bluuebunny/crossref_metadata_2025 huggingface dataset:
Peperomin E reactivates silenced tumor suppressor genes in lung cancer cells by inhibition of DNA methyltransferase
Authors: Wang Xin‐zhi , Cheng Ying , Wang Kui‐long , Liu Rui , Yang Xiao‐lin , Wen Hong‐mei , Chai Chuan , Liang Jing‐yu , Wu Hao
Published: August 2016

Advanced lung cancer has poor prognosis owing to its low sensitivity to current chemotherapy agents. Therefore, discovery of new therapeutic agents is urgently needed. In this study, we investigated the antitumor effects of peperomin E, a secolignan isolated from Peperomia dindygulensis, a frequently used Chinese folk medicine for lung cancer treatment. The results indicate that peperomin E has antiproliferative effects, promoting apoptosis and cell cycle arrest in non‐small‐cell lung cancer (NSCLC) cell lines in a dose‐dependent manner, while showing lower toxicity against normal human lung epidermal cells. Peperomin E inhibited tumor growth in A549 xenograft BALB/c nude mice without significant secondary adverse effects, indicating that it may be safely used to treat NSCLC. Furthermore, the mechanisms underlying the anticancer effects of peperomin E have been investigated. Using an in silico target fishing method, we observed that peperomin E directly interacts with the active domain of DNA methyltransferase 1 (DNMT1), potentially affecting its genome methylation activity. Subsequent experiments verified that peperomin E decreased DNMT1 activity and expression, thereby decreasing global methylation and reactivating the epigenetically silenced tumor suppressor genes including RASSF1A, APC, RUNX3, and p16INK4, which in turn activates their mediated pro‐apoptotic and cell cycle regulatory signaling pathways in lung cancer cells. The observations herein report for the first time that peperomin E is a potential chemotherapeutic agent for NSCLC. The anticancer effects of peperomin E may be partly attributable to its ability to demethylate and reactivate methylation‐silenced tumor suppressor genes through direct inhibition of the activity and expression of DNMT1.
Design and synthesis of new 2‐anilinoquinolines bearing N‐methylpicolinamide moiety as potential antiproliferative agents
Authors: El‐Damasy Ashraf Kareem , Seo Seon Hee , Cho Nam‐Chul , Pae Ae Nim , Kim Eunice Eunkyeong , Keum Gyochang
Published: August 2016

A series of new 2‐anilinoquinolines 6a–o possessing the substantial N‐methylpicolinamide motif at C5 has been designed and synthesized as sorafenib analogs. The antiproliferative activities of the target compounds were preliminarily appraised against a panel of three human cancer cell lines (MCF‐7, SK‐BR3, and HCT116), and a selected array was further tested over a panel of approximately 60 cancer cell lines at NCI at 10 μM concentration. Interestingly, compounds 6c, 6d, 6j, 6k, and 6l showed promising selective anticancer activities (growth inhibition >80%) toward certain cancer cells at 10 μM testing dose. Compounds 6d and 6j were advanced to five‐dose testing mode to determine their GI50 values and compared with our previously reported ureidoquinoline B and sorafenib as reference compounds. The 4‐chloro‐3‐trifluoromethylaniline derivative 6j manifested superior potency than both compound B and sorafenib over eleven and eight cell lines, respectively. It showed GI50 values of 0.36, 0.66, 0.68, and 0.60 μM against the breast MDA‐MB‐468, renal A498, and melanoma SK‐MEL‐5 and UACC‐62 cell lines, respectively. Moreover, both 6d and 6j exerted low cytotoxic effects against HFF‐1 normal cell line. Furthermore, compounds 6d and 6j were tested against both B‐RafV600E and C‐Raf kinases and displayed modest inhibitory activities, which were justified by molecular docking study. Compound 6j could serve as a promising candidate for further development of potent anticancer chemotherapeutics.
Subjective sleep measures for adolescents: a systematic review
Authors: Ji X. , Liu J.
Published: August 2016

Background

Sleep disturbances in adolescents have received significant attention because of their high prevalence and the negative health outcomes. Relative to objective measures, subjective sleep instruments have been the most practical tools used to identify sleep problems and assess responses to interventions in research and clinical settings. This systematic review aims to examine the psychometric properties of subjective measures that are used to assess sleep quality and disturbances among adolescents, identify the strength and limitation of each measurement and inform recommendations for practice.

Methods

PubMed, Embase and PsycInfo were searched from 2000 through May 2016. The reference lists of important articles were included if they met the inclusion criteria. The available measures were evaluated and classified as positive, intermediate or poor according to the quality criteria for health status questionnaires.

Results

Thirteen self‐reported or parent‐reported sleep measures met the inclusion criteria. Of the measurements reviewed, six were generic instruments assessing overall sleep quality and disturbances; five were dimension‐specific instruments measuring daytime sleepiness, sleep insufficiency and sleep hygiene; and two were condition‐specific instruments for insomnia. None of the subjective sleep measures for adolescents has a psychometric profile with all essential measurement properties. Specifically, the generic sleep measurements capture multiple dimensions but face issues of participant burden and compatibility. Among the domain‐specific tools, the Cleveland Adolescent Sleepiness Questionnaire and the Chronic Sleep Reduction Questionnaire have achieved good psychometric merits but need further evaluation for responsiveness. Likewise, essential measurement properties of condition‐specific tools for insomnia have yet to be established.

