bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensive Care Unit Admission Following Surgery for Pediatric Spinal Deformity: An Analysis of the ACS-NSQIP Pediatric Spinal Fusion Procedure Targeted Dataset
Authors: Malik Azeem Tariq , Yu Elizabeth , Kim Jeffery , Khan Safdar N.
Published: April 2019

Study Design:

Retrospective cohort.

Objective:

To understand which patient and surgical factors are predictive of an increased odds of undergoing an admission and a prolonged stay >2 days in an intensive care unit (ICU) following corrective surgery for pediatric deformity.

Methods:

The 2016 American College of Surgeons–National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric Spinal Fusion Procedure Targeted database records, merged with original 2016 ACS-NSQIP Pediatric file variables, were used for this study. Univariate and multivariate analyses were used to identify independent risk factors associated with admission, as well as a prolonged length of stay in the ICU following surgery.

Results:

A total of 1398 (39.5%) patients required an ICU admission following the procedure—out of whom 416 (29.8%) stayed for more than 2 days. Following adjusted analysis, patient and surgical factors independently associated with an ICU admission were black/African American versus white race, anterior fusion, combined fusion, nonidiopathic scoliosis, preoperative ventilator dependence, asthma, having structural pulmonary abnormality, developmental delay, having a neuromuscular disorder, requiring nutritional support and a total operative time >270 minutes. The only significant factors associated with a prolonged length of ICU stay >2 days were preoperative ventilator dependence, nutritional support requirement, and undergoing anterior or combined fusion.

Conclusions:

This study is the first of its kind to identify significant patient- and procedure-level factors associated with an ICU admission, and also explores predictors for a prolonged stay in the ICU. Surgeons can use this data to preoperatively counsel families and ensure postoperative course of care is appropriately planned ahead of time.
Posterior circulation stroke diagnosis using HINTS in patients presenting with acute vestibular syndrome: A systematic review
Authors: Krishnan Kailash , Bassilious Kerolos , Eriksen Erik , Bath Philip M , Sprigg Nikola , Brækken Sigrun Kierulf , Ihle-Hansen Hege , Horn Morten Andreas , Sandset Else Charlotte
Published: April 2019

Purpose

Acute vestibular syndrome – vertigo, nausea/vomiting, nystagmus and gait unsteadiness – is common, and differentiating posterior circulation stroke from a peripheral cause can be challenging. The National Institute of Health Stroke Scale (NIHSS) does not include acute vestibular syndrome, and early computed tomography scanning cannot rule out acute ischaemia. A positive Head Impulse–Nystagmus–Test of Skew (HINTS) test suggests posterior circulation stroke in acute vestibular syndrome when any of three signs are present: normal horizontal head impulse, gaze-direction nystagmus or eye skew deviation. This systematic review examined the accuracy of positive HINTS in identifying posterior circulation stroke in acute vestibular syndrome patients.

Methods

We searched MEDLINE (1966 to 21 December 2017), EMBASE (1980 to December 2017), Web of Science and scanned bibliographies. Two authors independently screened relevant articles and extracted data. We included studies where HINTS was used to identify posterior circulation stroke with diagnosis confirmed using magnetic resonance imaging.

Findings

Six studies (n = 644 patients) were identified. Acute stroke was confirmed in 200 (31.1%) patients. There was a 15-fold increased risk of posterior circulation stroke in patients with positive HINTS test compared to those with no abnormality (RR: 15.84, 95% CI: 5.25–47.79). For any stroke, the pooled sensitivity was 95.5% (95% CI: 92.6–98.4%) and specificity was 71.2% (95% CI: 67.0–75.4%).

Discussion and Conclusion

The data suggest that the HINTS test as one element of clinical evaluation is useful to differentiate posterior circulation stroke from peripheral causes in acute vestibular syndrome. Further studies are needed to validate HINTS as a clinical prediction tool in emergency department settings and selection of patients for reperfusion treatment.
Slow violence and toxic geographies: ‘Out of sight’ to whom?
Authors: Davies Thom
Published: April 2019

Toxic pollution is a form of violence. This article explores the gradual brutalities that communities surrounded by petrochemical infrastructure endure over time. Contributing to political geographies of violence and environmental justice, this paper puts the concept of ‘slow violence’ into critical comparison with work on ‘structural violence’. In doing so, the paper makes two key contributions: First, it emphasizes the intimate connections between structural and slow forms of harm, arguing that structural inequality can mutate into noxious instances of slow violence. Second, the paper pushes back against framings of toxic landscapes as entirely invisible to the people they impact. Instead of accepting the standard definition of slow violence as ‘out of sight’, we have to instead ask the question: ‘out of sight to whom?’ In asking this question, and taking seriously the knowledge claims of communities who inhabit toxic spaces, we can begin to unravel the political structures that sustain the uneven geographies of pollution. Based on long-term ethnographic research in a postcolonial region of Louisiana, nicknamed ‘Cancer Alley’, this paper reveals how people gradually ‘witness’ the impacts of slow violence in their everyday lives. Finally, drawing on the notion of ‘epistemic violence’, the paper suggests that slow violence does not persist due to a lack of arresting stories about pollution, but because these stories do not count, thus rendering certain populations and geographies vulnerable to sacrifice.
Glia maturation factor-γ regulates murine macrophage iron metabolism and M2 polarization through mitochondrial ROS
Authors: Aerbajinai Wulin , Ghosh Manik C. , Liu Jie , Kumkhaek Chutima , Zhu Jianqing , Chin Kyung , Rouault Tracey A. , Rodgers Griffin P.
Published: April 2019

