bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoimmune myocarditis is not associated with left ventricular systolic dysfunction
Authors: Mirna Moritz , Paar Vera , Kraus Theo , Sotlar Karl , Wernly Bernhard , Pistulli Rudin , Hoppe Uta C. , Lichtenauer Michael
Published: May 2019

Background

Experimental autoimmune myocarditis (EAM) is a common animal model for the investigation of the pathophysiology of myocarditis. Because of diverging findings from previous studies, we performed serial echocardiographic examinations throughout the course of the disease and investigated the dimensions of the murine heart and left ventricular (LV) systolic function.

Materials and Methods

Experimental autoimmune myocarditis was induced in male Balb/c mice by subcutaneous injection of a fragment of the α‐myosin heavy chain (MyHC‐α 614‐629: Ac‐SLKLMATLFSTYASAD). Transthoracic echocardiography was performed on days 0, 7 and 21 in healthy animals and mice with EAM.

Results

Experimental autoimmune myocarditis was associated with a reduction in LV systolic function and an increase in LV internal diameter in diastole (LVIDd) and systole (LVIDs) 7 days postimmunization. After 21 days, EAM led to a significant increase in LV‐thickness (1.3‐fold increase in LV anterior wall diameter in diastole [LVAWDd]), but there was no difference in LV systolic function between immunized animals and healthy controls. LV‐thickness correlated well with the severity of myocarditis in the histopathological examination (LVAWDd: rs = 0.603, P = 0.003, LV anterior wall diameter in systole (LVAWDs): rs = 0.718, P < 0.0001).

Conclusion

Our results indicate that EAM leads to an initial dilatation of the LV that is followed by ventricular “hypertrophy.” On day 21, there was no significant difference in LV systolic function between immunized animals and controls. Furthermore, the ageing of the animals had a major impact on the echocardiographic parameters; therefore, the use of healthy age‐matched controls seems warranted when echocardiography is performed in rodents.
COMPARING BEHAVIORAL MODELS USING DATA FROM EXPERIMENTAL CENTIPEDE GAMES
Authors: Georgalos Konstantinos
Published: May 2019

The centipede game posits one of the most well‐known paradoxes of backward induction in the literature of experimental game theory. Given that deviations from the unique subgame perfect Nash equilibrium generates a Pareto improvement, several theoretical models have been employed in order to rationalize this kind of behavior in this social dilemma. The available explanations range from social preferences including fairness, altruism or cooperation motives, errors in playing, inability to perform backward induction or different depths of reasoning. In the present study, we use the Blavatskyy's theoretical contribution, and relax the assumptions of Expected Utility maximization and risk‐neutral attitudes, to test an alternative explanation. We compare various probabilistic decision theory models in terms of their descriptive (in‐sample) and predictive (out‐of‐sample fit) performance, using data from experimental centipede games. We find that introducing non‐Expected Utility preferences to the Quantal Response Equilibrium model, along with a nonlinear utility function, provides a better explanation compared to alternative specifications such as the Level‐k or the Quantal Response Equilibrium model with altruistic motives. (JEL C72, C92, D81, D82)
The role of seasonal timing and phenological shifts for species coexistence
Authors: Rudolf Volker H. W.
Published: May 2019

Shifts in the phenologies of coexistence species are altering the temporal structure of natural communities worldwide. However, predicting how these changes affect the structure and long‐term dynamics of natural communities is challenging because phenology and coexistence theory have largely proceeded independently. Here, I propose a conceptual framework that incorporates seasonal timing of species interactions into a well‐studied competition model to examine how changes in phenologies influence long‐term dynamics of natural communities. Using this framework I demonstrate that persistence and coexistence conditions strongly depend on the difference in species’ mean phenologies and how this difference varies across years. Consequently, shifts in mean and interannual variation in relative phenologies of species can fundamentally alter the outcome of interactions and the potential for persistence and coexistence of competing species. These effects can be predicted by how per‐capita effects scale with differences in species’ phenologies. I outline how this approach can be parameterized with empirical systems and discuss how it fits within the context of current coexistence theory. Overall, this synthesis reveals that phenology of species interactions can play a crucial yet currently understudied role in driving coexistence and biodiversity patterns in natural systems and determine how species will respond to future climate change.
Hypervascularization in mTOR‐dependent focal and global cortical malformations displays differential rapamycin sensitivity
Authors: Zhang Longbo , Huang Tianxiang , Teaw Shannon , Bordey Angélique
Published: May 2019

Objectives

Patients with mammalian target of rapamycin (mTOR)–dependent malformations of cortical development (MCDs) associated with seizures display hyperperfusion and increased vessel density of the dysmorphic cortical tissue. Some studies have suggested that the vascular defect occurred independently of seizures. Here, we further examined whether hypervascularization occurs in animal models of global and focal MCD with and without seizures, and whether it is sensitive to the mTOR blocker, rapamycin, that is approved for epilepsy treatment in tuberous sclerosis complex.

Methods

We used two experimental models of mTOR‐dependent MCD consisting of conditional transgenic mice containing Tsc1null cells in the forebrain generating a global malformation associated with seizures and of wild‐type mice containing a focal malformation in the somatosensory cortex generated by in utero electroporation (IUE) that does not lead to seizures. Alterations in blood vessels and the effects of a 2‐week–long rapamycin treatment on these phenotypes were assessed in juvenile mice.

