bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Hurricane Katrina on healthcare delivery for New Orleans patients, 2005–2014
Authors: Raulji Chittalsinh , Velez Maria C. , Prasad Pinki , Rousseau Cierra , Gardner Renee V.
Published: September 2018

Background and objectives

Hematology/oncology patients have special health needs. To identify barriers to care, we surveyed patients/parents at Children's Hospital of New Orleans 1 year after Hurricane Katrina. We then implemented a “Hurricane Action Plan”—identification of families’ evacuation plans at each hurricane season's onset; of hospital(s) and pharmacies in the intended evacuation area; updating roadmaps/treatment plans; giving information to families requiring hematology/oncology services in evacuation areas. Administration of a second survey was initiated 7 years post Katrina to assess the efficacy of the “Hurricane Action Plan.”

Methods

Both surveys were conducted on random patients attending Children's Hospital. Survey #1 was performed in 2006, while survey #2 was conducted in 2013–2014.

Results

Eighty‐nine percent of 124 families left New Orleans during Hurricane Katrina; only 50% had an evacuation plan. Twenty‐five percent of families had difficulty physically accessing care; others (13%) could not find a hematology/oncology provider for follow‐up and had difficulty reaching their primary provider or making appointments. An additional 25 percent did not have access to medical records. There was no access to mental health services. Eighty‐ two patients/representatives were surveyed in 2013/2014; 72% of families were evacuated during subsequent hurricane seasons with 78% of families having an evacuation plan. Thirty‐six percent of patients had a roadmap/treatment plan with them; 71% had a 2‐week medication supply. Ninety‐two percent found information given to them by providers helpful.

Conclusions

Interventions instituted to allow greater access to care by our hematology/oncology patients after Hurricane Katrina resulted in better preparedness, easier acquisition of information, and possibly better continuity of care.
Feasibility of high‐dose chemotherapy protocols to treat infants with malignant central nervous system tumors: Experience from a middle‐income country
Authors: Elshahoubi Alya , Khattab Eman , Halalsheh Hadeel , Khaleifeh Kawther , Bouffet Eric , Amayiri Nisreen
Published: September 2018

Background

Results of high‐dose chemotherapy (HDCT) protocols for the management of malignant central nervous system (CNS) tumors in infants are mostly reported in high‐income countries. We evaluated the feasibility and results of such protocols in a middle‐income country (Jordan).

Methods

A retrospective study of infants’ charts with CNS tumors between 2006 and 2015 who were treated according to HeadStart (HS) protocols. Data included patients’ demographics, chemotherapy complications, and cost.

Results

We identified 18 patients with median age 29 months (range, 9–62 months) at diagnosis (12 HS‐I and six HS‐II). Distribution according to pathology was: atypical teratoid rhabdoid tumors (ATRT) (nine), primitive neuoroectodermal tumors (PNET)/pineoblastoma (five), and medulloblastoma (four). Six patients (33%) had metastatic disease, and 14 (78%) had an incomplete resection. Eleven patients achieved partial or complete remission, two stabilized, and five progressed. Ten patients did not proceed to HDCT due to progression (five), financial reasons (two), failure to collect stem cells (one), and undocumented reasons (two). Seventy‐eight chemotherapy cycles were administered (median interval 26 days). Main complications during induction and consolidation were febrile neutropenia (73% and 100%), documented infections (8% and 13%), and mucositis (12% and 88%), respectively. Three patients developed moderate hearing loss. No protocol‐related mortality was reported. At the last follow‐up, five patients were alive: three with medulloblastoma (19, 29, and 89 months) and two with ATRT (18 and 42 months). Three survivors received focal/craniospinal radiation. The median cost of a complete HS protocol, excluding surgery/radiotherapy, was $103 500 per patient; 39% of the median cost was related to pharmacy expenses.

Conclusions

These protocols were manageable in our context of limited health care resources. However, considering the significant costs and the modest survival rate, better selection criteria need to be used to identify patients likely to benefit from this approach.
Hearing loss in children with sickle cell disease: A prospective French cohort study
Authors: Bois Emilie , Francois Martine , Benkerrou Malika , Van Den Abbeele Thierry , Teissier Natacha
Published: September 2018

Background

Sickle cell disease (SCD) is the most common genetic disease in France. In developing countries, it is associated with a high incidence of hearing loss. The aim of this study was to determine the prevalence of hearing loss in French children with SCD in order to determine if they need a close audiological follow‐up.

Methods

We performed a single‐center prospective cross‐sectional study of children with SCD. The children, without specific hearing symptom, underwent an ear, nose and throat examination with a hearing assessment between 2015 and 2016.

Results

Eighty‐nine children were included, aged from 5 to 19 years, with 73% of SS or Sβ0 genotype and 27% of SC or Sβ+ genotype. Ten children (11.2%) had hearing thresholds higher than 20 dB in at least one ear: one child with subnormal hearing, six otitis media with effusion (OME), and three sensorineural hearing loss. Late age at diagnosis of SCD, a high platelet count and a low hematocrit level were significantly associated with OME; moreover, children with OME had more severe clinical and biological characteristics than children with normal hearing. Furthermore, 12.4% of the children complained of tinnitus. The rate of sudden hearing loss was 2.2%. Finally, 7.1% of patients with normal hearing showed a speech discrimination disorder.