In macrophages, cellular iron metabolism status is tightly integrated with macrophage phenotype and associated with mitochondrial function. However, how molecular events regulate mitochondrial activity to integrate regulation of iron metabolism and macrophage phenotype remains unclear. Here, we explored the important role of the actin-regulatory protein glia maturation factor-γ (GMFG) in the regulation of cellular iron metabolism and macrophage phenotype. We found that GMFG was downregulated in murine macrophages by exposure to iron and hydrogen peroxide. GMFG knockdown altered the expression of iron metabolism proteins and increased iron levels in murine macrophages and concomitantly promoted their polarization toward an anti-inflammatory M2 phenotype. GMFG-knockdown macrophages exhibited moderately increased levels of mitochondrial reactive oxygen species (mtROS), which were accompanied by decreased expression of some mitochondrial respiration chain components, including the iron-sulfur cluster assembly scaffold protein ISCU as well as the antioxidant enzymes SOD1 and SOD2. Importantly, treatment of GMFG-knockdown macrophages with the antioxidant N-acetylcysteine reversed the altered expression of iron metabolism proteins and significantly inhibited the enhanced gene expression of M2 macrophage markers, suggesting that mtROS is mechanistically linked to cellular iron metabolism and macrophage phenotype. Finally, GMFG interacted with the mitochondrial membrane ATPase ATAD3A, suggesting that GMFG knockdown–induced mtROS production might be attributed to alteration of mitochondrial function in macrophages. Our findings suggest that GMFG is an important regulator in cellular iron metabolism and macrophage phenotype and could be a novel therapeutic target for modulating macrophage function in immune and metabolic disorders.
RETRACTED ARTICLE: Large tumor suppressor kinase 2 overexpression attenuates 5-FU-resistance in colorectal cancer via activating the JNK-MIEF1-mitochondrial division pathway
Authors: Yao Weilong , Zhu Shengtao , Li Peng , Zhang Shutian
Published: April 2019

Background

5-Fluorouracil (5-FU) is a standard treatment for colorectal cancer, but most patients develop 5-FU resistance. Here, we conducted experiments to identify an effective approach to augment 5-FU-based treatment in colorectal cancer in vitro.

Methods

SW480 cells were in the present study and treated with 5-FU. Besides, LATS2 adenovirus vectors were infected into SW480 cells. Western blotting, immunofluorescence and ELISA were used to evaluate cell death and mitochondrial function. Pathway blocker was used to verify the role of MAPK-JNK pathway in SW480 cell death.

Results

An obvious drop in large tumor suppressor kinase 2 (LATS2) expression was observed in SW480 cells after treatment with 5-FU. In addition, upregulation of LATS2 expression through infection with LATS2 adenovirus further increased the reduction of SW480 cell viability induced by 5-FU. Functional exploration showed that 5-FU treatment suppressed mitochondrial membrane potential, enhanced cyt-c release into the nucleus, induced an oxidative injury environment by promoting ROS production, and eventually upregulated Bax-related mitochondrial apoptosis. Besides, LATS2 overexpression in combination with 5-FU treatment further perturbed mitochondrial homeostasis, and this effect was achieved by elevating mitochondrial division. Mechanistically, LATS2 overexpression and 5-FU co-treatment amplified mitochondrial division by upregulating MIEF1 expression in a manner dependent on MAPK-JNK axis. Knockdown of MIEF1 using an siRNA-mediated loss of function assay and/or inhibition of the MAPK-JNK pathway using the specific inhibitor SP600125 abolished LATS2/5-FU-mediated deleterious effects on mitochondrial performance and SW480 cell viability.

Conclusions

In light of the above findings, LATS2 downregulation could be a potential mechanism of low response to 5-FU treatment. Overexpression of LATS2 to further disrupt mitochondrial function via the JNK-MIEF1 signalling pathway might be a method to optimize 5-FU-based chemotherapy.
The use of urea for the treatment of onychomycosis: a systematic review
Authors: Dars S. , Banwell H. A. , Matricciani L.
Published: April 2019

Background

Onychomycosis, a fungal infection affecting the nail plate, is a common condition often requiring prolonged treatment regimens, with low success rates. Urea is one treatment option, which is thought to improve the efficacy of topical and oral antifungal agents. Despite a theoretical basis for the use of urea for the treatment of onychomycosis, the evidence‐base for this treatment has not been systematically reviewed.

Aim

The purpose of this study was to conduct a systematic literature review to determine the efficacy and safety of urea as a monotherapy and as adjunct therapy, compared to other treatment regimens for onychomycosis.

Method

A systematic literature search of ten electronic databases was conducted. Only studies that used microscopy and culture or other validated laboratory‐based testing method to confirm the presence of a fungal infection before treatment were included. The outcome measures assessed were efficacy (defined in terms of mycological, clinical and complete cure) and safety (defined as self‐reported adverse events).

Results

The systematic search yielded 560 unique studies for review. Of these, only six were eligible for inclusion. All studies were observed to have methodological concerns, most studies consisted of small sample sizes and were difficult to compare given heterogeneity in outcome measures and follow‐up time. Despite this, a trend was observed to suggest that urea, when added to topical or oral antifungal treatment regimens, improved efficacy of the treatment.