Results

Blood vessels in both the focal and global MCDs of postnatal day 14 mice displayed significant increase in vessel density, branching index, total vessel length, and decreased tissue lacunarity. In addition, rapamycin treatment (0.5 mg/kg, every 2 days) partially rescued vessel abnormalities in the focal MCD model, but it did not ameliorate the vessel abnormalities in the global MCD model that required higher rapamycin dosage for a partial rescue.

Significance

Here, we identified hypervascularization in mTOR‐dependent MCD in the absence of seizures in young mice, suggesting that increased angiogenesis occurs during development in parallel to alterations in corticogenesis. In addition, a predictive functional outcome is that dysplastic neurons forming MCD will have better access to oxygen and metabolic supplies via their closer proximity to blood vessels. Finally, the difference in rapamycin sensitivity between a focal and global MCD suggest that rapamycin treatment will need to be titrated to match the type of MCD.
Cutaneous nociception: Role of keratinocytes
Authors: Talagas Matthieu , Lebonvallet Nicolas , Berthod François , Misery Laurent
Published: May 2019

Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra‐epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells.
Mitigation potential and environmental impact of centralized versus distributed BECCS with domestic biomass production in Great Britain
Authors: Albanito Fabrizio , Hastings Astley , Fitton Nuala , Richards Mark , Martin Mike , Mac Dowell Niall , Bell Dave , Taylor Simon C. , Butnar Isabela , Li Pei‐Hao , Slade Raphael , Smith Pete
Published: May 2019

New contingency policy plans are expected to be published by the United Kingdom government to set out urgent actions, such as carbon capture and storage, greenhouse gas removal and the use of sustainable bioenergy to meet the greenhouse gas reduction targets of the 4th and 5th Carbon Budgets. In this study, we identify two plausible bioenergy production pathways for bioenergy with carbon capture and storage (BECCS) based on centralized and distributed energy systems to show what BECCS could look like if deployed by 2050 in Great Britain. The extent of agricultural land available to sustainably produce biomass feedstock in the centralized and distributed energy systems is about 0.39 and 0.5 Mha, providing approximately 5.7 and 7.3 MtDM/year of biomass respectively. If this land‐use change occurred, bioenergy crops would contribute to reduced agricultural soil GHG emission by 9 and 11 /year in the centralized and distributed energy systems respectively. In addition, bioenergy crops can contribute to reduce agricultural soil ammonia emissions and water pollution from soil nitrate leaching, and to increase soil organic carbon stocks. The technical mitigation potentials from BECCS lead to projected CO2 reductions of approximately 18 and 23 /year from the centralized and distributed energy systems respectively. This suggests that the domestic supply of sustainable biomass would not allow the emission reduction target of 50 /year from BECCS to be met. To meet that target, it would be necessary to produce solid biomass from forest systems on 0.59 or 0.49 Mha, or alternatively to import 8 or 6.6 MtDM/year of biomass for the centralized and distributed energy system respectively. The spatially explicit results of this study can serve to identify the regional differences in the potential capture of CO2 from BECCS, providing the basis for the development of onshore CO2 transport infrastructures.
MOB1 regulates thymocyte egress and T‐cell survival in mice in a YAP1‐independent manner
Authors: Kato Wakako , Nishio Miki , To Yoko , Togashi Hideru , Mak Tak Wah , Takada Hidetoshi , Ohga Shouichi , Maehama Tomohiko , Suzuki Akira
Published: May 2019

Mammalian STE20‐like protein kinase 1/2 (MST1/2) and nuclear Dbf2‐related kinase 1/2 (NDR1/2) are core components of Hippo signaling that are also known to be important regulators of lymphocyte trafficking. However, little is understood about the roles of other Hippo pathway molecules in these cells. Here, we present the first analysis of the function of Mps one binder kinase activator‐1 (MOB1) in T lymphocytes in vivo. T‐cell‐specific double knockout (DKO) of MOB1A/B in mice [tMob1 DKO mice] reduces the number of naïve T cells in both the circulation and secondary lymphoid organs, but leads to an accumulation of CD4+CD8− and CD4−CD8+ single‐positive (SP) cells in the thymus. In vitro, naïve MOB1A/B‐deficient T cells show increased apoptosis and display impaired trafficking capacity in response to the chemokine CCL19. These defects are linked to suppression of the activation of MST and NDR kinases, but are independent of the downstream transcriptional co‐activator Yes‐associated protein 1 (YAP1). Thus, MOB1 proteins play an important role in thymic egress and T‐cell survival that is mediated by a pathway other than conventional Hippo‐YAP1 signaling.
The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults
Authors: He Cong , Peng Chao , Wang Huan , Ouyang Yaobin , Zhu Zhenhua , Shu Xu , Zhu Yin , Lu Nonghua
Published: May 2019

Background

The eradication of Helicobacter pylori (H pylori) has been suggested to reduce the risk of gastric cancer, but its impact on the gut microbiota has attracted public attention. This study aimed to investigate the short‐term and long‐term effects of bismuth quadruple therapy on both gastric and fecal microbiota.