Conclusions

Several causes were identified for hearing loss in children with SCD. They therefore need a close audiological follow‐up in order to avoid complications due to curable phenomena and to enable appropriate management for progressive complications.
Positive expiratory pressure breathing speeds recovery of postexercise dyspnea in chronic obstructive pulmonary disease
Authors: Ubolsakka‐Jones Chulee , Pongpanit Khajonsak , Boonsawat Watchara , Jones David A.
Published: September 2018

Objectives

Faster recovery of postexertional dyspnea might enable chronic obstructive pulmonary disease (COPD) patients to undertake more physical activity. The purpose of this study was to determine whether breathing with a positive expiratory load to reduce dynamic hyperinflation (DH) would hasten recovery.

Methods

Thirteen male COPD patients (59 ± 7 years; Global Initiative for Obstructive Lung Disease Stages II and III) took part in a randomized cross‐over trial in which they exercised by self‐paced spot marching. Interventions at the end of exercise consisted of six breaths against either a 5‐cm H2O expiratory load (positive expiratory pressure [PEP]) or no load (Sham), with 3‐hr rest between interventions. Recovery was followed for the next 10 min. Primary outcome measures were dyspnea during recovery and inspiratory capacity (IC), measured at rest, at the end of exercise and after the intervention; oxygen saturation, end‐tidal CO2, heart rate, and breathing frequency were also monitored.

Results

Patients exercised for 5 min reaching a heart rate of 70% age‐predicted maximum and developed dyspnea of 3–4 on the Modified Borg CR10 scale. Dyspnea recovered significantly faster after the PEP intervention in all patients, taking 2.8 ± 0.4 min to return to baseline compared with 5.1 ± 0.6 min for Sham (p < 0.01). IC declined at the end of exercise and was improved by PEP (+270 220–460 ml, median, interquartile range) more than Sham (+100, 40–160 ml). However, PEP was equally effective in reducing dyspnea in all patients irrespective of the degree of DH. Changes in oxygen saturation, end‐tidal CO2, heart rate, and breathing frequency were similar in PEP and Sham.

Conclusions

Positive expiratory pressure breathing is an effective means of reducing postexercise dyspnea and DH in COPD. The benefits were not limited to patients with high DH suggesting PEP may be used to speed recovery and increase the volume of exercise during pulmonary rehabilitation sessions and physical activity at home or work.
DelPhiPKa: Including salt in the calculations and enabling polar residues to titrate
Authors: Pahari Swagata , Sun Lexuan , Basu Sankar , Alexov Emil
Published: September 2018

DelPhiPKa is a widely used and unique approach to compute pKa's of ionizable groups that does not require molecular surface to be defined. Instead, it uses smooth Gaussian‐based dielectric function to treat computational space via Poisson‐Boltzmann equation (PBE). Here, we report an expansion of DelPhiPKa functionality to enable inclusion of salt in the modeling protocol. The method considers the salt mobile ions in solvent phase without defining solute‐solvent boundary. Instead, the ions are penalized to enter solute interior via a desolvation penalty term in the Boltzmann factor in the framework of PBE. Hence, the concentration of ions near the protein is balanced by the desolvation penalty and electrostatic interactions. The study reveals that correlation between experimental and calculated pKa's is improved significantly by taking into consideration the presence of salt. Furthermore, it is demonstrated that DelphiPKa reproduces the salt sensitivity of experimentally measured pKa's. Another new development of DelPhiPKa allows for computing the pKa's of polar residues such as cysteine, serine, threonine and tyrosine. With this regard, DelPhiPKa is benchmarked against experimentally measured cysteine and tyrosine pKa's and for cysteine it is shown to outperform other existing methods (DelPhiPKa RMSD of 1.73 vs RMSD between 2.40 and 4.72 obtained by other existing pKaprediction methods).
Real‐time examination of cAMP activity at relaxin family peptide receptors using a BRET‐based biosensor
Authors: Valkovic Adam L. , Leckey Miranda B. , Whitehead Alice R. , Hossain Mohammed A. , Inoue Asuka , Kocan Martina , Bathgate Ross A. D.
Published: September 2018