Conclusion

This review suggests that topical urea, as an adjunct to topical and oral antifungal treatment regimens, may improve the efficacy of treatment. However, further research is needed.
Association of glucose and blood pressure variability on oxidative stress in patients with type 2 diabetes mellitus and hypertension: a cross-sectional study
Authors: Ohara Makoto , Kohata Yo , Nagaike Hiroe , Koshibu Masakazu , Gima Hiroya , Hiromura Munenori , Yamamoto Takeshi , Mori Yusaku , Hayashi Toshiyuki , Fukui Tomoyasu , Hirano Tsutomu
Published: April 2019

Background

The present study evaluated the effects of glucose and blood pressure (BP) variability on oxidative stress in patients with type 2 diabetes mellitus (T2DM) and hypertension.

Methods

A total of 60 inpatients with T2DM underwent continuous glucose monitoring (CGM) and ambulatory BP monitoring (ABPM). Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. Glucose variability, mean glucose level, percentage coefficient of variation for glucose, mean amplitude of glycemic excursions (MAGE), and area under the postprandial plasma glucose curve were determined through CGM. BP variability was assessed by measuring average BP, standard deviation (SD) of systolic and diastolic BP, and coefficient of variation (CV) of systolic and diastolic BP during daytime and nighttime ABPM.

Results

Participants had a mean age of 64.5 ± 13.3 years with the duration of the disease 13.9 ± 12.4 years and HbA1c of 8.5 ± 1.2%. Univariate analysis showed that MAGE, nighttime SDs of systolic and diastolic BP, and nighttime CV of systolic BP were significantly correlated with d-ROMs. Further, stepwise multiple regression analysis identified MAGE, nighttime SD and CV of diastolic BP, estimated glomerular filtration rate, and smoking as independent contributors to d-ROMs.

Conclusions

Oxidative stress was associated with daily glucose and nighttime diastolic BP variability in patients with T2DM and hypertension.

Trial registration UMIN Clinical Trial Registry UMIN000035615, Registered January 22, 2019—retrospectively registered
Emerin anchors Msx1 and its protein partners at the nuclear periphery to inhibit myogenesis
Authors: Ma Zhangjing , Shi Huiyuan , Shen Yi , Li Huixia , Yang Yu , Yang Jiange , Zhao Hui , Wang Gang , Wang Jingqiang
Published: April 2019

Background

Previous studies have shown that in myogenic precursors, the homeoprotein Msx1 and its protein partners, histone methyltransferases and repressive histone marks, tend to be enriched on target myogenic regulatory genes at the nuclear periphery. The nuclear periphery localization of Msx1 and its protein partners is required for Msx1’s function of preventing myogenic precursors from pre-maturation through repressing target myogenic regulatory genes. However, the mechanisms underlying the maintenance of Msx1 and its protein partners’ nuclear periphery localization are unknown.

Results

We show that an inner nuclear membrane protein, Emerin, performs as an anchor settled at the inner nuclear membrane to keep Msx1 and its protein partners Ezh2, H3K27me3 enriching at the nuclear periphery, and participates in inhibition of myogenesis mediated by Msx1. Msx1 interacts with Emerin both in C2C12 myoblasts and mouse developing limbs, which is the prerequisite for Emerin mediating the precise location of Msx1, Ezh2, and H3K27me3. The deficiency of Emerin in C2C12 myoblasts disturbs the nuclear periphery localization of Msx1, Ezh2, and H3K27me3, directly indicating Emerin functioning as an anchor. Furthermore, Emerin cooperates with Msx1 to repress target myogenic regulatory genes, and assists Msx1 with inhibition of myogenesis.

Conclusions

Emerin cooperates with Msx1 to inhibit myogenesis through maintaining the nuclear periphery localization of Msx1 and Msx1’s protein partners.
Improved multiobjective salp swarm optimization for virtual machine placement in cloud computing
Authors: Alresheedi Shayem Saleh , Lu Songfeng , Abd Elaziz Mohamed , Ewees Ahmed A.
Published: April 2019

In data center companies, cloud computing can host multiple types of heterogeneous virtual machines (VMs) and provide many features, including flexibility, security, support, and even better maintenance than traditional centers. However, some issues need to be considered, such as the optimization of energy usage, utilization of resources, reduction of time consumption, and optimization of virtual machine placement. Therefore, this paper proposes an alternative multiobjective optimization (MOP) approach that combines the salp swarm and sine-cosine algorithms (MOSSASCA) to determine a suitable solution for virtual machine placement (VMP). The objectives of the proposed MOSSASCA are to maximize mean time before a host shutdown (MTBHS), to reduce power consumption, and to minimize service level agreement violations (SLAVs). The proposed method improves the salp swarm and the sine-cosine algorithms using an MOP technique. The SCA works by using a local search approach to improve the performance of traditional SSA by avoiding trapping in a local optimal solution and by increasing convergence speed. To evaluate the quality of MOSSASCA, we perform a series of experiments using different numbers of VMs and physical machines. The results of MOSSASCA are compared with well-known methods, including the nondominated sorting genetic algorithm (NSGA-II), multiobjective particle swarm optimization (MOPSO), a multiobjective evolutionary algorithm with decomposition (MOEAD), and a multiobjective sine-cosine algorithm (MOSCA). The results reveal that MOSSASCA outperforms the compared methods in terms of solving MOP problems and achieving the three objectives. Compared with the other methods, MOSSASCA exhibits a better ability to reduce power consumption and SLAVs while increasing MTBHS. The main differences in terms of power consumption between the MOSCA, MOPSO, MOEAD, and NSGA-II and the MOSSASCA are 0.53, 1.31, 1.36, and 1.44, respectively. Additionally, the MOSSASCA has higher MTBHS value than MOSCA, MOPSO, MOEAD, and NSGA-II by 362.49, 274.70, 585.73 and 672.94, respectively, and the proposed method has lower SLAV values than MOPSO, MOEAD, and NSGA-II by 0.41, 0.28, and 1.27, respectively.
The corporate headquarters in organization design theory: an organizational economics perspective
Authors: Foss Nicolai J.
Published: April 2019

