bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary results of a novel hay-hole fall prevention initiative
Authors: Batra Erich K. , Gross Brian W. , Jammula Shreya , Bradburn Eric H. , Baier Ronald D. , Reihart Michael J. , Murphy Dennis , Moyer Kay , Hess Joseph , Lackmann Susan , Miller Jo Ann , Rogers Frederick B.
Published: December 2017

BACKGROUND

Hay-hole falls are a prevalent source of trauma among Anabaptists—particularly Anabaptist youth. We sought to decrease hay-hole falls in South Central Pennsylvania through the development and distribution of all-weather hay-hole covers to members of the at-risk Anabaptist community.

METHODS

Following the creation of a rural trauma prevention syndicate, hay-hole cover prototypes co-designed and endorsed by the Pennsylvania Amish Safety Committee were developed and distributed throughout South Central Pennsylvania. Preintervention and postintervention surveys were distributed to recipients to gain an understanding of the hay-hole fall problem in this population, to provide insight into the acceptance of the cover within the community, and to determine the efficacy of the cover in preventing falls.

RESULTS

A total of 231 hay-hole covers were distributed throughout eight rural trauma-prone counties in Pennsylvania. According to preintervention survey data, 52% of cover recipients reported at least one hay-hole fall on their property, with 46% reporting multiple falls (median fall rate, 1.00 [1.00–2.00] hay-hole falls per respondent). The median self-reported distance from hay-hole to ground floor was 10.0 (8.00–12.0) feet, and the median number of hay-holes present on-property was 3.00 (2.00–4.00) per respondent. Postintervention survey data found 98% compliance with hay-hole cover installation and no subsequent reported hay-hole falls.

CONCLUSION

With the support of the Pennsylvania Amish Safety Committee, we developed a well-received hay-hole cover which could effectively reduce fall trauma across other rural communities in the United States.

LEVEL OF EVIDENCE

Epidemiological study, Level III.
Variations in outcomes of emergency general surgery patients across hospitals: A call to establish emergency general surgery quality improvement program
Authors: Ogola Gerald O. , Crandall Marie L. , Shafi Shahid
Published: December 2017

BACKGROUND

National Surgical Quality Improvement Program and Trauma Quality Improvement Program have shown variations in risk-adjusted outcomes across hospitals. Our study hypothesis was that there would be similar variation in risk-adjusted outcomes of emergency general surgery (EGS) patients.

METHODS

We undertook a retrospective analysis of the National Inpatient Sample database for 2010. Patients with EGS diseases were identified using American Association for the Surgery of Trauma definitions. A hierarchical logistic regression model was used to model in-hospital mortality, accounting for patient characteristics, including age, sex, race, ethnicity, insurance type, and comorbidities. Predicted-to-expected mortality ratios with 90% confidence intervals were used to identify hospitals as low mortality (ratio significantly lower than 1), high mortality (ratio significantly higher than 1), or average mortality (ratio overlapping 1).

RESULTS

Nationwide, 2,640,725 patients with EGS diseases were treated at 943 hospitals in 2010. About one-sixth of the hospitals (139, 15%) were low mortality, a quarter were high mortality (221, 23%), and the rest were average mortality. Mortality ratio at low mortality hospitals was almost four times lower than that of high mortality hospitals (0.57 vs. 2.03, p < 0.0001). If high and average mortality hospitals performed at the same level as low mortality hospitals, we estimate 16,812 (55%) more deaths than expected.

CONCLUSION

There are significant variations in risk-adjusted outcomes of EGS patients across hospitals, with several thousand higher than expected number of deaths nationwide. Based on the success of National Surgical Quality Improvement Program and Trauma Quality Improvement Program, we recommend establishing EGS quality improvement program for risk-adjusted benchmarking of hospitals for EGS patients.

LEVEL OF EVIDENCE

Care management, level III.
One-Year Retention Study of Adjunctive Perampanel Treatment in Epilepsy Patients
Authors: Kim Dong Wook , Oh Jeeyoung
Published: December 2017

Objectives

Perampanel is a recently introduced antiepileptic drug (AED) with a unique action mechanism of noncompetitive and selective α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist. Because of delayed approval of perampanel in most Asian countries, there is limited information on the clinical usefulness of perampanel in the Asian population. We performed a retrospective analysis of retention rate, seizure outcome, and adverse events for perampanel treatment in South Korea.

Methods

This was a retrospective, single-center, 1-year observational study. A total of 137 epilepsy patients (86 men, 51 women; age, 17–86 years) who were treated with perampanel as an adjunctive treatment were included. Perampanel was administered at a starting dose of 2 mg/d, and optimal-dose adjustments were made according to individual clinical responses. Efficacy and tolerability were analyzed during a 1-year follow-up.