Relaxin family peptide (RXFPs) 1‐4 receptors modulate the activity of cyclic adenosine monophosphate (cAMP) to produce a range of physiological functions. RXFP1 and RXFP2 increase cAMP via Gαs, whereas RXFP3 and RXFP4 inhibit cAMP via Gαi/o. RXFP1 also shows a delayed increase in cAMP downstream of Gαi3. In this study we have assessed whether the bioluminescence resonance energy transfer (BRET)‐based biosensor CAMYEL (cAMP sensor using YFP‐Epac‐Rluc), which allows real‐time measurement of cAMP activity in live cells, will aid in understanding ligand‐ and cell‐specific RXFP signaling. CAMYEL detected concentration‐dependent changes in cAMP activity at RXFP1‐4 in recombinant cell lines, using a variety of ligands with potencies comparable to those seen in conventional cAMP assays. We used RXFP2 and RXFP3 antagonists to demonstrate that CAMYEL detects dynamic changes in cAMP by reversing cAMP activation or inhibition respectively, with real‐time addition of antagonist after agonist stimulation. To demonstrate the utility of CAMYEL to detect cAMP activation in native cells expressing low levels of RXFP receptor, we cloned CAMYEL into a lentiviral vector and transduced THP‐1 cells, which express low levels of RXFP1. THP‐1 CAMYEL cells demonstrated robust cAMP activation in response to relaxin. However, the CAMYEL assay was unable to detect the Gαi3‐mediated phase of RXFP1 cAMP activation in PTX‐treated THP‐1 cells or HEK293A cells with knockout of Gαs. Our data demonstrate that cytoplasmically‐expressed CAMYEL efficiently detects real‐time cAMP activation by Gαs or inhibition by Gαi/o but may not detect cAMP generated in specific intracellular compartments such as that generated by Gαi3 upon RXFP1 activation.
Effect of cellular polyanion mimetics on tau peptide aggregation
Authors: Ismail Tania , Kanapathipillai Mathumai
Published: September 2018

Tau protein aggregation is believed to be one of the key drivers of Alzheimer's disease. The two hexapeptide amino acid sequences 306VQIVYK311 and 275VQIINK280 of the tau protein are responsible for aggregation, and subsequent functional loss leading to Alzheimer's progression. Hence, it is important to understand the factors that promote the self‐aggregation of this tau peptide fragments. Cellular microenvironmental polyanions are known to play a major role in tau protein aggregation and loss of function. Previous studies mainly focused on the effect of heparin and heparan sulfate solution on the full tau protein aggregation. Here, we study the effect of cellular polyanion mimetics, glycosaminoglycans (GAGs) in solution and on surface to mimic intracellular and extracellular conditions, and cellular RNA on the aggregation of tau hexapeptide 306VQIVYK311, and mutant tau peptide 273GKVQIIN_KLDL284 found frequently in taupathy. Characterization techniques used for the study include biochemical assays, electron microscopy, and spectroscopy techniques to investigate the aggregation vitro. Results show while all the GAGs in solution form play a role in tau peptides aggregation, heparin, chondroitin sulfate, and dermatan sulfate in particular significantly promote the tau peptides aggregation formation. On the other hand, surface‐coated GAGs did not promote significant tau aggregation. As far as cellular RNA is concerned, results show significant increase in tau peptides aggregation and toxicity in neuroblastoma cells. The study on the tau peptides fragments aggregation in the presence of GAGs and cellular RNA could provide novel information on the tau aggregation mechanism and could open ways for developing cellular polyanions modulating therapeutics for treating Alzheimer's disease.
Interaction of Radiation‐Induced Self‐Interstitials with Vacancy‐Oxygen Related Defects VnO2 (n from 1 to 3) in Silicon
Authors: Murin Leonid I. , Tolkacheva Ekaterina A. , Lastovskii Stanislau B. , Markevich Vladimir P. , Mullins Jack , Peaker Anthony R. , Svensson Bengt G.
Published: September 2018

Two stage electron irradiation with thermal heat‐treatments after each stage is used for vacancy‐oxygen‐related defect engineering in Czochralski‐grown silicon (Cz‐Si). The Cz‐Si samples are first irradiated at room temperature with 2.5 MeV electrons and then heat‐treated at 320 °C to anneal out the VO, V2O, and V3O centers and generate the VO2, V2O2, and V3O2 complexes as the dominant vacancy‐oxygen‐related defects. Subsequently, the samples are irradiated at room temperature again and subjected to 30‐min isochronal annealing in the temperature range 75–350 °C. Defect evolution upon the treatments is monitored by means of the local vibrational mode (LVM) absorption spectroscopy. From an analysis of changes in intensity of the LVM lines it is revealed that the second irradiation results in a noticeable decrease in the concentrations of the VO2, V2O2, and V3O2 complexes and an increase in the concentrations of the oxygen dimer and the VO2* defect (metastable state of VO2, which consists of the VO and Oi components). The observed defect transformations are argued to be related to interactions of the radiation‐induced self‐interstitial silicon atoms (I) with the vacancy‐oxygen complexes via the following reactions: VO2 + I → O2i, V3O2 + I → V2O2, V2O2 + I → VO2*.
Stevia rebaudianatea prevents experimental cirrhosis via regulation of NF‐κB, Nrf2, transforming growth factor beta, Smad7, and hepatic stellate cell activation
Authors: Ramos‐Tovar Erika , Flores‐Beltrán Rosa E. , Galindo‐Gómez Silvia , Vera‐Aguilar Eunice , Diaz‐Ruiz Araceli , Montes Sergio , Camacho Javier , Tsutsumi Víctor , Muriel Pablo
Published: September 2018

