bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐intensity exercise training ameliorates aberrant expression of markers of mitochondrial turnover but not oxidative damage in skeletal muscle of men with essential hypertension
Authors: Fiorenza Matteo , Gunnarsson Thomas P. , Ehlers Thomas S. , Bangsbo Jens
Published: October 2018

Aim

To examine whether hypertensive individuals exhibit altered muscle mitochondrial turnover and redox homeostasis compared with healthy normotensive counterparts, and whether the antihypertensive effect of high‐intensity exercise training is associated with improved mitochondrial quality and enhanced anti‐oxidant defence.

Methods

In a cross‐sectional and longitudinal parallel design, 24 essential hypertensive (HYP) and 13 healthy normotensive (NORM) men completed 6 weeks of high‐intensity interval training (HIIT). Twenty four‐hour ambulatory blood pressure, body composition, cardiorespiratory fitness, exercise capacity and skeletal muscle characteristics were examined before and after HIIT. Expression of markers of mitochondrial turnover, anti‐oxidant protection and oxidative damage was determined in vastus lateralis muscle biopsies. Muscle protein levels of eNOS and VEGF, and muscle capillarity were also evaluated.

Results

At baseline, HYP exhibited lower expression of markers of mitochondrial volume/biogenesis, mitochondrial fusion/fission and autophagy along with depressed eNOS expression compared with NORM. Expression of markers of anti‐oxidant protection was similar in HYP and NORM, whereas oxidative damage was higher in HYP than in NORM. In HYP, HIIT lowered blood pressure, improved body composition, cardiorespiratory fitness and exercise capacity, up‐regulated markers of mitochondrial volume/biogenesis and autophagy and increased eNOS and VEGF protein content. Furthermore, in HYP, HIIT induced divergent responses in markers of mitochondrial fusion and anti‐oxidant protection, did not affect markers of mitochondrial fission, and increased apoptotic susceptibility and oxidative damage.

Conclusion

The present results indicate aberrant muscle mitochondrial turnover and augmented oxidative damage in hypertensive individuals. High‐intensity exercise training can partly reverse hypertension‐related impairments in muscle mitochondrial turnover, but not redox imbalance.
Examining Cross‐Cultural Differences in Academic Faking in 41 Nations
Authors: Fell Clemens B. , König Cornelius J.
Published: October 2018

This study examines cross‐cultural differences in students’ academic faking (indicated by claiming to have impossible knowledge about mathematical concepts) by relating data from the Programme for International Student Assessment (PISA) to the comprehensive cultural framework of the Global Leadership and Organizational Behavior Effectiveness (GLOBE) project. Data of N = 233,428 students from 41 countries showed a substantial amount of variance in academic faking between cultures. Students’ academic faking was positively related to the cultural dimensions of gender egalitarianism, humane orientation, and in‐group collectivism. Additionally, the similarity between female and male students’ academic faking was slightly greater in more gender‐egalitarian cultures than in less gender‐egalitarian cultures. Thus, educational stakeholders (e.g., teachers, principals, and policy‐makers) should be made aware of cross‐cultural differences in academic faking because faking gives fakers an unfair advantage.
The enigmatic ATP supply of the endoplasmic reticulum
Authors: Depaoli Maria R. , Hay Jesse C. , Graier Wolfgang F. , Malli Roland
Published: October 2018

The endoplasmic reticulum (ER) is a functionally and morphologically complex cellular organelle largely responsible for a variety of crucial functions, including protein folding, maturation and degradation. Furthermore, the ER plays an essential role in lipid biosynthesis, dynamic Ca2+ storage, and detoxification. Malfunctions in ER‐related processes are responsible for the genesis and progression of many diseases, such as heart failure, cancer, neurodegeneration and metabolic disorders. To fulfill many of its vital functions, the ER relies on a sufficient energy supply in the form of adenosine‐5′‐triphosphate (ATP), the main cellular energy source. Despite landmark discoveries and clarification of the functional principles of ER‐resident proteins and key ER‐related processes, the mechanism underlying ER ATP transport remains somewhat enigmatic. Here we summarize ER‐related ATP‐consuming processes and outline our knowledge about the nature and function of the ER energy supply.
Next generation sequencing‐based gene panel tests for the management of solid tumors
Authors: Nagahashi Masayuki , Shimada Yoshifumi , Ichikawa Hiroshi , Kameyama Hitoshi , Takabe Kazuaki , Okuda Shujiro , Wakai Toshifumi
Published: October 2018

Next generation sequencing (NGS) has been an invaluable tool to put genomic sequencing into clinical practice. The incorporation of clinically relevant target sequences into NGS‐based gene panel tests has generated practical diagnostic tools that enable individualized cancer‐patient care. The clinical utility of gene panel testing includes investigation of the genetic basis for an individual's response to therapy, such as signaling pathways associated with a response to specific therapies, microsatellite instability and a hypermutated phenotype, and deficiency in the DNA double‐strand break repair pathway. In this review, we describe the concept of precision cancer medicine using target sequences in gene panel tests as well as the importance of the control of sample quality in routine NGS‐based genomic testing. We describe geographic and ethnic differences in cancer genomes, and discuss issues that need to be addressed in the future based on our experiences in Japan.
Influence of novel implant selective laser melting framework design on mechanical durability of acrylic veneer
Authors: Abduo Jaafar , Curtis Michael , Budhwar Vandana , Palamara Joseph
Published: October 2018

Background

A novel implant framework design is proposed to improve the mechanical durability of acrylic veneer.

