bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative structure–activity relationship and molecular docking studies on designing inhibitors of the perforin
Authors: Song Fucheng , Cui Lianhua , Piao Jinmei , Liang Hui , Si Hongzong , Duan Yunbo , Zhai Honglin
Published: March 2017

Quantitative structure–activity relationship (QSAR) studies were performed on a series of 5‐arylidene‐2thioxoimidazolidin‐4‐ones derivatives as the inhibitors of perforin and to gain insights about the structural determinants for designing new drug molecules. The heuristic method could explore the descriptors responsible for bioactivity and gain a best linear model with R2 .82. Gene expression programming method generated a novel nonlinear function model with R2 .92 for training set and R2 .85 for test set. The predicted IC50 by QSAR, molecular docking analysis, and property explorer applet show that 42a acts as a well‐pleasing potent inhibitor for perforin. This study may lay a reliable theoretical foundation for the development of designing perforin inhibitor structures.
Human gestation-associated tissues express functional cytosolic nucleic acid sensing pattern recognition receptors
Authors: Bryant A H , Menzies G E , Scott L M , Spencer-Harty S , Davies L B , Smith R A , Jones R H , Thornton C A
Published: March 2017

The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal–fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, −7, −8 and −9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model. Immunohistochemistry revealed that these PRRs were expressed by the term placenta, choriodecidua and amnion. A statistically significant increase in interleukin (IL)-6 and/or IL-8 production in response to specific agonists for TLR-3 (Poly(I:C); low and high molecular weight), TLR-7 (imiquimod), TLR-8 (ssRNA40) and RIG-I/MDA5 (Poly(I:C)LyoVec) was observed; there was no response to a TLR-9 (ODN21798) agonist. A hierarchical clustering approach was used to compare the response of each tissue type to the ligands studied and revealed that the placenta and choriodecidua generate a more similar IL-8 response, while the choriodecidua and amnion generate a more similar IL-6 response to nucleic acid ligands. These findings demonstrate that responsiveness via TLR-3, TLR-7, TLR-8 and RIG-1/MDA5 is a broad feature of human term gestation-associated tissues with differential responses by tissue that might underpin adverse obstetric outcomes.
Constitutional LZTR1 mutation presenting with a unilateral vestibular schwannoma in a teenager
Authors: Gripp K.W. , Baker L. , Kandula V. , Piatt J. , Walter A. , Chen Z. , Messiaen L.
Published: March 2017

Schwannomatosis is a rare neurofibromatosis clinically diagnosed by age‐dependent criteria, with bilateral vestibular schwannoma and/or a constitutional NF2 mutation representing exclusion criteria. Following SMARCB1 germline mutations, constitutional mutations in LZTR1 were discovered. We report on the molecular investigation in a patient presenting at 14 years with a unilateral vestibular schwannoma, ultimately causing blindness and unilateral hearing loss, in the absence of other schwannomas or a positive family history.

In DNA derived from frozen tumor tissue, a comprehensive NF2, SMARCB1 and LZTR1 analysis showed an NF2 truncating mutation c.1006_1021delins16; an LZTR1 mutation c.791+1G>A; and a partial 22q deletion including NF2, SMARCB1 and LZTR1. Sequence analysis on peripheral blood derived DNA showed the LZTR1 mutation to be constitutional, but the NF2 mutation and partial 22q deletion were not found, indicating them to be somatic events. RNA‐based targeted analysis confirmed missplicing of LZTR1 intron 8, predicted to result in a premature stop codon. This LZTR1 mutation was paternally inherited.

While isolated vestibular schwannoma or NF2 may be considered in a young individual with a unilateral vestibular schwannoma, this report suggests that
LZTR1
‐related schwannomatosis be added to this differential diagnosis.
Cutaneous Crohn's disease with superimposed psoriasis: A unique case with overlapping histology
Authors: Friedman Ben J. , Dasgeb Bahar , Lee Jason B.
Published: March 2017

Crohn's disease (CD) is an idiopathic, chronic inflammatory disorder of the gastrointestinal tract. We recently encountered a unique case in which a patient with longstanding CD presented with skin lesions with histopathologic features of both psoriasis and granulomatous inflammation suggestive of cutaneous CD. To our knowledge, this has not been described concomitantly in the same patient, in the same lesions. Review of the literature suggests that the intersection of these 2 histopathological reaction patterns may not be pure coincidence. Clinical‐pathologic correlation of this case will be discussed, along with a review of the potential mechanisms of this unique disease presentation.
Gaze‐based rehearsal in children under 7: a developmental investigation of eye movements during a serial spatial memory task
Authors: Morey Candice C. , Mareva Silvana , Lelonkiewicz Jaroslaw R. , Chevalier Nicolas
Published: March 2017