Conclusions

Because of the limited evidence, no definite recommendations can be made at this point. However, each available measurement has its own uniqueness and strength despite the limitations. Future research on measurement development and evaluation for adolescent sleep is needed to ensure the relevance and suitability to different stages of adolescence and social contexts.
Half‐century of Dental Public Health research: bibliometric analysis of world scientific trends
Authors: Celeste Roger Keller , Broadbent Jonathan M. , Moyses Samuel Jorge
Published: August 2016

Objectives

To describe the characteristics of Dental Public Health (DPH) scientific publications within core DPH journals over time and to compare DPH journals with DPH content from other journal types.

Methods

The Scopus database was used to identify DPH‐relevant articles published from 1965 to 2014 in three core DPH journals (DPHJs) and from 2005 to 2014 in Dental Journals (DJs), Public Health (PHJs) and General Journals (GJs). To identify DPH‐relevant articles, a search strategy with words about oral health and public health was applied to each group of journals. Research themes were created by grouping similar keywords to report changes in the focus of articles over time. The most productive journals, countries, institutions and authors were also estimated for each set of journals.

Results

In 2005–2014, 60 297 articles were identified, of which 2.7% in DPHJs, 10.4% from PHJs, 38.2% from GJs and 48.7% from DJs. DPH‐relevant articles published in the core DPHJs, DJs and PHJs tended to share a strong emphasis on dental caries, healthcare/services research on children and adolescents. Over time, the focus in the DPHJs has increased towards health behaviour/promotion/education, quality of life and socioeconomic factors. In the last decade, those themes were more frequent in DPH journals than in the other groups.

Conclusions

DPH research published in DPHJs had some unique features and greater focus on the themes of quality of life, socioeconomic factors and health behaviour/education/promotion than other groups of journals.
Adjuvant endocrine therapy in women with oestrogen‐receptor‐positive breast cancer: how should the skeletal and vascular side effects be assessed and managed?
Authors: Ramchand Sabashini K. , Lim Elgene , Grossmann Mathis
Published: August 2016

Adjuvant endocrine therapy provides oncological benefits in women with early oestrogen‐receptor‐positive breast cancer, but has adverse effects consequent to induced oestradiol deficiency. Bone loss is accelerated, predisposing to increased fracture risk. Metabolic effects include changes in lipid metabolism and body composition although effects on cardiovascular risk are still unclear. Women commencing endocrine therapy should be proactively counselled about and monitored for these and other therapy‐related complications including arthralgia and vasomotor symptoms. We provide strategies for prevention and management of these adverse effects, based, where available, on randomized controlled trial evidence specific to breast cancer survivors receiving endocrine treatment.
Bone turnover markers and bone mineral density in healthy mother–daughter pairs from South India
Authors: Shetty Sahana , Kapoor Nitin , Dian Bondu Joseph , Antonisamy Belavendra , Thomas Nihal , Paul Thomas Vizhalil
Published: August 2016

Bone turnover markers (BTMs) provide important insights into the dynamics of bone remodelling and are subjected to preanalytical and ethnic variations in addition to influence of genetic and environmental factors.

Aim/Objectives

To derive ethnicity specific reference range for BTMs and to study their correlation with Bone Mineral Density (BMD) in a cohort of healthy postmenopausal women and their premenopausal daughters and to look at the impact of maternal bone mineral status on daughters bone health.

Material and Methods

This community based cross sectional study included 300 subjects (150 mother‐daughter pairs). Demographic details were collected. Fasting blood and a second void morning urine samples were obtained for measurement of BTMs (sCTX, sPTNP1, sOC and urine DPD respectively) and bone mineral parameters. BMD was measured by DXA scan.

Results

Osteoporosis was seen in 44·7% of the postmenopausal women. Ethnicity specific reference ranges of BTMs were derived for the study population. Significant inverse correlation was found between all BTMs (except urine DPD) and BMD(P < 0·05). Daughters of mothers with osteoporosis at spine and femoral neck had lower BMD, compared to daughters of mothers without osteoporosis(P = 0·03 & 0·05).

Conclusion

Apart from deriving the ethnicity specific reference range for BTMs and finding a significant inverse correlation between BTM and BMD, this study found significantly lower BMD in daughters of mothers with osteoporosis at spine and femoral neck implicating the probable interplay of genetic, epigenetic and similar environmental factors.
Are the literacy difficulties that characterize developmental dyslexia associated with a failure to integrate letters and speech sounds?
Authors: Nash Hannah M. , Gooch Debbie , Hulme Charles , Mahajan Yatin , McArthur Genevieve , Steinmetzger Kurt , Snowling Margaret J.
Published: August 2016

