bluuebunny/crossref_metadata_2025 huggingface dataset:
Retracted:MicroRNA‐219 decreases hippocampal long‐term potentiation inhibition and hippocampal neuronal cell apoptosis in type 2 diabetes mellitus mice by suppressing theNMDARsignaling pathway
Authors: Zhang Ling , Chen Zheng‐Wen , Yang Shu‐Fen , Shaer Muyasi , Wang Ying , Dong Jun‐Jie , Jiapaer Beili
Published: May 2018

Objective

Type 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%‐95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA‐219 (miR‐219) on inhibition of long‐term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DMmice through the N‐methyl‐d‐aspartate receptor (NMDAR) signaling pathway regulation.

Methods

The T2DMmouse models were established, after whichLTPin vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured. Next, the density of pyramidal neurons in each group was calculated. Additionally, the expression levels of miR‐219, theNMDARsignaling pathway [NMDAR1 (NR) 1,NR2A, andNR2B), downstream target proteins [calmodulin‐dependent protein kinase‐II(CaMK‐II) andcAMPresponse element binding protein (CREB)], and apoptosis‐related factors [Bcl2‐associated X protein (Bax), c‐caspase‐9 and c‐caspase‐3] in the hippocampal tissues were determined. Finally, immunohistochemistry was applied to detect and measure the positive expression of Bax, caspase‐9, and caspase‐3 proteins.

Results

The results showed that upregulation of miR‐219 increasesLTPand density of pyramidal neurons in the hippocampal tissues of mice, while it decreases blood glucose of db/db mice. In addition, miR‐219 upregulation also leads to decreasedmRNAlevels ofNR1,NR2A,NR2B, CaMK‐II, andCREBand protein levels ofNR1,NR2A,NR2B, CaMK‐II,CREB, p‐CREB, Bax, c‐caspase‐9, and c‐caspase‐3. Furthermore, upregulation of miR‐219 inhibits positive expression of Bax, caspase‐9, and caspase‐3 proteins, leading to the suppression of hippocampal neuronal cell apoptosis.

Conclusion

The findings from this study indicated that the upregulation of miR‐219 decreasesLTPinhibition and hippocampal neuronal cell apoptosis in T2DMmice by downregulating theNMDARsignaling pathway, therefore suggesting that MiR‐219 might be a future therapeutic strategy for T2DM.
Cardiac diseases among liver transplant candidates
Authors: Gitman Marina , Albertz Megan , Nicolau‐Raducu Ramona , Aniskevich Stephen , Pai Sher‐Lu
Published: May 2018

Improvements in early survival after liver transplant (LT) have allowed for the selection of LT candidates with multiple comorbidities. Cardiovascular disease is a major contributor to post‐LT complications. We performed a literature search to identify the causes of cardiac disease in the LT population and to describe techniques for diagnosis and perioperative management. As no definite guidelines for preoperative assessment (except for pulmonary heart disease) are currently available, we recommend an algorithm for preoperative cardiac work‐up.
Gender disparities in liver transplant candidates with nonalcoholic steatohepatitis
Authors: Loy Veronica M. , Joyce Cara , Bello Sofia , VonRoenn Natasha , Cotler Scott J.
Published: May 2018

Background

Nonalcoholic steatohepatitis (NASH) is the fastest growing indication for liver transplantation (LT). Data from the UNOS database were used to compare rates of listing and LT between men and women with NASH.

Methods

The study population consisted of 76 149 patients listed for LT between 2005 and 2012, 5 492 (7.2%) of who were listed for NASH. Patient characteristics and outcomes were compared by gender.

Results

Nonalcoholic steatohepatitis was a more frequent indication for transplant listing in women than men throughout the study period. Women had lower serum creatinine levels at listing (1.18 ± 0.76 mg/dL vs 1.28 ± 0.79 mg/dL, P < .001) and were less likely to be listed with exception points (17.7% vs 24.9%, P < .001). Transplantation was less common among women than men with NASH (52.4% vs 64.3%), and women were more likely to experience death on the waiting list (17.1% vs 11.4%) In multivariable analysis adjusting for covariates, the rate of LT remained lower for women with NASH (aHR 0.81 95% CI: 0.75‐0.88).

Conclusions

Women with NASH cirrhosis had a higher risk of death on the LT waiting list and were less likely to receive LT compared to men.
Lung transplantation in the Lung Allocation Score era: Medium‐term analysis from a single center
Authors: Iyengar Amit , Kwon Oh Jin , Sanaiha Yas , Eisenring Christian , Biniwale Reshma , Ross David , Ardehali Abbas
Published: May 2018