The emergence of strategic verbal rehearsal at around 7 years of age is widely considered a major milestone in descriptions of the development of short‐term memory across childhood. Likewise, rehearsal is believed by many to be a crucial factor in explaining why memory improves with age. This apparent qualitative shift in mnemonic processes has also been characterized as a shift from passive visual to more active verbal mnemonic strategy use, but no investigation of the development of overt spatial rehearsal has informed this explanation. We measured serial spatial order reconstruction in adults and groups of children 5–7 years old and 8–11 years old, while recording their eye movements. Children, particularly the youngest children, overtly fixated late‐list spatial positions longer than adults, suggesting that younger children are less likely to engage in covert rehearsal during stimulus presentation than older children and adults. However, during retention the youngest children overtly fixated more of the to‐be‐remembered sequences than any other group, which is inconsistent with the idea that children do nothing to try to remember. Altogether, these data are inconsistent with the notion that children under 7 do not engage in any attempts to remember. They are most consistent with proposals that children's style of remembering shifts around age 7 from reactive cue‐driven methods to proactive, covert methods, which may include cumulative rehearsal.
Towards a comprehensive profile of dyskinetic cerebral palsy
Authors: Pueyo Roser
Published: March 2017

This commentary is on the original article by Monbaliu et al. on pages 634–640 of this issue.
Salsalate improves glycaemia in overweight persons with diabetes risk factors of stable statin‐treated cardiovascular disease: A 30‐month randomized placebo‐controlled trial
Authors: Salastekar Ninad , Desai Tanvi , Hauser Thomas , Schaefer Ernst J. , Fowler Kristen , Joseph Stacey , Shoelson Steven E. , Goldfine Allison B. ,   on behalf of the TINSAL‐CVD study team
Published: March 2017

Objective

To assess long‐term efficacy and safety of salsalate to improve glycemia in persons with diabetes risk, who are overweight with statin‐treated, stable coronary heart disease.

Methods

Glycemic status was assessed in 192 persons without diabetes at baseline in a pre‐specified secondary analysis from Targeting INflammation Using SALsalate in CardioVascular Disease (TINSAL‐CVD), a multi‐center, double‐masked, randomized (1:1), placebo‐controlled, parallel clinical trial.

Results

Participants were mostly Caucasian males, age 60±7 years, BMI 31.4±3.0 kg/m2, fasting glucose 92.8±11.0 mg/dL, and HbA1c 5.8±0.3%. Reductions in mean fasting glucose ‐5.70 mg/dL (95%CI: ‐7.44 to ‐3.97 mg/dL, P<0.001), HbA1c ‐0.11% (95%CI: ‐0.210 to ‐0.002%, P=0.046) and glycated serum protein ‐81.8 μg/mL (95%CI: ‐93.7 to ‐69.9 μg/mL, P<0.001) were demonstrated in salsalate compared to placebo‐assigned groups over 30 months. Reductions in fasting glucose and glycated serum protein were greater with salsalate compared to placebo in participants with prediabetes compared to a normoglycemic sub‐group (Pinteraction=0.018). Salsalate lowered total white blood cell counts (mean difference ‐0.7x103/μL, 95%CI: ‐1.0 to ‐0.4 x103/μL, P<0.001) and increased adiponectin (mean difference 1.8 μg/mL, 95%CI: 0.9 to 2.6 μg/mL, P<0.001) and albuminurea (16.7 μg/mg, 95%CI: 6.4 to 27.1 μg/mg, P<0.001) compared to placebo, consistent with previous results for patients with type 2 diabetes taking salsalate for shorter times.

Conclusions

Salsalate improves glycemia in obese persons at increased risk for diabetes, and hence may decrease risk of incident type 2 diabetes. Salsalate may inform new therapeutic approaches for diabetes prevention, but renal safety may limit clinical utility.
Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy: Results of a Phase IV open‐label randomized controlled study (the SMART study)
Authors: Du Jin , Liang Li , Fang Hui , Xu Fengmei , Li Wei , Shen Liya , Wang Xueying , Xu Chun , Bian Fang , Mu Yiming
Published: March 2017

Aim

To investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy.

Methods

SMART was a 24‐week, multicentre, randomized, parallel‐group, open‐label Phase IV study conducted at 35 sites in China (September 24, 2014 to September 29, 2015). The primary outcome was absolute change from baseline in HbA1c at Week 24. Secondary outcomes assessed at Week 24 included the proportion of patients achieving HbA1c < 7.0%, the proportion of patients with gastrointestinal adverse events (GI AEs), and the proportion of patients achieving HbA1c < 7.0% without GI AEs. Safety and tolerability were also assessed in all patients who received ≥1 dose of study medication.

Results

Four‐hundred and eighty‐eight patients were randomized (1:1) to saxagliptin or acarbose via a central randomization system (interactive voice/web response system); 241 and 244 patients received saxagliptin and acarbose, respectively, and 238 and 243 of these had ≥1 pre‐ and ≥1 post‐baseline efficacy values recorded. Saxagliptin was non‐inferior to acarbose for glycaemic control [Week 24 HbA1c change: −0.82% and −0.78%, respectively; difference (95% confidence interval): −0.04 (−0.22, 0.13)%], with similar proportions of patients in both treatment groups achieving HbA1c < 7.0%. However, fewer GI AEs were reported with saxagliptin compared with acarbose, and a greater number of patients who received saxagliptin achieved HbA1c < 7.0% without GI AEs compared with those receiving acarbose.

Conclusion

Both therapies had similar efficacy profiles. However, saxagliptin was associated with fewer GI AEs, suggesting it might be preferential for clinical practice.