Stevia has been shown to prevent oxidative stress and inflammation in carbon tetrachloride‐induced cirrhosis models. This study aimed to investigate the ability of an aqueous extract of stevia (AES) to prevent thioacetamide (TAA)‐induced cirrhosis in rats and to explore its mechanism of action. Liver cirrhosis was established by administering TAA (200 mg/kg by i.p. injections three times a week for 10 weeks); AES was administered (100 mg/kg by gavage daily) during the TAA treatment. Liver damage and fibrosis were evaluated, and the profibrotic pathways were analyzed by western blotting and immunohistochemistry. TAA increased nuclear factor kappa B (NF‐κB) and pro‐inflammatory cytokine production, as well as the malondialdehyde and 4‐hydroxynonenal levels, whereas the glutathione/glutathione disulfide and nuclear factor‐E2‐related factor 2 (Nrf2) levels were decreased. Moreover, TAA increased collagen production, hepatic stellate cell (HSC) activation, and expression of profibrogenic mediators. TAA‐treated rats that had been exposed to Mn2+ exhibited altered striatal dopamine turnover, indicating hepatic encephalopathy. AES partially or completely prevented all of these effects. AES showed antioxidant, anti‐inflammatory, and antifibrotic properties, probably because of its capacity to induce Nrf2 expression, reduce NF‐κB expression, and block several profibrogenic signaling pathways, subsequently inhibiting HSC activation and preventing fibrosis and dopamine turnover.
Cyanidin‐3‐glucoside attenuates the angiogenesis of breast cancer via inhibiting STAT3/VEGF pathway
Authors: Ma Xiao , Ning Shilong
Published: September 2018

Angiogenesis plays a pivotal role in breast cancer progression. Cyanidin‐3‐glucoside (C3G), one of the most widely distributed anthocyanins in edible fruits, shows antioxidative and anti‐inflammatory property as well as induction of breast cancer cells apoptosis. However, the effect of C3G on breast cancer‐induced angiogenesis remains unknown. In the present study, we found that C3G could attenuate breast cancer‐induced angiogenesis via inhibiting VEGF, a key cytokine for angiogenesis, expression and secretion. Furthermore, signal transducer and activator of transcription 3 (STAT3) could transcriptionally activate VEGF, and C3G reduced STAT3 expression at both mRNA and protein level. Subsequently, our data showed that C3G induced miR‐124 expression. Moreover, miR‐124 could directly repress STAT3 expression, and miR‐124‐mediated STAT3 down‐regulation was responsible for the inhibition of C3G on VEGF and angiogenesis. Taken together, we supplied more evidence to the anti‐breast cancer property of C3G.
Selective binding of an organoruthenium complex to G‐rich human telomeric sequence by tandem mass spectrometry
Authors: Cheng Yiyu , Zeng Wenjuan , Cheng Yang , Zhang Jishuai , Zou Tao , Wu Kui , Wang Fuyi
Published: September 2018

Rationale

Human telomeric DNA is reported to be a potential target for anticancer organometallic ruthenium(II) complexes, however, the interaction sites were not clearly discriminated and identified.

Methods

In the current study, tandem mass spectrometry (MS/MS) using collision‐induced dissociation (CID) was firstly introduced to identify the interaction sites of an organometallic ruthenium(II) complex [(η6‐biphenyl)Ru(en)Cl][PF6] (1; en = ethylenediamine) with 5′‐T1T2A3G4G5G6‐3′ (I), the repeating unit of human telomeric DNA, in both positive‐ and negative‐ion mode at a low reaction molar ratio (1/I = 0.2) which was applied to preserve the site selectivity.

Results

Mass spectrometric results showed that mono‐ruthenated I was the main product under the conditions. In positive‐ion mode, MS/MS results indicated that ruthenium complex 1 binds to T2 or G6 in strand I. However, in negative‐ion mode, no efficient information was obtained for exact identification of ruthenation sites which may be attributed to losses of fragment ions due to charge neutralization by the coordination of the positively charged ruthenium complex to the short MS/MS fragments.

Conclusions

This is the first report of using top‐down MS to characterize the interactions of organometallic ruthenium(II) complexes and human telomeric DNA. Thymine can be thermodynamically competitive with guanine for binding to ruthenium complexes even at low reaction molar ratio, which inspired us to explore in greater depth the significance of thymine binding.
Emerging trends of Nipah virus: A review
Authors: Sharma Vikrant , Kaushik Sulochana , Kumar Ramesh , Yadav Jaya Parkash , Kaushik Samander
Published: September 2018

Since emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population associated with high rate of mortality. NiV has been placed along with Hendra virus in genus Henipavirus of family Paramyxoviridae. Fruit bats (Genus Pteropus) are known to be natural host and reservoir of NiV. During the outbreaks from Malaysia and Singapore, the roles of pigs as intermediate host were confirmed. The infection transmitted from bats to pigs and subsequently from pigs to humans. Severe encephalitis was reported in NiV infection often associated with neurological disorders. First NiV outbreak in India occurred in Siliguri district of West Bengal in 2001, where direct transmission of the NiV virus from bats‐to‐human and human‐to‐human was reported in contrast to the role of pigs in the Malaysian NiV outbreak. Regular NiV outbreaks have been reported from Bangladesh since 2001 to 2015. The latest outbreak of NiV has been recorded in May, 2018 from Kerala, India which resulted in the death of 17 individuals. Due to lack of vaccines and effective antivirals, Nipah encephalitis poses a great threat to public health. Routine surveillance studies in the infected areas can be useful in detecting early signs of infection and help in containment of these outbreaks.
Frequency of Opercular Deformities in Age‐0 Native Catostomids in the San Juan River from 1998 to 2012
Authors: Barkstedt Judith M. , Clark Barkalow Stephani L. , Farrington Michael A. , Kennedy Jennifer L. , Platania Steven P.
Published: September 2018