Methods

Ten asymptomatic young adults with H pylori‐related gastritis were treated with bismuth quadruple therapy for 14 days, and 7 age‐matched adults without H pylori infection were enrolled as healthy controls. Both fecal and gastric mucosa samples were collected from H pylori‐positive patients at weeks 0, 6, and 26, while fecal samples were collected from healthy controls. The gastric and gut microbiota were analyzed by 16S rRNA gene sequencing.

Results

The structure of the gastric microbiota was significantly changed after the eradication of H pylori with increased alpha diversity over time. The relative abundance of H pylori sharply decreased from more than 70% to nearly 0% after treatment, while some beneficial bacteria, such as Lactobacillus and Bifidobacterium, were increased. The microbial diversity of gut microbiota was higher in H pylori‐infected patients than in healthy controls, which tended to decrease after eradication. The potentially beneficial gut bacteria Blautia and Lachnoclostridium were enriched at week 26 compared to week 0, while the pathogenic Alistipes were depleted to a level close to that of the healthy controls.

Conclusions

Bismuth quadruple therapy for H pylori eradication can restore the diversity of gastric microbiota with enrichment of beneficial bacteria. The composition of gut microbiota after H pylori eradication trends toward healthy status instead of becoming dysbiotic.
Self‐reported oral health–related habits, attitudes and knowledge in adults from Portugal, Romania and Sweden—A comparative study
Authors: Cuculescu Marian , Slusanschi Oana , Boscaiu Voicu Radu , Luis Henrique Pedro Soares , Fernandes Ribeiro Graça Sandra Maria , Ramos Esteves Gonçalves dos Santos Albuquerque Teresa Maria Beatriz , Abreu Assunção Victor , Galuscan Atena , Podariu Angela Codruta , Malmqvist Sebastian , Johannsen Gunnar , Johannsen Annsofi
Published: May 2019

Objective

The aim of the present study was to compare the self‐reported oral health knowledge, habits and attitudes of adults in Portugal, Romania and Sweden, each benefitting from a different oral health system.

Methods

A cross‐sectional study was conducted on 1081 adults in the three countries, using an adapted version of the WHO oral health questionnaire. This survey took place between November 2015 and June 2016.

Results

The mean age of the respondents was 46.85 with 95% CI (45.84, 47.86). Over 85% of the Portuguese and the Swedish, but only 55% of the Romanians, reported having 20 or more teeth left (P < 0.001). Most Swedes visit the dental office regularly, but only 50.5% of the Portuguese and 20.6% of the Romanians do so (P < 0.001). Interdental cleaning aids and fluoridated toothpaste were used the most in Sweden and the least in Romania. Daily consumption of sweets was lowest for Portugal and highest for Romania (P < 0.001), and daily intake of fresh fruits and vegetables was lowest for Sweden (P < 0.001).

Conclusions

There is a difference between the three countries regarding oral health, diet, dental attendance and oral health–related quality of life, with Romania being in most need of improvement in these areas. The differences could be explained by the distinct healthcare systems adopted by the countries.
Effects of osmotic pretreatment and frying conditions on quality and storage stability of vacuum‐fried pumpkin chips
Authors: Piyalungka Pattaraporn , Sadiq Muhammad Bilal , Assavarachan Rittichai , Nguyen Loc Thai
Published: May 2019

The effects of osmotic (OP), ultrasound‐assisted osmotic pretreatment (UAOP) and frying conditions on quality and storage stability of vacuum fried pumpkin chips were investigated. The pumpkin samples were pretreated in maltodextrin solution and subsequently fried at different temperatures (90–110 °C) and time periods (10–30 min). The results demonstrated that the moisture content, water activity, lightness, yellowness and carotenoid content of the fried chips decreased, while oil content, hardness and a* (dark brown colour) value increased with increasing frying temperature and time. UAOP reduced about 16.0% of oil absorption and enhanced approximately 70% of carotenoid retention in the fried chips. UAOP samples were also more stable during storage than the untreated ones, indicated by lower degradation kinetics constants of key quality parameters. The proposed pretreatment could be an effective method for food industries to develop vacuum fried pumpkin chips with improved quality and stability.
Developing a consistent approach to advanced practice nursing worldwide
Authors: Schober Madrean , Stewart David
Published: May 2019

Integration of advanced practice nurses into the healthcare workforce is an increasing trend worldwide. An important step forward for supporting this trend was the development of a definition of advanced practice nursing by the International Council of Nurses in 2002, for the presence of such nurses internationally has increased significantly. Although initially beneficial, the generic nature of the definition has contributed to disagreement and confusion regarding the role. In response to this critique and to facilitate improved role clarity for advanced practice nurses, the International Council of Nurses is reviewing and revising its original position. The intent is to provide a clearer understanding of the components of the specialty to key stakeholders, the public and other healthcare professionals. This article describes the process for updating and clarifying the International Council of Nurses’ description of advanced practice nursing, specifically the clinical nurse specialist and nurse practitioner. Key elements for best practice, policy and a professional standard are identified to facilitate role development and implementation.
Copy number variations and polymorphisms in HSP90AB1 and risk of systemic lupus erythematosus and efficacy of glucocorticoids
Authors: Zhang Man , Gu Yuanyuan , Huang Shunwei , Lou Qiuyue , Xie Qiaomei , Xu Zhiwei , Chen Yangfan , Pan Faming , Xu Shengqian , Liu Shengxiu , Tao Jinhui , Liu Shuang , Cai Jing , Chen Peiling , Qian Long , Wang Chunhuai , Liang Chunmei , Huang Hailiang , Pan Haifeng , Su Hong , Cheng Jian , Zhang Yuzhou , Hu Wenbiao , Zou Yanfeng
Published: May 2019