Clinical trial registration number: NCT02243176, clinicaltrials.gov.
Larger right atrium than left atrium is associated with all‐cause mortality in elderly patients with heart failure
Authors: Almodares Qays , Wallentin Guron Cecilia , Thurin Anders , Fu Michael , Kontogeorgos Silvana , Thunstrom Erik , Johansson Magnus C.
Published: March 2017

Background

While left atrial (LA) enlargement is known as an early sign of left heart disease with prognostic implications in heart failure (HF), the importance of right atrial (RA) enlargement is less well studied, and the prognostic implications of interatrial size comparison are insufficiently understood. The aim of this study was to test the hypothesis that RA area larger than LA area in apical four‐chamber view is associated with all‐cause mortality in elderly patients with HF independent of left ventricular ejection fraction (LVEF).

Methods

Retrospectively, 289 patients above 65 years hospitalized for HF between April 2007 and April 2008, and who underwent an echocardiogram, were enrolled. All‐cause mortality was registered during a follow‐up of at least 56 months. Baseline parameters measured were RA area, LA area, LA volume, LVEF, left ventricular mass (LVM), tissue Doppler systolic velocity of right ventricular free wall (SmRV), presence of severe tricuspid regurgitation (TR), tricuspid gradient, central venous pressure, systolic pulmonary artery pressure, as well as some parameters of diastolic function.

Results

In univariate analysis RA larger than LA was associated with all‐cause mortality (hazard ratio [HR] of 1.88, P<.001). The relation of RA larger than LA to all‐cause mortality remained even after adjusting for age, heart rate, LVEF, atrial fibrillation, percutaneous coronary intervention, LVM index, LA volume index, SmRV, and the presence of severe TR (HR: 1.79, P=.04).

Conclusion

RA larger than LA, independently of LVEF, is associated with all‐cause mortality in elderly patients hospitalized due to HF.
Pneumopericardium as a rare complication after esophagopericardial fistula
Authors: Liao Hai‐Qin , Zhou Dan , Shang Quan‐Liang , Shi Yi‐Fan , Zhang Ming
Published: March 2017

Pneumopericardium is a rare clinical entity which is often complicated by trauma. Pneumoperdicardium resulting after esophagopericardial fistula is much rarer. We present a case of pneumopericardium as the complication of esophagopericardial fistula in a 53‐year‐old man. After undergoing radiotherapy for 26 times, the patient got a fever and an unspecified thoracic pain. Echocardiography showed the rectilinear echoes in the pericardium. Chest computed tomography revealed pneumopericardium, pericardial effusion, recurrence of lung cancer, and pneumonia in right lower and left lung.
Rule‐Following and Rule‐Breaking: Kierkegaard and Wittgenstein
Authors: Watts Daniel
Published: March 2017

My aim in this paper is twofold: to establish that Kierkegaard's so‐called theory of the leap strongly anticipates a line of argument that is central to Wittgenstein's so‐called rule‐following considerations; and to begin to show how Kierkegaard's work has fruitful contributions of its own to make to on‐going discussions about rules and rule‐following. The paper focuses throughout on the question of how, if at all, human rule‐following can be distinguished from behaviour that is merely mechanical or instinctual. I identify a central line of argument in Wittgenstein that problematizes this question by establishing the basis our ability to follow rules in our spontaneous responses. I argue that Kierkegaard not only strongly anticipates this line of argument but also offers a distinctive story about what, at bottom, makes the difference between human rule‐following and behaviour that is merely mechanical or instinctual. In a word, on Kierkegaard's story, what makes the difference is: anxiety.
Magel2 knockout mice manifest altered social phenotypes and a deficit in preference for social novelty
Authors: Fountain M. D. , Tao H. , Chen C.‐A. , Yin J. , Schaaf C. P.
Published: March 2017

MAGEL2 is one of five protein‐coding, maternally imprinted, paternally expressed genes in the Prader–Willi syndrome (PWS)‐critical domain on chromosome 15q11‐q13. Truncating pathogenic variants of MAGEL2 cause Schaaf‐Yang syndrome (SHFYNG) (OMIM #615547), a neurodevelopmental disorder related to PWS. Affected individuals manifest a spectrum of neurocognitive and behavioral phenotypes, including intellectual disability and autism spectrum disorder (ASD). Magel2 knockout mice carrying a maternally inherited, imprinted wild‐type (WT) allele and a paternally inherited Magel2‐lacZ knock‐in allele, which abolishes endogenous Magel2 gene function, exhibit several features reminiscent of the human Prader–Willi phenotypes, including neonatal growth retardation, excessive weight gain after weaning and increased adiposity in adulthood. They were shown to have altered circadian rhythm, reduced motor activity and reduced fertility. An extensive assessment for autism‐like behaviors in this mouse model was warranted, because of the high prevalence of ASD in human patients. The behavior of Magel2 knockout mice and their WT littermates were assayed via open field, elevated plus maze, tube, three‐chamber and partition tests. Our studies confirm decreased horizontal activity of male and female mice and increased vertical activity of females, in the open field. Both sexes spent more time in the open arm of the elevated plus maze, suggestive of reductions in anxiety. Both sexes displayed a lack of preference for social novelty, via a lack of discrimination between known and novel partners in the partition test. The in‐depth investigation of behavioral profiles caused by Magel2 loss‐of‐function helps to elucidate the etiology of behavioral phenotypes both for SHFYNG and PWS in general.
Climatic changes can drive the loss of genetic diversity in a Neotropical savanna tree species
Authors: Lima Jacqueline S. , Ballesteros‐Mejia Liliana , Lima‐Ribeiro Matheus S. , Collevatti Rosane G.
Published: March 2017