In 2005, the Lung Allocation Score (LAS) was implemented as the allocation system for lungs in the US. We sought to compare 5‐year lung transplant outcomes before and after the institution of the LAS. Between 2000 and 2011, 501 adult patients were identified, with 132 from January 2000 to April 2005 (Pre‐LAS era) and 369 from May 2005 to December 2011 (Post‐LAS era). Kruskal‐Wallis or chi‐squared test was used to determine significance between groups. Survival was censored at 5 years. Overall, the post‐LAS era was associated with more restrictive lung disease, higher LAS scores, shorter wait‐list times, more preoperative immunosuppression, and more single lung transplantation. In addition, post‐LAS patients had higher O2 requirements with greater preoperative pulmonary impairment. Postoperatively, 30‐day mortality improved in post‐LAS era (1.6% vs 5.3%, P = .048). During the pre‐ and post‐LAS eras, 5‐year survival was 52.3% and 55.3%, respectively (P = .414). The adjusted risk of mortality was not different in the post‐LAS era (P = .139). Freedom from chronic lung allograft dysfunction was significantly higher in the post‐LAS era (P = .002). In this single‐center report, implementation of the LAS score has led to allocation to sicker patients without decrement in short‐ or medium‐term outcomes. Freedom from CLAD at 5 years is improving after LAS implementation.
Motor function daily living skills 5 years after paediatric arterial ischaemic stroke: a prospective longitudinal study
Authors: Cooper Anna N , Anderson Vicki , Greenham Mardee , Hearps Stephen , Hunt Rod W , Mackay Mark T , Ditchfield Michael , Coleman Lee , Monagle Paul , Gordon Anne L
Published: May 2018

Aim

To describe 5‐year motor and functional outcomes after paediatric arterial ischaemic stroke (AIS) and to explore factors associated with poorer long‐term outcome.

Method

Thirty‐three children (21 males, 12 females) with AIS were recruited to a single‐site, cross‐sectional study, from a previously reported prospective longitudinal stroke outcome study. Children were stratified according to age at diagnosis: neonates (≤30d), preschool (>30d–5y), and school age (≥5y). Motor and functional outcomes were measured at 5 years after stroke. Neurological outcomes were evaluated using the Pediatric Stroke Outcome Measure (PSOM) at 1 month and more than 4 years after stroke.

Results

At 5 years after stroke, motor function, quality of life, fatigue, adaptive behaviour, activities of daily living, and handwriting speed were significantly poorer than age expectations. The preschool group had the highest percentage of fine and gross motor impairment. Poorer fine motor skills were associated with subcortical‐only lesions and large lesion size. Poorer gross motor outcomes correlated with preschool age, bilateral lesions, and PSOM impairment at 1 month.

Interpretation

Children are at elevated risk for motor and functional impairments after AIS, with the preschool age group most vulnerable. Identifying early predictors of poorer outcomes facilitates targeted early intervention and long‐term rehabilitation.

What this paper adds

Following paediatric stroke, children are at elevated risk of motor and functional difficulties.

Stroke occurring between 30 days and 5 years of age may result in poorer motor and functional outcomes.
Computerised working memory‐based cognitive remediation therapy does not affect Reading the Mind in The Eyes test performance or neural activity during a Facial Emotion Recognition test in psychosis
Authors: Mothersill David , Dillon Rachael , Hargreaves April , Castorina Marco , Furey Emilia , Fagan Andrew J. , Meaney James F. , Fitzmaurice Brian , Hallahan Brian , McDonald Colm , Wykes Til , Corvin Aiden , Robertson Ian H. , Donohoe Gary
Published: May 2018

Working memory‐based cognitive remediation therapy (CT) for psychosis has recently been associated with broad improvements in performance on untrained tasks measuring working memory, episodic memory and IQ, and changes in associated brain regions. However, it is unclear whether these improvements transfer to the domain of social cognition and neural activity related to performance on social cognitive tasks. We examined performance on the Reading the Mind in the Eyes test (Eyes test) in a large sample of participants with psychosis who underwent working memory‐based CT (N = 43) compared to a control group of participants with psychosis (N = 35). In a subset of this sample, we used functional magnetic resonance imaging (fMRI) to examine changes in neural activity during a facial emotion recognition task in participants who underwent CT (N = 15) compared to a control group (N = 15). No significant effects of CT were observed on Eyes test performance or on neural activity during facial emotion recognition, either at p < 0.05 family‐wise error or at a p < 0.001 uncorrected threshold, within a priori social cognitive regions of interest. This study suggests that working memory‐based CT does not significantly impact an aspect of social cognition which was measured behaviourally and neurally. It provides further evidence that deficits in the ability to decode mental state from facial expressions are dissociable from working memory deficits, and suggests that future CT programmes should target social cognition in addition to working memory for the purposes of further enhancing social function.
Development, organization and plasticity of auditory circuits: Lessons from a cherished colleague
Authors: Lohse Michael , Bajo Victoria M. , King Andrew J.
Published: May 2018

Ray Guillery was a neuroscientist known primarily for his ground‐breaking studies on the development of the visual pathways and subsequently on the nature of thalamocortical processing loops. The legacy of his work, however, extends well beyond the visual system. Thanks to Ray Guillery's pioneering anatomical studies, the ferret has become a widely used animal model for investigating the development and plasticity of sensory processing. This includes our own work on the auditory system, where experiments in ferrets have revealed the role of sensory experience during development in shaping the neural circuits responsible for sound localization, as well as the capacity of the mature brain to adapt to changes in inputs resulting from hearing loss. Our research has also built on Ray Guillery's ideas about the possible functions of the massive descending projections that link sensory areas of the cerebral cortex to the thalamus and other subcortical targets, by demonstrating a role for corticothalamic feedback in the perception of complex sounds and for corticollicular projection neurons in learning to accommodate altered auditory spatial cues. Finally, his insights into the organization and functions of transthalamic corticocortical connections have inspired a raft of research, including by our own laboratory, which has attempted to identify how information flows through the thalamus.
Structural changes within trophic levels are constrained by within‐family assembly rules at lower trophic levels
Authors: Song Chuliang , Altermatt Florian , Pearse Ian , Saavedra Serguei
Published: May 2018