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single‐nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health‐related quality of life (HRQoL) was also measured by SF‐36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (PBH = 0.039), and this association was more pronounced in the female subgroup (PBH = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role‐emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs.
Short versus longer implants with osteotome sinus floor elevation for moderately atrophic posterior maxillae: A 1‐year randomized clinical trial
Authors: Shi Jun‐Yu , Li Yuan , Qiao Shi‐Chong , Gu Ying‐Xin , Xiong Yao‐Yang , Lai Hong‐Chang
Published: May 2019

Purpose

To compare the clinical, radiographic outcomes and patient satisfaction of short‐6‐mm implants and longer implants combined with osteotome sinus floor elevation (OSFE).

Materials and Methods

Two hundred and twenty‐five patients with 225 implants were included and randomly assigned into three groups (each group: 75 implants) using randomizing table method: group 6 mm (6 mm implants alone), group 8 mm + O (8 mm implants + OSFE) and group 10 mm + O (10 mm implants + OSFE). Outcomes measures were as follows: implant survival, complication, resonance frequency analysis measurement, surgical time, bleeding on probing (BOP), pocket probing depth (PPD), modified plaque index (mPI), marginal bone loss (MBL) and patient satisfaction.

Results

The dropout rate was 3.6% at 1 year. Implant survival rates were 96%, 100% and 100% in group 6 mm, group 8 mm + O and group 10 mm + O, respectively. In group 6 mm, the survival rates of implants with diameter of 4.1 mm were 90% (27/30), while the survival rates of implants with diameter of 4.8 mm were 100% (42/42). The surgical time (min) in group 6 mm was significantly shorter than those in group 8 mm + O and group 10 mm + O (13.6 ± 2.2, 19.4 ± 3.7 and 18.3 ± 4.3, respectively, p = 0.03). No significant differences in ISQ values, BOP, PPD, mPI and MBL were found among three groups. Significant higher value of intra‐operative discomfort was found in group 6 mm (p = 0.02).

Conclusion

All treatment options provided acceptable clinical and radiographic results up to 1 year after loading. The current 1‐year results must be confirmed by longer follow‐ups of at least 5 years.
Actinic keratoses: what classification is useful to predict the risk of progression? PROs and cons
Authors: Rongioletti F.
Published: May 2019

Linked article: L. Schmitz et al. J Eur Acad Dermatol Venereol 2019; 33: 1092–1097. https://doi.org/10.1111/jdv.15580.
Growth‐band counts from elephantfish Callorhinchus milii fin spines do not correspond with independently estimated ages
Authors: Francis Malcolm P. , Ó Maolagáin Caoimhghin
Published: May 2019

Fin spines from elephantfish Callorhinchus milii were sectioned and viewed with transmitted white light under a compound microscope. The sections displayed growth bands but their interpretation and significance were unclear. Three different methods were used for counting growth bands. The results were compared with reference growth curves based on length‐at‐age estimates for six juvenile year classes derived from length‐frequency distributions, and tagging data that showed longevity is at least 20 years. None of the three ageing methods showed good correspondence with the reference curves and all methods departed markedly from the reference curves at ages above 2 years old. Therefore, growth bands present in C. milii spines are not useful for ageing, at least with the three methods tested here. Spine bands may not represent age marks, but instead may be layers of material deposited irregularly to strengthen the spine.
Review and analysis of vehicle stability models during floods and proposal for future improvements
Authors: Bocanegra Ricardo A. , Vallés‐Morán Francisco J. , Francés Félix
Published: May 2019

Flood water can affect vehicles significantly, which in turn can increase the negative effects of floods as vehicles are washed away by the flow and become a form of debris. In cities, most fatalities during floods occur inside vehicles. Consequently, it is necessary to establish thresholds for vehicle stability during this type of event to provide information necessary for flood risk management. This article analyses the available stability models developed over recent years to determine such thresholds. The stability models were grouped according to the way in which they approached car watertightness and the stability thresholds proposed by each of them were compared. It was found that these thresholds vary over a relatively wide range. Additionally, the experimental data were compared with the results provided by these studies leading to the conclusion that several of the stability models analysed do not fit measured data well. New research is required to overcome the simplifications made by the state‐of‐the‐art models and to try to standardise the decision criteria which should be adopted to define stability thresholds for vehicles of different characteristics.
Barrio BravoTransformed: Tourism, Cultural Politics, and Image Making in Mexico City
Authors: Vodopivec Barbara , Dürr Eveline
Published: May 2019