The ‘automatic letter‐sound integration hypothesis’ (Blomert, ) proposes that dyslexia results from a failure to fully integrate letters and speech sounds into automated audio‐visual objects. We tested this hypothesis in a sample of English‐speaking children with dyslexic difficulties (N = 13) and samples of chronological‐age‐matched (CA; N = 17) and reading‐age‐matched controls (RA; N = 17) aged 7–13 years. Each child took part in two priming experiments in which speech sounds were preceded by congruent visual letters (congruent condition) or Greek letters (baseline). In a behavioural experiment, responses to speech sounds in the two conditions were compared using reaction times. These data revealed faster reaction times in the congruent condition in all three groups. In a second electrophysiological experiment, responses to speech sounds in the two conditions were compared using event‐related potentials (ERPs). These data revealed a significant effect of congruency on (1) the P1 ERP over left frontal electrodes in the CA group and over fronto‐central electrodes in the dyslexic group and (2) the P2 ERP in the dyslexic and RA control groups. These findings suggest that our sample of English‐speaking children with dyslexic difficulties demonstrate a degree of letter‐sound integration that is appropriate for their reading level, which challenges the letter‐sound integration hypothesis.
A computational biomarker of idiopathic generalized epilepsy from resting state EEG
Authors: Schmidt Helmut , Woldman Wessel , Goodfellow Marc , Chowdhury Fahmida A. , Koutroumanidis Michalis , Jewell Sharon , Richardson Mark P. , Terry John R.
Published: August 2016

Epilepsy is one of the most common serious neurologic conditions. It is characterized by the tendency to have recurrent seizures, which arise against a backdrop of apparently normal brain activity. At present, clinical diagnosis relies on the following: (1) case history, which can be unreliable; (2) observation of transient abnormal activity during electroencephalography (EEG), which may not be present during clinical evaluation; and (3) if diagnostic uncertainty occurs, undertaking prolonged monitoring in an attempt to observe EEG abnormalities, which is costly. Herein, we describe the discovery and validation of an epilepsy biomarker based on computational analysis of a short segment of resting‐state (interictal) EEG. Our method utilizes a computer model of dynamic networks, where the network is inferred from the extent of synchrony between EEG channels (functional networks) and the normalized power spectrum of the clinical data. We optimize model parameters using a leave‐one‐out classification on a dataset comprising 30 people with idiopathic generalized epilepsy (IGE) and 38 normal controls. Applying this scheme to all 68 subjects we find 100% specificity at 56.7% sensitivity, and 100% sensitivity at 65.8% specificity. We believe this biomarker could readily provide additional support to the diagnostic process.
Ocean acidification has little effect on developmental thermal windows of echinoderms from Antarctica to the tropics
Authors: Karelitz Sam E. , Uthicke Sven , Foo Shawna A. , Barker Mike F. , Byrne Maria , Pecorino Danilo , Lamare Miles D.
Published: August 2016

As the ocean warms, thermal tolerance of developmental stages may be a key driver of changes in the geographical distributions and abundance of marine invertebrates. Additional stressors such as ocean acidification may influence developmental thermal windows and are therefore important considerations for predicting distributions of species under climate change scenarios. The effects of reduced seawater pH on the thermal windows of fertilization, embryology and larval morphology were examined using five echinoderm species: two polar (Sterechinus neumayeri and Odontaster validus), two temperate (Fellaster zelandiae and Patiriella regularis) and one tropical (Arachnoides placenta). Responses were examined across 12–13 temperatures ranging from −1.1 °C to 5.7 °C (S. neumayeri), −0.5 °C to 10.7 °C (O. validus), 5.8 °C to 27 °C (F. zelandiae), 6.0 °C to 27.1 °C (P. regularis) and 13.9 °C to 34.8 °C (A. placenta) under present‐day and near‐future (2100+) ocean acidification conditions (‐0.3 pH units) and for three important early developmental stages 1) fertilization, 2) embryo (prehatching) and 3) larval development. Thermal windows for fertilization were broad and were not influenced by a pH decrease. Embryological development was less thermotolerant. For O. validus, P. regularis and A. placenta, low pH reduced normal development, albeit with no effect on thermal windows. Larval development in all five species was affected by both temperature and pH; however, thermal tolerance was not reduced by pH. Results of this study suggest that in terms of fertilization and development, temperature will remain as the most important factor influencing species' latitudinal distributions as the ocean continues to warm and decrease in pH, and that there is little evidence of a synergistic effect of temperature and ocean acidification on the thermal control of species ranges.
Cricket farming as a livelihood strategy in Thailand
Authors: Halloran Afton , Roos Nanna , Hanboonsong Yupa
Published: August 2016

While many important aspects of wild and farmed insects have been discussed by scholars, such as nutritional value, conservation and farming techniques, no study has addressed how insect farming contributes to rural livelihoods. Furthermore, the roles that interactions between insect farmers, their peers and institutions play in insect farming as a livelihood strategy are even less well understood. This paper presents a preliminary assessment of cricket farming as a livelihood strategy in Thailand. Fortynine cricket farmers participated in in‐depth interviews designed to gain insight into how cricket farming contributes to rural livelihoods. This exploratory study investigates the following research questions: What are the characteristics of Thai cricket farmers and their farms? How do crickets contribute to the lives of rural farmers in Thailand? What role has social and human capital played in cricket farming communities? And what can be learned from the experience of cricket farming in Thailand? Findings suggest that cricket farming has improved the lives of many rural farmers in Thailand not only through the provision of an alternative income source, but through strengthening human and social capital. As such, further empirical data and case study analyses are needed in order to advance our understanding of this particular livelihood strategy.
Housing, population and region in Spain: a currently saturated property market with marked regional differences
Authors: Serrano‐Martínez José‐María , García‐Marín Ramón , Lagar‐Timón David
Published: August 2016

