bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of Extrafloral Nectaries and Their Relationship with Growth and Survival of Lowland Tropical Rain Forest Trees
Authors: Muehleisen Andrew , Queenborough Simon A. , Alvia Pablo , Valencia Renato , Fiala Brigitte
Published: February 2016

Mutualistic relationships between organisms have long captivated biologists, and extrafloral nectaries, or nectar‐producing glands, found on many plants are a good example. The nectar produced from these glands provides food for ants, which may defend the plant from potential herbivores in turn. However, relatively little is known about their impact on the long‐term growth and survival of plants that produce them. To better understand the ecological significance of extrafloral nectaries, we examined their incidence on lowland tropical rain forest trees in Yasuní National Park in Amazonian Ecuador, and collated data from two other tropical lowland forest sites (Barro Colorado Island, Panamá and Pasoh Forest Reserve, Malaysia). At Yasuní, extrafloral nectaries were found on 137 of 1123 species censused (12.2%), widely distributed among different angiosperm families. This rate of incidence is high but consistent with other tropical locations. Furthermore, this study adds 18 new genera and two new families (Urticaceae and Caricaceae) to the list of taxa exhibiting extrafloral nectaries. Using demographic data from long‐term forest dynamics plots at each site, we compared the growth and mortality rates of species with extrafloral nectaries to those without. After controlling for phylogeny, no general relationship between extrafloral nectary presence and demographic rates could be detected, suggesting little demographic signal from any community‐wide ecological effects.
MicroRNA‐761 is upregulated in hepatocellular carcinoma and regulates tumorigenesis by targeting Mitofusin‐2
Authors: Zhou Xiaohu , Zhang Linshi , Zheng Bichun , Yan Yingcai , Zhang Yuan , Xie Haiyang , Zhou Lin , Zheng Shusen , Wang Weilin
Published: February 2016

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third leading cause of cancer‐related deaths worldwide. The fate of a cell is determined by the balance between the processes of fission and fusion that constantly occur in the mitochondria of cells. We previously showed that overexpression of Mitofusin‐2 can induce apoptosis in HCC cells by triggering an influx of Ca2+ into the mitochondria from the ER. The function of Mitofusin‐2 has been studied extensively, but the mechanism underlying the post‐transcriptional regulation of Mitofusin‐2 has not been elucidated. In the present study, we aimed to identify the mechanism of Mitofusin‐2 regulation in HCC. We demonstrated that Mitofusin‐2 is a direct target of miR‐761, which was found to be upregulated in HCC tissues. Furthermore, a miR‐761 inhibitor impaired mitochondrial function by upregulating Mitofusin‐2 and effectively repressed tumor growth and metastasis both in vivo and in vitro. Our findings provide new insight into the mechanism underlying Mitofusin‐2 regulation and the potential role of miR‐761 in HCC, making it a potential candidate for use in HCC therapy in the future.
Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor‐tyrosine kinase inhibitor in lung cancer
Authors: Mizuuchi Hiroshi , Suda Kenichi , Murakami Isao , Sakai Kazuko , Sato Katsuaki , Kobayashi Yoshihisa , Shimoji Masaki , Chiba Masato , Sesumi Yuichi , Tomizawa Kenji , Takemoto Toshiki , Sekido Yoshitaka , Nishio Kazuto , Mitsudomi Tetsuya
Published: February 2016

Mutant selective epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs), such as rociletinib and AZD9291, are effective for tumors with T790M secondary mutation that become refractory to first‐generation EGFR‐TKI. However, acquired resistance to these prospective drugs is anticipated considering the high adaptability of cancer cells and the mechanisms remain largely obscure. Here, CNX‐2006 (tool compound of rociletinib) resistant sublines were established by chronic exposure of HCC827EPR cells harboring exon 19 deletion and T790M to CNX‐2006. Through the analyses of these resistant subclones, we identified two resistant mechanisms accompanied by MET amplification. One was bypass signaling by MET amplification in addition to T790M, which was inhibited by the combination of CNX‐2006 and MET‐TKI. Another was loss of amplified EGFR mutant allele including T790M while acquiring MET amplification. Interestingly, MET‐TKI alone was able to overcome this resistance, suggesting that oncogenic dependence completely shifted from EGFR to MET. We propose describing this phenomenon as an “oncogene swap.” Furthermore, we analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an “oncogene swap” from EGFR to MET is a novel resistant mechanism to the EGFR‐TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene.
Less than human: a qualitative study into the experience of parents involved in the child protection system
Authors: Smithson Rosie , Gibson Matthew
Published: February 2016