El presente artículo analiza los procesos del desarrollo urbano y la política cultura en la Ciudad de México, concentrándose en la manera en que la restructuración de las ciudades, guidada por políticas neoliberales y la economía simbólica, impacta distritos desfavorecidos. A partir de la investigación etnográfica, hacemos uso del turismo en el conocido barrio Tepito como lente para explorar cómo los diferentes actores interactúan con estos procesos. A medida que los espacios urbanos son recreados para el consumo cultural, una gama de actores intenta convertir los “slums” en destinos atractivos y experiencias de consumo. Estas estrategias de desarrollo reescriben el significado y valor de estas conocidas áreas en la ciudad, generando conflictos por el control sobre la representación y la venta de los espacios. Sostenemos que mientras la reestructuración de la economía neoliberal y el crecimiento de la economía simbólica agravan las desigualdades socio‐espaciales y al mismo tiempo abren espacios en donde se dan nuevas oportunidades para impugnarlas. [Ciudad de México, desarrollo urbano, desigualdad social, turismo urbano]
Can Nonthermal Plasma Improve the Adhesion between Acrylic Resin for Ocular Prostheses and Silicone‐Based Relining Material?
Authors: Nagay Bruna Egumi , Goiato Marcelo Coelho , da Silva Emily Vivianne Freitas , de Medeiros Rodrigo Antonio , Rangel Elidiane Cipriano , da Cruz Nilson Cristino , de Caxias Fernanda Pereira , dos Santos Daniela Micheline
Published: May 2019

Purpose

To investigate the influence of nonthermal plasma (NTP) treatment on the tensile bond strength between heat‐polymerized acrylic resin for ocular prostheses and silicone reliner, with and without the use of an adhesive primer.

Materials and Methods

One‐hundred and sixty‐four acrylic resin specimens were fabricated and randomly distributed into four groups according to the type of surface treatment: Sofreliner Primer, NTP, Sofreliner Primer + NTP, and NTP + Sofreliner Primer. Two specimens interposed with relining material (Sofreliner) formed one test sample to perform the tensile bond strength tests, before (initial) and after storage (final) in saline solution (37°C, 90 days, n = 10). Surface characterization was performed by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The failure type was classified as cohesive, adhesive, or mixed. The data were analyzed statistically using the two‐way ANOVA and Tukey test, as well as the chi‐squared test (α = 0.05), Bonferroni correction (α = 0.005), and Spearman correlation coefficient (α = 0.05).

Results

The SEM and EDS analyses showed the presence of a thin, homogenous organic film in the groups treated with NTP. The NTP + Sofreliner Primer group presented the largest bond strength mean values in the initial period (p < 0.05). Sofreliner Primer and NTP + Sofreliner Primer groups presented the first and second largest tensile bond strength mean values in the final period (p < 0.05), respectively. NTP + Sofreliner Primer group also had the largest number of cohesive (70%, initial) and mixed (90%, final) failures.

Conclusions

The NTP treatment performed before the primer application enhanced the bond between the acrylic resin ocular prosthesis and the Sofreliner silicone‐based reliner, even after 90 days of immersion in saline solution.
Staying hepatitis C negative: A systematic review and meta‐analysis of cure and reinfection in people who inject drugs
Authors: Latham Ned H. , Doyle Joseph S. , Palmer Anna Y. , Vanhommerig Joost W. , Agius Paul , Goutzamanis Stelliana , Li Zinia , Pedrana Alisa , Gottfredsson Magnus , Bouscaillou Julie , Luhmann Niklas , Mazhnaya Alyona , Altice Frederick L. , Saeed Sahar , Klein Marina , Falade‐Nwulia Oluwaseun O. , Aspinall Esther , Hutchinson Sharon , Hellard Margaret E. , Sacks‐Davis Rachel
Published: May 2019

Background and Aims

Direct‐acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in  people who inject drugs (PWID).

Methods

A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle‐Ottawa Scale. Meta‐analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models.

Results

The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%‐92%) and 91% (95% CI 88%‐95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non‐recent PWID was 0.99 (95% CI, 0.94‐1.06). The pooled treatment discontinuation was 2% (95% CI, 1%‐4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87‐4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17‐1.76).

Conclusions

Treatment outcomes were similar in recent PWID compared to non‐PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.
The gut microbial influence on cholestatic liver disease
Authors: Kummen Martin , Hov Johannes R.
Published: May 2019

Patients with cholestatic liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) have a different gut microbiome composition than healthy controls. In contrast with PBC, PSC has a strong association with inflammatory bowel disease and is the prototypical disease of the gut‐liver axis. Still, there are some distinct overlapping microbial features in the microbiome of patients with PSC and PBC suggesting similarities in cholestatic diseases, although the possible pathogenetic involvement of these shared microbial changes is unknown. Herein, we present an overview of the available data and discuss the relevance for potential disease relevant host‐microbiota interactions. In general, the microbiome interacts with the host via the immunobiome (interactions between the host immune system and the gut microbiome), the endobiome (where the gut microbiome contributes to host physiology by producing or metabolizing endogenous molecules) and the xenobiome (gut microbial transformation of exogenous compounds, including nutrients and drugs). Experimental and human observational evidence suggest that the presence and functions of gut microbes are relevant for the severity and progression of cholestatic liver disease. Interestingly, the majority of new drugs that are currently being tested in PBC and PSC in clinical trials act on bile acid homeostasis, where the endobiome is important. In the future, it will be paramount to perform longitudinal studies, through which we can identify new intervention targets, biomarkers or treatment‐stratifiers. In this way, gut microbiome‐based clinical care and therapy may become relevant in cholestatic liver disease within the foreseeable future.
Population substructure and signals of divergent adaptive selection despite admixture in the sponge Dendrilla antarctica from shallow waters surrounding the Antarctic Peninsula
Authors: Leiva Carlos , Taboada Sergi , Kenny Nathan J. , Combosch David , Giribet Gonzalo , Jombart Thibaut , Riesgo Ana
Published: May 2019