In the San Juan River, the recruitment of early ontogenetic stages of federally endangered Razorback Sucker Xyrauchen texanus to subadult or adult stages is rare. Opercular deformities have been detected in larval and early juvenile Razorback Suckers in the San Juan River and were investigated as an impediment to recovery of the species. Larval and early juvenile (age‐0) native San Juan River catostomids taken from 1998 to 2012 were examined for presence of opercular deformities. The frequency and severity of opercular deformities in Razorback Suckers were compared with opercular deformities in Bluehead Sucker Catostomus discobolus and Flannelmouth Sucker Catostomus latipinnis and with hatchery‐produced Razorback Suckers. Deformities were primarily observed in larval stages and occurred both unilaterally and bilaterally. Opercular deformities were relatively consistent among years for all three species. The frequency of opercular deformities in Razorback Suckers was more than three times higher than in Bluehead Suckers and more than five times higher than in Flannelmouth Suckers. Opercular deformities in all species were high when compared with Razorback Sucker brood stock and with wild fish in other river basins. This high rate of deformity in larvae and early juvenile San Juan River Razorback Suckers likely increases mortality and inhibits recruitment to later life stages.
Involvement of P38 and ERK1/2 in mitochondrial pathways independent cell apoptosis in oviduct magnum epithelial cells of layers challenged with vanadium
Authors: Wang Jian‐Ping , Huang Xuan‐Yang , Zhang Ke‐Ying , Ding Xue‐Mei , Zeng Qiu‐Feng , Bai Shi‐Ping , Celi Pietro , Yan Lei , Peng Huan‐Wei , Mao Xiang‐Bing
Published: September 2018

Vanadium (V) can induce cell apoptosis in layers' oviduct resulting in egg quality reduction. In this study, we investigated the relationship between the mitogen‐activated protein kinase (MAPK)‐signaling pathway and V‐induced apoptosis in poultry oviduct magnum epithelial cells (OMECs). Cultured OMECs were divided into 8 treatment groups: 0 μmol/L V (control), 100 μmol/L V (V100), V100 + P38MAPK inhibitor (SB203580), SB203580, V100 + extracellular signal‐regulated kinases 1 and 2 (ERK1/2) inhibitor (U0126), U0126, V100 + c‐JUN NH2‐terminal kinase (JNK) inhibitor (SP600125), and SP600125. The OMECs were pretreated with the MAPK inhibitors before their treatment with V100 for 12 h. V100 increased the apoptosis of OMECs (P < .05), while 3 MAPK inhibitors suppressed V100‐induced apoptosis P < .05); V100 enhanced the depolarization of △ψm (P < .05), and SB203580 and U0126 alleviated the V100‐induced △ψm decrease (P < .05); V100 downregulated B‐cell lymphoma‐2 (Bcl‐2) and poly [Adenosine diphosphate ribose] polymerase 1 (PARP1) mRNA expression (P < .05), meanwhile it upregulated Bcl‐2 associated x (Bax), Apaf1, cytochrome C (CytC) and cysteine aspartase (caspase) 3, 8, 9 mRNA expression (P < .05). All MAPKs inhibitors alleviated the up‐regulation of V100 for Bax and caspase 3 mRNA expression and down‐regulation of V100 for Bcl‐2 expression (P < .05). SB203580 and U0126 upregulated CytC expression treated by V100 (P < .05), except SP600125, while SB203580 administration resulted in a similar upregulation of PARP1 expression (P < .05). SP600125 can alleviated V triggered p‐P38MAPK (phosphor‐P38), p‐ERK1/2 (phosphor‐ERK1/2), p‐JNK (phosphor‐JNK) increase on OME cells, and SB203580 and U0126 had a similar response to phosphor‐P38 and p‐JNK (P < .05). It concluded that V‐induced apoptosis in OMECs through the activation of P38 and ERK1/2, and by increasing the ratio of Bax/Bcl‐2, which resulted in △ψm decrease, CytC release into the cytosol; consequently caspase 3 is recruited and activated, PARP1 is cleaved, eventually leading to apoptosis.
Propamocarb exposure decreases the secretion of neurotransmitters and causes behavioral impairments in mice
Authors: Zhang Yi , Jin Cuiyuan , Wang Xiaoyu , Shen Manlu , Zhou Jiajie , Wu Sisheng , Fu Zhengwei , Jin Yuanxiang
Published: September 2018