This paper reports on the findings from a qualitative study into the experiences of parents who were involved in the English child protection system in 2013. Seventeen in‐depth interviews were conducted involving 19 parents and/or partners, and a framework approach was used to analyse the data. There were positive experiences of individual social workers and some positive experiences of the child protection system. However, the overwhelming theme of the parents' experiences was that the system was uncaring, inflexible and for some harmful to both themselves and their children. Despite being included in the child protection process, parents felt they were not afforded the same rights as a participant, as a decision‐maker or as a partner in seeking to improve the situation. The threat of consequences silenced parents who felt unable to speak out or challenge the things they disagreed with or coerced others into signing agreements they did not agree to. Such experiences related to a sense that they were being treated as ‘less than human’. These findings are considered within the context of recent reforms within the English child protection system.
“It's like he just goes off, BOOM!”: mothers and grandmothers make sense of child‐to‐parent violence
Authors: Williams Megan , Tuffin Keith , Niland Patricia
Published: February 2016

Child to parent violence (CPV) involves continual and cumulative abusive actions perpetrated by children and adolescents towards their parents or caregivers. This abuse produces short‐term distress and ongoing long‐term harmful consequences for parents and their families. Practitioners, researchers and policy‐makers are increasingly challenged to identify, conceptualize and respond to this form of family violence. A major challenge is that parents and caregivers under‐report this abuse so there is a lack of awareness and understanding of their psychological experiences in relation to CPV. This research adopts an interpretative phenomenological approach to explore the psychological experience of CPV. Interviews were conducted with six New Zealand mothers and two grandmothers who all experienced CPV. This abuse was experienced as an ‘emotional bloody roller coaster’ of unconditional love through to hatred; as ‘judgement’ – self‐blame and others' blame of their parenting skills; and the ‘absent father’ in their adolescents' lives was drawn on as an explanation for the abuse. Taken together, these psychological experiences identify the silencing of CPV is related to parents' conflicting emotions towards their children, their thoughts and feelings about themselves and how other people view them, and the impact of an absent father figure in their children's everyday lives.
Expression Profile of Long Noncoding RNAs in Peripheral Blood Mononuclear Cells from Multiple Sclerosis Patients
Authors: Zhang Fang , Gao Chao , Ma Xiao‐Feng , Peng Xiao‐Lin , Zhang Rong‐Xin , Kong De‐Xin , Simard Alain R. , Hao Jun‐Wei
Published: February 2016

Aims

Long noncoding RNAs (lncRNAs) play a key role in regulating immunological functions. Their impact on the chronic inflammatory disease multiple sclerosis (MS), however, remains unknown. We investigated the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with MS and attempt to explain their possible role in the process of MS.

Methods

For this study, we recruited 26 patients with MS according to the revised McDonald criteria. Then, we randomly chose 6 patients for microarray analysis. Microarray assays identified outstanding differences in lncRNA expression, which were verified through real‐time PCR. LncRNA functions were annotated for target genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and regulatory relationships between lncRNAs and target genes were analyzed using the “cis” and “trans” model.

Results

There were 2353 upregulated lncRNAs, 389 downregulated lncRNAs, 1037 upregulated mRNAs, and 279 downregulated mRNAs in patients with MS compared to healthy control subjects (fold change >2.0). Real‐time PCR results of six aberrant lncRNAs were consistent with the microarray data. The coexpression network comprised 864 lncRNAs and 628 mRNAs. Among differentially expressed lncRNAs, 10 lncRNAs were predicted to have 10 cis‐regulated target genes, and 33 lncRNAs might regulate their trans target genes.

Conclusions

We identified a subset of dysregulated lncRNAs and mRNAs. The differentially expressed lncRNAs may be important in the process of MS. However, the specific molecular mechanisms and biological functions of these lncRNAs in the pathogenesis of MS need further study.
Vessel Dilation Attenuates Endothelial Dysfunction Following Middle Cerebral Artery Occlusion in Hyperglycemic Rats
Authors: Mu Zhi‐Hao , Jiang Zhen , Lin Xiao‐Jie , Wang Li‐Ping , Xi Yan , Zhang Zhi‐Jun , Wang Yong‐Ting , Yang Guo‐Yuan
Published: February 2016

Objectives

Dynamically observe cerebral vascular changes in hyperglycemic rats in vivo and explore the effect of diabetes on endothelial function after ischemic stroke.

Background

Diabetes affects both large and small vessels in the brain, but the dynamic process and mechanism are unclear.

Methods

We investigated the structural and functional changes of brain vasculature in living hyperglycemic rats and their impact on stroke outcomes via a novel technique: synchrotron radiation angiography. We also examined the effect of prolonged fasudil treatment on arterial reactivity and hemorrhagic transformation. Adult Sprague Dawley rats were treated by streptozotocin to induce type 1 diabetes. These hyperglycemic rats received fasudil pretreatment and then underwent transient middle cerebral artery occlusion.

Results

We found that diabetes caused arteries narrowing in the circus Willis as early as 2 weeks after streptozotocin injection (P < 0.05). These vessels were further constricted after middle cerebral artery occlusion. L‐NAME could induce regional constrictions and impaired relaxation in hyperglycemic animals. Furthermore, hemorrhagic transformation was also increased in the hyperglycemic rats compared to the control (P < 0.05). In fasudil‐treated rats, the internal carotid artery narrowing was ameliorated and L‐NAME‐induced regional constriction was abolished. Importantly, stroke prognosis was improved in fasudil‐treated rats compared to the control (P < 0.05).