The high rates of future climatic changes, compared with the rates reported for past changes, may hamper species adaptation to new climates or the tracking of suitable conditions, resulting in significant loss of genetic diversity. Trees are dominant species in many biomes and because they are long‐lived, they may not be able to cope with ongoing climatic changes. Here, we coupled ecological niche modelling (ENM) and genetic simulations to forecast the effects of climatic changes on the genetic diversity and the structure of genetic clusters. Genetic simulations were conditioned to climatic variables and restricted to plant dispersal and establishment. We used a Neotropical savanna tree as species model that shows a preference for hot and drier climates, but with low temperature seasonality. The ENM predicts a decreasing range size along the more severe future climatic scenario. Additionally, genetic diversity and allelic richness also decrease with range retraction and climatic genetic clusters are lost for both future scenarios, which will lead genetic variability to homogenize throughout the landscape. Besides, climatic genetic clusters will spatially reconfigure on the landscape following displacements of climatic conditions. Our findings indicate that climate change effects will challenge population adaptation to new environmental conditions because of the displacement of genetic ancestry clusters from their optimal conditions.
CO2 exchange and evapotranspiration across dryland ecosystems of southwestern North America
Authors: Biederman Joel A. , Scott Russell L. , Bell Tom W. , Bowling David R. , Dore Sabina , Garatuza‐Payan Jaime , Kolb Thomas E. , Krishnan Praveena , Krofcheck Dan J. , Litvak Marcy E. , Maurer Gregory E. , Meyers Tilden P. , Oechel Walter C. , Papuga Shirley A. , Ponce‐Campos Guillermo E. , Rodriguez Julio C. , Smith William K. , Vargas Rodrigo , Watts Christopher J. , Yepez Enrico A. , Goulden Michael L.
Published: March 2017

Global‐scale studies suggest that dryland ecosystems dominate an increasing trend in the magnitude and interannual variability of the land CO2 sink. However, such analyses are poorly constrained by measured CO2 exchange in drylands. Here we address this observation gap with eddy covariance data from 25 sites in the water‐limited Southwest region of North America with observed ranges in annual precipitation of 100–1000 mm, annual temperatures of 2–25°C, and records of 3–10 years (150 site‐years in total). Annual fluxes were integrated using site‐specific ecohydrologic years to group precipitation with resulting ecosystem exchanges. We found a wide range of carbon sink/source function, with mean annual net ecosystem production (NEP) varying from ‐350 to +330 gCm−2 across sites with diverse vegetation types, contrasting with the more constant sink typically measured in mesic ecosystems. In this region, only forest‐dominated sites were consistent carbon sinks. Interannual variability of NEP, gross ecosystem production (GEP), and ecosystem respiration (Reco) was larger than for mesic regions, and half the sites switched between functioning as C sinks/C sources in wet/dry years. The sites demonstrated coherent responses of GEP and NEP to anomalies in annual evapotranspiration (ET), used here as a proxy for annually available water after hydrologic losses. Notably, GEP and Reco were negatively related to temperature, both interannually within site and spatially across sites, in contrast to positive temperature effects commonly reported for mesic ecosystems. Models based on MODIS satellite observations matched the cross‐site spatial pattern in mean annual GEP but consistently underestimated mean annual ET by ~50%. Importantly, the MODIS‐based models captured only 20–30% of interannual variation magnitude. These results suggest the contribution of this dryland region to variability of regional to global CO2 exchange may be up to 3–5 times larger than current estimates.
Family Matters: an Arendtian Critique of Organizational Structures
Authors: Gardiner Rita A. , Fulfer Katy
Published: March 2017

In this paper, we use Hannah Arendt's conception of praxis and her critique of family to diagnose how praxis and diversity initiatives may suffer when family is used as an organizing principle. As an organizing principle, notions of family function to promote hierarchical sameness within organizations, thereby suppressing diversity. In response to hierarchical sameness, Arendtian praxis can destabilize homogenizing tendencies, and effect social change by challenging ‘business as usual’. Further, because praxis is situated within a diverse, plural community of actors, it is able to appreciate diversity within organizations. Hence, we suggest that organizations can ‘do’ diversity better with a structure that enables praxis to emerge. In addition, we point to ways in which family as an organizational principle privileges a narrow conception of family that obscures gender, racial, sexual and class‐based inequities. This project contributes to the feminist scholarship on diversity and organizational inequities.
An Update on Non‐Pharmacological Neuromodulation for the Acute and Preventive Treatment of Migraine
Authors: Puledda Francesca , Goadsby Peter J.
Published: March 2017

Objective

To review current neuromodulation treatments available for migraine therapy, both in the acute and preventive setting.

Methods

The published literature was reviewed for studies reporting the effects of different neuromodulation strategies in migraine with and without aura. The use of non‐invasive: single pulse transcranial magnetic stimulation, non‐invasive vagal nerve stimulation, supraorbital nerve stimulation, and transcranial direct current stimulation, as well as invasive methods such as occipital nerve stimulation and sphenopalatine ganglion stimulation, are assessed.

