.5%), six (3.8%), 28 (17.7%) and 120 (75.9%) TBBs. MI and ALI were rare but more frequent in C4d1–3+ TBBs than in the absence of C4d. C4d2+ was frequently observed with concomitant infection. Among the surveillance TBBs, only two (2.7%) showed MI. Neither ALI nor C4d3+ was diagnosed on surveillance TBBs. No significant association was found between histopathological findings and DSAs. All four patients with C4d3+ could retrospectively be diagnosed with AMR and developed CLAD.

Conclusion

Although rare, diffuse C4d deposition appears to be a strong indication of acute clinical AMR in lung transplant patients, whereas intermediate C4d2+ requires more investigations. In stable patients, histopathology and C4d may lack the sensitivity to diagnose subclinical AMR. This emphasises the need for a multidisciplinary evaluation of each suspected AMR case, and the need for complementary diagnostic tools.
Flocking behaviour in the twilight ascents of Common Swifts Apus apus
Authors: Nilsson Cecilia , Bäckman Johan , Dokter Adriaan M.
Published: January 2019

Among the many unique flight behaviours of Common Swifts Apus apus, the most puzzling may be their ascents to high altitudes during both dusk and dawn. Twilight ascents have been hypothesized to be functionally related to information acquisition, including integration of celestial orientation cues, high‐altitude visual landmarks and sampling of weather conditions. However, their exact purpose remains unknown. We tracked Common Swifts with tracking radar at their breeding grounds in southern Sweden, and present evidence that during the dusk ascent and dawn descent they often occur in flocks, whereas during the dusk descent and dawn ascent phase they do not. This flocking behaviour suggests that swifts may benefit from conspecific interactions during twilight ascents and descents, possibly through more robust cue acquisition and information exchange in groups, or extending social behaviour also seen in screaming parties before dusk.
Male post‐breeding movements and stopover habitat selection of an endangered short‐distance migrant, the Little Bustard Tetrax tetrax
Authors: Alonso Hany , Correia Ricardo A. , Marques Ana Teresa , Palmeirim Jorge M. , Moreira Francisco , Silva João Paulo
Published: January 2019

Migratory decisions, such as the selection of stopover sites, are critical for the success of post‐breeding migratory movements and subsequent survival. Recent advances in bio‐logging have revealed the stopover strategies of many long‐distance migrants, but far less attention has been given to short‐distance migrants. We investigated the stopover ecology of an endangered grassland bird, the Little Bustard Tetrax tetrax, a short‐distance migrant in Iberia. Using high‐resolution spatial GPS/GSM data, 27 male Little Bustards breeding in southern Portugal were tracked between 2009 and 2011. We studied post‐breeding movements using Dynamic Brownian Bridge models to identify the main stopover sites, and generalized linear mixed models to examine habitat selection in stopovers. During their post‐breeding movements, males were essentially nocturnal migrants, making frequent stopovers while maintaining a relatively fast pace to reach more productive agricultural post‐breeding areas. Stopovers occurred in most post‐breeding movements (83%) regardless of the total distance covered (average 64.3 km), and most stopovers (84%) lasted less than 24 h. Birds used mostly agricultural non‐irrigated and irrigated croplands as stopover sites and avoided other land uses and rugged terrain. There was a negative relationship between stopovers and the proximity to roads, but not to power lines. The high frequency of stopovers during post‐breeding movements, despite the short distances travelled, together with the nocturnal migratory behaviour of bustards, may impose additional risks to a bird mainly threatened by collision with power lines in non‐breeding areas. We also conclude that even for short‐distance migrants, habitat connectivity between breeding and post‐breeding areas is likely to be a key conservation concern.
Serum pleiotrophin as a diagnostic and prognostic marker for small cell lung cancer
Authors: Xu Chunhua , Wang Yuchao , Yuan Qi , Wang Wei , Chi Chuanzhen , Zhang Qian , Zhang Xiuwei
Published: January 2019