Purposes

Comparing the mechanical durability of acrylic veneer on implant frameworks fabricated from selective laser melting (SLM) with novel design against conventional computer numeric controlled (CNC) milled frameworks.

Materials and Methods

Implant titanium frameworks with distal cantilever were fabricated by SLM (n = 10) and CNC milling (n = 10). The CNC frameworks had multiple vertical pins, while the SLM frameworks had 3D metal networks of horizontal beams connected by vertical struts. All the frameworks were veneered with acrylic teeth and resin material and were subjected to a static load‐to‐failure test at the cantilever region. The load‐to‐failure readings and the pattern of prosthesis damage were recorded for each prosthesis.

Results

The CNC and SLM prostheses failed at statistically similar loads. The acrylic veneer around the CNC frameworks tend to initially crack around the distal implant followed by acrylic chipping. Six SLM prostheses failed at the framework connector on the mesial implant by separation of the screw seat. After reloading these prostheses, they failed by acrylic veneer chipping. The SLM prostheses had significantly less incidence of acrylic flexure and severity of acrylic veneer chipping than CNC prostheses.

Conclusions

The SLM framework with novel design is efficient in reinforcing acrylic veneering. However, the SLM frameworks appeared weak in thin sections, such as the screw seat.
Evaluating Supervision Models in Functional Family Therapy: Does Adding Observation Enhance Outcomes?
Authors: Robbins Michael S. , Waldron Holly Barrett , Turner Charles W. , Brody Janet , Hops Hyman , Ozechowski Timothy
Published: October 2018

This study examined the effects of observation‐based supervision Building Outcomes with Observation‐Based Supervision of Therapy (BOOST therapists = 26, families = 105), versus supervision as usual (SAU therapists = 21, families = 59) on (a) youth externalizing behavior problems and (b) the moderating effects of changes in family functioning on youth externalizing behaviors for adolescents receiving Functional Family Therapy (FFT). Exploratory analyses examined the impact of supervision conditions on youth internalizing problems. In 8 community agencies, experienced FFT therapists (M = 1.4 years) received either BOOST or SAU supervision in a quasi‐experimental design. Male (59%) or female (41%) adolescents were referred for the treatment of behavior problems (e.g., delinquency, substance use). Clients were Hispanic (62%), African American (19%), Non‐Hispanic White (12%), or Other (7%) ethnic/racial origins. Therapists (female, 77%) were Hispanic 45%, African American (19%), White Non‐Hispanic (30%), or other (4%) ethnic/racial backgrounds. Analyses controlled for the presence or absence of clinically elevated symptoms on outcome variables. Clinical outcomes were measured at baseline, 5 months, and 12 months after treatment initiation. Clients with externalizing behavior above clinical thresholds had significantly greater reductions in problem behaviors in the BOOST versus the SAU conditions. Clients below thresholds did not respond differentially to conditions. Supervisors in BOOST had more experience with the FFT model; as such, the observed results may be a result of supervisor experience. The BOOST supervision was associated with improved outcomes on problem behaviors that were above clinical thresholds. The findings demonstrate the importance of addressing client case mix in implementation studies in natural environments.
Scene‐Based Psychodramatic Family Therapy With Troubled Adolescents and Parents: A Pilot Study
Authors: Maya Jesús , Jiménez Lucía , Lorence Bárbara , del Moral Gonzalo , Hidalgo Victoria
Published: October 2018

Scene‐Based Psychodramatic Family Therapy (SB‐PFT) is an innovative treatment used with troubled adolescents and their parents to improve family relationships and reduce adolescents’ problematic behavior. It integrates the principles of family therapy, psychodrama, and multiple‐family group methodology. This research is a pilot study to obtain empirical evidence on theSB‐PFTtherapeutic process by gauging the perception of change of troubled adolescents and their parents, and assess the perceived helpfulness of its methodology and techniques. Ten multiple‐family intervention groups were drawn up, with 110 participants (63 adolescents and 47 parents), and we adopted a qualitative methodology with focus groups, using an inductive analysis of 290 active constructions of participant narratives. Concerning perception of change, the adolescents reported mainly gaining in social support, prosocial attitudes, keys to problem solving, and expression of emotions due to the treatment. The parents perceived improvement in social support, keys for educational practices, emotional well‐being, and expression of emotions due to the treatment. Regarding the perceived helpfulness of methodology and techniques, both adolescents and parents highlighted the usefulness of the group methodology for gaining social support, relativizing the problem, and expressing emotions. Additionally, participants referred to role‐playing and mirror techniques as the most useful techniques. In conclusion, this first study onSB‐PFTpresents and describes its treatment for troubled adolescents and their parents. The participants’ positive perception of their personal and relational change after treatment should serve to promote further studies with quantitative methodology in order to verify the effectiveness ofSB‐PFTtreatment.
Social Services Professionals' Views of Barriers to Supporting Homeless Noncustodial Fathers
Authors: Rogers Tiana N. , Rogers Charles R.
Published: October 2018

Objective

To investigate barriers to service for homeless noncustodial fathers from the perspective of social service professionals who work directly to assist men with securing housing while meeting the demands of fatherhood.