Results

The available evidence shows that non‐invasive techniques represent promising treatment strategies, whereas an invasive approach should only be used where patients are refractory to other preventives, including non‐invasive methods.

Conclusions

Neuromodulation is emerging as an exciting approach to migraine therapy, especially in the context of failure of commonly used medicines or for patients who do not tolerate common side effects. More studies with appropriate blinding strategies are needed to confirm the results of these new treatment opportunities.
Mucin‐rich variant of traditional serrated adenoma: a distinct morphological variant
Authors: N Kalimuthu Sangeetha , Serra Stefano , Hafezi‐Bakhtiari Sara , Colling Richard , Wang Lai Mun , Chetty Runjan
Published: March 2017

Aims

Traditional serrated adenomas (TSAs) account for 5% of serrated polyps, and have a villiform architecture, eosinophilic cells with a brush border, and indented, flat‐topped luminal serrations. However, some are composed of mucin‐filled goblet cells (GCs): mucin‐rich TSA (MrTSA). The aim of this study was to determine whether this variant has unique features as compared with classic TSA (cTSA).

Methods and results

One hundred and fifty‐six TSAs were retrieved from the period 2010–2016. Patient demographics, site of polyps and 16 microscopic variables were evaluated. TSAs containing ≥50% GCs were classified as MrTSAs. Ectopic crypt foci (ECFs) were quantified as low (1–10) or high (>10), counted at ×200 magnification, and the average was taken for 10 fields. Twenty‐four fulfilled the criteria for MrTSA. In males, MrTSAs (65%) were more prevalent than cTSAs (55%). There was no age difference, and both variants had a predilection for the left colon, although, in the right colon, MrTSAs were more frequent (39%) than cTSAs (10%) (P = 0.012). Adenomatous dysplasia was present in four of 24 MrTSAs (low grade, 3; high grade, 1). The most distinctive features of MrTSAs were: a variable growth pattern [endophytic (9%), mixed (30%), or villiform/exophytic (61%)], and a lower frequency of ECFs (P = 0.001) and more intraepithelial lymphocytes (P < 0.05) than in cTSAs. MrTSAs retain characteristic luminal serrations, at least focally. Inflamed MrTSAs can mimic inflammatory polyps and hamartomatous polyps (when there are >95% GCs).

Conclusions

MrTSA is characterized by >50% GCs, and fewer ECFs than cTSA, but with preservation of archetypal luminal serrations. Awareness of this variant will prevent misdiagnosis, given the association of TSA with the accelerated pathway to colorectal cancer.
High prevalence of willingness to use direct‐acting antiviral‐based regimens for hepatitis C virus (HCV) infection among HIV/HCV coinfected people who use drugs
Authors: Socías ME , Ti L , Dong H , Shoveller J , Kerr T , Montaner J , Milloy M‐J
Published: March 2017

Objectives

Despite the high burden of hepatitis C virus (HCV)‐related morbidity and mortality among HIV‐positive people who use illicit drugs (PWUD), uptake of interferon‐based treatments for HCV infection has been negligible among this group. Direct‐acting antiviral (DAA) therapies offer an opportunity to expand treatment access among this population. The aim of this study was to explore willingness to use DAA‐based regimens among HIV/HCV‐coinfected PWUD in Vancouver, Canada.

Methods

Data were drawn from the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), a prospective cohort of HIV‐positive PWUD. Using logistic regression analyses, we investigated factors associated with willingness to use DAA‐based regimens among HIV/HCV‐coinfected participants.

Results

Of 418 HIV/HCV‐coinfected PWUD surveyed between June 2014 and May 2015, 295 (71%) were willing to use DAA‐based regimens. In multivariable analysis, participants enrolled in methadone maintenance therapy [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.04–2.51], those with a recent assessment by an HCV specialist (AOR 2.02; 95% CI 1.28–3.19) and those who perceived that HCV infection was affecting their health (AOR 2.49; 95% CI 1.41–4.37) were more likely to be willing to use DAA‐based regimens.

Conclusions

Overall, this study found a high prevalence of willingness to use DAA‐based regimens among HIV/HCV‐coinfected PWUD in Vancouver. Importantly, enrolment in methadone maintenance therapy was positively associated with willingness, suggesting that integrated models of HIV, HCV and addiction care should be explored as a way to address HCV‐related morbidity and mortality among HIV/HCV‐coinfected PWUD.
T regulatory cells are critical for the maintenance, anamnestic expansion and protection elicited by vaccine‐induced CD8 T cells
Authors: Bhattacharyya Mitra , Penaloza‐MacMaster Pablo
Published: March 2017

T regulatory (Treg) cells are critical for preventing autoimmunity and suppressing immune responses during cancer and chronic infection. However, the role of Treg cells in the generation of vaccine‐induced immune memory remains ill‐defined. Using the mouse model of lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate that transient absence of Treg cells during effector to memory CD8 T‐cell transition results in a permanent impairment in the maintenance, function and recall capacity of CD8 T cells. Memory CD8 T cells in mice that were transiently depleted of Treg cells exhibited defective up‐regulation of memory markers with a significant decrease in polyfunctionality. However, Treg‐depleted mice showed no significant change in CD4 T‐cell responses, and antibody levels relative to control. Altogether, this study evaluates the role of Treg cells in the formation of immune memory and demonstrates an important role for Treg cells in promoting memory CD8 T‐cell differentiation and vaccine‐induced immune protection against intracellular pathogens.
Nursing clinical practice changes to improve self‐management in chronic obstructive pulmonary disease
Authors: Padilha J.M. , Sousa P.A.F. , Pereira F.M.S.
Published: March 2017

Aim

To propose nursing clinical practice changes to improve the development of patient self‐management.