The corporate headquarters (CHQ) is an important part of the organization of large firms; yet, it is neglected in organization design theory. In this brief essay, I argue that we need a better understanding of the CHQ to further our understanding of the link between the top-management team and the rest of the organization, and to improve our understanding of the costs and benefits of hierarchical organization in general. I outline a number of organizational economics ideas that may help addressing these challenges.
Expanded Analysis of Secondary Germline Findings From Matched Tumor/Normal Sequencing Identifies Additional Clinically Significant Mutations
Authors: Ileana Dumbrava Ecaterina , Brusco Lauren , Daniels Molly S. , Wathoo Chetna , Shaw Kenna R. , Lu Karen H. , Zheng Xiaofeng , Strong Louise C. , Litton Jennifer , Arun Banu K. , Eterovic A. Karina , Routbort Mark J. , Patel Keyur P. , Qi Yuan , Piha-Paul Sarina A. , Subbiah Vivek , Hong David S. , Rodon Jordi , Kopetz Scott , Mendelsohn John , Mills Gordon B. , Chen Ken , Meric-Bernstam Funda
Published: April 2019

Purpose

Next-generation sequencing (NGS) for tumor molecular profiling can reveal secondary germline likely pathogenic and pathogenic variants (LPV/PV). The American College of Medical Genetics and Genomics (ACMG) recommends return of secondary results for a subset of 59 genes, but other genes with evidence of clinical utility are emerging. We previously reported that 4.3% of patients who underwent NGS of a targeted panel of 201 genes had LPV/PV on the basis of the ACMG list. We report the frequency of additional germline cancer-related gene variants and discuss their clinical utility.

Patients and Methods

Matched tumor and germline DNA NGS of a targeted panel of 201 genes was performed in a research laboratory on samples from 1,000 patients with advanced or metastatic solid tumors enrolled in a molecular testing protocol ( ClinicalTrials.gov identifier: NCT01772771). The frequency of germline LPV/PV in 54 cancer-related genes, beyond the genes in ACMG list, were analyzed.

Results

Among 1,000 patients who underwent tumor/normal DNA sequencing, 46 (4.6%) were found to have a germline LPV/PV in the following genes: AR (n = 5), ATM (n = 4), BAP1 (n = 1), CDH1 (n = 1), CDKN2A (n = 1), CHEK1 (n = 2), CHEK2 (n = 10), EGFR (n = 1), ERCC3 (n = 4), ERCC5 (n = 1), HNF1B (n = 1), HRAS (n = 1), MITF (n = 4), MLL3 (n = 1), NF1 (n = 3), PKHD1 (n = 4), PTCH1 (n = 1), and SMARCA4 (n = 1). Thus, 8.7% of patients had an LPV/PV, with two patients having two concomitant germline LPV/PV. Five mutations in high-penetrance hereditary cancer predisposition genes were selected to be returned to patients or their representatives: BAP1, CDH1, CDKN2A, EGFR, and SMARCA4.

Conclusion

Broader genomic testing is likely to identify additional secondary pathogenic germline alterations, some with potential clinical utility for return to patients and their relatives. The recommended genes for which germline results should be returned are continually changing, which warrants continued study.
Safety of Beach Chair Position Shoulder Surgery: A Review of the Current Literature
Authors: Murphy Glenn S. , Greenberg Steven B. , Szokol Joseph W.
Published: April 2019

Although uncommon, severe neurological events have been reported in patients undergoing shoulder surgery in the beach chair position. The presumed etiology of central nervous system injury is hypotension and subsequent cerebral hypoperfusion that occurs after alterations in positioning under general anesthesia. Most clinical trials have demonstrated that beach chair positioning results in reductions in regional brain oxygenation, cerebral blood flow, and jugular bulb oxygenation, as well as impairment in cerebral autoregulation and electroencephalographic/processed electroencephalographic variables. Further studies are needed to define the incidence of adverse neurological adverse events in the beach chair position, identify the best intraoperative neurological monitors that are predictive of neurocognitive outcomes, the lowest “safe” acceptable blood pressure during surgery for individual patients, and the optimal interventions to treat intraoperative hypotension.
Improvement in Oxygenation Utilizing Transpulmonary Pressure Monitoring for Optimal Positive End-Expiratory Pressure in Pediatric Acute Respiratory Distress Syndrome: A Case Report
Authors: Gleich Stephen J. , Schiltz Brenda M. , Ouellette Yves , Baker James E. , Aganga Devon O.
Published: April 2019

In severe pediatric acute respiratory distress syndrome, data are lacking on methods to measure and set optimal positive end-expiratory pressure. We present a 2-year-old girl with Trisomy 21 who developed severe pediatric acute respiratory distress syndrome and refractory hypoxemia from human metapneumovirus pneumonia. Esophageal manometry was utilized to measure transpulmonary pressure, and positive end-expiratory pressure was increased to 19 cm H2O, resulting in rapid improvement in oxygenation. Hemodynamics remained adequate without intervention. The patient improved and survived without sequelae. Our case suggests that transpulmonary pressure monitoring should be studied as an adjunct to improve outcomes in pediatric acute respiratory distress syndrome.
Anesthetic Considerations of Hereditary Neuropathy With Liability to Pressure Palsies in an Obstetric Patient: A Case Report
Authors: Bolger Alexandra Amy , Stewart Paul Anthony
Published: April 2019