Background

The population of homeless fathers in the United States is increasing. Longitudinal studies show that although homeless noncustodial fathers and mothers face similar risk factors and barriers to services, research on minimizing risk factors and barriers for noncustodial fathers is limited compared with that for noncustodial mothers.

Method

The sample included 7 administrators and 12 direct service professionals engaged with fathers transitioning from homelessness. Data were collected via face‐to‐face, semistructured interviews and analyzed using a qualitative inductive approach. Multiple‐cycle coding was used to capture emerging themes.

Results

Three major themes, encompassing emotional, relational, and systemic factors, emerged regarding participants' experiences serving homeless noncustodial fathers.

Conclusion

Effective approaches to supporting fathers require empathy, relationship building, and collaboration between service providers and policymakers.

Implications

Future policies and interventions should be based on input from direct service professionals and homeless noncustodial fathers themselves, with the aim of best supporting their efforts toward securing housing while meeting the demands of fatherhood.
Transnationalism, diaspora, and development: A purposive review of the literature
Authors: Tan Yan , Liu Xuchun , Rosser Andrew , Yeoh Brenda , Guo Fei
Published: October 2018

In view of the observation of some scholars and policymakers that contemporary international migration and its developmental effects are better understood from a transnational perspective, this paper attempts a systematic review of the impact of the transnational perspective on the relationship between migration and development in the fields of migration studies, population studies, and demography. Based on a study of 666 publications on transnationalism, diaspora, and development derived using keyword searches of the Web of Science database and a more in‐depth review of a subset of 60 influential papers on transnational linkages, the paper discusses five types of transnational linkages—familial, political, economic, sociocultural, and subjective. While the influence of transnationalism has been profound, stimulating an innovative body of work on changing migration patterns, the linkages between diaspora and their homelands, and the impact of these linkages on development, the review also identified significant gaps, namely, the inadequate attention to generating evidence of the developmental impact of transnational migration, particular in the Global South; the lack of consideration for the way diaspora from single homelands is internally differentiated and distributed across multiple transnational social spaces; and the need to identify data sources for more robust quantitative analyses of the multiple linkages between diaspora and development.
Moral dilemmas reflect professional core values of pharmacists in community pharmacy
Authors: Kruijtbosch Martine , Göttgens-Jansen Wilma , Floor-Schreudering Annemieke , van Leeuwen Evert , Bouvy Marcel L
Published: October 2018

Objectives

The aim was to recognise the professional core values in the moral dilemmas of pharmacists in community pharmacy and to customise the descriptions of these values for community pharmacy practice.

Methods

The narratives of 128 moral dilemmas, collected from Dutch PharmD students and early career pharmacists who experienced these dilemmas in practice, were qualitatively analysed. An expert panel deductively coded relevant portions of these narratives with the core values as formulated by the Royal Dutch Pharmacists Association. Other values that emerged were inductively coded and if possible used to further customise the respective core values.

Key findings

The expert panel identified all four professional core values, that is, commitment to the patient’s well-being (117, 91.4%), reliable and caring (116, 90.6%), pharmaceutical expertise (72, 56.2%) and responsibility to society (30, 23.4%) in the 128 moral dilemma narratives. Thirteen other values that emerged in the analysis could all be used for the customisation of the professional core values in descriptions that better reflect community pharmacy practice.

Conclusions

Professional core values were identified in moral dilemma narratives of pharmacists in community pharmacy and customised for their practice. These customised core values can enable pharmacists to better recognise moral dilemmas in practice. This can add to the advancement of the profession as a pharmaceutical care practice.
HMGB1 deficiency reduces H2O2‐induced oxidative damage in human melanocytes via the Nrf2 pathway
Authors: Mou Kuanhou , Liu Wei , Miao Yi , Cao Fang , Li Pan
Published: October 2018

Oxidative stress leads to melanocyte death and has been implicated in the pathogenesis of vitiligo. The nuclear factor, E2‐related factor 2 (Nrf2), is a critical transcription factor in protecting cells from oxidative damage. High‐mobility group box 1 (HMGB1) is a chromatin‐associated nuclear protein and an extracellular damage‐associated molecular pattern molecule. Extracellular HMGB1 released from activated immune cells, necrotic or injured cells, becomes a proinflammatory mediator through binding to cell‐surface receptors of responding cells. In this study, we investigated the role of HMGB1 from melanocytes in the response to oxidative stress and the mechanism involved. We showed that HMGB1 is expressed by primary normal human epidermal melanocytes (NHEMs). H2O2 treatment increased cytoplasmic translocation and extracellular release of HMGB1. HMGB1 knockdown by small interfering RNA (siRNA) led to decreased apoptosis of NHEMs. HMGB1 inhibition enhanced the expression of Nrf2 and its target genes. The expression of Nrf2 and its downstream antioxidant genes was downregulated after the supernatant of H2O2‐treated NHEMs was added to HMGB1‐deficient cells. HMGB1 knockdown by siRNA suppressed the expression of the autophagosome marker, LC3, and enhanced p62 expression. Coimmunoprecipitation with Keap1 showed a reduced Nrf2‐Keap1 interaction and an increased p62‐Keap1 interaction under oxidative stress. These data demonstrated that external stimuli (eg, oxidative stress) may trigger autocrine HMGB1 translocation and release by melanocytes, suppressing the expression of Nrf2 and downstream antioxidant genes to induce melanocyte apoptosis, and thereby participate in the pathological process of vitiligo.
MiR‐17 family‐mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling
Authors: Ye Dan , Lou Guohua , Zhang Tianbao , Dong Fengqin , Liu Yanning
Published: October 2018