Results

The overall retention rate was 71.3% at the 6-month follow-up and 61.0% at the 1-year follow-up. Retention rates were similar between patients with 1 concomitant AED and those taking 2 or more concomitant AEDs. The most common adverse event was somnolence, followed by dullness and psychiatric reactions, and the presence of psychiatric comorbidity was significantly associated with the development of psychiatric adverse reactions.

Conclusions

We showed that the retention rate and adverse events for adjunctive perampanel treatment in the Korean population were comparable with those in Western countries. Our study also suggests that adjuvant perampanel treatment may be effective in patients taking a higher number of concomitant AEDs and that psychiatric comorbidity may be a risk factor for perampanel-induced psychiatric reactions.
Anger Assessment in Patients Treated With Brivaracetam
Authors: Ortega Gemma , Abraira Laura , Martí Glòria , Quintana Manuel , Mazuela Gonzalo , Santamarina Estevo , Salas-Puig Xavier , Toledo Manuel
Published: December 2017

Objectives

To assess state and trait anger, adjusted by epilepsy type, seizure control, anxiety-depression status and quality of life, in patients treated with brivaracetam (BRV) from an open study.

Methods

We evaluated prospectively consecutive patients with partial onset seizures in an open-label study. Patients had 5 years or longer of epilepsy and were taking between 1 and 3 antiepileptic drugs. They were treated with BRV and compared with a control group selected from outpatients attending our epilepsy unit who met the following criteria: age ≥16 years and diagnosis of epilepsy with focal-onset seizures at least 1 year before inclusion in the study. The following tests were assessed: State-Trait Anger with the Expression Inventory-2, Hospital Anxiety and Depression Scale, and Quality of Life in Epilepsy Inventory.

Results

We recruited 39 patients, 17 treated with BRV and 22 with other drugs, including 13 with levetiracetam (LEV). Mean age was 47.3 years, 43.6% were men. Symptomatic cases, 66% and 52% temporal lobe epilepsy. Antiepileptic drug polytherapy was present in 82.1% of the cases (100% BRV vs 68.2% control group). Demographic and clinical characteristics, as well as Quality of Life in Epilepsy Inventory and Hospital Anxiety and Depression Scale scores were similar in both groups. When compared with the subgroup of LEV groups did not differ significantly on their Hospital Anxiety and Depression Scale scores.

Conclusions

This small, open study suggests that BRV increases anger measures less than LEV in epilepsy patients. However, larger, blinded control studies are required to establish whether this apparent difference can be confirmed.
Drug-Associated Spontaneous Orgasm: A Case Report and Systematic Review of Literature
Authors: Chen Wei-Hsi , Chu Yuan-Hsiang , Chen Kuo-Yen
Published: December 2017

Objectives

Spontaneous orgasm is characterized by a spontaneous onset of orgasm without any preceding sexual or nonsexual trigger. It sheds insight on the mechanisms underlying orgasms and the sexual response cycle in humans.

Methods

We report a male patient of repetitive spontaneous orgasm under trazodone treatment and systematically review the literature on drug-associated spontaneous orgasm (DASO).

Results

A total of 25 patients (18 women and 7 men), including our reported case, experienced 27 DASO events. Over half of them were under 50 years of age during the DASO event. Depression was the leading morbidity for these patients, and a limited list of antidepressants and antipsychotics were involved in 92.5% of all DASO events. Although offending drugs possess variable pharmacological properties, their common effect is an augmentation of serotonin-1A (5HT1A) neurotransmission. Offending drugs seemingly increase personal susceptibility to DASO. Over half of the patients, especially men, did not concurrently experience sexual arousal or desire during the DASO event. In the remaining patients, the orgasm was accompanied by or ensued with arousal or desire. A reduction of dose or discontinuation of the offending drug usually abolished DASO.

Conclusions

It appears that 5HT1A has a key role in generating orgasm. Orgasms may be activated through arousal-independent or arousal-dependent pathways, and both orgasms and sexual arousal are bidirectionally activated. This double-bidirectional model of sexual response cycle may promote the success of sexual procreation and recreation, and further research on this pathway could offer an innovative method to manage anorgasmia in the future.
Integrating Multiplex SiMPull and Computational Modeling to Evaluate Combinatorial Aspects of EGFR Signaling
Authors: Salazar-Cavazos Emanuel , Nitta Carolina Franco , Mitra Eshan D. , Wilson Bridget S. , Lidke Keith A , Hlavacek William S. , Lidke Diane S.
Published: December 2017

The Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1) plays an important role in both physiological and cancer-related processes. To study the factors that influence receptor phosphorylation, we have coupled Single Molecule Pull-down (SiMPull) measurements with rule-based modeling of EGFR signaling. Using SiMPull, we quantified the phosphorylation state of thousands of individual receptors. These measurements enabled the first direct detection of multisite phosphorylation on full-length EGFR and revealed that the extent of phosphorylation varies by tyrosine site and is dependent on the relative abundance of signaling partners that limit access by tyrosine phosphatases. We also evaluated the impact of oncogenic mutations and ligands with varying affinity on phosphorylation kinetics. Simulations highlight the importance of dimer lifetimes on EGFR phosphorylation and signaling output.
Collateral sensitivity to β-lactam drugs in drug-resistant tuberculosis is driven by the transcriptional wiring of BlaI operon genes
Authors: Trigos AS , Goudey BW , Bedő J , Conway TC , Faux NG , Wyres KL
Published: December 2017