Antarctic shallow‐water invertebrates are exceptional candidates to study population genetics and evolution, because of their peculiar evolutionary history and adaptation to extreme habitats that expand and retreat with the ice sheets. Among them, sponges are one of the major components, yet population connectivity of none of their many Antarctic species has been studied. To investigate gene flow, local adaptation and resilience to near‐future changes caused by global warming, we sequenced 62 individuals of the sponge Dendrilla antarctica along the Western Antarctic Peninsula (WAP) and the South Shetlands (spanning ~900 km). We obtained information from 577 double digest restriction site‐associated DNA sequencing (ddRADseq)‐derived single nucleotide polymorphism (SNP), using RADseq techniques for the first time with shallow‐water sponges. In contrast to other studies in sponges, our 389 neutral SNPs data set showed high levels of gene flow, with a subtle substructure driven by the circulation system of the studied area. However, the 140 outlier SNPs under positive selection showed signals of population differentiation, separating the central–southern WAP from the Bransfield Strait area, indicating a divergent selection process in the study area despite panmixia. Fourteen of these outliers were annotated, being mostly involved in immune and stress responses. We suggest that the main selective pressure on D. antarctica might be the difference in the planktonic communities present in the central–southern WAP compared to the Bransfield Strait area, ultimately depending on sea‐ice control of phytoplankton blooms. Our study unveils an unexpectedly long‐distance larval dispersal exceptional in Porifera, broadening the use of genome‐wide markers within nonmodel Antarctic organisms.
A novel LuxR‐type solo of Sinorhizobium meliloti, NurR, is regulated by the chromosome replication coordinator, DnaA and activates quorum sensing
Authors: McIntosh Matthew , Serrania Javier , Lacanna Egidio
Published: May 2019

The genome of Sinorhizobium meliloti, a model for studying plant‐bacteria symbiosis, contains eight genes coding for LuxR‐like proteins. Two of these, SinR and ExpR, are essential for quorum sensing (QS). Roles and regulation surrounding the others are mostly unknown. Here, we reveal the DNA recognition sequence and regulon of the LuxR‐like protein SMc00877. Unlike ExpR, which uses the long‐chain acyl homoserine lactones (AHLs) as inducers, SMc00877 functioned independently of AHLs and was even functional in Escherichia coli. A target of SMc00877 is SinR, the major regulator of AHL production in S. meliloti. Disruption of SMc00877 decreased AHL production. A weaker production of AHLs resulted in smaller microcolonies, starting from single cells, and delayed AHL‐dependent regulation. SMc00877 was expressed only in growing cells in the presence of replete nutrients. Therefore, we renamed it NurR (nutrient sensitive LuxR‐like regulator). We traced this nutrient‐sensitive expression to transcription control by the DNA replication initiation factor, DnaA, which is essential for growth. These results indicate that NurR has a role in modulating the threshold of QS activation according to growth. We propose growth behavior as an additional prerequisite to population density for the activation of QS in S. meliloti.
Association between exercise training in haemodialysis patients and burden of their family caregivers: A cross‐sectional study
Authors: Garcia Rodrigo S A , Pinheiro Bruno V , Lucinda Leda M F , Pimentel André L , Júnior José M P , Paula Rogério B , Reboredo Maycon M
Published: May 2019

Aim

Considering that exercise programmes are related with a range of benefits for end‐stage renal disease patients, we evaluated the association between haemodialysis (HD) patients’ involvement in intradialytic exercise training with the burden of their family caregivers.

Methods

In this cross‐sectional study, 60 caregivers of HD patients were recruited, 30 of them who cared for patients that regularly participated in an exercise programme during dialysis sessions and 30 caregivers who looked after patients undergoing usual HD treatment without intradialytic exercise. The caregivers were submitted to the Caregiver Burden Scale (CBS) and their quality of life (short‐form‐36 (SF‐36)), anxiety and depression levels were assessed. Data were expressed as mean ± SD or median (interquartile range).

Results

Multiple linear regression showed that the global CBS score was significantly associated with the exercise training after adjusting for age, educational level and anxiety level of caregivers, and dependency level of patients measured by the Lawton scale (coefficient of determination = 0.53; adjusted coefficient of determination = 0.48). Additionally, the caregivers of HD patients submitted to intradialytic exercise (42.0 ± 12.9 years, 33.3% male) compared to caregivers of patients undergoing usual treatment (50.7 ± 17.5 years, 26.7% male) exhibited less caregiver burden (global CBS score = 1.2 (0.2) vs 1.9 (0.7), P < 0.001), better quality of life (physical component score = 53.7 (9.6) vs 49.7 (16.2) and mental component score = 50.6 (17.5) vs 28.2 (32.5), P < 0.05) and lower anxiety (7.2 ± 4.2 vs 10.8 ± 4.1, P = 0.001) and depression levels (3.0 (3.3) vs 6.0 (5.3), P = 0.034), respectively.