The aberrant expression of Pknox1 is associated with hepatic glucose and lipid dysmetabolism status of type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism causing Pknox1 overexpression in this pathological status remains unclear. By using miRNA target prediction programs, we found that the 3′‐UTR of the Pknox1 mRNA sequence contains highly conserved target sites of miR‐17 family. In a rat model of streptozotocin and high‐fat diet‐induced T2DM and NAFLD complication, the increased hepatic expression of Pknox1 was consistent with decreased expressions of miR‐17 family, especially miR‐17 and miR‐20a. Furthermore, an inverse correlation was observed between Pknox1 and miR‐17 and miR‐20a in free fatty acids‐induced hepatocyte steatosis. Dual‐luciferase reporter assay further showed that Pknox1 was a valid target gene of miR‐17 family. The ectopic expression of miR‐17 or miR‐20a could markedly suppress Pknox1 expression in hepatocytes. MiR‐17 or miR‐20a overexpression also resulted in significantly enhanced insulin sensitivity and reduced hepatocyte steatosis in HepG2 and L02 cells, which were determined by altered phosphorylation on insulin receptor signaling pathway proteins and decreased intracellular triglyceride and lipid accumulation, respectively. These data implicate the upregulated hepatic expression of Pknox1 in T2DM complicated with NAFLD may be caused by the reduced expression of miR‐17 family, indicating that developing miRNA‐mediated regulation strategies on Pknox1 may provide new therapeutic options for metabolic disease.
The applications of CRISPR/Cas system in molecular detection
Authors: Zhou Li , Peng Rongxue , Zhang Rui , Li Jinming
Published: October 2018

The Streptococcus pyogenes CRISPR/Cas system has found widespread applications as a gene‐editing and regulatory tool for the simultaneous delivery of the Cas9 protein and guide RNAs into the cell, thus making the recognition of specific DNA sequences possible. The recent study that shows that Cas9 can also bind to and cleave RNA in an RNA‐programmable manner is suggestive of potential utility of this system as a universal nucleic‐acid recognition tool. To increase the signal intensity of the CRISPR/Cas system, a signal amplification technique has to be exploited appropriately; this requirement is also a challenge for the detection of DNA or RNA. Furthermore, the CRISPR/Cas system may be used to detect point mutations or single‐nucleotide variants because of the specificity of the recognition between the target sequence and the CRISPR/Cas system. These lines of evidence make this technique capable of detecting pathogens during infection via analysis of their DNA or RNA. Thus, here we summarize applications of the CRISPR/Cas system to the recognition and detection of DNA and RNA molecules as well as the signal amplification. We also describe its potential ability to detect mutations and single‐nucleotide variants. Finally, we sum up its applications to testing for pathogens and potential barriers for its implementation.
Systematic identification and analysis of dysregulated miRNA and transcription factor feed‐forward loops in hypertrophic cardiomyopathy
Authors: Shi Hongbo , Li Jiayao , Song Qiong , Cheng Liang , Sun Haoran , Fan Wenjing , Li Jianfei , Wang Zhenzhen , Zhang Guangde
Published: October 2018

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. Although some genes and miRNAs related with HCM have been studied, the molecular regulatory mechanisms between miRNAs and transcription factors (TFs) in HCM have not been systematically elucidated. In this study, we proposed a novel method for identifying dysregulated miRNA‐TF feed‐forward loops (FFLs) by integrating sample matched miRNA and gene expression profiles and experimentally verified interactions of TF‐target gene and miRNA‐target gene. We identified 316 dysregulated miRNA‐TF FFLs in HCM, which were confirmed to be closely related with HCM from various perspectives. Subpathway enrichment analysis demonstrated that the method was outperformed by the existing method. Furthermore, we systematically analysed the global architecture and feature of gene regulation by miRNAs and TFs in HCM, and the FFL composed of hsa‐miR‐17‐5p, FASN and STAT3 was inferred to play critical roles in HCM. Additionally, we identified two panels of biomarkers defined by three TFs (CEBPB, HIF1A, and STAT3) and four miRNAs (hsa‐miR‐155‐5p, hsa‐miR‐17‐5p, hsa‐miR‐20a‐5p, and hsa‐miR‐181a‐5p) in a discovery cohort of 126 samples, which could differentiate HCM patients from healthy controls with better performance. Our work provides HCM‐related dysregulated miRNA‐TF FFLs for further experimental study, and provides candidate biomarkers for HCM diagnosis and treatment.
Upregulation of AMPK by 4‐O‐methylascochlorin promotes autophagy via the HIF‐1α expression
Authors: Seok Ji‐Young , Jeong Yun‐Jeong , Hwang Soon‐Kyung , Kim Cheorl‐Ho , Magae Junji , Chang Young‐Chae
Published: October 2018