Background:

The evolution and spread of antimicrobial resistance is a major global public health threat. In some cases the evolution of resistance to one antimicrobial seemingly results in enhanced sensitivity to another (known as ‘collateral sensitivity’). This largely underexplored phenomenon represents a fascinating evolutionary paradigm that opens new therapeutic possibilities for patients infected with pathogens unresponsive to classical treatments. Intrinsic resistance to β-lactams in Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis) has traditionally curtailed the use of these low-cost and easy-to-administer drugs for tuberculosis treatment. Recently, β-lactam sensitivity has been reported in strains resistant to classical tuberculosis drug therapy, leading to a resurgence of interest in using β-lactams in the clinic. Unfortunately though, there remains a limited understanding of the mechanisms driving β-lactam sensitivity.

Methods:

We used a novel combination of systems biology and computational approaches to characterize the molecular underpinnings of β-lactam sensitivity in Mtb. We performed differential gene expression and coexpression analyses of genes previously associated with β-lactam sensitivity and genes associated with resistance to classical tuberculosis drugs. Protein-protein interaction and gene regulatory network analyses were used to validate regulatory interactions between these genes, and random walks through the networks identified key mediators of these interactions. Further validation was obtained using functional in silico knockout of gene pairs.

Results:

Our results reveal up regulation of the key regulatory inhibitor of β-lactamase production, blal, following treatment with classical drugs. Co-expression and network analyses showed direct co-regulation between genes associated with β-lactam sensitivity and those associated with resistance to classical tuberculosis treatment. blal and its downstream genes (sigC and atpH) were found to be key mediators of these interactions.

Conclusions:

Our results support the hypothesis that Mtb β-lactam sensitivity is a collateral consequence of the evolution of resistance to classical tuberculosis drugs, mediated through changes to transcriptional regulation. These findings support continued exploration of β-lactams for the treatment of tuberculosis, particularly for patients infected with strains resistant to classical therapies that are otherwise difficult to treat. Importantly, this work also highlights the potential of systems-level and network biology approaches to improve our understanding of collateral drug sensitivity.
Intraflagellar transport proteins undergo nonaxonemal staged hindrance between the recruiting distal appendages and the cilium
Authors: Tony Yang T. , Thi Tran Minh Nguyet , Chong Weng Man , Huang Chia-En , Liao Jung-Chi
Published: December 2017

Primary cilia play a vital role in cellular sensing and signaling [1]. An essential component of ciliogenesis is intraflagellar transport (IFT), which first requires IFT-protein recruitment, IFT-protein–motor-protein assembly, axonemal engagement of IFT-protein complexes, and transition zone (TZ) gating [2–9]. The mechanistic understanding of these processes at the ciliary base was largely missing, because it is exceedingly challenging to observe the motion of IFT proteins in this crowded region using conventional microscopy. Here, we report short trajectory tracking of IFT proteins at the base of mammalian primary cilia by optimizing single-particle tracking photoactivated localization microscopy (sptPALM) [10, 11], balancing the imaging requirements of tracking speed, tracking duration, and localization precision for IFT88-mEOS4b in live human retinal pigment epithelial (hTERT-RPE-1) cells. Intriguingly, we found that mobile IFT proteins “switched gears” multiple times from the distal appendages (DAPs) to the ciliary compartment (CC), moving slowly in the DAPs, relatively fast in the proximal TZ, slowly again in the distal TZ, and then much faster in the CC. They could travel through the space between the DAPs and the axoneme without following DAP structures, and reached the space enveloped by the ciliary pocket in the proximal TZ. Together, our live-cell superresolution imaging revealed region-dependent slowdown of IFT proteins at the ciliary base, shedding light on staged control of ciliogenesis homeostasis.
Shifts in plant functional strategies over the course of wheat domestication
Authors: Roucou Agathe , Violle Cyrille , Fort Florian , Roumet Pierre , Ecarnot Martin , Vile Denis
Published: December 2017

Human selection, changes in environmental conditions and management practices drove the phenotypic trajectory of crops during domestication. The characterization of the crop domestication syndrome lies mostly on reproductive characters. However, biophysical and ecophysiological constraints during vegetative growth are also at play and can strongly impact crop phenotypes. It has been argued that a broadened examination of crop phenotypes through a functional trait‐based lens should improve our understanding of the domestication syndrome.

We used a collection of 39 genotypes representative of key steps during tetraploid wheat domestication and grew them in a common garden experiment. We quantified the vegetative phenotype of each genotype through the measurements of 13 functional traits related to root, leaf and whole‐plant dimensions.