In this paper we analyse the property market in Spain within a regional framework, according to the boundaries of the Spanish Autonomous Communities. Our analysis is based on the central hypothesis that there is an oversupply of housing in Spain, although there are some regional differences within this phenomenon. We first examine the stage known as the ‘property boom’, and we then produce an analysis that aims to simplify the housing market in Spain. After combining numerous variables and applying multivariate statistical techniques, we have obtained a classification with the following three categories: dried‐up markets, saturated markets and less distressed markets. Our analyses confirm the fact that there are disparate realities throughout Spain, and even contrasting realities between the Autonomous Communities.
Self‐perceived taste disturbance: a 20‐year prospective study of a Swedish 1942 birth cohort
Authors: Ekbäck Gunnar , Ordell Sven
Published: August 2016

Objectives

The aim of this study was to assess the impact of dental care factors, general health factors and socio‐economic factors on perceived taste disturbance (PTD) over time and to assess the stability of or change in PTD in a panel of individuals as they progressed from middle age (50 years) to early old age (70 years).

Materials and methods

Data collection was conducted from a cohort study beginning in 1992, when the participants were 50 years old, and again 5, 10, 15 and 20 years later. Stability and change in PTD were described using cross‐tabulation. Perceived taste disturbance over the 20‐year survey period was modelled using the generalised estimating equation (GEE).

Results

The prevalence of PTD during a 5‐year period found in this study ranged from 2.4 to 2.9%, the latter in individuals between 60 and 70 years of age. Women generally had PTD more often than men. The longitudinal analysis showed that problems with bad breath (OR = 3.6), blisters (OR = 3.4), burning mouth (OR = 3.4) and self‐perceived health (OR = 2.7) were the most important factors explaining PTD.

Conclusions

This study showed that PTD does not increase between 50 and 70 years of age in ordinary community‐living individuals. There were no long‐term impacts on PTD over time from socio‐economic factors, and over time, there were a limited number of factors contributing to the effect. Bad breath, blisters, burning mouth and self‐perceived health are important factors for the dentist to discuss with the patient in the case of PTD.
Validated programmed cell death ligand 1 immunohistochemistry assays (E1L3N and SP142) reveal similar immune cell staining patterns in melanoma when using the same sensitive detection system
Authors: Schats Kelly A , Van Vré Emily A , De Schepper Stefanie , Boeckx Carolien , Schrijvers Dorien M , Waelput Wim , Fransen Erik , Vanden Bempt Isabelle , Neyns Bart , De Meester Ingrid , Kockx Mark M
Published: August 2016

Aims

Tumour cell and/or immune cell programmed cell death ligand 1 (PD‐L1) expression is considered as a potential biomarker for anti‐PD1 and anti‐PD‐L1 immunotherapy. Currently, different PD‐L1 assays are used. This study aims to compare the staining patterns of two PD‐L1 antibody clones in melanoma metastases and correlate them with PD‐L1 mRNA expression.

Methods and results

The immunohistochemistry assays were optimized and validated independently on a Ventana Benchmark Ultra (Ventana Medical Systems Inc., Tucson, AZ, USA) (E1L3N) and XT (SP142), using the same detection system. In total, 46 melanoma metastases were stained with both validated immunohistochemistry assays. Stained slides were digitized for qualitative and semi‐quantitative evaluation; done by pathologist and semi‐automated software analysis. A subset of 21 melanoma metastases was selected for quantification of the PD‐L1 mRNA expression. Accuracy and precision criteria were met for both assays. PD‐L1 protein and mRNA expression showed remarkably good Spearman's coefficients of 0.90 (E1L3N) and 0.87 (SP142). Despite the remarkable correlation between both PD‐L1 assays in expression patterns and quantification values (ρ > 0.90), E1L3N showed significantly more tumour cell staining than SP142.

Conclusions

E1L3N and SP142 IHC assays were optimized and validated successfully and independently for sensitive and accurate PD‐L1 detection. Concordance was best for immune cell scoring, while E1L3N tended to detect more tumour cells. Determination of the clinically relevant cut‐off values for immune cell versus tumour cell detection requires further research.
Reducing laundering frequency to prolong the life of denim jeans
Authors: McQueen Rachel H. , Batcheller Jane C. , Moran Lori J. , Zhang Han , Hooper Peter M.
Published: August 2016