4‐O‐methylascochlorin (MAC) is a derivative of ascochlorin, a prenyl‐phenol compound antibiotic isolated from the fungus Ascochyta viciae. MAC induces caspase/poly (ADP‐ribose) polymerase‐mediated apoptosis in leukemia cells. However, the effects of MAC on autophagy in cancer cells and the underlying molecular mechanisms remain unknown. Here, we show that MAC induces autophagy in lung cancer cells. MAC significantly induced the expression of autophagy marker proteins including LC3‐II, Beclin1, and ATG7. MAC promoted AMP‐activated protein kinase (AMPK) phosphorylation and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream signalling proteins P70S6K and 4EBP1. The AMPK activator AICAR upregulated LC3‐II expression through the AMPK/mTOR pathway similar to the effects of MAC. MAC‐induced LC3‐II protein expression was slightly reduced in AMPK siRNA transfected cells. MAC upregulated hypoxia‐inducible factor‐1α (HIF‐1α) and BNIP3, which are HIF‐1α‐dependent autophagic proteins. Treatment with CoCl2, which mimics hypoxia, induced autophagy similar to the effect of MAC. The HIF‐1α inhibitor YC‐1 and HIF‐1α siRNA inhibited the MAC‐induced upregulation of LC3‐II and BNIP3. These results suggest that MAC induces autophagy via the AMPK/mTOR signalling pathway and by upregulating HIF‐1α and BNIP3 protein expression in lung cancer cells.
Detecting early‐warning signals of influenza outbreak based on dynamic network marker
Authors: Chen Pei , Chen Ely , Chen Luonan , Zhou Xianghong Jasmine , Liu Rui
Published: October 2018

The seasonal outbreaks of influenza infection cause globally respiratory illness, or even death in all age groups. Given early‐warning signals preceding the influenza outbreak, timely intervention such as vaccination and isolation management effectively decrease the morbidity. However, it is usually a difficult task to achieve the real‐time prediction of influenza outbreak due to its complexity intertwining both biological systems and social systems. By exploring rich dynamical and high‐dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics. In order to detect the early‐warning signals before the influenza outbreak by applying DNM method, the historical information of clinic hospitalization caused by influenza infection between years 2009 and 2016 were extracted and assembled from public records of Tokyo and Hokkaido, Japan. The early‐warning signal, with an average of 4‐week window lead prior to each seasonal outbreak of influenza, was provided by DNM‐based on the hospitalization records, providing an opportunity to apply proactive strategies to prevent or delay the onset of influenza outbreak. Moreover, the study on the dynamical changes of hospitalization in local district networks unveils the influenza transmission dynamics or landscape in network level.
Advanced glycation end products‐related modulation of cathepsin L and NF‐κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα
Authors: Sharif Umar , Mahmud Nur Musfirah , Kay Paul , Yang Yit C. , Harding Simon P. , Grierson Ian , Kamalden Tengku Ain , Jackson Malcolm J. , Paraoan Luminita
Published: October 2018

The retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age‐related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)—known to accumulate on the ageing RPE's underlying Bruch's membrane in situ—on both key lysosomal cathepsins and NF‐κB signalling in RPE. Cathepsin L activity and NF‐κB effector levels decreased significantly following 2‐week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE‐related change of NF‐κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE‐exposed cells had significantly higher ratio of phospho‐p65(Ser536)/total p65 compared to non‐AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE‐related activation of NF‐κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF‐κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para‐inflammatory) mechanism but renders them more responsive to pro‐inflammatory stimuli.
Cardiac‐specific Mst1 deficiency inhibits ROS‐mediated JNK signalling to alleviate Ang II‐induced cardiomyocyte apoptosis
Authors: Cheng Zheng , Zhang Mingming , Hu Jianqiang , Lin Jie , Feng Xinyu , Wang Shanjie , Wang Tingting , Gao Erhe , Wang Haichang , Sun Dongdong
Published: October 2018

Apoptosis is associated with various myocardial diseases. Angiotensin II (Ang II) plays a central role in the pathogenesis of RAAS‐triggered cardiac apoptosis. Our previous studies showed that mammalian Ste20‐like kinase 1 (Mst1) aggravates cardiac dysfunction in cardiomyocyte under pathological conditions, but its role in Ang II‐mediated cardiomyocyte apoptosis is not known. We addressed this in the present study by investigating whether cardiac‐specific Mst1 knockout can alleviate Ang II‐induced cardiomyocyte apoptosis along with the underlying mechanisms. In vitro and in vivo experiments showed that Ang II increased intracellular reactive oxygen species (ROS) production and cardiomyocyte apoptosis; these were reversed by administration of the ROS scavenger N‐acetylcysteine and by Mst1 deficiency, which suppressed c‐Jun N‐terminal kinase (JNK) phosphorylation and downstream signaling. Interestingly, Mst1 knockout failed to alleviate Ang II‐induced phosphorylation of extracellular signal‐regulated kinase 1/2, and inactivated apoptosis signal‐regulating kinase1 (ASK1) by promoting its association with thioredoxin (Trx), which reversed the Ang II‐induced activation of the ASK1–JNK pathway and suppressed Ang II‐induced cardiomyocyte apoptosis. Thus, cardiac‐specific Mst1 knockout inhibits ROS‐mediated JNK signalling to block Ang II‐induced cardiomyocyte apoptosis, suggesting Mst1 as a potential therapeutic target for treatment of RAAS‐activated heart failure.
MiR‐30‐5p suppresses cell chemoresistance and stemness in colorectal cancer through USP22/Wnt/β‐catenin signaling axis
Authors: Jiang Shixiong , Miao Dazhuang , Wang Muhong , Lv Jiachen , Wang Yihui , Tong Jinxue
Published: October 2018