Propamocarb (PM) is a type of fungicide, which is widely used in the greenhouse‐based production of vegetables and fruits globally. It has been considered to have generally low toxicity. However, the teratogenicity or neurotoxicity for mammals remains unclear. In this study, we aimed to explore its effect on the secretion of neurotransmitters and behavioral impairments. Male adult mice were exposed to 10 and 40 mg/L PM for 2 weeks (acute exposure) or 3 and 10 mg/L PM for 10 weeks (chronic exposure). It was observed that acute or chronic exposure to PM changed the levels of serotonin (5‐HT) and dopamine in the serum and colon and the transcription of TPH2 and DRD2 in the colons of mice. In addition, the locomotor test, the open field test, and the Morris water maze analysis also showed that acute exposure to PM caused behavioral impairments to some extent. The results obtained in the present study indicated that PM has the potential to induce neurotoxicity in animals.
Learning from deaths in the NHS: a new but necessary challenge
Authors: Bourke Trisha , Vale Justin
Published: September 2018

Since 2016 NHS organisations have been expected to review all deaths and assess avoidability. This is a significant task and presents many challenges. However, as Justin Vale discusses in this article it is a vital part of the learning process.
Holding on to medical students and junior doctors
Authors: Ralph Oliver
Published: September 2018

The strikes over the new junior doctor contract and low morale are having a damaging effect on medical students' and junior doctors' attitudes and willingness to work in the NHS. In this opinion piece, Oliver Ralph gives his perspective and describes how it has impacted his view of his future.
Dynamic and reversible RNA N6‐methyladenosine methylation
Authors: Duan Hong‐Chao , Wang Ye , Jia Guifang
Published: September 2018

N6‐methyladenosine (m6A) is the most abundant internal chemical modification in eukaryotic messenger RNAs (mRNAs). The discovery in 2011 that m6A is reversed by the fat mass and obesity‐associated protein stimulated extensive worldwide research efforts on the regulatory biological functions of dynamic m6A and other RNA modifications. The epitranscriptomic mark m6A is written, read, and erased through the activities of a complicated network of enzymes and other proteins. m6A‐binding proteins read m6A marks and transduce their downstream regulatory effects by altering RNA metabolic processes. In this review, we summarize the current knowledge of m6A modifications, with particular focus on the functions of its writer, eraser, and reader proteins in posttranscriptional gene regulation and discuss the impact of m6A marks on human health.

This article is categorized under:

RNA Processing > RNA Editing and Modification

RNA in Disease and Development > RNA in Disease
Synthesis and X‐ray Crystal Structures of β‐Ketoiminate Complexes
Authors: Steiniger Phillip , Dittrich Dennis , Scheiper Christoph , John Christoph , Wölper Christoph , Schulz Stephan
Published: September 2018

Heteroleptic zinc complexes containing side‐arm donor‐functionalized tridentate β‐ketoiminate ligands were obtained from metalation reactions of β‐ketoimines L1/2/3Do1/2/3/4H [L1 = {(OC(Me)C(H)C(Me)NCH2CH2Do)}, L2 = {(OC(Me)C(H)C(Me)NCH2CH2CH2Do)}, L3 = {(OC(OMe)C(H)C(Me)NCH2CH2Do)}; Do1 = NMe2, Do2 = NEt2; Do3 = Pyr, Do4 = OMe] with equimolar amounts of Zn[N(SiMe3)2]2[L1Do1ZnN(SiMe3)2(1), L1Do2ZnN(SiMe3)2(2)] and ZnEt2[L1Do3ZnEt (3), L2Do3ZnEt (4), L3Do1ZnEt (5), L3Do4ZnEt (6)]. Analogous reactions of AlMe3and Cp*MMe3with L1Do1/2H yielded homoleptic aluminum [L1Do1AlMe2(7), L1Do2AlMe2(8), L2Do1AlMe2(9)], titanium [L1Do2Ti(Me2)Cp* (10)] and zirconium complexes [L1Do2Zr(Me2)Cp* (11)]. In addition,7reacts with an ethereal HCl solution with methane elimination and formation of L1Do1Al(Cl)Me (12) and L1Do1AlCl2(13), whereas the reaction with one and two equivalents of 2,6‐dimethylphenol yielded L1Do1Al(Me)O‐2,6‐Me2C6H3(14) and L1Do1Al(O‐2,6‐Me2C6H3)2(15). The complexes were characterized by elemental analysis,1H,13C NMR, and IR spectroscopy and single‐crystal X‐ray analysis (2,4,7,10,12–14).
Three‐dimensional vibration analysis of simply supported laminated cylindrical shells and panels by a strong SaS formulation
Authors: Kulikov G. M. , Plotnikova S. V. , Kulikov M. G.
Published: September 2018