In modern cultivars, compared to ancestral forms, leaf longevity was shorter, while net photosynthetic rate, leaf production rate and nitrogen content were higher. Modern cultivars had a shallower root system and exhibited a larger proportion of fine roots, preferring to invest biomass above‐rather than below‐ground. We found ancestral forms to be integrated phenotypes characterized by coordination between above‐ and below‐ground functioning. Conversely, in modern forms, human selection appeared to have broken this coordination and to have generated a new type of network of trait covariations.

Synthesis and applications. The examination of leaf, root and whole‐plant traits of wheat accessions indicated a strong shift in plant functional strategies over the course of domestication. Elite genotypes tended to better optimize resource‐use acquisition strategies than ancestral ones. The characterization of the crop phenotype based on vegetative traits thus suggests a much more complete domestication syndrome. Our findings highlight the benefits of using a functional trait‐based characterization of crop phenotypes to document the extent of domestication syndrome and to further advance the agroecological management of cereals.
Great Expectations: The Job at the Top and the People who do it
Authors: Allen Nicholas
Published: December 2017

Anthony King thought and wrote a great deal about British prime ministers and political leadership more generally. But in contrast to the way in which single papers embodied his contribution to our understanding of ‘government overload’, ‘executive‐legislative relations’ and ‘career politicians’, his contribution to our understanding of the prime ministership was defined by a body of work. This essay explores that body of work and identifies some of the themes that characterised it. It then relates King's work to claims about the ‘presidentialisation’ of the office, as well as the importance of the expectations surrounding contemporary prime ministers. As Britain grapples with the challenge of Brexit, we should all take note of his counsel against expecting too much in the way of ‘strong’ prime ministerial leadership.
Remembering Tony King
Authors: Wright Tony
Published: December 2017

Tony King combined scholarship with a real‐world grasp that few could match. This was evident both in his public activities and in his published work. His studies of legislatures and of career politicians changed the way in which issues were viewed and he was skilled at identifying emerging trends before anyone else. He analysed the failings of government, but always as a practical improver. He was a natural communicator in the Bagehot tradition, as evidenced in his writings on the constitution, and he wanted a less adversarial political culture. He showed political scientists that it was possible to combine good scholarship with an ability to communicate.
Anthony King and the United States
Authors: Wilson Graham K.
Published: December 2017

Anthony King was a keen follower of American politics. His writings on the subject combined his respect for democratic practices with a strong concern for deliberation in governance. These concerns, familiar from his writings on the UK, caused him to worry that American politicians campaigned too much and governed too little.
Friends of the Court? Why EU governments file observations before the Court of Justice
Authors: DEDERKE JULIAN , NAURIN DANIEL
Published: December 2017

The preliminary reference procedure under which the Court of Justice of the European Union (CJEU) responds to questions from national courts regarding the interpretation of EU law is a key mechanism in many accounts of the development of European integration and law. While the significance of the procedure has been broadly acknowledged, one aspect has been largely omitted: The opportunity for member state governments to submit their views (‘observations’) to the Court in ongoing cases. Previous research has shown that these observations matter for the Court's decisions, and thus that they are likely to have a significant impact on the course of European integration. Still, little is known about when and why member states decide to engage in the preliminary reference procedure by submitting observations. This article shows that there is significant variation, both between cases and between member states, in the number of observations filed. A theoretical argument is developed to explain this variation. Most importantly, a distinction is made between legal and political reasons for governments to get involved in the preliminary reference cases, and it is argued that both types of factors should be relevant. By matching empirical data from inter‐governmental negotiations on legislative acts in the Council of the EU with member states’ subsequent participation in the Court procedures, a research design is developed to test these arguments. It is found that the decision to submit observations can be tied both to concerns with the doctrinal development of EU law and to more immediate political preferences. The conclusion is that the legal (the CJEU) and political (the Council) arenas of the EU system are more interconnected than some of the previous literature would lead us to believe.
Concomitant Psychiatric and Nonalcohol‐Related Substance Use Disorders Among Hospitalized Patients with Alcoholic Liver Disease in the United States
Authors: Jinjuvadia Raxitkumar , Jinjuvadia Chetna , Puangsricharoen Pimpitcha , Chalasani Naga , Crabb David W. , Liangpunsakul Suthat ,   the Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium
Published: December 2017

Background

Despite that the epidemiological studies on the comorbidity of alcohol misuse and psychiatric disorders have been studied, less is known about the magnitude of these disorders among patients with alcoholic liver disease (ALD). Our aim was to determine the prevalence of psychiatric and substance use disorders among hospitalized ALD patients in the United States.

Methods

We utilized a single‐level clinical classification software to identify patients with ALD and psychiatric/substance use disorders from the 2011 National Inpatient Sample data. The primary outcome was the prevalence of these disorders among hospitalized patients with ALD (n = 74,972) compared to those with chronic liver diseases not caused by alcohol (n = 350,140) and those without underlying liver diseases (n = 1,447,063).