Historical contingency broadly refers to the proposition that even random historical events can constrain the ecological and evolutionary pathways of organisms and that of entire communities. Focusing on communities, these pathways can be reflected into specific structural changes within and across trophic levels – how species interact with and affect each other – which has important consequences for species coexistence. Using the registry of the last 2000 years of plant introductions and their novel herbivores encountered in Central Europe, we find that the order of arrival of closely related (but not of distantly related) plant species constrained the structural changes within the trophic level formed by herbivore species across the observation period. Because it is difficult for field and lab experiments to be conducted over hundreds of years to record and replay the assembly history of a community, our study provides an alternative to understand how structural changes have occurred across extensive periods of time.
Photosynthetic capacity and leaf nitrogen decline along a controlled climate gradient in provenances of two widely distributed Eucalyptus species
Authors: Crous Kristine Y. , Drake John E. , Aspinwall Michael J. , Sharwood Robert E. , Tjoelker Mark G. , Ghannoum Oula
Published: May 2018

Climate is an important factor limiting tree distributions and adaptation to different thermal environments may influence how tree populations respond to climate warming. Given the current rate of warming, it has been hypothesized that tree populations in warmer, more thermally stable climates may have limited capacity to respond physiologically to warming compared to populations from cooler, more seasonal climates. We determined in a controlled environment how several provenances of widely distributed Eucalyptus tereticornis and E. grandis adjusted their photosynthetic capacity to +3.5°C warming along their native distribution range (~16–38°S) and whether climate of seed origin of the provenances influenced their response to different growth temperatures. We also tested how temperature optima (Topt) of photosynthesis and Jmax responded to higher growth temperatures. Our results showed increased photosynthesis rates at a standardized temperature with warming in temperate provenances, while rates in tropical provenances were reduced by about 40% compared to their temperate counterparts. Temperature optima of photosynthesis increased as provenances were exposed to warmer growth temperatures. Both species had ~30% reduced photosynthetic capacity in tropical and subtropical provenances related to reduced leaf nitrogen and leaf Rubisco content compared to temperate provenances. Tropical provenances operated closer to their thermal optimum and came within 3% of the Topt of Jmax during the daily temperature maxima. Hence, further warming may negatively affect C uptake and tree growth in warmer climates, whereas eucalypts in cooler climates may benefit from moderate warming.
Inclusion of alfalfa improves nutritive value and in vitro digestibility of various straw–grass mixed silages in Tibet
Authors: Wang Siran , Li Junfeng , Dong Zhihao , Chen Lei , Shao Tao
Published: May 2018

To enlarge the feed resources and enhance the utilization efficiency of straws as ruminant feed in Tibet, four kinds of local crop straws with tall fescue (Festuca arundinacea Schreb.) based on the ratio of 40/60 (fresh weight) were ensiled with four levels (0, 10%, 20% and 30% of fresh weight) of alfalfa (Medicago sativa L.), respectively. The laboratory silos (1L) were opened after 45 days of ensiling, and the fermentation characteristics, nutritive value and in vitro digestibility of the mixed silages were analysed. The silages including alfalfa had significantly (p < 0.05) or numerically (p > 0.05) higher lactic acid and crude protein contents, lactic acid bacteria counts, in vitro digestibility of dry matter, neutral detergent fibre (NDF) and acid detergent fibre (ADF), and lower NDF and ADF contents than controls. The results suggest that inclusion of alfalfa to mixtures of straws and tall fescue had favourable effects on fermentation quality and obviously improved the nutritive value and in vitro digestibility of mixed silages. This effect was most evident when the inclusion proportion of alfalfa was 30% in oat straw mixed silage.
Copper‐alumina nanocomposites derived from CuAlO2: Phase transformation and microstructural coarsening
Authors: Kracum Michael Robert , Marvel Christopher J. , Albu Mihaela , Hofer Ferdinand , Harmer Martin P. , Chan Helen M.
Published: May 2018

Partial reduction of bulk CuAlO2 results in hierarchical structures wherein there are copper‐alumina regions with widely differing morphologies and scale. At the finest level, the distribution of the 2 phases is at the nanoscale. By means of atomic resolution STEM and electron diffraction, the nanocomposite regions were shown to consist of a dense array of metallic copper platelets dispersed in a matrix of θ‐Al2O3. The copper nanoplatelets were single crystal, and they all exhibited the same orientation relationship with the matrix, namely [110]Cu//[010]θ‐Al2O3, (111)Cu//()θ‐Al2O3. It was shown that the 2‐phase regions where the copper exhibited a significantly coarser, globular morphology, resulted from discontinuous coarsening. Interestingly, a change in the matrix phase from θ‐ to δ‐alumina was also observed as a result of the coarsening reaction. It is believed that in the nanocomposite regions, the θ‐alumina phase was stabilized by the lower interfacial energy between the copper (110) platelets and the matrix.
Baseline adverse electrical remodeling and the risk for ventricular arrhythmia in Cardiac Resynchronization Therapy Recipients (MADIT CRT)
Authors: Biton Yitschak , Ng Chee Yuan , Xia Xiaojuan , Baman Jayson R. , Couderc Jean‐Philippe , Moss Arthur J. , Kutyifa Valentina , McNitt Scott , Polonsky Bronislava , Zareba Wojciech
Published: May 2018

Introduction

Adverse electrical remodeling (AER), represented here as the sum absolute QRST integral (SAI QRST), has previously been shown to be directly associated with the risk for ventricular arrhythmia (VA). Cardiac resynchronization therapy (CRT) is known to reduce the risk for VA through various mechanisms, including reverse remodeling, and we aimed to evaluate the association between baseline AER and the risk for VA in CRT recipients.