The use and disposal phase in a garment's life cycle is highly dependent on the choices made by the consumer. Maintenance procedures such as laundering and drying require energy and water use. Garment disposal increases waste in landfill sites, unless incinerated, which can take a toll on the environment through greenhouse gas emissions. Therefore, encouraging consumers to launder less frequently and finding ways to extend the useful life of clothing are two ways of increasing sustainability within the clothing industry. Denim jeans are one of the most popular items of clothing worldwide. Changing habits such as reducing the frequency with which a person washes their denim jeans could have a positive impact on the environment through less water and energy use. However, environmental knowledge about what is detrimental to the environment may not necessarily lead to pro‐environmental behaviour. In denim jeans fibre loss results in thinning and loss in colour due to use. Laundering in particular can degrade clothing due to the abrasive forces applied to the surface of wet fibres. Therefore, this study highlights the effect that frequent laundering can have on the degradation of jeans with the aim to provide additional motivation to encourage change in consumers’ laundering habits. Consumers wore jeans for the equivalent of 60 days and either washed their jeans after approximately 2 days of wear or after approximately every 20 days of wear. The findings confirmed that frequent laundering reduced mass, increased colour loss, and reduced tensile strength in the warp direction of the fabric. Although washing is a major contributor to the degradation of jeans, the process of wearing denim jeans also naturally degrades the denim as the thigh region of the jeans showed greater colour loss and reduction in tensile strength than the shin region, which is typically less prone to abrasion through wear. The findings from this study provide compelling evidence to encourage consumers to reconsider their laundering habits in terms of wash frequency as both a means to behave in a more environmentally sustainable way, and to preserve their favourite garments.
Impact of various maceration techniques on the phenolic and volatile composition of Chenin Blanc wines
Authors: Wang Jun , Huo Sufang , Zhang Yuxiu , Liu Yaping , Fan Weixin
Published: August 2016

Chenin Blanc, cultivated in cool climate regions, was chosen to evaluate the impact of different maceration techniques on polyphenolic profiles and volatile compounds. Control with no skin contact (CK), cold maceration (CM), cryogenic maceration (CR), separate fermentation before blending (SFB) and extended skin contact during fermentation (ESF) were the five maceration techniques being studied. SFB and ESF techniques resulted in significantly increased polyphenolic compounds compared to the control (P < 0.05), while CM and CR maceration techniques resulted in almost no effect. Meanwhile, for aromatic components, the maximum change was observed in ESF wine, which had significantly highest levels of terpenes, alcohols, esters and acids. However, compared with control wine, CR wine had higher levels of terpenes and esters and SFB wine had higher levels of terpenes and alcohols. This study provides information about prefermentation techniques and additional options for oenologists to produce Chenin Blanc wines with different characteristics.
Cooperation or resistance? Representing workers' health and safety in a hazardous industry
Authors: Walters David , Quinlan Michael , Johnstone Richard , Wadsworth Emma
Published: August 2016

This study considers the actions of worker health and safety representatives in coalmines in Queensland, where there is little evidence of the facilitating role of management previous studies have associated with the successful operation of worker representation in occupational health and safety. It examines how worker representatives deliver their pluralist representational role in a context characterised by essentially unitary thinking amongst their employers and the effectiveness of the strategies they use.
Disparities in Unmet Service Needs Among Adults with Intellectual and Other Developmental Disabilities
Authors: Burke Meghan M. , Heller Tamar
Published: August 2016

Background

Due to long waiting lists for services, many adults with intellectual and developmental disabilities in the United States have unmet service needs. Little research, however, has identified the characteristics of caregivers and individuals with intellectual and developmental disabilities that relate to the unmet service needs among individuals who are waiting for services.

Method

The present authors conducted a statewide mail survey of 234 caregivers of individuals with intellectual and developmental disabilities who were waiting for services. The present authors identified which parent and individual with intellectual and developmental disability characteristics were significantly associated with the number of unmet service needs.

Results

Individuals with intellectual and developmental disabilities who were in poor health, from minority backgrounds and non‐verbal were significantly more likely to have a greater number of unmet service needs. Additionally, individuals with younger caregivers and individuals with caregivers from low‐income backgrounds were significantly more likely to report a greater number of unmet service needs.

Discussion

Implications for research and policy are discussed.
When and how should biotic interactions be considered in models of species niches and distributions?
Authors: Anderson Robert P.
Published: August 2016

Biotic interactions can influence the ranges and abundances of species, but no clear guidelines exist for integrating them into correlative models of niches and distributions. Niche/distributional models characterize environmental/habitat suitability or species presence using predictor variables unaffected by (= unlinked to) the population of the focal species. Such variables (termed ‘scenopoetic’) typically have been considered to include only abiotic factors. In contrast, population–demographic approaches model the abundance of the focal species by including linked predictor variables, which frequently are biotic interactors. Nevertheless, a focal species might hold no, or negligible, population‐level effects on its biotic interactors. Hence, contrary to current theory, such interactors would represent unlinked variables valid and potentially very useful for niche/distributional models. Consideration of population‐level effects indicates that facilitators and affecting amensals (species that negatively affect another species but are not affected by it) constitute unlinked variables, but commensals and affected amensals do not. For competitors, mutualists, predators/prey, consumers/resources, and parasites/hosts, additional information is necessary. Specifically, available ecological/natural history information for the particular species involved (e.g. regarding specificity) and theory regarding ecological networks can allow identification of interactors that are likely to be unlinked or nearly so. Including an unlinked biotic interactor as a predictor variable in a niche/distributional model should improve predictions when the effects of the biotic interactor vary across the study region, or in another place or time period. Other relevant interactors must be taken into account by post‐processing a niche/distributional model, or via population–demographic models that require abundance data over time. This framework should improve current correlative models and highlights areas requiring progress.
Historical biogeography of Boraginales: West Gondwanan vicariance followed by long‐distance dispersal?
Authors: Luebert Federico , Couvreur Thomas L. P. , Gottschling Marc , Hilger Hartmut H. , Miller James S. , Weigend Maximilian
Published: August 2016

Aim

To examine the historical biogeography of the Boraginales using molecular dating and ancestral area reconstruction.