Hereditary neuropathy with liability to pressure palsies is an autosomal dominant condition occurring in up to 16 per 100,000 people and predisposes to neural compressive injury. Given the rarity of this condition, no guidelines currently exist for the anesthetic management of hereditary neuropathy with liability to pressure palsies. We describe the management of analgesia during labor in a woman diagnosed with hereditary neuropathy with liability to pressure palsies and a history of nerve palsy after obstetric anesthesia. Our report highlights the necessity of clinician awareness of hereditary neuropathy with liability to pressure palsies and the anesthetic precautions used to successfully avoid neural injury in this case.
The fate of cells undergoing spontaneous DNA damage during development
Authors: Miermont Agnes , Antolović Vlatka , Lenn Tchern , Nichols John M. E. , Millward Lindsey J. , Chubb Jonathan R.
Published: April 2019

Embryonic development involves extensive and often rapid cell proliferation. An unavoidable side effect of cell proliferation is DNA damage. The consequences of spontaneous DNA damage during development are not clear. Here, we define an approach to determine the effects of DNA damage on cell fate choice. Using single cell transcriptomics, we identified a subpopulation of Dictyostelium cells experiencing spontaneous DNA damage. Damaged cells displayed high expression of rad51, with the gene induced by multiple types of genotoxic stress. Using live imaging, we tracked high Rad51 cells from differentiation onset until cell fate assignment. High Rad51 cells were shed from multicellular structures, excluding damaged cells from the spore population. Cell shedding resulted from impaired cell motility and defective cell-cell adhesion, with damaged cells additionally defective in activation of spore gene expression. These data indicate DNA damage is not insulated from other aspects of cell physiology during development and multiple features of damaged cells prevent propagation of genetic error. Our approach is generally applicable for monitoring rare subpopulations during development, and permits analysis of developmental perturbations occurring within a physiological dynamic range.
A unique role for clathrin light chain A in cell spreading and migration
Authors: Tsygankova Oxana M. , Keen James H.
Published: April 2019

Clathrin heavy chain is the structural component of the clathrin triskelion, but unique functions for the two distinct and highly conserved clathrin light chains (CLCa and CLCb, also known as CLTA and CLTB, respectively) have been elusive. Here, we show that following detachment and replating, CLCa is uniquely responsible for promoting efficient cell spreading and migration. Selective depletion of CLCa, but not of CLCb, reduced the initial phase of isotropic spreading of HeLa, H1299 and HEK293 cells by 60–80% compared to siRNA controls, and wound closure and motility by ∼50%. Surface levels of β1-integrins were unaffected by CLCa depletion. However, CLCa was required for effective targeting of FAK (also known as PTK2) and paxillin to the adherent surface of spreading cells, for integrin-mediated activation of Src, FAK and paxillin, and for maturation of focal adhesions, but not their microtubule-based turnover. Depletion of CLCa also blocked the interaction of clathrin with the nucleation-promoting factor WAVE complex, and altered actin distribution. Furthermore, preferential recruitment of CLCa to budding protrusions was also observed. These results comprise the first identification of CLCa-specific functions, with implications for normal and neoplastic integrin-based signaling and cell migration.
STIM1 phosphorylation at Y316 modulates its interaction with SARAF and the activation of SOCE and ICRAC
Authors: Lopez Esther , Frischauf Irene , Jardin Isaac , Derler Isabella , Muik Martin , Cantonero Carlos , Salido Gines M. , Smani Tarik , Rosado Juan A. , Redondo Pedro C.
Published: April 2019

Stromal interaction molecule 1 (STIM1) is one of the key elements for the activation of store-operated Ca2+ entry (SOCE). Hence, identification of the relevant phosphorylatable STIM1 residues with a possible role in the regulation of STIM1 function and SOCE is of interest. By performing a computational analysis, we identified that the Y316 residue is susceptible to phosphorylation. Expression of the STIM1-Y316F mutant in HEK293, NG115-401L and MEG-01 cells resulted in a reduction in STIM1 tyrosine phosphorylation, SOCE and the Ca2+ release-activated Ca2+ current (ICRAC). STIM1–Orai1 colocalization was reduced in HEK293 cells transfected with YFP–STIM1-Y316F compared to in cells with wild-type (WT) YFP-tagged STIM1. Additionally, the Y316F mutation altered the pattern of interaction between STIM1 and SARAF under resting conditions and upon Ca2+ store depletion. Expression of the STIM1 Y316F mutant enhanced slow Ca2+-dependent inactivation (SCDI) as compared to STIM1 WT, an effect that was abolished by SARAF knockdown. Finally, in NG115-401L cells transfected with shRNA targeting SARAF, expression of STIM1 Y316F induced greater SOCE than STIM1 WT. Taken together, our results provide evidence supporting the idea that phosphorylation of STIM1 at Y316 plays a relevant functional role in the activation and modulation of SOCE.
The very-long-chain fatty acid elongase Elo2 rescues lethal defects associated with loss of the nuclear barrier function in fission yeast cells
Authors: Kinugasa Yasuha , Hirano Yasuhiro , Sawai Megumi , Ohno Yusuke , Shindo Tomoko , Asakawa Haruhiko , Chikashige Yuji , Shibata Shinsuke , Kihara Akio , Haraguchi Tokuko , Hiraoka Yasushi
Published: April 2019