Methods and results

The study population comprised 961 CRT‐D implanted patients from the MADIT CRT study. The relationship between SAI QRST, VA risk, and VA risk/death was evaluated as a continuous and as a categorical variable–tertiles (T1 ≤ 0.527, T2 0.528–0.766, T3 > 0.766). In a multivariable model, AER was inversely associated with the risk of VA. Each unit increase in SAI QRST was associated with 64% (P  =  0.007) and 54% (P  =  0.003) decrease in the risk of VA and VA/death, respectively. Patients with high SAI QRST (T3) and medium SAI QRST (T2) had 52% (P < 0.001) and 32% (P  =  0.027) reduced risk for VA and 44% (P  =  0.002) and 26% (P  =  0.055) reduced risk for VA/death as compared with patients with low SAI QRST (T1), respectively.

Conclusion

In CRT implanted patients with mild heart failure, baseline AER was inversely associated with the risk for VA and VA/death; this is a finding that contradicts the relationship previously reported in non‐CRT implanted patients. We theorize that CRT may abate the process of AER; however, characterization of this mechanism requires further study.
Ten‐day high‐dose proton pump inhibitor triple therapy versus sequential therapy for Helicobacter pylori eradication
Authors: Auesomwang Chonticha , Maneerattanaporn Monthira , Chey William D , Kiratisin Pattarachai , Leelakusolwong Somchai , Tanwandee Tawesak
Published: May 2018

Background and Aim

Eradication rates of Helicobacter pylori following standard triple therapy are declining worldwide, but high‐dose proton pump inhibitor‐based triple therapy (HD‐PPI‐TT) and sequential therapy (ST) have demonstrated higher cure rates. We aimed to compare the efficacy and tolerability of HD‐PPI‐TT and ST in H. pylori‐associated functional dyspepsia (FD).

Methods

One hundred and twenty H. pylori‐associated functional dyspepsia patients were randomized to receive 10‐day HD‐PPI‐TT (60 mg lansoprazole/500 mg clarithromycin/1 g amoxicillin, each administered twice daily for 10 days) or 10‐day ST (30 mg lansoprazole/1 g amoxicillin, each administered twice daily for 5 days followed by 30 mg lansoprazole/500 mg clarithromycin/400 mg metronidazole, each administered twice daily for 5 days). H. pylori status was determined in post‐treatment week 4 by 14C‐urea breath test. Eradication and antibiotic resistance rates, dyspeptic symptoms, drug compliance, and adverse effects were compared.

Results

Intention‐to‐treat eradication rates were similar in the ST and HD‐PPI‐TT groups (85% vs. 80%; P = 0.47). However, the eradication rate was significantly higher following ST compared with HD‐PPI‐TT in per protocol analysis (94.4% vs. 81.4%; P = 0.035). ST achieved higher cure rates than HD‐PPI‐TT in clarithromycin‐resistant H. pylori strains (100% vs. 33.3%; P = 0.02). Treatment compliance was similar in the HD‐PPI‐TT and ST groups, although nausea and dizziness were more common in the ST group.

Conclusions

Sequential therapy achieved better H. pylori eradication than HD‐PPI‐TT in patients with FD. However, the eradication rate for ST fell from 94.4% in per protocol to 85% in intention‐to‐treat analysis. Adverse effects might result in poorer compliance and compromise actual ST efficacy (ClinicalTrials.gov: NCT01888237).
Subventricular zone lipidomic architecture loss in Huntington's disease
Authors: Hunter Mandana , Demarais Nicholas J. , Faull Richard L. M. , Grey Angus C. , Curtis Maurice A.
Published: May 2018

The human subventricular zone (SVZ) has a defined cytological and neurochemical architecture, with four constituent laminae that act in concert to support its neurogenic activity. Lipidomic specialisation has previously been demonstrated in the neurologically normal human SVZ, with enrichment of functionally important lipid classes in each lamina. The SVZ is also responsive to neurodegenerative disorders, where thickening of the niche and enhanced proliferation of resident cells were observed in Huntington's disease (HD) brains. In this study, we hypothesised lipidomic changes in the HD SVZ. Using matrix‐assisted laser desorption/ionisation (MALDI) imaging mass spectrometry, this analysis shows differences in the lipidomic architecture in the post‐mortem Vonsattel grade III cases. Relative to matched, neurologically normal specimens (N = 4), the lipidomic signature of the HD SVZ (N = 4) was characterized by loss of sulfatides and triglycerides in the myelin layer, with an ectopic and focal accumulation of sphingomyelins and ceramide‐1‐phosphate observed in this lamina. A striking loss of lipidomic patterning was also observed in the ependymal layer, where the local abundance of phosphatidylinositols was significantly reduced in HD. This comprehensive spatially resolved lipidomic analysis of the human HD SVZ identifies alterations in lipid architecture that may shed light on the mechanisms of SVZ responses to neurodegeneration in HD.