Background

Chronic obstructive pulmonary disease is one of the main causes of chronic morbidity, loss of quality of life and high mortality rates.

Introduction

Control of the disease's progression, the preservation of autonomy in self‐care and maintenance of quality of life are extremely challenging for patients to execute in their daily living. However, there is still little evidence to support nursing clinical practice changes to improve the development of self‐management.

Methods

A participatory action research study was performed in a medicine inpatient department and the outpatient unit of a Portuguese hospital. The sample comprised 52 nurses and 99 patients. For data collection, we used interviews, participant observation and content analysis.

Results

The main elements of nursing clinical practice that were identified as a focus for improvement measures were the healthcare model, the organization of healthcare and the documentation of a support decision‐making process.

The specific guidelines, the provision of material to support decision‐making and the optimization of information sharing between professionals positively influenced the change process.

This change improved the development of self‐management skills related to the awareness of the need for ‘change’, hope, involvement, knowledge and abilities.

Discussion

The implemented changes have improved health‐related behaviours and clinical outcomes.

Conclusion

To support self‐management development skills, an effective nursing clinical practice change is needed. This study has demonstrated the relevance of a portfolio of techniques and tools to help patients adopt healthy behaviours.

Implications for nursing and/or health policy

The involvement and participation of nurses and patients in the conceptualization, implementation and evaluation of policy change are fundamental issues to improve the quality of nursing care and clinical outcomes.
Rethinking thresholds for serological evidence of influenza virus infection
Authors: Zhao Xiahong , Siegel Karen , Chen Mark I‐Cheng , Cook Alex R.
Published: March 2017

Introduction

For pathogens such as influenza that cause many subclinical cases, serologic data can be used to estimate attack rates and the severity of an epidemic in near real time. Current methods for analysing serologic data tend to rely on use of a simple threshold or comparison of titres between pre‐ and post‐epidemic, which may not accurately reflect actual infection rates.

Methods

We propose a method for quantifying infection rates using paired sera and bivariate probit models to evaluate the accuracy of thresholds currently used for influenza epidemics with low and high existing herd immunity levels, and a subsequent non‐influenza period. Pre‐ and post‐epidemic sera were taken from a cohort of adults in Singapore (n=838). Bivariate probit models with latent titre levels were fit to the joint distribution of haemagglutination‐inhibition assay‐determined antibody titres using Markov chain Monte Carlo simulation.

Results

Estimated attack rates were 15% (95% credible interval: 12%‐19%) for the first H1N1 pandemic wave. For a large outbreak due to a new strain, a threshold of 1:20 and a twofold rise (if pared sera is available) would result in a more accurate estimate of incidence.

Conclusion

The approach presented here offers the basis for a reconsideration of methods used to assess diagnostic tests by both reconsidering the thresholds used and by analysing serological data with a novel statistical model.
The effects of development, vegetation‐type conversion, and fire on low‐elevation Southern California spider assemblages
Authors: Spear Dakota M. , Adams Tessa A. , Boyd Elise S. , Dipman Madison M. , Staubus Weston J. , Meyer Wallace M.
Published: March 2017

California sage scrub (CSS), a native ecosystem type of low‐elevation areas of Southern California, is increasingly threatened by urban development, altered fire regimes, and vegetation‐type conversion to non‐native grasslands. Using pitfall traps, we examined how suburbanization, type conversion, and fire influence ground‐dwelling spider assemblages in eastern Los Angeles County, CA, by surveying spiders in three habitats (CSS, non‐native grasslands, and suburban areas) before and after a fire that occurred in a small portion of our study site. Spider assemblages in the suburban habitat differed from those in CSS and non‐native grassland habitats, but CSS and grassland assemblages did not significantly differ. This suggests that the urban development, but not vegetation‐type conversion to non‐native grasslands, has significant effects on ground‐dwelling spider assemblages. Fire had no observable effect on assemblages. Because ground‐dwelling spiders were not impacted by fire and type conversion, increased fire frequencies, which often result in the establishment of non‐native grasses, may not deleteriously influence this animal group, a differing pattern from other taxonomic groups. However, the rapid urban development occurring in low‐elevation areas of Southern California means that species requiring non‐suburban sites for their survival (15 species, 24.1%) may be threatened and require conservation assessment.
Renal denervation beyond the bifurcation: The effect of distal ablation placement on safety and blood pressure
Authors: Beeftink Martine M. A. , Spiering Wilko , De Jong Mark R. , Doevendans Pieter A. , Blankestijn Peter J. , Elvan Arif , Heeg Jan‐Evert , Bots Michiel L. , Voskuil Michiel
Published: March 2017