Results

The prevalence of adjustment disorder, anxiety disorder, posttraumatic stress disorder, and depression was significantly higher among hospitalized patients with ALD when compared to those with chronic liver diseases not caused by alcohol (all with p‐values <0.05). Younger age, female gender, and White race were the independent predictors of psychiatric/substance use disorders among hospitalized patients with ALD.

Conclusions

Hospitalized patients with ALD have significantly high prevalence of concomitant psychiatric and substance abuse disorders when compared to those with chronic liver diseases not caused by alcohol and those without underlying liver diseases. Screening and appropriate intervention should be implemented as part of routine clinical care for these patients.
Epidemiology and morphology of full‐thickness macular holes
Authors: Forsaa Vegard Asgeir , Lindtjørn Birger , Kvaløy Jan Terje , Frøystein Torbjørn , Krohn Jørgen
Published: December 2017

Purpose

To investigate the incidence of full‐thickness macular holes (FTMHs) and their morphological features according to the International Vitreomacular Traction Study (IVTS) classification.

Methods

The clinical records of all new patients with FTMH, referred between 2008 and 2014, were reviewed for demographics, cause of the FTMH, age at diagnosis, symptom duration, laterality, visual acuity (VA), axial length and lens status. A detailed analysis of the patients’ spectral domain optical coherence tomography (SD‐OCT) images was performed, and the primary FTMHs were classified in clinical stages according to the IVTS classification. From the SD‐OCT, accurate macula drawings were made by means of a computer‐drawing software. By merging these drawings and displaying them as colour‐coded maps, the morphology and shape of the FTMH were visualized.

Results

The study included 177 eyes (152 primary and 25 secondary FTMH) in 166 patients. In primary FTMH, the male‐to‐female ratio was 1:2.2. The age‐ and gender‐adjusted annual incidences of primary FTMH were 7.9 eyes and 7.4 individuals per 100 000 inhabitants. Mean primary FTMH minimum linear diameter (MLD) and basal diameter (BD) were 435 μm and 872 μm, respectively, and 13% were classified as small, 31% as medium and 55% as large. Vitreomacular traction (VMT) and epiretinal membrane (ERM) were present in 34% and 36% of the eyes, respectively.

Conclusion

This study provides data on the incidence rates of FTMH adjusted to different standard populations. The morphological analysis and novel computational visualization technique offer new insight into the structural complexity of FTMH and how VMT and ERM significantly influence FTMH configuration.
Testicular orphan receptor 4 promotes tumor progression and implies poor survival through AKT3 regulation in seminoma
Authors: Chen Yuanlei , Lu Jieyang , Xia Liqun , Xue Dingwei , Yu Xiaoming , Shen Danyang , Xu Liwei , Li Gonghui
Published: December 2017

Seminoma is the most common testicular germ cell tumor worldwide and mainly occurs in 15‐35‐year‐old young men. Early studies have indicated that testicular nuclear receptor 4 (TR4) first cloned from testis is involved in the invasion and metastasis of several human tumors; however, little attention is paid to the function of TR4 in seminoma. Our immunohistochemical (IHC) staining results showed that patients with advanced stage tumors tended to have higher expression of TR4. Importantly, there was a significant association between elevated TR4 expression and reduced overall survival in seminoma patients. In vitro MTS, western blot and transwell assays, after manipulating TR4 expression in Tcam‐2 cells, revealed that TR4 induced epithelial‐to‐mesenchymal transition (EMT) and promoted Tcam‐2 cell proliferation and invasion. Mechanism dissection demonstrated that AKT3, a critical component in the signaling pathway, played a crucial role in mediating TR4‐promoted Tcam‐2 cell proliferation and invasion. We further revealed that TR4 modulated AKT3 at the transcriptional level via chromatin immunoprecipitation and luciferase assays. Meanwhile, addition of the AKT3 siRNA blocked the function of TR4. Overall, these findings first elucidate that TR4 is a novel prognostic marker and plays a critical role in the metastatic capacity of Tcam‐2 cells by EMT regulation and, consequently, targeting TR4‐AKT3 pathway may serve as a potential therapeutic approach for seminoma.
Design, synthesis, and molecular docking studies of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives as xanthine oxidase inhibitors
Authors: Zhang Ting‐Jian , Li Song‐Ye , Yuan Wei‐Yan , Zhang Yi , Meng Fan‐Hao
Published: December 2017