Conclusions

Intradialytic exercise training in HD patients was associated with lower burden of their family caregivers.
Examining variation in hydraulic and resource acquisition traits along climatic gradients tests our understanding of plant form and function
Authors: Skelton Robert P. , Anderegg Leander D. L. , Lamarque Laurent J.
Published: May 2019

This article is a Commentary on Rosas et al. 223: 632–646.
Comparative analysis of genetic effects of wheat‐Dasypyrum villosum translocations T6V#2S·6AL and T6V#4S·6DL
Authors: Zhao Renhui , Liu Bingliang , Jiang Zhengning , Chen Tiantian , Wang Ling , Ji Yaoyong , Hu Zhubing , He Huagang , Bie Tongde
Published: May 2019

Wheat‐Dasypyrum villosum translocations T6V#2S·6AL and T6V#4S·6DL, carriers of Pm21 and PmV, respectively, confer high resistance to wheat powdery mildew. For better understanding of the difference in genetic effect between them, a RIL population was constructed based on the cross between “Yangmai 18” carrying T6V#2S·6AL and “Yangmai 22” carrying T6V#4S·6DL. Analysis of distribution of the translocations showed that T6V#2S·6AL is much more transmittable than T6V#4S·6DL. By comparing their effects on main agronomic traits, we firstly found that T6V#2S·6AL contributes greatly to top spikelet fecundity, but causes a decrease of 6.7%–10.5% of spike number. No stable effects of T6V#4S·6DL on agronomic traits were found, except for positive effect on plant height. Excitingly, a new recombinant, T6V#4S‐6V#2S·6AL carrying PmV, was screened and proved to have a higher transmission rate than the original translocation T6V#4S·6DL, which will greatly promote the utilization of PmV. The above conclusions of this research will provide important guidance for utilization of Pm21 and PmV more effectively, in wheat powdery mildew resistance breeding.
Cerebral bioenergetic differences measured by phosphorus‐31 magnetic resonance spectroscopy between bipolar disorder and healthy subjects living in two different regions suggesting possible effects of altitude
Authors: Hwang Jaeuk , DeLisi Lynn E. , Öngür Dost , Riley Colin , Zuo Chun , Shi Xianfeng , Sung Young‐Hoon , Kondo Douglas , Kim Tae‐Suk , Villafuerte Rosemond , Smedberg Diane , Yurgelun‐Todd Deborah , Renshaw Perry F.
Published: May 2019

Aim

Increased oxidative stress in cerebral mitochondria may follow exposure to the systemic hypobaric hypoxia associated with residing at higher altitudes. Because mitochondrial dysfunction is implicated in bipolar disorder (BD) pathophysiology, this may impact the cerebral bioenergetics in BD. In this study, we evaluated the cerebral bioenergetics of BD and healthy control (HC) subjects at two sites, located at sea level and at moderate altitude.

Methods

Forty‐three veterans with BD and 33 HC veterans were recruited in Boston (n = 22) and Salt Lake City (SLC; n = 54). Levels of phosphocreatine, β nucleoside triphosphate (βNTP), inorganic phosphate, and pH over total phosphate (TP) were measured using phosphorus‐31 magnetic resonance spectroscopy in the following brain regions: anterior cingulate cortex and posterior occipital cortex, as well as bilateral prefrontal and occipitoparietal (OP) white matter (WM).

Results

A significant main effect of site was found in βNTP/TP (Boston > SLC) and phosphocreatine/TP (Boston < SLC) in most cortical and WM regions, and inorganic phosphate/TP (Boston < SLC) in OP regions. A main effect analysis of BD diagnosis demonstrated a lower pH in posterior occipital cortex and right OP WM and a lower βNTP/TP in right prefrontal WM in BD subjects, compared to HC subjects.

Conclusion

The study showed that there were cerebral bioenergetic differences in both BD and HC veteran participants at two different sites, which may be partly explained by altitude difference. Future studies are needed to replicate these results in order to elucidate the dysfunctional mitochondrial changes that occur in response to hypobaric hypoxia.
Atypical Café‐au‐Lait Macules in a Patient with Koolen‐de Vries Syndrome (17q21.31 Microdeletion Syndrome)
Authors: Han Allison M. , Kusari Ayan , Soeprono Fred , Eichenfield Lawrence F.
Published: May 2019

Koolen‐de Vries syndrome (KdVS), also referred to as the 17q21.31 microdeletion syndrome, is a rare genetic disorder characterized by developmental delay, typical facial dysmorphism, and congenital defects. Associated anomalies include many cutaneous findings. Here, we report a 17‐year‐old boy with KdVS (17q21.31 microdeletion syndrome) who presented with diffuse freckling and multiple pigmented lesions, found to be most consistent with atypical café‐au‐lait macules (CALMs) on biopsy. We review the cutaneous findings commonly associated with KdVS (17q21.31 microdeletion syndrome) and propose the addition of diffuse freckling and atypical CALMs, histologically similar to those that may be found in neurofibromatosis type 1, to the cutaneous findings associated with KdVS (17q21.31 microdeletion syndrome).
Clinicopathologic characteristics of de novo nodular regenerative hyperplasia in pediatric liver transplant
Authors: González Iván , Lu Hsiang‐Chih , Ritter Jon H. , Maluf Horacio M. , Dehner Louis P. , He Mai
Published: May 2019