Conclusions

Our dynamic angiographic data demonstrated that diabetes could impair the cerebral arterial reactivity. Prolonged fasudil treatment could attenuate arterial dysfunction and improve the prognosis of ischemic stroke by affecting both the large and small vasculature.
The Neural Basis of Postural Instability Gait Disorder Subtype of Parkinson's Disease: A PET and fMRI Study
Authors: Zhang Li , Li Tian‐Nv , Yuan Yong‐Sheng , Jiang Si‐Ming , Tong Qing , Wang Min , Wang Jian‐Wei , Chen Hua‐Jun , Ding Jian , Xu Qin‐Rong , Zhang Ke‐Zhong
Published: February 2016

Aims

The aim of this study is to further uncover the neural basis of postural instability gait disorder (PIGD) subtype of Parkinson's disease.

Methods

With F‐18 fluorodeoxyglucose PET (FDG‐PET), brain glucose metabolism of patients with PIGD (n = 15) was compared with healthy controls (n = 17) and tremor‐dominant (TD) patients (n = 15), and the correlation between metabolism and PIGD symptoms was also assessed. Within PIGD symptom‐correlated hypometabolic areas, the relationship of functional connectivity (FC) with motor and cognitive symptoms was examined by using functional MRI.

Results

Compared with controls, patients with PIGD displayed a distributed pattern of brain hypometabolism including striatal, frontal, and parietal areas. Relative to the pattern of TD patients, the pattern of patients with PIGD had additional metabolic decreases in caudate and inferior parietal lobule (IPL, Brodmann area [BA] 40). In PIGD group, the metabolic reductions in IPL (BA 40), middle frontal gyrus (MFG, BA 9) and fusiform gyrus (FG, BA 20) were associated with severe PIGD symptoms. Regions showing such correlation were chosen for further seed‐based FC analysis. Decreased FC within the prefrontal–parietal network (between the MFG and IPL) was associated with severe PIGD symptoms.

Conclusion

The involvement of the caudate, FG, and prefrontal–parietal network may be associated with the prominent gait impairments of PIGD subtype. Our findings expand the pathophysiological knowledge of PIGD subtype and provide valuable information for potential neuromodulation therapies alleviating gait disorders.
The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone‐Induced Central Nervous System Demyelination
Authors: Tomas‐Roig Jordi , Wirths Oliver , Salinas‐Riester Gabriela , Havemann‐Reinecke Ursula
Published: February 2016

Aim and methods

Different types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells. With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination.

Results

The synthetic cannabinoid agonist WIN55212.2 at 1 μM increased the myelin basic protein mRNA and protein expression in vitro. During cuprizone‐induced acute demyelination, the administration of 0.5 mg/kg WIN55212.2 confers more myelinated axons, increased the expression of retinoid X receptor alpha, and declined nogo receptor expression. Controversially, 1 mg/kg of the drug increased the number of demyelinated axons and reduced the expression of nerve growth factor inducible, calreticulin and myelin‐related genes coupling specifically with a decrease in 2′,3′‐cyclic nucleotide 3′ phosphodiesterase expression.

Conclusion

The cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation in vitro. Moreover, 0.5 mg/kg of the drug confers neuroprotection during cuprizone‐induced demyelination, while 1 mg/kg aggravates the demyelination process.
Presymptomatic MPTP Mice Show Neurotrophic S100B/mRAGE Striatal Levels
Authors: Viana Sofia D. , Fernandes Rosa C. , Canas Paula M. , Silva Andréa M. , Carvalho Félix , Ali Syed F. , Fontes Ribeiro Carlos A. , Pereira Frederico C.
Published: February 2016

Aims

Astrocytic S100B and receptor for advanced glycation endproducts (RAGE) have been implicated in Parkinson׳s disease (PD) pathogenesis through yet unclear mechanisms. This study attempted to characterize S100B/mRAGE (signaling isoform) axis in a dying‐back dopaminergic (DAergic) axonopathy setting, which mimics an early event of PD pathology.

Methods

C57BL/6 mice were submitted to a chronic MPTP paradigm (20 mg/kg i.p., 2 i.d‐12 h apart, 5 days/week for 2 weeks) and euthanized 7 days posttreatment to assess mRAGE cellular distribution and S100B/mRAGE density in striatum, after probing their locomotor activity (pole test and rotarod). Dopaminergic status, oxidative stress, and gliosis were also measured (HPLC‐ED, WB, IHC).

Results

This MPTP regimen triggered increased oxidative stress (augmented HNE levels), gliosis (GS/Iba1‐reactive morphology), loss of DAergic fibers (decreased tyrosine hydroxylase levels), and severe hypodopaminergia. Biochemical deficits were not translated into motor abnormalities, mimicking a presymptomatic PD period. Remarkably, striatal neurotrophic S100B/mRAGE levels and major neuronal mRAGE localization coexist with compensatory responses (3‐fold increase in DA turnover), which are important to maintain normal motor function.