In eukaryotic cells, chromosomes are confined to the nucleus, which is compartmentalized by the nuclear membranes; these are continuous with the endoplasmic reticulum membranes. Maintaining the homeostasis of these membranes is an important cellular activity performed by lipid metabolic enzymes. However, how lipid metabolic enzymes affect nuclear membrane functions remains to be elucidated. We found that the very-long-chain fatty acid elongase Elo2 is located in the nuclear membrane and prevents lethal defects associated with nuclear membrane ruptures in mutants of the nuclear membrane proteins Lem2 and Bqt4 in the fission yeast Schizosaccharomyces pombe. Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe. The quantity of this ceramide is reduced in the absence of Lem2, and restored by increased expression of Elo2. Furthermore, loss of S. pombe Elo2 can be rescued by its human orthologs. These results suggest that the conserved very-long-chain fatty acid elongase producing the ceramide component is essential for nuclear membrane integrity and cell viability in eukaryotes.

This article has an associated First Person interview with the first author of the paper.
Effects of a gut microbiota transfer on emotional reactivity in Japanese quails (Coturnix japonica)
Authors: Kraimi Narjis , Calandreau Ludovic , Zemb Olivier , Germain Karine , Dupont Christèle , Velge Philippe , Guitton Edouard , Lavillatte Sébastien , Parias Céline , Leterrier Christine
Published: April 2019

The interaction between the gut microbiota (GM) and the brain has led to the concept of the microbiota-gut-brain axis but data in birds remain scarce. We tested the hypothesis that colonization of germ-free chicks from a quail line selected for a high emotional reactivity (E+) with GM from a line with low emotional reactivity (E-) would reduce their emotional behaviour in comparison with germ-free chicks from E+ line colonized with GM from the same E+ line. The GM composition analysis of both groups revealed a shift in term of microbial diversity and richness between Day 21 and Day 35 and the GM of the two groups of quails were closer to each other at Day 35 than at Day 21 at a phylum level. Quails that received GM from the E- line expressed a lower emotional reactivity than the quails colonized by GM from the E+line in the tonic immobility and the novel environment tests proceeded during the second week of age. This result was reversed in a second tonic immobility test and an open-field run two weeks later. These behavioural and GM modifications over time could be the consequence of the resilience of the GM to recover its equilibrium present in the E+ host, which is in part driven by the host genotype. This study shows for the first time that a gut microbiota transfer can influence emotional reactivity in Japanese quails strengthening the existence of a microbiota-gut-brain axis in this species of bird.
Water relations of an insular pit viper
Authors: Sandfoss Mark R. , Lillywhite Harvey B.
Published: April 2019

Colonization of novel habitats often requires plasticity or adaptation to local conditions. There is a critical need to maintain hydration in terrestrial environments having limited water. Atypical populations of Florida cottonmouth snakes, Agkistrodon conanti, inhabit continental islands with no permanent sources of fresh water. Here we report investigations related to how these insular snakes maintain water balance considering the mainland conspecifics are semi-aquatic and typically associate with freshwater mesic habitats. We tested three hypotheses related to water relations of insular populations of cottonmouths compared to those on the mainland. (1) Voluntary drinking of fresh water in free-ranging insular snakes should reflect a relationship to recency of rainfall more strongly than in mainland snakes. (2) Insular snakes will tolerate greater dehydration before drinking than will mainland snakes. (3) Insular snakes will avoid drinking seawater more strongly than will those from the mainland. Between 2001 and 2018, we quantitatively estimated the hydration status of 337 individual cottonmouths from insular populations and 30 cottonmouths from mainland Florida, as judged by the tendency of wild-caught snakes to drink fresh water immediately following capture. We found that insular cottonmouths had a higher incidence of dehydration than did mainland cottonmouths (64% vs. 23%), and the hydration status of the insular snakes correlated with patterns of precipitation. We also determined experimentally the dehydration threshold for drinking fresh water in insular (mean=−5.64±4.3%, n=34) and mainland cottonmouths (mean=−5.74±4.5%, n=21), and these were not significantly different. Discrimination tests for drinking serially from a graded series of brackish water showed that mainland snakes did not discriminate against the highest brackish value (10.5 ppt or 30% seawater), whereas insular snakes showed a preference for <15% seawater. Naïve neonates from insular and mainland cohorts behaved similarly. The preference of insular snakes for fresh water represents an important aspect of the maintenance of water balance that differs from the mainland conspecifics and is likely a habituated or adaptive response to dependence on rainfall.
Diverse Exercises Similarly Reduce Older Adults’ Mobility Limitations
Authors: TOLLÁR JÓZSEF , NAGY FERENC , MOIZS MARIANN , TÓTH BÉLA E. , SANDERS LIANNE M. J. , HORTOBÁGYI TIBOR
Published: April 2019

Introduction/Purpose

Little is known about the comparative effectiveness of exercise programs, especially when delivered at a high intensity, in mobility-limited older adults. We compared the effects of 25 sessions of high-intensity agility exergaming (EXE) and stationary cycling (CYC) at the same cardiovascular load on measured and perceived mobility limitations, balance, and health-related quality of life in mobility-limited older adults.