Liver NRH is seen in all patients age; however, more frequently in those over the age of 60 years and associated with multiple systemic diseases. In liver allograft recipients, the development of DnNRH has been linked with the use of azathioprine or vascular abnormalities. We present the clinicopathologic characteristics of 17 pediatric patients who underwent liver transplantation and subsequently developed DnNRH. The patients were divided into early and late onset depending if DnNRH was diagnosed within or beyond 4 years after transplant. Eight patients (47%) presented as early onset, of which two had normal ultrasound at time of diagnosis. One patient (12.5%) with early onset lost the graft secondary to DnNRH. Nine patients (53%) presented as late onset, of which two (22%) had normal ultrasound at time of diagnosis. Two patients (25%) of the late onset lost their graft secondary to chronic rejection and DnNRH. Two patients (12%) died secondary to cytomegalovirus pneumonitis and pancolitis. Furthermore, both groups presented with symptoms differing from the adult population in prior studies and were not associated with the use of azathioprine or vascular abnormalities. Interestingly, episodes of acute cellular rejection were more common in the early‐onset group compared to the late‐onset group. In conclusion, DnNRH in the pediatric age group has a different clinical presentation, possibly reflecting a different pathogenesis compared to the adult population.
New‐onset diabetes after pediatric heart transplantation: A review of the Pediatric Heart Transplant Study
Authors: Sparks Joshua D. , Cantor Ryan S. , Pruitt Elizabeth , Kirklin James K. , Carboni Michael , Dreyer William , Kindel Steven , Ryan Thomas D. , Morrow W. Robert
Published: May 2019

NDT is a well‐defined complication after solid organ transplantation. Little has been published describing the incidence, risk factors, and effect on outcome after pediatric heart transplantation. We performed a retrospective evaluation of pediatric patients from the PHTS registry from 2004 to 2014. Group comparison, associated factors, incidence using Kaplan‐Meier method, and risk factor and outcome analysis for NDT at 1 year post‐transplant. Of the 2185 recipients, 1756 were alive and followed at 1 year. Overall freedom from NDT was 98.9%, 94.7%, and 92.6% at 1, 5, and 10 years, respectively. Patients with NDT were more likely to be black (non‐Hispanic; P = 0.002), older at time of transplant (P < 0.0001), and have a higher BMI percentile at time of transplant (P < 0.0001). Adjusted risk factors for NDT at 1 year were older age at transplant (years; >12 years, OR: 8.8 and 5‐12 years, HR: 8.0), obese BMI percentile at time of transplant (OR: 3.8), and steroid use at 30 days after transplant (OR: 4.7). Though uncommon, NDT occurs with a constant hazard after pediatric heart transplant; it occurs more often in older patients at transplant, those who are of black race, those who are obese, and those who use steroids. Therefore, targeted weight reduction and selective steroid use in at‐risk populations could reduce the incidence of early NDT. Further data are needed to determine the risk imparted by transplantation, factors that predict late‐onset NDT, and whether NDT alters the outcome after transplant.
CYP3A5 genotype affects time to therapeutic tacrolimus level in pediatric kidney transplant recipients
Authors: Yanik Megan V. , Seifert Michael E. , Locke Jayme E. , Hauptfeld‐Dolejsek Vera , Crowley Michael R. , Cutter Gary R. , Mannon Roslyn B. , Feig Daniel I. , Limdi Nita A.
Published: May 2019

Background

Optimal management of immunosuppression in kidney transplantation requires a delicate balance of efficacy and toxicity. Tacrolimus (TAC) dose requirements are significantly impacted by genetic variation in CYP3A5 polymorphisms, however the impact that genotype has on clinical outcomes in the pediatric kidney transplant population remains unclear.

Methods

We evaluated a retrospective cohort of 98 pediatric kidney transplant recipients. The primary exposure was CYP3A5 genotype, which classified each recipient into the expresser (at least one CYP3A5*1 allele) or non‐expresser group (only CYP3A5*3 alleles). The primary outcome was time to achieve a steady therapeutic TAC concentration. Secondary outcomes include incidence of early allograft rejection and calcineurin inhibitor (CNI) nephrotoxicity during the first year post‐transplant.

Results

The study cohort included 55 (56%) expressers and 43 (44%) non‐expressers of the CYP3A5*1 allele. Expressers had a significantly longer time to achieve a steady therapeutic TAC concentration than non‐expressers (log rank, P = 0.03). Expressers had a trend for higher incidence of early allograft rejection (29.1% vs 16.3%, log rank, P = 0.16). Early biopsy‐proven CNI nephrotoxicity was seen in 60% of recipients, with no differences in the rate between expressers and non‐expressers.

Conclusions

Pediatric kidney transplant recipients with the CYP3A5*1 allele (expressers) take a longer time to achieve therapeutic TAC levels than those with the CYP3A5*3 allele (non‐expressers). However, we observed no significant differences in acute rejection or CNI nephrotoxicity based on CYP3A5 genotype. Thus CYP3A5 genotype was not observed to have an immediate impact on early transplant outcomes.