In this paper, the strong sampling surfaces (SaS) formulation developed earlier by the authors to solve the statics problems for plates and shells is extended to the three‐dimensional (3D) vibration analysis of laminated composite shells. The SaS formulation is based on choosing the arbitrary number of SaS parallel to the middle surface in order to introduce the displacements of these surfaces as basic shell unknowns. Such choice of unknowns with the use of Lagrange polynomials in approximations of displacements and strains through the layer thicknesses leads to a robust laminated shell formulation. The feature of the proposed strong SaS formulation is that all SaS are located inside the layers at Chebyshev polynomial nodes. The use of outer surfaces and interfaces is avoided that makes possible to minimize uniformly the error due to Lagrange interpolation. Therefore, the strong SaS formulation based on direct integration of equations of motion of the elastic body can be applied efficiently for the 3D vibration analysis of laminated cylindrical shells and panels.
Introduction: The Study and Reception of Aristotle’s Parva naturalia
Authors: Bydén Börje
Published: September 2018

The thirteen essays that make up the bulk of this volume all began as papers or comments on papers presented at the first Representation and Reality conference in Gothenburg on 6–8 June 2014 (“Cross-Cultural Dialogues: The Parva naturalia in Greek, Arabic and Latin Aristotelianism”). They are perhaps most straightforwardly read as accounts of so many episodes in the history of the ancient and medieval reception of a classical philosophical work, Aristotle’s Parva naturalia. By and large, they can also be read as inquiries into different passages in the development of a specific theme (psycho-physiology, for want of a better term) in the history of ancient and medieval philosophy. For in ancient and medieval times, the reception of classical philosophical works, not least Aristotle’s, was part of the daily business of philosophers, not historians. Each of these accounts (or inquiries) presents original research designed to widen and deepen our understanding of the episode in hand.
Mothers, Media, and Individualism in Public Policy
Authors: Crane Jennifer
Published: September 2018

‘Mothers, Media, and Individualism’ focuses on the role of television and newspapers in constructing concerns about child protection in the late twentieth century, particularly through focus on the experiences and emotions of mothers. The chapter demonstrates that media interest in mothers has often portrayed women as hysterical, and has focused particularly on women’s campaigning against paedophilia. Nonetheless, the chapter also traces cases in which women themselves exerted control over media representations, harnessing journalistic interest to direct attention to their own agendas or cases. Looking to the late 1990s, and to the New Labour moment, the chapter further demonstrates that parental campaigning has become more embedded in public policy over the late twentieth century, shifting from disorganised protest to calculated collective action, whereby mothers held influential individual positions in Tony Blair’s ‘sofa government’.
The Visibility of Survivors and Experience as Expertise
Authors: Crane Jennifer
Published: September 2018

This chapter explores a variety of spaces in which people who had been abused in childhood—survivors—began to speak publicly about their experiences from the 1970s, 1980s, and in particular from the 1990s. It analyses survivor testimony in agony aunt columns, memoirs, academic study, and through newly formed campaign groups. In doing so, the chapter assesses why and how public policy interest in survivors developed decades after focus on children and parents, alongside broader interest in tracing trauma through the life course. Survivor representatives developed significant positions of influence in public policy and media in the last decade of the twentieth century, though nonetheless voluntary groups also struggled to gain government funding, and often felt that their inclusion in political processes was tokenistic. This chapter again traces a growing public policy focus on individual community representatives in the New Labour years, and it demonstrates how voluntary leaders drew on professional, experiential, and emotional expertise.
Chaos, diffusivity, and spreading of entanglement in magnetic branes, and the strengthening of the internal interaction
Authors: Ávila Daniel , Jahnke Viktor , Patiño Leonardo
Published: September 2018

Abstract

We use holographic methods to study several chaotic properties of a super Yang-Mills theory at temperature T in the presence of a background magnetic field of constant strength B. The field theory we work on has a renormalization flow between a fixed point in the ultraviolet and another in the infrared, occurring in such a way that the energy at which the crossover takes place is a monotonically increasing function of the dimensionless ratio ℬ/T
2. By considering shock waves in the bulk of the dual gravitational theory, and varying ℬ/T
2, we study how several chaos-related properties of the system behave while the theory they live in follows the renormalization flow. In particular, we show that the entanglement and butterfly velocities generically increase in the infrared theory, violating the previously suggested upper bounds but never surpassing the speed of light. We also investigate the recent proposal relating the butterfly velocity with diffusion coefficients. We find that electric diffusion constants respect the lower bound proposed by Blake. All our results seem to consistently indicate that the global effect of the magnetic field is to strengthen the internal interaction of the system.
Spinning conformal defects
Authors: Kobayashi Nozomu , Nishioka Tatsuma
Published: September 2018

Abstract

We consider conformal defects with spins under the rotation group acting on the transverse directions. They are described in the embedding space formalism in a similar manner to spinning local operators, and their correlation functions with bulk and defect local operators are determined by the conformal symmetry. The operator product expansion (OPE) structure of spinning conformal defects is examined by decomposing it into the spinning defect OPE block that packages all the contribution from a conformal multiplet. The integral representation of the block derived in the shadow formalism is facilitated to deduce recursion relations for correlation functions of two spinning conformal defects. In simple cases, we construct spinning defect correlators by acting differential operators recursively on scalar defect correlators.
Production of purely gravitational dark matter
Authors: Ema Yohei , Nakayama Kazunori , Tang Yong
Published: September 2018