Renal denervation may be more effective if performed distal in the renal artery because of smaller distances between the lumen and perivascular nerves. The authors reviewed the angiographic results of 97 patients and compared blood pressure reduction in relation to the location of the denervation. No significant differences in blood pressure reduction or complications were found between patient groups divided according to their spatial distribution of the ablations (proximal to the bifurcation in both arteries, distal to the bifurcation in one artery and distal in the other artery, or distal to the bifurcation in both arteries), but systolic ambulatory blood pressure reduction was significantly related to the number of distal ablations. No differences in adverse events were observed. In conclusion, we found no reason to believe that renal denervation distal to the bifurcation poses additional risks over the currently advised approach of proximal denervation, but improved efficacy remains to be conclusively established.
Circulating long non‐coding RNAs NRON and MHRT as novel predictive biomarkers of heart failure
Authors: Xuan Lina , Sun Lihua , Zhang Ying , Huang Yuechao , Hou Yan , Li Qingqi , Guo Ying , Feng Bingbing , Cui Lina , Wang Xiaoxue , Wang Zhiguo , Tian Ye , Yu Bo , Wang Shu , Xu Chaoqian , Zhang Mingyu , Du Zhimin , Lu Yanjie , Yang Bao Feng
Published: March 2017

This study sought to evaluate the potential of circulating long non‐coding RNAs (lncRNAs) as biomarkers for heart failure (HF). We measured the circulating levels of 13 individual lncRNAs which are known to be relevant to cardiovascular disease in the plasma samples from 72 HF patients and 60 non‐HF control participants using real‐time reverse transcription‐polymerase chain reaction (real‐time RT‐PCR) methods. We found that out of the 13 lncRNAs tested, non‐coding repressor of NFAT (NRON) and myosin heavy‐chain‐associated RNA transcripts (MHRT) had significantly higher plasma levels in HF than in non‐HF subjects: 3.17 ± 0.30 versus 1.0 ± 0.07 for NRON (P < 0.0001) and 1.66 ± 0.14 versus 1.0 ± 0.12 for MHRT (P < 0.0001). The area under the ROC curve was 0.865 for NRON and 0.702 for MHRT. Univariate and multivariate analyses identified NRON and MHRT as independent predictors for HF. Spearman's rank correlation analysis showed that NRON was negatively correlated with HDL and positively correlated with LDH, whereas MHRT was positively correlated with AST and LDH. Hence, elevation of circulating NRON and MHRT predicts HF and may be considered as novel biomarkers of HF.
Annual Research Review: Childhood maltreatment, latent vulnerability and the shift to preventative psychiatry – the contribution of functional brain imaging
Authors: McCrory Eamon J. , Gerin Mattia I. , Viding Essi
Published: March 2017

Background

Childhood maltreatment is a potent predictor of poor mental health across the life span. We argue that there is a need to improve the understanding of the mechanisms that confer psychiatric vulnerability following maltreatment, if we are to progress from simply treating those with a manifest disorder, to developing effective preventative approaches that can help offset the likelihood that such disorders will emerge in the first place.

Methods

We review extant functional neuroimaging studies of children and adolescents exposed to early neglect and/or maltreatment, including physical, sexual and emotional abuse across four neurocognitive domains: threat processing, reward processing, emotion regulation and executive control. Findings are discussed in the context of ‘latent vulnerability’, where alterations in neurocognitive function are considered to carry adaptive value in early adverse caregiving environments but confer long‐term risk.

Results

Studies on threat processing indicate heightened as well as depressed neural responsiveness in maltreated samples, particularly in the amygdala, thought to reflect threat hypervigilance and avoidance respectively. Studies on reward processing generally report blunted neural response to anticipation and receipt of rewards, particularly in the striatum, patterns associated with depressive symptomatology. Studies on emotion regulation report increased activation of the anterior cingulate cortex (ACC) during active emotion regulation, possibly reflecting greater effortful processing. Finally, studies of executive control report increased dorsal ACC activity during error monitoring and inhibition.

Conclusions

An emerging body of work indicates that altered neurocognitive functioning following maltreatment: (a) is evident even in the absence of overt psychopathology; (b) is consistent with perturbations seen in individuals presenting with psychiatric disorder; (c) can predict future psychiatric symptomatology. These findings suggest that maltreatment leads to neurocognitive alterations that embed latent vulnerability to psychiatric disorder, establishing a compelling case for identifying those children at most risk and developing mechanistically informed models of preventative intervention. Such interventions should aim to offset the likelihood of any future psychiatric disorder.
Acquired perforating dermatosis: clinicopathological study of 31 cases, emphasizing pathogenesis and treatment
Authors: García‐Malinis A.J. , del Valle Sánchez E. , Sánchez‐Salas M.P. , del Prado E. , Coscojuela C. , Gilaberte Y.
Published: March 2017

Background

Acquired perforating dermatosis (APD) is a rare group of skin disorders of unknown aetiology and pathogenesis and is associated with several systemic diseases.

Objective

We review the clinicopathological features, associated systemic diseases and treatment response in a series of APD patients.

Methods

We conducted a retrospective observational study of all patients histologically diagnosed with APD in Hospital San Jorge (Huesca, Spain) between 2002 and 2014. Demographic and clinical features were collected from medical records. Statistical analyses were carried out using SPSS software (version 20.0; IBM Corp, Armonk, NY, USA).