Conclusion

Our findings rule out the involvement of S100B/mRAGE axis in striatal reactive gliosis, DAergic axonopathy and warrant further exploration of its neurotrophic effects in a presymptomatic compensatory PD stage, which is a fundamental period for successful implementation of therapeutic strategies.
Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis
Authors: Martel Britta C. , Litman Thomas , Hald Andreas , Norsgaard Hanne , Lovato Paola , Dyring‐Andersen Beatrice , Skov Lone , Thestrup‐Pedersen Kristian , Skov Søren , Skak Kresten , Poulsen Lars K.
Published: February 2016

Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The primary aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD. In contrast to severe AD, expression of the majority of genes associated with skin barrier formation was unchanged or upregulated in patients with mild AD compared to normal healthy skin. Among these, no significant differences in the expression of filaggrin (FLG) and loricrin at both mRNA and protein level were found in lesional skin from patients with mild AD, despite the presence of heterozygous FLG mutations in the majority of patients with mild extrinsic AD. Several inflammation‐associated genes such as S100A9, MMP12, CXCL10 and CCL18 were highly expressed in lesional skin from patients with mild psoriasis and were also increased in patients with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation‐associated genes found among patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD.
Numerical characterization of compact pipe specimen for stretch zone width assessment
Authors: Mahajan G. , Saxena S. , Mohanty A.
Published: February 2016

Present work focuses on evaluating the suitability of newly proposed compact pipe (CP) fracture specimen geometry for determining critical SZW. The effect of varying the parameter of CP specimen (outer diameter, thickness, a/W ratio and straight and radial crack front) on critical SZW have been studied. It is found that SZWc values decreases slightly with the increase in outer diameter of CP specimen. In CP specimen, thickness greater than a specified value is to be used for geometry independent evaluation of SZWc. Critical SZW shows significant variation with a/W ratio, straight and radial crack front. The CP specimen and Three Point Bend (TPB) specimen also compared in terms of stress tri‐axiality.
Island species–area relationships and species accumulation curves are not equivalent: an analysis of habitat island datasets
Authors: Matthews Thomas J. , Triantis Kostas A. , Rigal François , Borregaard Michael K. , Guilhaumon François , Whittaker Robert J.
Published: February 2016

Aim

The relationship between species number and area is of fundamental importance in macroecology and conservation science, yet the implications of different means of quantitative depiction of the relationship remain contentious. We set out (1) to establish the variation in form of the relationship between two distinct methods applied to the same habitat island datasets, (2) to explore the relevance of several key dataset properties for variation in the parameters of these relationships, and (3) to assess the implications for application of the resulting models.

Locations

Global.

Methods

Through literature search we compiled 97 habitat island datasets. For each we analysed the form of the island species–area relationship (ISAR) and several versions of species accumulation curve (SAC), giving priority to a randomized form (Ran‐SAC). Having established the validity of the power model, we compared the slopes (z‐values) between the ISAR and the SAC for each dataset. We used boosted regression tree and simulation analyses to investigate the effect of nestedness and other variables in driving observed differences in z‐values between ISARs and SACs.

Results

The Ran‐SAC was steeper than the ISAR in 77% of datasets. The differences were primarily driven by the degree of nestedness, although other variables (e.g. the number of islands in a dataset) were also important. The ISAR was often a poor predictor of archipelago species richness.

Main conclusions

Slopes of the ISAR and SAC for the same data set can vary substantially, revealing their non‐equivalence, with implications for applications of species–area curve parameters in conservation science. For example, the ISAR was a poor predictor of archipelagic richness in datasets with a low degree of nestedness. Caution should be employed when using the ISAR for the purposes of extrapolation and prediction in habitat island systems.
Von Willebrand factor for menorrhagia: a survey and literature review
Authors: Ragni M. V. , Machin N. , Malec L. M. , James A. H. , Kessler C. M. , Konkle B. A. , Kouides P. A. , Neff A. T. , Philipp C. S. , Brambilla D. J.
Published: February 2016

Background

von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non‐hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia.

Methods

We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms ‘von Willebrand factor,’ ‘menorrhagia’ and ‘von Willebrand disease’ to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics.

Results

Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011–2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first‐line therapies for menorrhagia, whereas VWF was third‐line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33–100 IU kg−1 on day 1–6 of menstrual cycle.

Conclusions

This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings.
Persistent left superior vena cava: Two case reports and a review from nephrologists’ perspective
Authors: Sahutoglu Tuncay , Sakaci Tamer , Kara Ekrem , Ahbap Elbis , Basturk Taner , Koc Yener , Sevinc Mustafa , Akgol Cuneyt , Kayarlar Arzu Ozdemir , Ucar Zuhal Atan , Caglayan Feyza Bayraktar , Hasbal Nuri Baris , Nazif Perin , Isleem Mahmoud , Sahutoglu Elif , Unsal Abdulkadir
Published: February 2016