A series of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives (1a–j) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D‐phenylalanine derivatives (1d and 1i) and the L/D‐tryptophan derivatives (1e and 1j) were effective with micromolar level potency. In particular, the L‐phenylalanine derivative 1d (IC50 = 3.0 μm) and the D‐phenylalanine derivative 1i (IC50 = 2.9 μm) presented the highest potency and were both more potent than the positive control allopurinol (IC50 = 8.1 μm). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D‐amino acid derivative presented equal or greater potency compared to its L‐enantiomer; and the 9,10‐anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.
The association between irisin and muscle metabolism in different thyroid disorders
Authors: Zybek‐Kocik Ariadna , Sawicka‐Gutaj Nadia , Szczepanek‐Parulska Ewelina , Andrusiewicz Mirosław , Waligórska‐Stachura Joanna , Białas Piotr , Krauze Tomasz , Guzik Przemysław , Skrobisz Jerzy , Ruchała Marek
Published: December 2017

Background

Irisin is a new adipo‐myokine, encoded by the FNDC5 gene. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This prospective study assesses the influence of thyrometabolic changes on serum irisin concentration in association with altered muscle metabolism. This is performed on a large cohort of patients affected by severe hypo‐ or hyperthyroidism, as well as by the expression of the FNDC5 gene in thyroid tissue affected by different pathologies.

Methods

The study group comprised 119 patients with newly diagnosed severe hyperthyroidism or hypothyroidism, and a control group of 45 healthy subjects. Body composition, serum irisin concentrations, and thyroid‐related hormones, creatine kinase, dystrophin and titin concentrations were evaluated. FNDC5 expression was also analysed in tissue samples from 80 patients with nontoxic multinodular goitre, toxic goitre, Graves’ disease and papillary thyroid cancer.

Results

Irisin concentration was lower in patients with prolonged hypothyroidism. There was a tendency towards lower dystrophin and titin concentrations in patients with hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with hypothyroidism resulted in a decreased muscle mass with an increase in irisin concentrations, while the hyperthyroid group showed an increase in fat mass. Statistically significant overexpression of FNDC5 gene was found in patients with toxic goitre as compared to Graves’ disease, papillary thyroid cancer and controls.

Conclusions

The presented data support the theory that irisin concentration changes are associated with prolonged hypothyroidism and might primarily constitute the result of prolonged myopathy. These changes are most likely not related to the expression of the FNDC5 gene in the thyroid gland.
Sustainability and depth of outreach: Evidence from microfinance institutions in sub‐Saharan Africa
Authors: Awaworyi Churchill Sefa
Published: December 2017

The feasibility of microfinance institutions (MFIs) to expand outreach to the poorest while remaining financially sustainable has long been debated. Using data from 206 MFIs in 33 African countries, we adopt the three‐stage least square technique to assess whether a trade‐off exists between sustainability and outreach depth. Our results confirm the existence of a trade‐off. The evidence also supports ongoing subsidies for MFIs with the aim of encouraging outreach. In addition, we examine whether there is an inflection point beyond which higher interest rates reduce profitability for MFIs. We find no evidence of a threshold beyond which profitability is reduced.
What is the role of mitochondrial dysfunction in skin photoaging?
Authors: Naidoo Khimara , Hanna Rebecca , Birch‐Machin Mark A.
Published: December 2017

Skin ageing is a complex process involving both internal and external factors, which leads to a progressive loss of cutaneous function and structure. Solar radiation is the primary environmental factor implicated in the development of skin ageing, and the term photoaging describes the distinct clinical, histological and structural features of chronically sun‐exposed skin. The changes that accompany photoaging are undesirable for aesthetic reasons and can compromise the skin and make it more susceptible to a number of dermatological disorders. As a result, skin ageing is a topic that is of growing interest and concern to the general population, illustrated by the increased demand for effective interventions that can prevent or ameliorate the clinical changes associated with aged skin. In this viewpoint essay, we explore the role that mitochondria play in the process of skin photoaging. There is continuing evidence supporting the proposal that mitochondrial dysfunction and oxidative stress are important contributing factors in the development of skin photoaging. Further skin‐directed mitochondrial research is warranted to fully understand the impact of mitochondrial status and function in skin health. A greater understanding of the ageing process and the regulatory mechanisms involved could lead to the development of novel preventative interventions for skin ageing.
Report card on ecosystem‐based fisheries management in tuna regional fisheries management organizations
Authors: Juan‐Jordá Maria José , Murua Hilario , Arrizabalaga Haritz , Dulvy Nicholas K , Restrepo Victor
Published: December 2017