Results

The study population consisted of 31 patients (19 women and 12 men), with a mean age of 54 years. Reactive perforating collagenosis (n = 15, 45%) was the most common histopathologic type. The most frequently affected area was the lower limbs (66.6%, n = 22), and pruritus was present in 19 patients (61.3%, P = 0.005). Arterial hypertension (30.3%) was the most common associated condition. Five patients were receiving treatment with infliximab when diagnosed with APD. Most patients responded to topical steroids and oral antihistamines (n = 15).

Limitations

This study is retrospective, and the sample size is limited.

Conclusion

Acquired perforating dermatosis is an underdiagnosed dermatosis frequently associated with systemic disorders. Its pathogenesis may involve vascular damage, not only in patients with diabetes, but also in those with arterial hypertension and chronic venous insufficiency. Control of pruritus and underlying extracutaneous disorders, as well as discontinuation of the treatment with biologics, are important aspects of the management of this dermatosis.
Formation and development of Staphylococcus biofilm: With focus on food safety
Authors: Miao Jian , Liang Yanrui , Chen Lequn , Wang Wenxin , Wang Jingwen , Li Bing , Li Lin , Chen Dingqiang , Xu Zhenbo
Published: March 2017

Staphylococcus is a common gram‐positive pathogen, which has been considered to be a leading concern to public health and food safety due to the multi‐drag resistance and virulence. As is known, most Staphylococcus tend to form biofilm both during various food processing procedures and in environment, and the bacteria in biofilms show a number of specific advantages over planktonic bacteria due to strong resistance ability. As a consequence, inhibition and removal of Staphylococcus biofilm is difficult for food safety during processing. The present review aims to discuss and demonstrate the formation and development of Staphylococcus biofilm based on food safety account under the background of both phenotype and genetic regulation, providing scientific reference for control strategy.

Practical application

As a common foodborne pathogen, Staphylococcus aureus in food industry is a potential harm to the health of both customer and stuff. Biofilm plays a significant role in bacterial survival, tolerant to environmental stresses. Thus, a comprehensive understanding of biofilm is of essential and urgent need. This review of biofilm of Staphylococcus aureus illustrated the biofilm in food industry and its formation, influential factor, quantification, genetic regulation mechanism, and control strategies, which provided a background of Staphylococcus aureus biofilm prevention in food industry.
Novel strategies for the treatment of acute pancreatitis based on the determinants of severity
Authors: Windsor John A , Escott Alistair , Brown Lisa , Phillips Anthony RJ
Published: March 2017

Acute pancreatitis (AP) is a common disease for which a specific treatment remains elusive. The key determinants of the outcome from AP are persistent organ failure and infected pancreatic necrosis. The prevention and treatment of these determinants provides a framework for the development of specific treatment strategies. The gut‐lymph concept provides a common mechanism for systemic inflammation and organ dysfunction. Acute and critical illness, including AP, is associated with intestinal ischemia and drastic changes in the composition of gut lymph, which bypasses the liver to drain into the systemic circulation immediately proximal to the major organ systems which fail. The external diversion of gut lymph and the targeting of treatments to counter the toxic elements in gut lymph offers novel approaches to the prevention and treatment of persistent organ failure. Infected pancreatic necrosis is increasingly treated with less invasive techniques, the mainstay of which is drainage, both endoscopic and percutaneous. Further improvements will occur with the strategies to accelerate liquefaction and through a fundamental re‐design of drains, both of which will increase drainage efficacy. The determinants of severity and outcome in patients admitted with AP provide the basis for innovative treatment strategies. The priorities are to translate the gut‐lymph concept to clinical practice and to improve the design and active use of drains for infected complications of AP.
Oral and Maxillofacial Lesions Diagnosed in Older People of a Brazilian Population: A Multicentric Study
Authors: Silva Leorik P. , Leite Rafaella B. , Sobral Ana P. V. , Arruda José A. , Oliveira Leni V. , Noronha Mariana S. , Kato Camila O. , Mesquita Ricardo A. , Schuch Lauren F. , Gomes Ana P. N. , Vasconcelos Ana C. U. , Souza Lélia B.
Published: March 2017

Objectives

The aim of this study was to investigate the prevalence of oral and maxillofacial lesions among older adults (≥60 years) from representative regions in Brazil.

Design

Retrospective descriptive cross‐sectional study.

Setting

Biopsy records were obtained from the archives of four Brazilian referral centers of oral diagnosis between 2000 and 2016.

Participants

A total of 45,506 biopsy records of all patients were analyzed, of these 7,259 persons aged 60 and older were selected.

Measurements

Data such as gender, age, race, anatomical location, and histopathological diagnosis were collected and categorized. Pearson's chi‐square test (P < .005) was used to evaluate differences in the frequency of the several groups of oral lesions.

Results

Oral and maxillofacial lesions were diagnosed in 7,259 older people, including 59.4% women (P < .001) and 61.3% white patients (P = .07). The most commonly affected sites were the cheek mucosa (20.3%) and mandible (8.9%) (P < .001). Reactive and inflammatory lesions were the most common lesions, followed by neoplasms. Oral squamous cell carcinoma was the most prevalent neoplasm (83.4%) (P < .001).

Conclusion

Knowledge of oral diseases obtained from biopsy records provides more accurate data about the diagnosis and oral health of elderly patients. These indicators thus support the development of specific health policies for the prevention and treatment of oral and maxillofacial lesions that affect this population.