Thoracic venous anomalies without congenital heart anomalies are present in minority of the population, but they are frequent enough to be encountered while placing hemodialysis catheters through the jugular or subclavian veins. Persistent left superior vena cava is the most commonly seen anomaly and it is rarely noticed before the observation of an unusual course of hemodialysis catheter or guidewire on chest X‐ray. We present two patients with previously unspotted persistent left superior vena cava and uncomplicated hemodialysis catheter insertions through the internal jugular veins with good catheter functions. Review of the relevant literature from a nephrologists’ perspective with technical aspects is provided.
The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma
Authors: Amary M Fernanda , Berisha Fitim , Mozela Rafael , Gibbons Rebecca , Guttridge Alice , O'Donnell Paul , Baumhoer Daniel , Tirabosco Roberto , Flanagan Adrienne M
Published: February 2016

Aims

We recently reported that 95% of chondroblastomas harbour a p.K36M mutation in either H3F3A (chromosome 1) or H3F3B (chromosome 17), with the majority involving H3F3B. The aim of this study was to assess the expression of the K36M‐mutated protein by immunohistochemistry in a large group of tumours.

Methods and results

One thousand eight hundred and ninety‐four tumours, including 85 chondroblastomas and 10 clear‐cell chondrosarcomas, were studied; of these, 82 chondroblastomas and one clear‐cell chondrosarcoma known to harbour the H3F3 p.K36M mutation expressed the mutated protein. Three chondroblastomas and nine clear‐cell chondrosarcomas wild type for H3F3A/H3F3B were negative for p.K36M immunoexpression. The remaining 1799 cases tested, 545 of which were known to be wild type for the H3F3A and H3F3B p.K36M mutations, included 1047 primary bone tumours, and 507 soft tissue and joint tumours. Two hundred and forty‐five other tumour types not expected to harbour the mutation were negative for p.K36M immunoexpression.

Conclusions

Our data demonstrate the specificity and sensitivity of this immunomarker, and will be a useful adjunct for reaching a diagnosis of chondroblastoma.
Increased expression of senescence markers p14ARF and p16INK4a in breast cancer is associated with an increased risk of disease recurrence and poor survival outcome
Authors: Pare Rahmawati , Shin Joo‐Shik , Lee Cheok Soon
Published: February 2016

Aims

Breast cancer is a hormonally driven disease. Cellular senescence is an age‐related irreversible cell cycle arrest at the G1 phase upon induction. The aim of this study was to characterize the expression patterns of the senescence markers p14ARF, p16INK4a and p21WAF1/Cip1 during breast cancer progression in a large patient cohort.

Methods and results

We conducted a retrospective study of 1080 patients with invasive ductal carcinoma, no special type, over an 11‐year period. We performed immunohistochemical staining on tissue microarrays that included normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma tissue from each patient. Invasive ductal carcinomas showed higher expression of p14ARF and p16INK4a but lower expression of p21WAF1/Cip1 than non‐malignant tissues. There were significant correlations of normal, benign, preinvasive and malignant tissues with p14ARF, p16INK4a and p21WAF1/Cip1 expression (P < 0.05). Univariate comparison showed a correlation between high p16INK4a expression and poor survival (P = 0.000) and an increased risk of relapse (P = 0.000), whereas high p14ARF expression correlated only with an increased risk of relapse (P = 0.038). Multivariate analysis showed p16INK4a to be an important prognostic factor for overall survival (P = 0.011) and disease‐free survival (P = 0.004), with p14ARF also being a significant prognostic factor for disease‐free survival (P = 0.043). Moreover, patients showing both high p16INK4a expression and and high p14ARF expression had an adjusted three‐fold increased risk of disease recurrence (P < 0.05) and a two‐fold increased risk of all‐cause‐related death (P < 0.05).

Conclusions

These finding suggest p16INK4a expression and p14ARF expression may play an important role in the progression of proliferative breast tissue to invasive cancer, and may be useful as prognostic factors.
A cross‐sectional study of dentine sensitivity in periodontitis patients in Trinidad and Tobago
Authors: Ramlogan S , Raman V , Rees JS , Legall G
Published: February 2016

Objective

This cross‐sectional study aimed to determine the prevalence, distribution and associated factors of dentine sensitivity (DS) among periodontitis patients in Trinidad.

Methods

Sequential patients meeting the periodontitis criteria (BPE 4/4*) were included and completed a questionnaire on DS prior to a full periodontal examination. Clinically elicited symptoms of DS and presence of cervical tooth wear were recorded.

Results

DS prevalence was 73.1% (n = 130; mean age 50 years). Mean number of sensitive teeth increased with increased severity of gingival recession. Most common initiating factors of DS were cold stimuli (70.5%), brushing (25.3%) and sour food (11.6%). Correlations were obtained for DS and race, toothbrush texture hardness, cervical tooth wear and gingival recession severity (P < 0.05; binary logistic regression). Cervical tooth wear was recorded in 46.3% of DS patients. Full‐mouth plaque scores (FMPS) and full‐mouth bleeding scores (FMBS) were statistically significantly (P < 0.05; Mann–Whitney U) test lower for DS versus non‐DS patients. Patients reported a low usage (27.4%) and satisfaction (53.8%) rating for desensitizing agents.