International instruments of fisheries governance have set the core principles for the management of highly migratory fishes. We evaluated the progress of tuna Regional Fisheries Management Organizations (tRFMOs) in implementing the ecological component of ecosystem‐based fisheries management (EBFM). We first developed a best case tRFMO for EBFM implementation. Second, we developed criteria to evaluate progress in applying EBFM against this best case tRFMO. We assessed progress of the following four ecological components: target species, bycatch species, ecosystem properties and trophic relationships, and habitats. We found that many of the elements necessary for an operational EBFM are already present, yet they have been implemented in an ad hoc way, without a long‐term vision and a formalized plan. Overall, tRFMOs have made considerable progress monitoring the impacts of fisheries on target species, moderate progress for bycatch species, and little progress for ecosystem properties and trophic relationships and habitats. The tRFMOs appear to be halfway towards implementing the ecological component of EBFM, yet it is clear that the “low‐hanging fruit” has been plucked and the more difficult, but surmountable, issues remain, notably the sustainable management of bycatch. All tRFMOs share the same challenge of developing a formal mechanism to better integrate ecosystem science and advice into management decisions. We hope to further discussion across the tRFMOs to inform the development of operational EBFM plans.
Structure and interaction ofCorynebacterium pseudotuberculosiscold shock protein A with Y‐box single‐strandedDNAfragment
Authors: Caruso Icaro P. , Panwalkar Vineet , Coronado Monika A. , Dingley Andrew J. , Cornélio Marinônio L. , Willbold Dieter , Arni Raghuvir K. , Eberle Raphael J.
Published: December 2017

Cold shock proteins (Csps) function to preserve cell viability at low temperatures by binding to nucleic acids and consequently control gene expression. The mesophilic bacteriumCorynebacterium pseudotuberculosisis the causative agent of caseous lymphadenitis in animals, and infection in livestock is a considerable economic burden worldwide. In this report, the structure of cold shock protein A fromCp(Cp‐CspA) and biochemical analysis of its temperature‐dependent interaction with a Y‐box ssDNA motif is presented. TheCp‐CspA structure contains five β‐strands making up a β‐barrel fold with 11 hydrophobic core residues and two salt bridges that confers it with a melting temperature of ~ 54°C that is similar to mesophilicBs‐CspB. Chemical shift perturbations analysis revealed that residues in the nucleic acid‐binding motifs (RNP1 and 2) and loop 3 are involved in binding to the Y‐box fragment either by direct interaction or by conformational rearrangements remote from the binding region. Fluorescence quenching experiments ofCp‐CspA showed that the dissociation constants for Y‐box ssDNAbinding is nanomolar and the binding affinity decreased as the temperature increased, indicating that the interaction is enthalpically driven and the hydrogen bonds and van der Waals forces are important contributions for complex stabilization. The Y31 ofCp‐CspA is a particular occurrence among Csps from mesophilic bacteria that provide a possible explanation for the higher binding affinity to ssDNAthan that observed forBs‐CspB. Anisotropy measurements indicated that the reduction in molecular mobility ofCp‐CspA upon Y‐box binding is characterized by a cooperative process.

Database

Resonance assignment and structural data are available in the Biological Magnetic Resonance Data Bank and Protein Data Bank under accession number 26802 and5O6F, respectively.
New insights on plant phenological response to temperature revealed from long‐term widespread observations in China
Authors: Zhang Haicheng , Liu Shuguang , Regnier Pierre , Yuan Wenping
Published: December 2017

Constraints of temperature on spring plant phenology are closely related to plant growth, vegetation dynamics, and ecosystem carbon cycle. However, the effects of temperature on leaf onset, especially for winter chilling, are still not well understood. Using long‐term, widespread in situ phenology observations collected over China for multiple plant species, this study analyzes the quantitative response of leaf onset to temperature, and compares empirical findings with existing theories and modeling approaches, as implemented in 18 phenology algorithms. Results show that the growing degree days (GDD) required for leaf onset vary distinctly among plant species and geographical locations as well as at organizational levels (species and community), pointing to diverse adaptation strategies. Chilling durations (CHD) needed for releasing bud dormancy decline monotonously from cold to warm areas with very limited interspecies variations. Results also reveal that winter chilling is a crucial component of phenology models, and its effect is better captured with an index that accounts for the inhomogeneous effectiveness of low temperature to chilling rate than with the conventional CHD index. The impact of spring warming on leaf onset is nonlinear, better represented by a logistical function of temperature than by the linear function currently implemented in biosphere models. The optimized base temperatures for thermal accumulation and the optimal chilling temperatures are species‐dependent and average at 6.9 and 0.2°C, respectively. Overall, plants’ chilling requirement is not a constant, and more chilling generally results in less requirement of thermal accumulation for leaf onset. Our results clearly demonstrate multiple deficiencies of the parameters (e.g., base temperature) and algorithms (e.g., method for calculating GDD) in conventional phenology models to represent leaf onset. Therefore, this study not only advances our mechanistic and quantitative understanding of temperature controls on leaf onset but also provides critical information for improving existing phenology models.
Immune response to hepatitis B vaccine in patients with chronic hepatitis C infection: A systematic review and meta‐analysis
Authors: Liu Jiaye , Wu Hui , Chen Hui
Published: December 2017