Location

World‐wide.

Methods

We constructed data sets that included all major clades of Boraginales and all orders of asterids using previously published sequences of four plastid markers (trnL‐trnF, rps16, ndhF, rbcL). We estimated divergence times using a Bayesian uncorrelated, lognormal relaxed clock approach with four different fossil calibration schemes. Ancestral areas were reconstructed using maximum likelihood methods (Dispersal‐Extinction‐Cladogenesis).

Results

Boraginales originated during the Early to Late Cretaceous and started its diversification in the Late Cretaceous. The inferred ancestral area of Boraginales includes the Americas and Africa. The two major clades of Boraginales diversified during the Early Paleogene from African and American ancestors respectively. Early branching families in both clades (Codonaceae and Wellstediaceae in one clade and Hydrophyllacee and Namaceae in the other) may have remained restricted to their areas of origin. The other families started diversifying in several regions of the world during the Eocene (Boraginaceae s.str., Heliotropiaceae, Ehretiaceae) or later (Cordiaceae).

Main conclusions

Molecular dating and ancestral area reconstruction may be broadly consistent with the idea of a vicariant origin of the two major clades of Boraginales after the break‐up of West Gondwana, followed by several independent trans‐oceanic dispersal events into most areas of the world. However, uncertainty in both divergence times and ancestral area reconstruction do not rule out the possibility of an origin involving long‐distance dispersal.
Characteristics and Methodological Quality of Meta‐Analyses on Hypertension Treatments—A Cross‐Sectional Study
Authors: Wu Xin Yin , Du Xin Jian , Ho Robin S.T. , Lee Clarence C.Y. , Yip Benjamin H.K. , Wong Martin C.S. , Wong Samuel Y.S. , Chung Vincent C.H.
Published: August 2016

Methodological quality of meta‐analyses on hypertension treatments can affect treatment decision‐making. The authors conducted a cross‐sectional study to investigate the methodological quality of meta‐analyses on hypertension treatments. One hundred and fifty‐eight meta‐analyses were identified. Overall, methodological quality was unsatisfactory in the following aspects: comprehensive reporting of financial support (1.9%), provision of included and excluded lists of studies (22.8%), inclusion of grey literature (27.2%), and inclusion of protocols (32.9%). The 126 non‐Cochrane meta‐analyses had poor performance on almost all the methodological items. Non‐Cochrane meta‐analyses focused on nonpharmacologic treatments were more likely to consider scientific quality of included studies when making conclusions. The 32 Cochrane meta‐analyses generally had good methodological quality except for comprehensive reporting of the sources of support. These results highlight the need for cautious interpretation of these meta‐analyses, especially among physicians and policy makers when guidelines are formulated. Future meta‐analyses should pay attention to improving these methodological aspects.
Atherosclerotic Surrogate Markers in Adults With Down Syndrome: A Case‐Control Study
Authors: Parra Pedro , Costa Ramón , de Asúa Diego Real , Moldenhauer Fernando , Suárez Carmen
Published: August 2016

The authors aimed to compare surrogate markers of atherosclerosis (pulse wave velocity, intima‐media thickness) between adults with and without Down syndrome (DS) and to assess the impact of parathyroid hormone levels and classic cardiovascular risk factors on arterial stiffness. After comparing 51 adults with DS and 51 healthy adults (siblings of DS individuals), the authors found that adults with DS seem to have lower arterial stiffness, as a result of chronic hypotension. Subclinical atherosclerosis parameters do not correlate with traditional cardiovascular risk factors in adults with DS, thus raising the hypothesis that classic predictive models for cardiovascular disease are not valid in this population. Hyperparathyroidism could play an important role in arterial damage in these individuals. The lower than expected prevalence of obesity and dyslipidemia could be explained by better eating habits, with this study being the first to address the anthropometric and clinical profile of a Mediterranean cohort of adults with DS.
Phase 3, open‐label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate‐to‐severe plaque psoriasis (UNCOVER‐A)
Authors: Callis Duffin K. , Bagel J. , Bukhalo M. , Mercado Clement I.J. , Choi S.L. , Zhao F. , Gill A. , Pangallo B. , Shuler C. , Mallbris L. , Jackson K.
Published: August 2016

Background

The efficacy of ixekizumab, an anti‐interleukin‐17A (anti‐IL‐17A) monoclonal IgG4 antibody, was demonstrated in moderate‐to‐severe psoriasis patients when administered via prefilled syringe (PFS).

Objective

To evaluate the effect of two drug delivery devices on the pharmacokinetics (PK) of ixekizumab as well as efficacy and safety with both devices.