Open Practices

This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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A single episode of binge alcohol drinking causes sleep disturbance, disrupts sleep homeostasis, and down‐regulates equilibrative nucleoside transporter 1
Authors: Sharma Rishi , Sahota Pradeep , Thakkar Mahesh M.
Published: May 2018

Binge alcohol drinking, a risky pattern of alcohol consumption, has severe consequences toward health and well‐being of an individual, his family, and society. Although, binge drinking has detrimental effects on sleep, underlying mechanisms are unknown. We used adult male C57BL/6J mice and exposed them to a single, 4‐h session of binge alcohol self‐administration, in stress‐free environment, to examine neuronal mechanisms affecting sleep. We first verified binge pattern of alcohol consumption. When allowed to self‐administer alcohol in a non‐stressful environment, mice consumed alcohol in a binge pattern. Next, effect of binge drinking on sleep–wakefulness was monitored. While sleep–wakefulness remained unchanged during drinking session, significant increase in non‐rapid eye movement (NREM) sleep was observed during 4 h of active period post‐binge, followed by increased wakefulness, reduced sleep during subsequent sleep (light) period; although the timing of sleep onset (at lights‐on) remained unaffected. Next, electrophysiological and biochemical indicators of sleep homeostasis were examined using sleep deprivation‐recovery sleep paradigm. Mice exposed to binge drinking did not show an increase in cortical theta power and basal forebrain adenosine levels during sleep deprivation; NREM sleep and NREM delta power did not increase during recovery sleep suggesting that mice exposed to binge alcohol do not develop sleep pressure. Our final experiment examined expression of genes regulating sleep homeostasis following binge drinking. While binge drinking did not affect adenosine kinase and A1 receptor, expression of equilibrative nucleoside transporter 1 (ENT1) was significantly reduced. These results suggest that binge alcohol consumption‐induced down‐regulation of ENT1 expression may disrupt sleep homeostasis and cause sleep disturbances.

Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/

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Significance of postmenopausal uterine leiomyomas: Focus on variants
Authors: Oi Yuka , Katayama Kayo , Hirata Go , Ishidera Yumi , Yoshida Hiroshi , Shigeta Hiroyuki
Published: May 2018

Aim

To investigate the differences in leiomyoma pathophysiology by patient age at the time of surgery and the possible significance of postmenopausal uterine leiomyomas, particularly variants.

Methods

We retrospectively reviewed data from 471 patients who underwent surgery for uterine leiomyomas and evaluated their clinical data.

Results

Overall, 441 (93.4%) women were premenopausal and 30 (6.4%) were postmenopausal. There were no differences in the frequency of the coexistence of ovarian steroid‐dependent diseases among age groups. Common histopathological features were observed in most cases despite menopausal status; however, the incidence of variants among postmenopausal patients was high compared to that among premenopausal women (23.3% [7/30] vs 3.2% [14/441], respectively). Among the variant leiomyomas in postmenopausal patients, lipoleiomyomas comprised six.

Conclusion

Although progesterone is known to play a vital role in promoting leiomyoma growth, it reportedly performs dual actions and does not always stimulate leiomyoma growth. Our study may support the idea that the dual action of progesterone is the primary reason for the surgical treatment required for uterine leiomyomas in the postmenopausal period. We also found that lipoleiomyoma might be the most common uterine leiomyoma variant requiring surgical treatment among postmenopausal women. Thus, we must consider the diagnosis of uterine lipoleiomyoma in postmenopausal women with uterine leiomyomas.
Response to letter: Observational studies investigating hip fracture risk: a fundamental methodological issue?
Authors: Bergholdt H. K. M. , Ellervik C. , Nordestgaard B. G.
Published: May 2018

Click here to view the Letter to the Editor by Dr. Sugiyama
Addressing diversity in tuberculosis using multidimensional approaches
Authors: Lerm M. , Dockrell H. M.
Published: May 2018

Tuberculosis is a complex disease, which can affect many organs other than the lungs. Initial infection may be cleared without inducing immunological memory, or progress directly to primary disease. Alternatively, the infection may be controlled as latent TB infection, that may progress to active tuberculosis at a later stage. There is now a greater understanding that these infection states are part of a continuum, and studies using PET/CT imaging have shown that individual lung granulomas may respond to infection independently, in an un‐synchronized manner. In addition, the Mycobacterium tuberculosis organisms themselves can exist in different states: as nonculturable forms, as ‘persisters’, as rapidly growing bacteria and a biofilm‐forming cording phenotype. The ‘omics’ approaches of transcriptomics, metabolomics and proteomics can help reveal the mechanisms underlying these different infection states in the host, and identify biosignatures with diagnostic potential, that can predict the development of disease, in ‘progressors’ as early as 12–18 months before it can be detected clinically, or that can monitor the success of anti‐TB therapy. Further insights can be obtained from studies of BCG vaccination and new TB vaccines. For example, epigenetic changes associated with trained immunity and a stronger immune responses following BCG vaccination can be identified. These omics approaches may be particularly valuable when linked to studies of mycobacterial growth inhibition, as a direct read‐out of the ability to control mycobacterial growth. The second generation of omics studies is identifying much smaller signatures based on as few as 3 or 4 genes. Thus, narrowing down omics‐derived biosignatures to a manageable set of markers now opens the way to field‐friendly point of care assays.
Vitamin D and tuberculosis: where next?
Authors: Brighenti S. , Bergman P. , Martineau A. R.
Published: May 2018