Colorectal cancer (CRC) remains both common and fatal, and its successful treatment is greatly limited by the development of stem cell‐like characteristics (stemness) and chemoresistance. MiR‐30‐5p has been shown to function as a tumor suppressor by targeting the Wnt/β‐catenin signaling pathway, but its activity in CRC has never been assessed. We hypothesized that miR‐30‐5p exerts anti‐oncogenic effects in CRC by regulating the USP22/Wnt/β‐catenin signaling axis. In the present study, we demonstrate that tissues from CRC patients and human CRC cell lines show significantly decreased miR‐30‐5p family expression. After identifying the 3’UTR of USP22 as a potential binding site of miR‐30‐5p, we constructed a luciferase reporter containing the potential miR‐30‐5p binding site and measured the effects on USP22 expression. Western blot assays showed that miR‐30‐5p decreased USP22 protein expression in HEK293 and Caco2 CRC cells. To evaluate the effects of miR‐30‐5p on CRC cell stemness, we isolated CD133 + CRC cells (Caco2 and HCT15). We then determined that, while miR‐30‐5p is normally decreased in CD133 + CRC cells, miR‐30‐5p overexpression significantly reduces expression of stem cell markers CD133 and Sox2, sphere formation, and cell proliferation. Similarly, we found that miR‐30‐5p expression is normally reduced in 5‐fluorouracil (5‐FU) resistant CRC cells, whereas miR‐30‐5p overexpression in 5‐FU resistant cells reduces sphere formation and cell viability. Inhibition of miR‐30‐5p reversed the process. Finally, we determined that miR‐30‐5p attenuates the expression of Wnt/β‐catenin signaling target genes (Axin2 and MYC), Wnt luciferase activity, and β‐catenin protein levels in CRC stem cells.
Liver X receptor activation reduces gastric cancer cell proliferation by suppressing Wnt signalling via LXRβ relocalization
Authors: Wang Qiang , Feng Fan , Wang Jiayou , Ren Meijia , Shi Zhonggang , Mao Xiang , Zhang Heng , Ju Xiaoli
Published: October 2018

Liver X receptors (LXRs) are involved in various diseases associated with lipid disorders, and in regulating cancer cell proliferation. However, the underlying molecular mechanisms, especially those in gastric cancer (GC) remain to be clarified. In this study, immunohistochemistry analysis revealed that LXRβ was mainly expressed in GC tissue, with less expression in adjacent normal tissues. The LXRβ agonist T0901317 efficiently suppressed the proliferation and colony formation of various GC cell lines. We further showed that LXRβ translocated from the cytoplasm to the nucleus when activated by T0901317. LXRβ nuclear localization suppressed the activation of Wnt signalling and decreased the expression of target genes such as MYC, BMP4, and MMP7 through binding to their promoters. Moreover, we demonstrated that the LXR agonist efficiently suppressed GC tumour growth in a nude mouse xenograft model. Taken together, these results revealed that LXRβ agonist inhibited GC cells proliferation by suppressing Wnt signalling via LXRβ relocalization. The results strongly suggest that LXRβ could be a promising target in GC therapy.
Molecular epidemiology of human papillomavirus genotypes in oral rinses from HIV‐positive and HIV‐negative Jamaican patients
Authors: Rajendra Santosh Arvind B. , Christian Nicole A. , Jones Thaon , Thoms‐Rodriguez Camille‐Ann A. , Condappa Andrew , Thompson Tamara , Pinkney Jodian , Barton Everard N. , Lindo John
Published: October 2018

Aim

Human papillomavirus (HPV) has been reported to be associated with oral and oropharyngeal cancer. However, little information is available about the epidemiology of oral HPV infection in Jamaica. The purpose of the present study was to assess the prevalence of oral HPV strains using the oral rinse method in HIV and non‐HIV Jamaican patients, as well as to determine the association of HPV with sexual practices, smoking, and alcohol use.

Methods

A cross‐sectional study was conducted on patients attending The University of the West Indies Mona Dental Polyclinic and the Centre for HIV/AIDS Research and Education Services. Salivary samples were tested through molecular analysis for 37 HPV genotypes using the linear array HPV genotyping test. A survey questionnaire was used to obtain demographic details, smoking history, alcohol practice, sexual practice, and history of HPV testing.