Methods

In the first 12 weeks of an open‐label, phase 3 study, moderate‐to‐severe psoriasis patients were randomized to ixekizumab delivery via PFS or autoinjector device. Randomization was stratified by weight (<80 kg, 80–100 kg, >100 kg), injection assistance (yes/no) and injection site (arm, thigh or abdomen). Following a 160‐mg initial dose at week 0, patients received subcutaneous 80‐mg ixekizumab as a single injection every 2 weeks for 12 weeks. Blood samples were collected following the initial 160‐mg dose on days 2, 4, 7, 10 and 14 for PK analysis. Primary PK parameters were maximum concentration (Cmax) and area under the curve (AUC0‐tlast) where tlast is the time of last sample (14 days ± 24 h). Efficacy was assessed by percent improvement on the Psoriasis Area and Severity Index (PASI) at week 12. Adverse event reporting, vital signs and clinical laboratory data were used to evaluate safety.

Results

Of 204 randomized patients, 192 were included in the PK analysis (PFS: 94; autoinjector: 98). The PFS and autoinjector showed similar geometric mean Cmax (90% CI) [15.0 μg/mL (13.9–16.1) vs. 14.8 μg/mL (13.8–15.9)] and geometric mean AUC0‐tlast (90% CI) [157 μg × day/mL (147–168) vs. 154 μg × day/mL (144–165)]. When comparing Cmax and AUC0‐tlast of the autoinjector to PFS, the geometric LS mean ratios were 0.97. At week 12, mean percent PASI improvement (via modified baseline observation carried forward) was similar with the PFS (89.3%) and autoinjector (86.9%). Both devices had safety results that were consistent with the known safety profile of ixekizumab.

Conclusion

The PK, efficacy and safety of ixekizumab administered subcutaneously by PFS and autoinjector were similar.

Clinicaltrials.gov number: NCT01777191 https://clinicaltrials.gov/ct2/show/NCT01777191
Disruption of host‐seeking behaviour by the salmon louse, Lepeophtheirus salmonis, using botanically derived repellents
Authors: O'Shea B , Wadsworth S , Pino Marambio J , Birkett M A , Pickett J A , Mordue (Luntz) A J
Published: August 2016

The potential for developing botanically derived natural products as novel feed‐through repellents for disrupting settlement of the salmon louse, Lepeophtheirus salmonis (Caligidae) upon farmed Atlantic salmon, Salmo salar, was investigated using an established laboratory vertical Y‐tube behavioural bioassay for assessing copepodid behaviour. Responses to artificial sea water conditioned with the odour of salmon, or to the known salmon‐derived kairomone component, α‐isophorone, in admixture with selected botanical materials previously known to interfere with invertebrate arthropod host location were recorded. Materials included oils extracted from garlic, Allium sativum (Amaryllidaceae), rosemary, Rosmarinus officinalis (Lamiaceae), lavender, Lavandula angustifolia (Lamiaceae), and bog myrtle, Myrica gale (Myricaceae), and individual components (diallyl sulphide and diallyl disulphide from garlic; allyl, propyl, butyl, 4‐pentenyl and 2‐phenylethyl isothiocyanate from plants in the Brassica genus). Removal of attraction to salmon‐conditioned water (SCW) or α‐isophorone was observed when listed materials were presented at extremely low parts per trillion (ppt), that is picograms per litre or 10−12 level. Significant masking of attraction to SCW was observed at a level of 10 ppt for diallyl disulphide and diallyl sulphide, and allyl isothiocyanate and butyl isothiocyanate. The potential of very low concentrations of masking compounds to disrupt Le. salmonis copepodid settlement on a host fish has been demonstrated in vitro.
Effectiveness of community‐based exercise intervention programme in obese adults with metabolic syndrome
Authors: Chang Shu‐Hung , Chen Miao‐Chuan , Chien Nai‐Hui , Lin Hsih‐Fong
Published: August 2016

Aims and objectives

The objective of this study was to change the anthropometric, clinical, biochemical indicators and the rate of metabolic syndrome among obese adults in community.

Background

Obesity is an indicator of metabolic syndrome and cardiometabolic diseases. Obesity increases national health care expenditure in Taiwan. The high prevalence of obesity is not only a public health issue but also an economic problem. Changes in lifestyle can help to prevent metabolic syndrome for individuals with obesity.

Design

A randomised controlled trial was applied.

Methods

In this randomised controlled trial by location, 136 metabolically abnormal obese individuals were included. The related indicators with metabolic syndrome were measured at baseline and after six months. The experimental group participated in a six‐month community‐based programme including provided exercise environments, exercise skills and volunteers' reminding. The control group was only provided environment and skills.

Results

One hundred and thirty‐one participants completed this trail. In comparison with the baseline, the intervention group showed a significant increase in high‐density lipoprotein cholesterol (2·34 mg/dl), and decrease in body weight (1·09 kg), waist circumference (3·63 cm), systolic blood pressure (10·52 mmHg), diastolic blood pressure (5·21 mmHg), fasting blood glucose (5·84 mg/dl) and body mass index (0·74 kg/m2). In the control group, significant decrease in body mass index and waist circumference were discovered. Compared to the changes between the two groups, the results showed there were significant differences in waist circumference, systolic blood pressure, diastolic blood pressure and high‐density lipoprotein cholesterol.