Tuberculosis (TB) has troubled mankind for millennia, but current treatment strategies are long and complicated and the disease remains a major global health problem. The risk of Mycobacterium tuberculosis (Mtb) infection or progression of active TB disease is elevated in individuals with vitamin D deficiency. High‐dose vitamin D was used to treat TB in the preantibiotic era, and in vitro experimental data show that vitamin D supports innate immune responses that restrict growth of Mtb. Several randomized controlled trials have tested whether adjunctive vitamin D supplementation enhances the clinical and microbiological response to standard antimicrobial chemotherapy for pulmonary TB. The effects have been modest at best, and attention is turning to the question of whether vitamin D supplementation might have a role in preventing acquisition or reactivation of latent Mtb infection. In this article, we describe the effects of vitamin D on host immune responses to Mtb in vitro and in vivo and review the results of clinical trials in the field. We also reflect on the findings of clinical trials of vitamin D supplementation for the prevention of acute respiratory tract infections, and discuss how these findings might influence the design of future trials to evaluate the role of vitamin D in the prevention and treatment of TB.
Friends and foes of tuberculosis: modulation of protective immunity
Authors: Brighenti S. , Joosten S. A.
Published: May 2018

Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN‐γ producing CD4+ T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T‐cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights into effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome, is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common comorbidities such as HIV, helminths and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease.
Sticky flatworms (Platyhelminthes) kill armored harvestmen (Arachnida, Opiliones) but are not immune to the prey′s weapons
Authors: Silva M. S. , Willemart R. H. , Carbayo F.
Published: May 2018

Asking how prey respond to different species of predators helps understanding the repertoire of defenses prey exhibit. This approach may also add to the knowledge on the efficiency of prey′s defenses against each predator and allows studying the costs of being attacked by different predators. Here, we studied interactions between the predatory terrestrial flatwormCephaloflexa bergiand the harvestmanMischonyx cuspidatus. The flatworm quickly strikes at the prey′s leg with its head, then crawls towards the prey′s body releasing mucus and thus subdues the harvestman. Harvestmen may release defensive chemicals and pinch the flatworm with spines on legsIV, sometimes cutting the predator in two pieces. We also experimentally assessed the benefits of harvestmen′ defense and the cost of being attacked by testing whether the chemical defense of the harvestmen is efficient against the flatworm and whether the harvestmen that had survived a flatworm attack would have their locomotion abilities hampered. Both hypotheses were corroborated. Previous studies on interactions between harvestmen and other predators, such as spiders and scorpions, had shown that defensive secretions and mechanical retaliation were seldom used and were often ineffective. Our results point to the exact opposite and suggest that different predators exert different selective pressures culminating in the array of defenses exhibited by the prey.
Pro‐inflammatory activation of microglia in the brain of patients with sepsis
Authors: Zrzavy T. , Höftberger R. , Berger T. , Rauschka H. , Butovsky O. , Weiner H. , Lassmann H.
Published: May 2018

Aims

Experimental data suggest that systemic immune activation may create a pro‐inflammatory environment with microglia activation in the central nervous system in the absence of overt inflammation, which in turn may be deleterious in conditions of neurodegenerative disease. The extent to which this is relevant for the human brain is unknown. The central aim of this study is to provide an in‐depth characterization of the microglia and macrophage response to systemic inflammation.

Methods

We used recently described markers to characterize the origin and functional states of microglia/macrophages in white and grey matter in patients who died under septic conditions and compared it to those patients without systemic inflammation.

Results

We found pro‐inflammatory microglia activation in septic patients in the white matter, with very little activation in the grey matter. Using a specific marker for resident microglia (TMEM119), we found that parenchyma microglia were activated and that there was additional recruitment of perivascular macrophages. Pro‐inflammatory microglia activation occurred in the presence of homeostatic microglia cells. In contrast to inflammatory or ischaemic diseases of the brain, the anti‐inflammatory microglia markers CD163 or CD206 were not expressed in acute sepsis. Furthermore, we found pronounced upregulation of inducible nitric oxide synthase not only in microglia, but also in astrocytes and endothelial cells.

Conclusion

Our results demonstrate the pronounced effects of systemic inflammation on the human brain and have important implications for the selection of control populations for studies on microglia activation in human brain disease.
Shwachman–Diamond syndrome: Nationwide survey and systematic review in Japan
Authors: Ikuse Tamaki , Kudo Takahiro , Arai Katsuhiro , Fujii Yoshimitsu , Ida Shinobu , Ishii Tomohiro , Mushiake Sotaro , Nagata Kouji , Tamai Hiroshi , Toki Akira , Tomomasa Takeshi , Ushijima Kosuke , Yanagi Tadahiro , Yonekura Takeo , Taguchi Tomoaki , Shimizu Toshiaki
Published: May 2018

Background

Shwachman–Diamond syndrome (SDS) is a rare multisystem disorder associated with exocrine pancreatic insufficiency. The present study reports the results of a nationwide survey and a systematic review on SDS to develop consensus guidelines for intractable diarrhea including SDS.