Conclusions

The high prevalence of DS was comparable to other studies on periodontitis patients. Progressive periodontal disease and toothbrush abrasion were possible aetiological factors for DS in this study. Knowledge of local dietary practices and the role of acidic (sour) foods in eliciting DS may aid in management. The high prevalence of cervical tooth wear and the lower FMPS and FMBS among DS patients may reflect more aggressive tooth brushing. DS does not seem to be a limitation to plaque control in DS versus non‐DS patients in this study.
Body mass index and oral health status in Korean adults: the Fifth Korea National Health and Nutrition Examination Survey
Authors: Kim Y‐S , Kim J‐H
Published: February 2016

Objectives

The objective of this study was to examine the relationship between body mass index (BMI) and oral health status in Korean adults.

Methods

We used the Fifth Korea National Health and Nutrition Examination Survey to investigate the association between BMI and oral health status. Subjects who were measured for weight and height and had an oral examination in 2010 and 2012 were included (n = 11 466). Using multiple logistic regression analyses adjusted for gender, age, educational level, household income, smoking, frequency of tooth brushing and history of diabetes mellitus, the risk of dental caries and periodontitis was estimated in association with BMI.

Results

In the study population, 90.4% had more than one decayed, missing and filled tooth (DMFT) for permanent tooth, and 23.4% had a community periodontal index score (CPI) of 3 or 4. Distribution of underweight, normal weight, overweight and obese was 4.8, 40.5, 22.4 and 32.2%, respectively. Decayed, missing and filled tooth was highest in the normal weight group, and CPI was significantly highest in the obese group. In the overweight and obese groups, the odds ratios for periodontitis (CPI ≥ 3) were 1.18 [95% confidence interval (CI), 1.01–1.37] before and 1.27 (95% CI, 1.10–1.48) after adjustment for confounding factors. However, the risk for dental caries (DMFT ≥ 1) was not significantly associated with BMI.

Conclusions

Body mass index was related to periodontitis, but not to dental caries, suggesting that obesity is a risk factor for periodontitis.
Breakfast consumption and adiposity among children and adolescents: an updated review of the literature
Authors: Blondin S. A. , Anzman‐Frasca S. , Djang H. C. , Economos C. D.
Published: February 2016

Background

Breakfast consumption has been associated with reduced risk of overweight and obesity among children, but previous evidence reviews fail to confirm a causal relationship.

Objectives

To review recent literature on breakfast consumption and adiposity among children and discuss potential underlying mechanisms.

Methods

A comprehensive literature search of studies published since the 2010 US National Evidence Library review (January 2010–January 2015) was conducted.

Results

Twelve studies met inclusion criteria. All were conducted in industrialized countries: six in Europe, four in the USA, one in China and one in Australia. Ten of the studies used observational longitudinal designs, with follow‐up periods ranging from 1 to 27 years (median: 3, mean: 7.4); of these, eight reported inverse associations between breakfast consumption and excess adiposity, while two found no association. The other studies (1 case‐control, 1 experimental) each reported a protective effect of breakfast consumption on overweight and obesity among children.

Conclusions

Findings corroborate results from previous reviews, adding support for a possible, protective role for breakfast consumption in preventing excess adiposity during childhood and adolescence. However, drawing a causal conclusion from the collective evidence is curtailed by methodological limitations and inconsistencies, including study design, follow‐up duration and frequency, exposure and outcome assessment, as well as limited consideration of confounding, mediating and effect‐modifying variables. More rigorous study designs employing valid and standardized measurement of relevant variables are needed.
Prenatal and early life exposure to traffic pollution and cardiometabolic health in childhood
Authors: Fleisch A. F. , Luttmann‐Gibson H. , Perng W. , Rifas‐Shiman S. L. , Coull B. A. , Kloog I. , Koutrakis P. , Schwartz J. D. , Zanobetti A. , Mantzoros C. S. , Gillman M. W. , Gold D. R. , Oken E.
Published: February 2016

Background

Prenatal exposure to traffic pollution has been associated with faster infant weight gain, but implications for cardiometabolic health in later childhood are unknown.

Methods

Among 1418 children in Project Viva, a Boston‐area pre‐birth cohort, we assessed anthropometric and biochemical parameters of cardiometabolic health in early (median age 3.3 years) and mid‐ (median age 7.7 years) childhood. We used spatiotemporal models to estimate prenatal and early life residential PM2.5 and black carbon exposure as well as traffic density and roadway proximity. We performed linear regression analyses adjusted for sociodemographics.

Results

Children whose mothers lived close to a major roadway at the time of delivery had higher markers of adverse cardiometabolic risk in early and mid‐childhood. For example, total fat mass was 2.1 kg (95%CI: 0.8, 3.5) higher in mid‐childhood for children of mothers who lived <50 m vs. ≥200 m from a major roadway. Black carbon exposure and traffic density were generally not associated with cardiometabolic parameters, and PM2.5 exposure during the year prior was paradoxically associated with improved cardiometabolic profile.