Pleiotrophin (PTN) is involved in tumour progression, angiogenesis and metastasis. The purpose of this study was to investigate the expression level of PTN in the serum of patients with small cell lung cancer (SCLC) and to explore the clinical significance of PTN. Serum samples from 128 patients with SCLC, 120 healthy volunteers (HV) and 60 patients with benign lung disease (BLD) were collected. The levels of serum PTN were determined with ELISA and its correlation with the clinical data was examined. The serum PTN levels in SCLC patients were significantly higher than that in BLD patients (P < 0.05) or HV (P < 0.05). With a cutoff value of 258.18 ng/mL, the sensitivity and specificity of PTN to SCLC patients and BLD patients, SCLC patients and HV were 79.2% and 91.7%, 86.7% and 95.8% respectively. An area under the curve for all stages of SCLC resulting from PTN, which was significantly better than the other tumour markers tested including progastrin‐releasing peptide and neuron‐specific enolase. High serum PTN levels appear to correlate with poor survival in patients with SCLC. These results suggest that PTN levels in the serum could be a new effective biomarker for the diagnosis and prognosis of SCLC.
Managing competition on a two‐sided platform
Authors: Belleflamme Paul , Peitz Martin
Published: January 2019

On many two‐sided platforms, users on one side not only care about user participation and usage levels on the other side, but they also care about participation and usage of fellow users on the same side. Most prominent is the degree of seller competition on a platform catering to buyers and sellers. In this paper, we address how seller competition affects platform pricing, product variety, and the number of platforms that carry trade.
Colonic diverticular bleeding and predictors of the length of hospitalization: An observational study
Authors: Wada Michiko , Nishizawa Toshihiro , Kato Motohiko , Hirai Yuichiro , Kinoshita Satoshi , Mori Hideki , Nakazato Yoshihiro , Fujimoto Ai , Kikuchi Masahiro , Uraoka Toshio , Kanai Takanori
Published: January 2019

Background and Aim

A significant percentage of patients with colonic diverticular bleeding (CDB) experience bleeding that is severe enough to necessitate prolonged hospitalization. Prolonged hospitalization causes deterioration in patients' quality of life, as well as difficulties with cost‐effective utilization of medical resources, and is a financial burden to the society. Therefore, we investigated the factors associated with the length of hospitalization for the optimal management of patients hospitalized with CDB.

Methods

This study included patients who were hospitalized for the treatment of CDB and underwent colonoscopy between July 2008 and February 2016. Logistic regression analysis was performed to investigate the association between the length of hospitalization and the patients' baseline characteristics, in‐hospital procedures performed, and the clinical outcomes.

Results

The study included 223 patients. Diabetes mellitus (odds ratio [OR] 3.4, P = 0.014) and blood transfusion (OR 3.1, P = 0.0006) were identified as risk factors for prolonged hospitalization (≥ 8 days). Urgent colonoscopy (OR 0.41, P = 0.0072) predicted a shorter length of hospitalization (≤ 7 days). The study also indicated that endoscopic treatment showed a stronger association with urgent colonoscopy (OR 7.8, P < 0.0001) than with elective colonoscopy and that urgent colonoscopy was not associated with an increased rate of adverse events or re‐bleeding.

Conclusions

Compared with elective colonoscopy, urgent colonoscopy shortens the length of hospitalization in patients with CDB. Moreover, it is not associated with an increased rate of adverse events. Urgent colonoscopy may be impracticable in a few cases; however, if possible, aggressive urgent colonoscopy should be considered for the efficient management of the patient's hospital stay.
Impact of Occlusal Intercuspal Angulation on the Quality of CAD/CAM Lithium Disilicate Crowns
Authors: Sadid‐Zadeh Ramtin , Li Rui , Patel Reena , Makowka Steven , Miller Lorin M.
Published: January 2019

Purpose

Modification of intercuspal angulation (ICA) influences the amount of tooth structure removal, which may impact the retention and resistance form of the preparation. This study evaluated the impact of ICA on the marginal gap of CAD/CAM crowns and the influence that tooth structure removal, caused by variation of ICA, has on the resistance and retention form of the preparation.