Results

The HPV prevalence was 8.65% in 18‐64 y olds (N = 104), with a slight female predilection (55%). No high‐risk HPV types were found. HPV‐84 was the most common type in both HIV and non‐HIV patients; 66.7% of HPV‐positive participants reported that they had six or more lifetime sexual partners.

Conclusion

The prevalence of oral HPV was similar to that in other countries. No statistically‐significant relationship was observed between the prevalence of HPV and either the number of sexual partners, smoking, or alcohol history. A nationwide study on oral HPV detection might be helpful in developing a HPV vaccination policy in Jamaica.
A case of uterine lymphangioleiomyomatosis in a young woman that was identified via peritonitis
Authors: Yoshizawa Hikari , Kawai Satoshi , Hirota Yutaka , Ueda Takahiro , Kuroda Makoto , Fujii Takuma
Published: October 2018

Although lymphangioleiomyomatosis is often observed with tuberous sclerosis, uterine lymphangioleiomyomatosis is rare. Our patient was 36 years old (gravida 0, para 0). She had a history of tuberous sclerosis, and many myometrial cystic lesions were identified during assisted reproductive therapy. Although we administered a gonadotropin‐releasing hormone analog, myometrial cystic lesions increased in size. Therefore, simple hysterectomy, bilateral salpingo‐oophorectomy and pelvic lymph node biopsy were performed. Postoperative histology showed lymphangioleiomyomatosis and myometrial abscess. For uterine lesions in young women with tuberous sclerosis, the possibility of uterine lymphangioleiomyomatosis should also be considered.
Antibodies: The major participants in maternal–fetal interaction
Authors: Yang Xin , Zhang Caiji , Chen Guozhen , Sun Chengming , Li Jinming
Published: October 2018

The aim of this study is to improve our understanding of the mechanisms involved in maternal–fetal immune tolerance. We searched the related literatures and overviewed the major antibodies associated with pregnancy and described in details their possible roles in mediating maternal–fetal interactions. Antibodies classified into different types based on their functional or structural characteristics were summarized, including immunoglobulin G, blocking antibody, nonprecipitating asymmetric antibody, antiphospholipid antibody, antitrophoblast antibody and antipaternal antibody. The presence and levels of various circulating antibodies in pregnancy may play a crucial role in the occurrence, development and termination of pregnancy.
Expertise in the Game of Go and Levels of Visuospatial and Pattern Recognition Abilities
Authors: Wojtasinski Marcin , Francuz Piotr
Published: October 2018

The results of existing research indicate higher levels of visuospatial and pattern recognition abilities in experts in the game of Go compared to novices. However, the tasks included in the research have been focused only on Go‐game situations. This study aimed to verify the hypothesis that experts in the game of Go would achieve higher scores, compared to novices, on behavioral tests measuring visuospatial abilities and that pattern recognition tests would be a predictor of group membership (experts, low‐skill players, novices). We consider that the game of Go can be treated as a special case of tasks related to visuospatial abilities and pattern recognition. Sixty men participated in the study, including 17 experts in the game of Go, 13 low‐skill players, and 30 novices. The results of behavioral tests—the advanced version of Raven's Progressive Matrices and the APIS‐Z Test's Visuospatial Abilities subscale, which measure pattern recognition and visuospatial abilities, respectively—confirmed the hypotheses.
Patterns of Alcohol Use Among Patients Living With HIV in Urban, Large Rural, and Small Rural Areas
Authors: Bensley Kara M. , McGinnis Kathleen A. , Fortney John , Chan K. C. Gary , Dombrowski Julia C. , Ornelas India , Edelman E. Jennifer , Goulet Joseph L. , Satre Derek D. , Justice Amy C. , Fiellin David A. , Williams Emily C.
Published: October 2018

Background

For people living with HIV (PLWH), alcohol use is harmful and may be influenced by unique challenges faced by PLWH living in rural areas. We describe patterns of alcohol use across rurality among PLWH.

Methods

Veterans Aging Cohort Study electronic health record data were used to identify patients with HIV (ICD‐9 codes for HIV or AIDS) who completed AUDIT‐C alcohol screening between February 1, 2008, and September 30, 2014. Regression models estimated and compared 4 alcohol use outcomes (any use [AUDIT‐C > 0] and alcohol use disorder [AUD; ICD‐9 codes for abuse or dependence] diagnoses among all PLWH, and AUDIT‐C risk categories: lower‐ [1‐3 men/1‐2 women], moderate‐ [4‐5 men/3‐5 women], higher‐ 6‐7]), and severe‐risk [8‐12], and heavy episodic drinking (HED; ≥1 past‐year occasion) among PLWH reporting use) across rurality (urban, large rural, small rural) and census‐defined region.

Findings

Among 32,699 PLWH (29,540 urban, 1,301 large rural, and 1,828 small rural), both any alcohol use and AUD were highest in urban areas, although this varied across region. Predicted prevalence of any alcohol use was 54.1% (53.5%‐54.7%) in urban, 49.6% (46.9%‐52.3%) in large rural, and 50.6% (48.3%‐52.9%) in small rural areas (P < .01). Predicted prevalence of AUD was 14.4% (14.0%‐14.8%) in urban, 11.8% (10.0%‐13.5%) in large rural, and 12.3% (10.8%‐13.8%) in small rural areas (P < .01). Approximately 12% and 25% had higher‐ or severe‐risk drinking and HED, respectively, but neither differed across rurality.