Conclusions

Infants whose mothers lived close to a major roadway at the time of delivery may be at later risk for adverse cardiometabolic health.
Greater Pupil Size in Response to Emotional Faces as an Early Marker of Social‐Communicative Difficulties in Infants at High Risk for Autism
Authors: Wagner Jennifer B. , Luyster Rhiannon J. , Tager‐Flusberg Helen , Nelson Charles A.
Published: February 2016

When scanning faces, individuals with autism spectrum disorder (ASD) have shown reduced visual attention (e.g., less time on eyes) and atypical autonomic responses (e.g., heightened arousal). To understand how these differences might explain subclinical variability in social functioning, 9‐month‐olds, with or without a family history of ASD, viewed emotionally expressive faces, and gaze and pupil diameter (a measure of autonomic activation) were recorded using eye‐tracking. Infants at high risk for ASD with no subsequent clinical diagnosis (HRA‐) and low‐risk controls (LRC) showed similar face scanning and attention to eyes and mouth; attention was overall greater to eyes than mouth, but this varied as a function of the emotion presented. As a group, HRA‐ showed significantly larger pupil size than LRC. Correlations between scanning at 9 months, pupil size at 9 months, and 18‐month social‐communicative behavior, revealed positive associations between pupil size and attention to both face and eyes at 9 months in LRC, and a negative association between 9‐month pupil size and 18‐month social‐communicative behavior in HRA‐.The present findings point to heightened autonomic arousal in HRA‐. Further, with greater arousal relating to worse social‐communicative functioning at 18 months, this work points to a mechanism by which unaffected siblings might develop atypical social behavior.
Seasonal influenza vaccine policy, use and effectiveness in the tropics and subtropics – a systematic literature review
Authors: Hirve Siddhivinayak , Lambach Philipp , Paget John , Vandemaele Katelijn , Fitzner Julia , Zhang Wenqing
Published: February 2016

Aim

The evidence needed for tropical countries to take informed decisions on influenza vaccination is scarce. This article reviews policy, availability, use and effectiveness of seasonal influenza vaccine in tropical and subtropical countries.

Method

Global health databases were searched in three thematic areas – policy, availability and protective benefits in the context of human seasonal influenza vaccine in the tropics and subtropics. We excluded studies on monovalent pandemic influenza vaccine, vaccine safety, immunogenicity and uptake, and disease burden.

Results

Seventy‐four countries in the tropics and subtropics representing 60% of the world's population did not have a national vaccination policy against seasonal influenza. Thirty‐eight countries used the Northern Hemisphere and 21 countries the Southern Hemisphere formulation. Forty‐six countries targeted children and 57 targeted the elderly; though, the age cut‐offs varied. Influenza vaccine supply increased twofold in recent years. However, coverage remained lower than five per 1000 population. Vaccine protection against laboratory‐confirmed influenza in the tropics ranged from 0% to 42% in the elderly, 20–77% in children and 50–59% in healthy adults. Vaccinating pregnant women against seasonal influenza prevented laboratory‐confirmed influenza in both mothers (50%) and their infants <6 months (49–63%).

Conclusion

Guidelines on vaccine composition, priority risk groups and vaccine availability varied widely. The evidence on vaccine protection was scarce. Countries in the tropics and subtropics need to strengthen and expand their evidence‐base required for making informed decisions on influenza vaccine introduction and expansion, and how much benefit to expect.
Nonadherence to Antihypertensive Medication Among Hypertensive Adults in the United States─HealthStyles, 2010
Authors: Tong Xin , Chu Elizabeth K. , Fang Jing , Wall Hilary K. , Ayala Carma
Published: February 2016

Nonadherence, or not taking medications as prescribed, to antihypertensive medications has been associated with uncontrolled hypertension. The authors analyzed data from HealthStyles 2010 to assess medication nonadherence among adults with hypertension. The overall prevalence of hypertension was 27.4% and the prevalence of nonadherence was 30.5% among hypertensive adult respondents. Nonadherence rates were highest among younger adults (aged 18–44 years), Hispanics, those who reported lowest annual income (<$25,000), and those who reported depression. The most common reason stated for nonadherence was “I cannot afford the medication” (35.1%). A multivariate logistic regression model showed age, race, and household income to be associated with nonadherence. These findings suggest that certain subgroups are more likely to report barriers to adherence. Interventions to support the management of hypertension should consider the identification of certain at‐risk subgroups and utilize community and clinical evidenced‐based resources to improve long‐term control.
F‐actin cytoskeleton and the fate of organelles in chromaffin cells
Authors: Villanueva José , Gimenez‐Molina Yolanda , Viniegra Salvador , Gutiérrez Luis M.
Published: February 2016