Methods

Questionnaires were sent to 616 departments of pediatrics or of pediatric surgery in Japan in a nationwide survey. A second questionnaire was sent to doctors who had treated SDS patients and included questions on clinical information. Additionally, a systematic review was performed using digital literature databases to assess the influence of medical (i.e. non‐surgical) treatment on SDS prognosis.

Results

Answers were received from 529 institutions (85.9%), which included information on 24 patients with SDS (median age, 10.4 years; male, n = 15) treated from January 2005 to December 2014. Although 75% of patients received pancreatic enzyme replacement therapy, there was no significant association between treatment and prognosis. Systematic review identified one clinical practice guideline, two case series, eight case reports and 26 reviews. Patient information from those studies was insufficient for meta‐analysis.

Conclusions

The rarity of SDS makes it difficult to establish evidence‐based treatment for SDS. According to the limited information from patients and published reports, medical treatment for malabsorption due to SDS should be performed to improve fat absorption and stool condition, but it is not clear whether this treatment improves the prognosis of malabsorption.
Regional disparities in obesity/emaciation and income in schoolchildren in Osaka City
Authors: Takaya Junji , Higashino Hirohiko , Ogasawara Hidenori , Konishi Kazutaka , Takaya Ryuzo , Tanoue Jitsuo , Higashide Takashi , Masuda Motoko , Nakao Masatoshi , Shigematsu Shigeto
Published: May 2018

Background

We assessed the association between socioeconomic status at residential area‐level in the 24 wards of Osaka City, differentiated by indices of mean income‐related deprivation, and inequalities in childhood obesity and emaciation.

Methods

Data from representative samples of 26 474 schoolchildren (first and fifth grades of elementary school, and third grade of junior high school [i.e. ninth grade of elementary school]) in Osaka City taken from a somatometric check in spring 2016 were analyzed. The cross‐sectional association between socioeconomic factors, that is, the census‐based annual income of each ward, and the prevalence of childhood overweight/obesity and emaciation, was examined.

Results

The prevalence of overweight/obesity in boys and girls in the first and fifth grades of elementary school and the third grade of junior high school was 3.98% and 4.53%, 10.18% and 8.69%, and 7.02% and 5.55%, respectively. The prevalence of emaciation in boys and girls in the first and fifth grades of elementary school, and the third grade of junior high school was 0.14% and 0.10%, 0.46% and 1.06% and 3.95% and 3.05%, respectively. Mean physical value, expressed as % degree of overweight, had a negative correlation with mean annual income of each ward in girls in the first and fifth grades of elementary school, girls in the third grade of junior high school and boys in the first grade of elementary school.

Conclusions

Overweight/obesity at school age is greatly affected by poverty. Efforts should be made to prevent emaciation not only in girls, but also in boys, in junior high school.
Zinc deficiency and its predictive capacity for anemia: Unique model in school children
Authors: Atasoy Halil Ibrahim , Bugdayci Guler
Published: May 2018

Background

Zinc deficiency is thought to be common in children, but its predictive capacity for anemia is unclear. Thus, this study identified zinc deficiency in school children, and investigated the association between zinc status and hemoglobin, together with other estimates of anemia.

Methods

For this case–control study, 349 of 483 children between 6.5 and 14.8 years old were included from primary schools in Bolu, Turkey. We measured weight, length, body mass index, and complete blood count with serum zinc, ferritin, vitamin B12 and folate. We investigated the differences between the groups and the effects of independent predictors such as age, gender, ferritin, zinc, vitamin B12 and folate on hemoglobin, on hierarchical multiple regression analysis.

Results

Thirty‐eight (10.9%) of 349 children had low serum zinc concentration, and 21 (6.0%) were anemic. There were 12 anemic children in the zinc‐deficient group and nine in the zinc‐sufficient control group (31.5% vs 2.9%) with similar ferritin levels. On regression analysis, zinc had the strongest association with hemoglobin. On receiver operating characteristic analysis, the cut‐off for serum zinc for prediction of anemia was 71.5 μg/dL.

Conclusions

The strongest association of zinc with hemoglobin suggests that low zinc contributed the most to the observed anemia in children.
A novel method to guide classification of para swimmers with limb deficiency
Authors: Hogarth L. , Payton C. , Van de Vliet P. , Connick M. , Burkett B.
Published: May 2018