Methods

Randomized to EXE (n = 28) and CYC (n = 27), mobility-impaired older adults (age 70 yr) exercised five times per week for 5 wk at 80% of age-predicted maximal heart rate. Waitlisted controls did not exercise (n = 28).

Results

Groups did not differ at baseline in any outcomes (P > 0.05). The primary outcomes (The Short Form-36-Health Survey: EXE, 6.9%; effect size, 2.2; CYC, 5.5%, 1.94; Western Ontario and McMaster Universities Osteoarthritis Index: EXE, −27.2%, −3.83; CYC, −17.2, −2.90) improved similarly (P > 0.05). Secondary outcomes, including body mass (−3.7%), depression (−18%), and walking capacity (13.5%) also improved (P < 0.05) similarly after the two interventions. Activities of daily living, Berg Balance Score, BestTest scores, and Dynamic Gait Index improved more (P < 0.05) after EXE than CYC. Center of pressure of standing sway path improved in one of six tests only after EXE (P < 0.05). Postexercise cardiovascular response improved in EXE (P = 0.019). CON did not change in any outcomes (P > 0.05).

Conclusions

When matched for cardiovascular and perceived effort, two diverse high-intensity exercise programs improved health-related quality of life, perceived mobility limitation, and walking capacity similarly and balance outcomes more in mobility-limited older adults, expanding these older adults’ evidence-based exercise options to reduce mobility limitations.
Estimating Energy Expenditure during Level, Uphill, and Downhill Walking
Authors: LOONEY DAVID P. , SANTEE WILLIAM R. , HANSEN ERIC O. , BONVENTRE PETER J. , CHALMERS CHRISTOPHER R. , POTTER ADAM W.
Published: April 2019

Introduction

The load carriage decision aid (LCDA) walking equation was developed from literature-aggregated group mean data to calculate standing and level walking energy expenditures in healthy, military-age adults. The LCDA walking equation has not been validated for use in individuals or graded walking.

Purpose

We aimed to validate the LCDA walking equation as a predictor of standing and level walking energy expenditure in individuals and expand to a new graded walking equation for uphill and downhill walking.

Methods

We compiled standing, level walking, and graded walking energy expenditures measured in 95 participants from 11 studies. Walking speeds reached up to 1.96 m·s−1 with grades ranging between −40% and 45%. The LCDA walking equation was validated against the aggregated standing and level walking data. The new LCDA graded walking equation was developed and cross-validated on the graded walking trials. We compared each equation against four reference predictive equations with the standard error of estimation (SEE) as the primary criterion.

Results

The LCDA walking equation accurately estimated standing and level walking energy expenditure (bias, −0.02 ± 0.20 W·kg−1; SEE, 0.20 W·kg−1). Addition of the novel grade term resulted in precise estimates of uphill and downhill walking energy expenditure (bias, 0.09 ± 0.40 W·kg−1; SEE, 0.42 W·kg−1).

Conclusions

The LCDA walking equation is a valid predictor of standing and walking energy expenditure in healthy, military-age individuals. We developed a novel grade term for estimating both uphill and downhill walking energy expenditure with a single equation. Practitioners can use the new LCDA graded walking equation to calculate energy expenditure during standing as well as walking on level, uphill, and downhill slopes.
Resistance Training Induces Antiatherogenic Effects on Metabolomic Pathways
Authors: SARIN HEIKKI V. , AHTIAINEN JUHA P. , HULMI JUHA J. , IHALAINEN JOHANNA K. , WALKER SIMON , KÜÜSMAA-SCHILDT MARIA , PEROLA MARKUS , PELTONEN HEIKKI
Published: April 2019

Introduction

Arising evidence suggests that resistance training has the potential to induce beneficial modulation of biomarker profile. To date, however, only immediate responses to resistance training have been investigated using high-throughput metabolomics whereas the effects of chronic resistance training on biomarker profile have not been studied in detail.

Methods

A total of 86 recreationally active healthy men without previous systematic resistance training background were allocated into (i) a resistance training (RT) group (n = 68; age, 33 ± 7 yr; body mass index, 28 ± 3 kg·m−2) and (ii) a non-RT group (n = 18; age, 31 ± 4 yr; body mass index, 27 ± 3 kg·m−2). Blood samples were collected at baseline (PRE), after 4 wk (POST-4wk), and after 16 wk of resistance training intervention (POST-16wk), as well as baseline and after the non-RT period (20–24 wk). Nuclear magnetic resonance–metabolome platform was used to determine metabolomic responses to chronic resistance training.

Results

Overall, the resistance training intervention resulted in favorable alterations (P < 0.05) in body composition with increased levels of lean mass (~2.8%), decreased levels of android (~9.6%), and total fat mass (~7.5%). These changes in body composition were accompanied by antiatherogenic alterations in serum metabolome profile (false discovery rate < 0.05) as reductions in non–high-density lipoprotein cholesterol (e.g., free cholesterol, remnant cholesterol, intermediate-density lipoprotein cholesterols, low-density lipoprotein cholesterols) and related apolipoprotein B, and increments in conjugated linoleic fatty acids levels were observed. Individuals with the poorest baseline status (i.e., body composition, metabolome profile) benefitted the most from the resistance training intervention.

Conclusions

In conclusion, resistance training improves cardiometabolic risk factors and serum metabolome even in previously healthy young men. Thus, suggesting attenuated risk for future cardiovascular disease.
Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder
Authors: MEYER JACOB D. , CROMBIE KEVIN M. , COOK DANE B. , HILLARD CECILIA J. , KOLTYN KELLI F.
Published: April 2019

The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults.