Hepatitis B virus and hepatitis C virus (HCV) co‐infection can add to the severity of hepatitis and the risks of liver cirrhosis and hepatocellular carcinoma. Whether chronic HCV infection decreases antibody response to hepatitis B vaccination is still controversial. We evaluate the influence of HCV infection on antibody response to hepatitis B vaccination by a systematic review of published works with a meta‐analysis of clinical trials. The random‐effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses were used in this study. The end‐point of interest was the rate of patients showing seroconversion of antibody responses at completion of hepatitis B vaccination schedule among patients with chronic HCV infection versus healthy controls. We identified 11 studies involving 704 patients with HCV and 812 controls. Our results show a significant decrease in antibody seroconversion rates among patients with HCV versus healthy controls (pooled odds ratio = 0.17 [95% confidence interval, 0.11–0.28]). The P‐value was 0.21 for our test of study heterogeneity. Stratified analysis in subgroups of interest and sensitivity analysis did not meaningfully change our results. Our meta‐analysis showed patients with hepatitis C infection have a statistically significant lower rate of seroconversion in comparison to healthy controls, both in cirrhotic and non‐cirrhotic patients. Chronic HCV infection can decrease the immune response to a standard schedule of hepatitis B vaccination. Further studies are needed to investigate the optimum vaccination schedule for patients with chronic HCV infection.
Invasion in breast lesions: the role of the epithelial–stroma barrier
Authors: Rakha Emad A , Miligy Islam M , Gorringe Kylie L , Toss Michael S , Green Andrew R , Fox Stephen B , Schmitt Fernando C , Tan Puay‐Hoon , Tse Gary M , Badve Sunil , Decker Thomas , Vincent‐Salomon Anne , Dabbs David J , Foschini Maria P , Moreno Filipa , Wentao Yang , Geyer Felipe C , Reis‐Filho Jorge S , Pinder Sarah E , Lakhani Sunil R , Ellis Ian O
Published: December 2017

Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is based typically on the presence of an intact barrier between the malignant epithelial cells and stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in‐situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non‐infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may also be absent around some malignant lesions such as some forms of papillary carcinoma, yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM‐like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics.
A biocompatible decellularized pulp scaffold for regenerative endodontics
Authors: Matoug‐Elwerfelli M. , Duggal M. S. , Nazzal H. , Esteves F. , Raïf E.
Published: December 2017

Aim

To investigate the feasibility of decellularizing the entire dental pulp using a mild treatment protocol to develop a decellularized biological extracellular matrix scaffold for use in regenerative endodontic procedures.

Methodology

Decellularized human dental pulps were assessed using histological and immunohistochemical methods, scanning electron microscope and DNA quantification assay. Cytotoxicity assays to determine decellularized scaffold biocompatibility were also performed. Decellularized scaffolds were seeded with human dental pulp stem cells and cell viability assessed using Live/Dead® stain. Quantitative data were analysed statistically using Student's t‐test and one‐way analysis of variance to compare mean values between groups depending on group numbers.

Results

Assessment of decellularized tissues revealed an acellular matrix with preservation of native tissue histoarchitecture and composition. Decellularized tissues showed no evidence of cytotoxicity, with cell growth in direct contact with the scaffold and no reduction in cellular activity following extract incubation. Furthermore, the scaffold was able to support human dental pulp stem cell viability and attachment following recellularization.

Conclusions

Promising results were observed in developing a decellularized biological scaffold derived from the dental pulp with the perseveration of extracellular structural components which are required for tissue‐specific regeneration.
Assessment of cardiovascular risk in an Italian psychiatric outpatient sample: A chart review of patients treated with second‐generation antipsychotics
Authors: Severi Elena , Ferrara Maria , Tedeschini Enrico , Vacca Francesca , Mungai Francesco , Amendolara Rocco , Baccari Flavia , Starace Fabrizio
Published: December 2017

Despite the call by the scientific community for a systematic monitoring of physical health in people with psychiatric illnesses, national and international audits have reported poor quality of cardiovascular risk assessments and management in this vulnerable population. Available evidence indicates that in people affected by mental illness, life expectancy is reduced by 10–20 years, mainly due to cardiovascular accidents and metabolic syndrome (MetS)‐related diseases. The primary aim of the present study was to evaluate the accuracy of cardiovascular risk monitoring in an outpatient sample of patients taking second‐generation antipsychotics. The sample consisted of 200 patients consecutively recruited from two community mental health centres. A clinical chart review was performed on the following laboratory tests: total cholesterol, high‐ and low‐density lipoprotein, serum triglycerides, fasting blood glucose, γ‐glutamyl transpeptidase. Blood pressure and waist circumference were measured. A complete cardiovascular risk assessment was available only in 60 patients out of 200 (33.3%). The only variable associated with laboratory tests for MetS was receiving three or more psychotropic medications, which increased fourfold the probability of metabolic screening. In the subsample of patients with full screening, the prevalence of MetS was 33.3%. Our findings suggest that mental health professionals working in community mental health services should incorporate a more systematic assessment of physical health in their practice, and intervene proactively to reduce the significant cardiovascular burden carried by people with several mental illness.