Materials and Methods

Sixty ivorine molars were manufactured with various ICAs (100°, 110°, 120°, 140°, 160°, and 180°; 10 per group). The preparations were digitized using an intraoral scanner, and the crowns were designed using a design software. The designed crowns were then manufactured from lithium disilicate using a 3‐axis milling machine, with the “detailed mode” selected for the manufacturing. The marginal gap of each crown was evaluated using a stereomicroscope at 20× magnification. Then, the marginal integrity and the resistance form of the preparation were assessed by tactile‐visual evaluation, and they were given a categorical score. Crowns were then secured on their associated preparations using a temporary luting agent, and retention force was measured on a universal testing machine under tension with a 0.5 mm/min crosshead speed. Wilcoxon test followed by post‐hoc tests (α = 0.05) were used to evaluate the impact of the ICA on the marginal gap and the retention form of the preparation. Fisher's exact test followed by post‐hoc tests (α = 0.05) were used to assess the impact of the occlusal preparation design on the marginal integrity and the resistance form of the preparation.

Results

The marginal gap was significantly larger for ICA‐180 preparations (72 μm), compared to the other groups (ICA‐180 vs ICA‐100, ICA‐110, ICA‐120, and ICA‐160 p = 0.0001; ICA‐180 vs. ICA‐140 p = 0.0017). None of the crowns for ICA‐180 preparations had clinically acceptable resistance form. Preparations with ICAs of 100°, 110°, and 120° had a significantly higher value of retention than the other groups (ICA‐100 vs. ICA‐120 p = 0.0119; ICA‐100 vs. ICA‐140, ICA‐160, and ICA‐180 p < 0.0001; ICA‐110 vs. ICA‐140, ICA‐160, and ICA‐180 p = 0.0001; ICA‐120 vs. ICA‐180 p = 0.0017).

Conclusions

Crowns fabricated for preparations with various ICAs had clinically acceptable marginal adaptation. Variation in ICA impacts the loss of tooth structure. This loss of tooth structure may influence the resistance and retention form of the preparation.
Human Gingival Epithelial Growth In Vitro on a Polymer‐Infiltrated Ceramic Network Restorative Material
Authors: Smallidge Martin J. , Sabol Jennifer V. , Aita‐Holmes Cynthia , Chuang Henry , Dickinson Douglas P.
Published: January 2019

Purpose

To investigate the growth of primary human gingival epithelial (HGE) cells on polymer‐infiltrated ceramic network (PICN) material (Vita Enamic) with different surface roughnesses.

Materials and Methods

PICN material specimens were polished with either silica carbide paper (grit‐polished) or the manufacturer's polishing wheels (wheel‐polished), and the surface roughness (Ra) measured. HGE cells were seeded and grown for 1, 3, or 6 days. Growth on tissue culture plastic was used as a control. Non‐linear regression analysis was used to examine the effect of surface roughness on cell growth.

Results

HGE cell growth on tissue culture plastic fitted an exponential growth model over the 6‐day experimental period (R2 = 0.966). Through day 6, cell density on PICN decreased with increasing surface roughness, with a fit to an exponential decay model (R2 = 0.666). A threshold Ra value of 0.254 μm (95% CI 0.177‐0.332) was determined as an upper limit for exponential growth. Cell growth was greatest on the group of specimens with Ra value below 0.127μm. Specimens polished by the manufacturer's method produced surface roughness of 0.118 μm and below.

Conclusions

PICN material polished to a smooth surface (Ra < 0.254 μm) resulted in exponential growth of HGE cell growth compared to rough surfaces. Polishing PICN material as smooth as possible (below a Ra of 0.127 μm) was found to maximize epithelial cell growth on the PICN material surface. The manufacturer's polishing method achieved a sufficiently smooth surface. These results are contrary to previous research regarding surface roughness of transgingival implant restoration components. The study results suggest that smoother restorative material surfaces could improve peri‐implant soft tissue health.
Associations between G6PD, OATP1B1 and BLVRA variants and susceptibility to neonatal hyperbilirubinaemia in a Chinese Han population
Authors: Li Yongpei , Wu Ting , Chen Ling , Zhu Yunxia
Published: January 2019

Aim

Hyperbilirubinaemia is a common disorder in newborns. The aim of this study was to investigate the associations between G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512 variants and the risk of neonatal hyperbilirubinaemia in a Chinese neonate population.