The International Paralympic Committee has directed International Federations that govern Para sports to develop evidence‐based classification systems. This study defined the impact of limb deficiency impairment on 100 m freestyle performance to guide an evidence‐based classification system in Para Swimming, which will be implemented following the 2020 Tokyo Paralympic games. Impairment data and competitive race performances of 90 international swimmers with limb deficiency were collected. Ensemble partial least squares regression established the relationship between relative limb length measures and competitive 100 m freestyle performance. The model explained 80% of the variance in 100 m freestyle performance and found hand length and forearm length to be the most important predictors of performance. Based on the results of this model, Para swimmers were clustered into four‐, five‐, six‐, and seven‐class structures using nonparametric kernel density estimations. The validity of these classification structures, and effectiveness against the current classification system, were examined by establishing within‐class variations in 100 m freestyle performance and differences between adjacent classes. The derived classification structures were found to be more effective than current classification based on these criteria. This study provides a novel method that can be used to improve the objectivity and transparency of decision‐making in Para sport classification. Expert consensus from experienced coaches, Para swimmers, classifiers, and sport science and medicine personnel will benefit the translation of these findings into a revised classification system that is accepted by the Para swimming community.
Performing “home” in the sharing economies of tourism: the Airbnb experience in Sofia, Bulgaria
Authors: Roelofsen Maartje
Published: May 2018

This article explores how “home” is performed in the emerging sharing economies of tourism, drawing on the example of Airbnb in Sofia, Bulgaria. Based on an (auto)ethnographic approach, this article analyses the sometimes contested ways in which both hosts and guests engage in the everyday embodied practices of home-making. In doing so, it challenges Airbnb’s essentialized idea of home as a site of belonging, “authenticity” or “localness”. It also shows how the political and historical specificities, as well as the materialities of people’s homes significantly shape the ways in which ordinary practices of homemaking play out and consequently affect feelings of (un)homeliness as part of the Airbnb experience. By using performance theory as an analytical framework, this article seeks to contribute to a critical understanding of the contemporary geographies of home in relation to the global sharing economies of tourism, one that is attuned to openness, interrelatedness, and a constant mode of becoming.
The suppression of welcome
Authors: Gill Nick
Published: May 2018

One way to interpret the organisation of refugee welcome in Europe is by thinking about the tension between the official response and the grassroots response to the events. This tension has evolved in different ways in different countries, but in general it is possible to distinguish between a bureaucratic tendency to abstract welcome into a specific problem or policy domain, and a different, often opposite, tendency to welcome in spontaneous, solidaristic and autonomous ways. Starting from the premise that welcome necessarily entails more than simply permitting entry and is inherently emotional and relational, this lecture explores a series of questions. How can genuine, spontaneous welcome be preserved under the pressure of statist and nationalistic logics and demands? How can we hold onto welcome as something meaningful when it seems to be under attack from not only right-wing nationalists and factions that draw spurious connections between refugees and security threats, but also the very architecture of bureaucracy? What relationship does welcome share with legalistic logics and practices? To what extent can welcomers and welcoming initiatives be supported by international cooperation, global organisational and communication systems, and resource-gathering mechanisms? And what role can research play in improving our understanding of welcome? By raising these questions the lecture aims to initiate a discussion about the nature, practicalities and possible futures of welcome in geography and the social sciences more broadly.
From welcome to well ... come: the mobilities, temporalities and geopolitics of contemporary hospitality – commentary to Gill
Authors: Norum Roger
Published: May 2018

In this reflection, I take Nick Gill’s contribution to this issue on the politics of hospitality and welcome as a point of departure to address three specific concerns, framed by the context of contemporary global mobility. First, I argue that various aspects of the recent so-called European migration crisis enable us to further question some of the long-fixed categories through which mobile actors are often classified. Second, I speak to the critical nature of temporality as a governing factor not just in how states manage mobile peoples, but in how people imagine, understand and experience individual and group processes of welcome. Finally, I suggest that just as geopolitical discourse plays a clear role in how migration is understood and experienced, so too are geopolitics deeply embedded in the encounters, practices and regimes of hospitality across tourism.
Two sides of the same coin: Monetary incentives concurrently improve and bias confidence judgments
Authors: Lebreton Maël , Langdon Shari , Slieker Matthijs J. , Nooitgedacht Jip S. , Goudriaan Anna E. , Denys Damiaan , van Holst Ruth J. , Luigjes Judy
Published: May 2018

Investigating the effects of incentive motivation on confidence accuracy and overconfidence.
Revealing the cluster of slow transients behind a large slow slip event
Authors: Frank William B. , Rousset Baptiste , Lasserre Cécile , Campillo Michel
Published: May 2018

A slow slip event is a cluster of small aseismic slip transients intermittently interrupted by relocking of the plate interface.
Proprioception from a neurally controlled lower-extremity prosthesis
Authors: Clites Tyler R. , Carty Matthew J. , Ullauri Jessica B. , Carney Matthew E. , Mooney Luke M. , Duval Jean-François , Srinivasan Shriya S. , Herr Hugh. M.
Published: May 2018

An agonist-antagonist myoneural interface in a subject with a transtibial amputation improves prosthetic control.
Draft Genome Sequence of Saccharospirillum sp. Strain MSK14-1, Isolated from Surface Seawater Collected at Aburatsubo Inlet in Japan
Authors: Hasegawa Masumi , Nakajima Yu , Wong Shu-Kuan , Nakamura Keiji , Ogura Yoshitoshi , Hayashi Tetsuya , Kogure Kazuhiro , Yoshizawa Susumu
Published: May 2018

Here, we report the draft genome sequence of
Saccharospirillum
sp. strain MSK14-1, isolated from surface seawater collected at Aburatsubo Inlet in Japan. The genome sequence of strain MSK14-1 should contribute to our understanding of the characteristics of the genus
Saccharospirillum
.