Purpose

We aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states.

Methods

Women with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise.

Results

Significant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen’s d = 0.58 and 0.41, respectively). Significant (P < 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P < 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB–mood relationships were not found for PREF.

Conclusion

Given the broad, moderate–strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercise.
Cárie dentária na América do Sul: realidade entre escolares do Brasil e Argentina
Authors: Gomes Viviane Elisângela , Ferreira Raquel Conceição , Morais Morgana Almeida Souza de , Houri Loliza Chalub Luiz Figueiredo , Bella Marcela Inés , Cornejo Lila Susana , Gigena Pablo Cristian , Verduci Patricia , Zarzar Patrícia Maria de Araújo Pereira , Pordeus Isabela Almeida , Vargas Andrea Maria Duarte , Ferreira Efigênia Ferreira e
Published: April 2019

Introdução: este estudo transversal multicêntrico objetivou determinar a proporção de cárie dentária, sua gravidade e atividade em escolares brasileiros e argentinos. Métodos: a amostra foi composta por escolares selecionados por conveniência, 406 do Brasil (Belo Horizonte - MG) e 241 da Argentina (Córdoba-Cba). Os dados foram coletados por seis dentistas previamente treinados e calibrados (kappaintra≥0,63; kappainter≥0,67). A proporção e gravidade da cárie foram medidas pelos índices ceod e CPOD. A alta experiência de cárie foi identificada pelo Significant Caries Index (SiC). A atividade de cárie foi avaliada segundo a reflexão e a textura da superfície (Nyvad et al., 1999) e o Índice de Cuidados (  foi mensurado. Resultados: a proporção de livres de cárie (ceod e CPOD = 0) no Brasil foi de 45,7% e 19,9% na Argentina. O ceod foi de 1,48 (IC95%: 1,26-1,71) e 2,38 (IC95%: 2,0-2,72) entre escolares do Brasil e da Argentina, respectivamente. Nos dois países, o componente cariado foi o mais frequente. Entre os indivíduos com experiência de cárie (ceod > 1 e/ou CPOD > 1), a atividade de cárie esteve presente em 77,5% das crianças examinadas no Brasil e em 26,4% na Argentina. No grupo SiC, o CPOD foi de 2,20 (IC95%: 1,95-2,20) no Brasil e 2,17 (IC95%: 1,91-2,43) na Argentina, e o ceod no Brasil foi de 3,37 (3,01-3,72) e na Argentina 5,56 (5,04-6,07). O Índice de Cuidados foi baixo. Conclusão: em ambos os países, a proporção de crianças com experiência de cárie foi alta. Concentração de carga e atividade de cárie foi encontrada em grupos de polarização. Cabe ressaltar que a cárie dentária na dentição decídua é um problema relevante que necessita de esforços direcionados em ambos os países.
NLRX1 is not involved in the host defense against Escherichia coli induced pyelonephritis
Authors: Kors Lotte , Butter Loes M. , Claessen Nike , Teske Gwendoline J.D. , Girardin Stephen E. , Florquin Sandrine , Leemans Jaklien C.
Published: April 2019

Background: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (E. coli) are one of the most prominent infections that have serious impact on kidney functioning and the development of chronic kidney disease. NOD-like receptor (NLR)X1 is an innate immune receptor that is important for immune metabolism and regulation, with as yet an unknown role in UTI and the pathophysiology of pyelonephritis.

Methods: Wild-type (WT) and NLRX1 Knock-out (KO) female mice were subjected to UTI by intravesically inoculation of uropathogenic E. coli and sacrificed at 24h and 48h after infection after which bacterial burden and the inflammatory response in the bladder and kidney were studied. Ex  vivo we studied the role of NLRX1 during the LPS induced pro-inflammatory cytokine response and phagocytosis of E. coli by granulocytes and monocytes.

Results: Here, we report that during early experimental UTI NLRX1 absence reduces bacterial clearance in the bladder and dampens the inflammatory cytokine response, whereas in the kidney NLRX1 does not affect bacterial burden or cytokine response. In addition, we found that NLRX1 is not essential for the pro-inflammatory cytokine secretion by granulocytes and monocytes in response to LPS nor for bacterial phagocytosis.

Conclusion: Together, we report that NLRX1 is important in enhancing the early host defense against uropathogenic E. coli in the bladder but does not affect the development of pyelonephritis.
The Image of the Teacher and the Dynamics of its Changes in the Views of Younger Students
Authors: Павлова Н. , Pavlova N.
Published: April 2019

The article is devoted to an actual pedagogical problem - the study of the personality of the teacher, whose relations with pupils in the classroom and outside directly affect the whole educational process, determine the success of the teacher and pupils. The article considers the submission of younger schoolchildren about the image of their teacher, changes in the attitude of children towards him and the reasons for these changes. The practical experience of implementing a personality-oriented approach to the training of first-grade pupils are analyzed.
Protection of Life and Health of Children on the Internet
Authors: Виноградова Наталья , Vinogradova Natalya
Published: April 2019

The article deals with an actual problem related to the provision of the physical and mental health of Russian schoolchildren using the Internet resources. The article gives consistent dynamics of the legal acts and amendments to the federal laws governing the activities of the World Wide Web area that prevent children and adolescents from accessing information that are dangerous for them, as well as tightening the responsibility (including criminal) for involving young Internet users into destructive online communities.