Conclusions

The community‐based intervention could help to improve high‐density lipoprotein cholesterol, reduce body weight, body mass index, waist circumference, blood pressure and fasting blood glucose in metabolically abnormal obese.

Relevance to clinical practice

This community‐based programme helped metabolically abnormal obese individuals become metabolically healthy. In the future, community nurses will work with village heads and volunteers. They can encourage residents in the communities to have healthy lifestyle. As a result, the goal of this programme will be successfully achieved with less time and effort.
The Intergenerational Consequences of Parental Health Limitations
Authors: Hardie Jessica Halliday , Turney Kristin
Published: August 2016

Scholars have theorized interrelationships between family members' health and well‐being. Though prior research demonstrates associations between parents' and children's health, less is known about the relationship between parental health limitations and children's behavioral and academic outcomes. This article uses data from the Fragile Families and Child Well being Study (N = 3,273) to estimate the relationship between parental health limitations and four aspects of children's well‐being. Findings reveal that mothers' health limitations, especially when they occur in middle childhood or chronically, are independently associated with greater internalizing and externalizing behaviors, lower verbal ability, and worse overall health at age 9. Fathers' health limitations are not associated with children's well‐being. Fathers exert influence in other ways, as the relationship between mothers' chronic health limitations and children's internalizing behaviors is concentrated among children not residing with their fathers. These findings support the development of policies and interventions aimed at families.
Father Absence and Adolescent Depression and Delinquency: A Comparison of Siblings Approach
Authors: Markowitz Anna J. , Ryan Rebecca M.
Published: August 2016

Although associations between having a nonresident father and increased internalizing and externalizing behaviors in adolescence have been well documented, research has yet to establish the plausible causality of these links or identify underlying mechanisms. Using data from the National Longitudinal Survey of Youth 1979 ‐ Young Adult survey, this study addresses these questions by comparing the depressive symptoms and delinquent behavior of siblings discordant for age at father departure. Findings indicate that father departure later in childhood is associated with increased adolescent delinquency but not depressive symptoms, whereas early childhood father departure was not associated with adolescent outcomes. Both findings suggests that parental monitoring—rather than socialization or emotional distress—may account for links between father departure and adolescent delinquency.
Identification of a combined biomarker for malignant transformation in oral submucous fibrosis
Authors: Bazarsad Shadavlonjid , Zhang Xianglan , Kim Ki‐Yeol , Illeperuma Rasika , Jayasinghe Ruwan D , Tilakaratne Wanninayake M , Kim Jin
Published: August 2016

Background

Oral submucous fibrosis (OSF) is a chronic progressive disease of the oral cavity that is considered a common potentially malignant disorder in South Asia. Areca nut chewing is the main etiological factor, but its carcinogenic mechanism has yet to be proven. The purpose of this study was to identify the useful biomarkers in predicting high‐risk patients with OSF.

Methods

Thirty‐six cases of OSF and six cases of normal oral mucosa (NOM) were used for this study. Immunohistochemical staining was performed for Ki67, cyclin D1, p16, p53, β‐catenin, c‐Jun, c‐Met, and insulin‐like growth factor II mRNA‐binding protein 3 (IMP3). The expression patterns of NOM served as guidelines for the scoring system.

Results

The expression of Ki67, cyclin D1, c‐Met, IMP3, and β‐catenin showed a significant difference between OSF and NOM samples. The combined biomarkers of Ki67 and p16 showed significantly different expression between the transformation and non‐transformation groups. With discriminant analysis, we proposed a noble formula and cutoff value for predicting high‐risk patients with OSF.

Conclusion

The notable biomarkers in our present study were Ki67 and p16 showing significantly different expression levels between the transformation and non‐transformation groups. With the identification of high‐risk patients with OSF, we can expect to develop more intensive treatment modalities, leading to the reduction in cancer transformation rate from OSF.
The Association Between Leaf Malondialdehyde and Lignin Content and Resistance to Spot Blotch in Wheat
Authors: Yusuf Comfort S. , Chand Ramesh , Mishra Vinod K. , Joshi Arun K.
Published: August 2016

Spot blotch (causative pathogen Bipolaris sorokiniana (Sacc.) Shoem) is a common disease of wheat in the Eastern Gangetic Plains region of India. The association of leaf malondialdehyde and lignin contents with the severity of spot blotch disease was studied using a correlation analysis based on a population of recombinant inbred lines bred from the cross cvs. Yangmai 6 (resistant) × Sonalika (susceptible). The material was field‐tested over two consecutive years and inoculated artificially with a highly virulent strain of the pathogen. Disease severity was assessed at three growth stages around and after anthesis. Leaf lignin content tended to be higher in the more resistant RILs, while the opposite was the case for leaf malondialdehyde content. Lesion size showed a positive correlation with disease severity and leaf malondialdehyde content, while disease severity and leaf lignin content were negatively correlated with one another, as were leaf malondialdehyde and leaf lignin content. Leaf malondialdehyde and/or leaf lignin content could be informative as markers for selection for higher levels of resistance against spot blotch in wheat.