Methods

A total of 447 Chinese neonates with hyperbilirubinaemia were selected as the study group and 544 healthy subjects were recruited as the control group matched by baseline sex, age, feeding pattern and delivery mode. About 2 mL of peripheral venous blood was taken from all subjects. The single nucleotide polymorphisms (SNPs) of G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512 loci were examined by the polymerase chain reaction and Sanger sequencing technique in the peripheral blood of all subjects.

Results

For the G6PD 1388 G>A SNP, individuals carrying the A‐allele were associated with a significantly increased risk of neonatal hyperbilirubinaemia (adjusted odds ratio (OR) = 1.49, P < 0.001, 95% confidence interval (CI): 1.31–1.67). This risk increased significantly in the CC genotype carriers at the rs4149056 locus of the SLCO1B1 gene (OR = 2.17, 95% CI: 1.87–2.33), whereas it decreased significantly in individuals carrying the G‐allele at the rs699512 locus of the BLVRA gene (adjusted OR = 0.84, P = 0.01, 95% CI: 0.75–0.95). The G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512 SNPs had a significant impact on serum total bilirubin levels. Moreover, individuals carrying the A‐allele of G6PD 1388 G>A and BLVRA rs699512 had a significantly increased risk of developing neonatal hyperbilirubinaemia (OR = 5.01, P < 0.001, 95% CI: 3.42–7.85).

Conclusion

Genetic variants of bilirubin metabolism genes, including G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512, are associated with the risk of neonatal hyperbilirubinaemia, and are potential markers for predicting the disorder.
First description of the environmental niche of the epibenthic dinoflagellate species Coolia palmyrensis, C. malayensis, and C. tropicalis (Dinophyceae) from Eastern Australia
Authors: Larsson Michaela E. , Smith Kirsty F. , Doblin Martina A.
Published: January 2019

Environmental variables such as temperature, salinity, and irradiance are significant drivers of microalgal growth and distribution. Therefore, understanding how these variables influence fitness of potentially toxic microalgal species is particularly important. In this study, strains of the potentially harmful epibenthic dinoflagellate species Coolia palmyrensis, C. malayensis, and C. tropicalis were isolated from coastal shallow water habitats on the east coast of Australia and identified using the D1‐D3 region of the large subunit (LSU) ribosomal DNA (rDNA). To determine the environmental niche of each taxon, growth was measured across a gradient of temperature (15–30°C), salinity (20–38), and irradiance (10–200 μmol photons · m−2 · s−1). Specific growth rates of Coolia tropicalis were highest under warm temperatures (27°C), low salinities (ca. 23), and intermediate irradiance levels (150 μmol photons · m−2 · s−1), while C. malayensis showed the highest growth at moderate temperatures (24°C) and irradiance levels (150 μmol photons · m−2 · s−1) and growth rates were consistent across the range of salinity levels tested (20–38). Coolia palmyrensis had the highest growth rate of all species tested and favored moderate temperatures (24°C), oceanic salinity (35), and high irradiance (>200 μmol photons · m−2 · s−1). This is the first study to characterize the environmental niche of species from the benthic harmful algal bloom genus Coolia and provides important information to help define species distributions and inform risk management.
Clinical features and determinants of chronicity in hepatitis E virus infection
Authors: Narayanan Shivakumar , Abutaleb Ameer , Sherman Kenneth E. , Kottilil Shyam
Published: January 2019

Hepatitis E virus (HEV) has traditionally been associated with an acute, self‐limiting hepatitis and is not known to have any chronic sequelae. HEV genotypes 1 and 2, which are human pathogens, have been associated with this self‐limiting presentation, in both sporadic and epidemic settings. HEV genotype 3, which is zoonotically transmitted, is increasingly being reported as a cause of chronic infection in immunocompromised patients. These include patients with solid organ transplants, patients receiving chemotherapy for haematologic malignancies and patients infected with HIV. Chronic infection is associated with rapidly progressing liver disease and extrahepatic manifestations including neurologic disorders. We review the clinical manifestations of chronic HEV infection and discuss factors determining persistence and chronicity of HEV.