In addition to playing a fundamental structural role, the F‐actin cytoskeleton in neuroendocrine chromaffin cells has a prominent influence on governing the molecular mechanism and regulating the secretory process. Performing such roles, the F‐actin network might be essential to first transport, and later locate the cellular organelles participating in the secretory cycle. Chromaffin granules are transported from the internal cytosolic regions to the cell periphery along microtubular and F‐actin structures. Once in the cortical region, they are embedded in the F‐actin network where these vesicles experience restrictions in motility. Similarly, mitochondria transport is affected by both microtubule and F‐actin inhibitors and suffers increasing motion restrictions when they are located in the cortical region. Therefore, the F‐actin cortex is a key factor in defining the existence of two populations of cortical and perinuclear granules and mitochondria which could be distinguished by their different location and mobility. Interestingly, other important organelles for controlling intracellular calcium levels, such as the endoplasmic reticulum network, present clear differences in distribution and much lower mobility than chromaffin vesicles and mitochondria. Nevertheless, both mitochondria and the endoplasmic reticulum appear to distribute in the proximity of secretory sites to fulfill a pivotal role, forming triads with calcium channels ensuring the fine tuning of the secretory response. This review presents the contributions that provide the basis for our current view regarding the influence that F‐actin has on the distribution of organelles participating in the release of catecholamines in chromaffin cells, and summarizes this knowledge in simple models.

image

In chromaffin cells, organelles such as granules and mitochondria distribute forming cortical and perinuclear populations whereas others like the ER present homogenous distributions. In the present review we discuss the role of transport systems and the existence of an F‐actin cortical structure as the main factors behind the formation of organelle subpopulations in this neuroendocrine cell model.

This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).

Cover image for this issue: doi: 10.1111/jnc.13322.
The evolution of the meatal chamber in crocodyliforms
Authors: Montefeltro Felipe C. , Andrade Denis V. , Larsson Hans C. E.
Published: February 2016

The unique outer ear of crocodylians consists of a large meatal chamber (MC) concealed by a pair of muscular earlids that shape a large part of the animal's head. This chamber is limited medially by the enlarged tympanic membrane. Yet, the anatomy of this distinctive and complex region is underexplored and its evolutionary history untraced. The osteology and soft tissues of the MC in extant crocodylians was analysed to describe it and establish osteological correlates within this region. A broad survey of the osteological correlates was conducted in major clades of fossil crocodyliforms to estimate evolutionary trends of the MC. The reorganization of the MC at the origin of crocodyliforms includes characters also present in more basal taxa such as ‘sphenosuchians’ as well as unique traits of crocodyliforms. Three major patterns are recognized in the MC of basal mesoeucrocodylians. The distinct ‘thalattosuchian pattern’ indicates that extensive modifications occurred in this clade of aquatic fossil crocodyliforms, even when multiple alternative phylogenetic positions are taken into account. Some traits already established in putative closely related clades are absent or modified in this group. The ‘basal notosuchian/sebecian pattern’ is widespread among basal metasuchians, and establishes for the first time characters maintained later in neosuchians and extant forms. The ‘advanced notosuchian pattern’ includes modifications of the MC possibly related to a terrestrial lifestyle and potentially a structure analogous to the mammalian pinna. The main variation in the MC of neosuchians is associated with the homoplastic secondary opening of the cranioquadrate passage. The inferred phylogenetic trends in the crocodyliform MC suggest the great anatomical disparity in this region followed a complex evolutionary pattern, and tympanic hearing played an important role in the origin and diversification of Crocodyliformes.
Accounting for the influence of inflammation on retinol‐binding protein in a population survey of Liberian preschool‐age children
Authors: Larson Leila Margaret , Addo O. Yaw , Sandalinas Fanny , Faigao Katherine , Kupka Roland , Flores‐Ayala Rafael , Suchdev Parminder S.
Published: February 2016

Vitamin A deficiency (VAD) is an important contributor to child morbidity and mortality. The prevalence of VAD, measured by retinol‐binding protein (RBP) or retinol, is overestimated in populations with a high prevalence of inflammation. We aimed to quantify and adjust for the effect of inflammation on VAD prevalence in a nationally representative survey of Liberian children 6 to 35 months of age. We compared five approaches to adjust RBP for inflammation and estimate VAD prevalence (defined as RBP < 0.7 µmol/L): (1) ignoring inflammation; (2) excluding individuals with inflammation (C‐reactive protein (CRP) >5 mg/L or alpha1‐acid glycoprotein (AGP) >1 g/)L; (3) multiplying each individual's RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP = exp(InRBP – β1(lnCRPobs‐lnCRPref) – β2(lnAGPobs‐lnAGPref)). Corrected RBP was based on a regression model where reference lnCRP and lnAGP were set to the maximum of the lowest decile. The unadjusted prevalence of VAD was 24.7%. Children with elevated CRP and/or AGP had significantly lower RBP concentrations than their apparently healthy peers (geometric mean RBP 0.79 µmol/L (95% CI: 0.76, 0.82) vs. 0.95 µmol/L (95% CI: 0.92, 0.97), P < 0.001). Using approaches 2–5 resulted in a prevalence of VAD of 11.6%, 14.3%, 13.5% and 7.3%, respectively. Depending on the approach, the VAD prevalence is reduced 10–17 percentage points when inflammation is taken into account. Further quantification of the influence of inflammation on biomarkers of vitamin A status from other national surveys is needed to compare and recommend the preferred adjustment approach across populations.