Conclusion

Though some variation across rurality and region was observed, alcohol‐related interventions are needed for PLWH across all geographic locations.
Overcoming Barriers to Prescribing Buprenorphine for the Treatment of Opioid Use Disorder: Recommendations from Rural Physicians
Authors: Andrilla C. Holly A. , Moore Tessa E. , Patterson Davis G.
Published: October 2018

Purpose

The United States is in the midst of a severe opioid use disorder epidemic. Buprenorphine is an effective office‐based treatment that can be prescribed by physicians, nurse practitioners, and physician assistants with a Drug Enforcement Administration (DEA) waiver. However, many providers report barriers that keep them from either getting a DEA waiver or fully using it. The study team interviewed rural physicians successfully prescribing buprenorphine to identify strategies for overcoming commonly cited barriers for providing this service.

Methods

Interview candidates were randomly selected from a list of rurally located physicians with a DEA waiver to prescribe buprenorphine who reported treating high numbers of patients on a 2016 survey. Forty‐three rural physicians, who were prescribing buprenorphine to a high number of patients, were interviewed about how they overcame prescribing barriers previously identified in that survey.

Findings

Interviewed physicians reported numerous ways to overcome common barriers to providing buprenorphine treatment in rural areas. Key recommendations included ways to (1) get started and maintain medication‐assisted treatment, (2) minimize DEA intrusion and medication diversion, and (3) address the lack of mental health providers and stigma surrounding opioid use disorder (OUD). Overall, physicians found providing this service to be very rewarding.

Conclusions

Despite known barriers, rural physicians around the country have been successful in adding buprenorphine treatment to their practices. Nonprescribing providers can learn from the strategies used by successful prescribers to add this service.
Sex hormone levels by presence and severity of cirrhosis in women with chronic hepatitis C virus infection
Authors: Sarkar Monika , Lai Jennifer C. , Sawinski Deirdre , Zeigler Toni E. , Cedars Marcelle , Forde Kimberly A.
Published: October 2018

Cirrhosis is associated with hormonal dysregulation, as evidenced by secondary amenorrhoea in reproductive‐aged women, and feminization of cirrhotic men. Whether hormone levels vary by severity of cirrhosis in women is not known. If identified, such changes may have important clinical relevance, particularly, as low sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) are known to promote metabolic and cardiovascular disease in women. In a cohort of post‐menopausal women with chronic hepatitis C virus (HCV) infection, we compared comprehensive sex hormone levels by presence of cirrhosis, as well as across Child‐Turcotte‐Pugh (CTP) class. Results: There were n = 18 cirrhotic and n = 21 noncirrhotic women with a median age of 57 years (interquartile range [IQR] 53‐62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0 pg/mL, P = 0.05) and oestrone levels (32.0 vs 8.0 ng/mL, P < 0.001), and lower sex hormone binding globulin (SHBG) (69.2 vs 155.6 nmol/L, P = 0.001), and FSH levels (4.9 vs 89.6 mIU/mL, P < 0.001). Among cirrhotic women, there was a progressive decline in FSH and SHBG and concurrent rise in oestrone levels from CTP class A to C (test of trend, P values ≤0.02). Cirrhosis is associated with lower FSH and SHBG levels in cirrhotic compared to noncirrhotic women with HCV infection. In cirrhotic women, these levels demonstrate steady decline by disease severity. Given known associations of low SHBG and FSH with cardio‐metabolic disease, the clinical implications of hormonal changes by cirrhosis severity in HCV‐infected women warrants investigation.
Which results of the standard test for community‐weighted mean approach are too optimistic?
Authors: Zelený David
Published: October 2018

Aims

The community‐weighted mean (CWM) approach is used to analyse the relationship between species attributes (traits, Ellenberg‐type indicator values) and sample attributes (environmental variables, richness) via the community matrix. It has recently been shown to suffer from inflated Type I error rate if tested by a standard test and the results of many published studies are probably affected. I review the current knowledge about this problem, and clarify which studies are likely affected and by how much.

Methods

I suggest classifying hypotheses commonly tested by CWM approach into three categories, which differ in the formulation of the null hypothesis. I use simulated and real data to show how the Type I error rate of the standard test is affected by data characteristics.

Results

The CWM approach with the standard test returns a correct Type I error rate for hypotheses assuming a link between species attributes and composition (Category A). However, for hypotheses assuming a link between composition and sample attributes (Category B) or not assuming any link (Category C), the standard test is inflated, and alternative tests are needed to control for this. The inflation of standard tests for Category C is negatively related to the compositional β‐diversity, and positively to the strength of the composition–sample attributes relationship and data set sample size. These results apply to CWM analyses with extrinsic sample attributes (not derived from the compositional matrix). CWM analysis with intrinsic sample attributes (derived from the composition, such as species richness) is a case of spurious correlation and can be tested using a column‐based (modified) permutation test.

Conclusions

The concept of three hypothesis categories offers a simple tool to evaluate which hypothesis has been tested and whether the results have correct or inflated Type I error rate. In the case of inflated results, the level of inflation can be estimated from the data characteristics.