Abstract

In the purely gravitational dark matter scenario, the dark matter particle does not have any interaction except for gravitational one. We study the gravitational particle production of dark matter particle in such a minimal setup and show that correct amount of dark matter can be produced depending on the inflation model and the dark matter mass. In particular, we carefully evaluate the particle production rate from the transition epoch to the inflaton oscillation epoch in a realistic inflation model and point out that the gravitational particle production is efficient even if dark matter mass is much larger than the Hubble scale during inflation as long as it is smaller than the inflaton mass.
Hydrodynamics of topological Dirac semi-metals with chiral and ℤ2 anomalies
Authors: Rogatko Marek , Wysokinski Karol I.
Published: September 2018

Abstract

We consider the hydrodynamical model of topological Dirac semi-metal possessing two Dirac nodes separated in momentum space along a rotation axis. It has been argued that the system in question, except the chiral anomaly, is endowed with the other one ℤ2. In order to model such a system we introduce two U(1)-gauge fields. The presence of the additional ℤ2anomaly leads to the non-trivial modifications of hydrodynamical equations and to the appearance of new kinetic coefficients bounded with the vorticity and the magnetic parts of Maxwell and auxiliary U(1)-gauge fields.
Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease
Authors: Müller Stephan , Preische Oliver , Sohrabi Hamid R. , Gräber Susanne , Jucker Mathias , Ringman John M. , Martins Ralph N. , McDade Eric , Schofield Peter R. , Ghetti Bernardino , Rossor Martin , Fox Nick N. , Graff‐Radford Neill R. , Levin Johannes , Danek Adrian , Vöglein Jonathan , Salloway Stephen , Xiong Chengjie , Benzinger Tammie , Buckles Virginia , Masters Colin L. , Sperling Reisa , Bateman Randall J. , Morris John C. , Laske Christoph ,   Dominantly Inherited Alzheimer Network (DIAN)
Published: September 2018

Introduction

Little is known about effects of physical activity (PA) in genetically driven early‐onset autosomal dominant Alzheimer's disease (AD).

Methods

A total of 372 individuals participating at the Dominantly Inherited Alzheimer Network study were examined to evaluate the cross‐sectional relationship of PA with cognitive performance, functional status, cognitive decline, and AD biomarkers in cerebrospinal fluid. Mutation carriers were categorized as high or low exercisers according to WHO recommendations.

Results

Mutation carriers with high PA showed significantly better cognitive and functional performance and significantly less AD‐like pathology in cerebrospinal fluid than individuals with low PA. Mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers.

Discussion

These results support a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven autosomal dominant AD.
Validation of Portuguese version of the low anterior resection syndrome score
Authors: Rama Nuno José , Ferreira Pedro Lopes , Pimentel João , Juul Therese ,   on behalf of the Portuguese PT LARS Collaborative Group
Published: September 2018

Objective The authors aim to perform a thorough translation with cultural adaptation of the patient reported outcome tool, Low Anterior Resection Syndrome (LARS) Score, to the Portuguese language (LARS-PT) in the Portuguese population with rectal cancer, after proctectomy with anastomosis.

Methods According to the current international recommendations, we designed this study encompassing three main phases: (i) cultural and linguistic validation to European Portuguese; (ii) feasibility and reliability tests of the version obtained in the previous phase; and (iii) validity tests to produce a final version. The questionnaire was completed by 154 patients from six Portuguese Colorectal Cancer Units, and 58 completed it twice.

Results Portuguese version of LARS score showed high construct validity. Regarding the test-retest, the global Intraclass Correlation showed very strong test-retest reliability. Looking at all five items, only items 3 and 5 present a moderate correlation. LARS score was able to discriminate symptoms showing worse quality of life, in patients submitted to preoperative radio and chemotherapy.

Conclusions LARS questionnaire has been properly translated into European Portuguese, demonstrating high construct validity and reliability. This is a precise, reproducible, simple, clear and user-friendly tool for evaluating bowel function in rectal cancer patients after sphincter saving operation.
Resistance Training Improves Quality of Life and Associated Factors in Patients With Fibromyalgia Syndrome
Authors: Andrade Alexandro , Sieczkowska Sofia M. , Vilarino Guilherme T.
Published: September 2018

Background

Patients with primary symptoms of fibromyalgia (FM) have a lower quality of life than healthy people of the same age. The current treatment for FM is palliative, as there is no cure. Therefore, among strategies used to alleviate the symptoms, physical exercise has been recommended.

Objective

To investigate the effects of a resistance training (RT) program on quality of life and associated factors in patients with FM.

Design

Nonrandomized clinical trial. Brazilian Clinical Trials: http://www.ensaiosclinicos.gov.br/ (no. RBR‐74pcmw).

Participants

Forty‐nine women with FM (mean age ± SD: 51.35 ± 9.34 years) allocated to an RT group (n = 26) or control group (CG; n = 23).

Intervention

The intervention consisted of 4 weeks of a supervised RT program. Three, 60‐minute, training sessions per week were conducted. Participants were evaluated before and after 4 weeks of exercise intervention.

Main Outcome Measurements

The Fibromyalgia Impact Questionnaire was used to assess quality of life, and secondary outcomes were assessed with the Pittsburgh Sleep Quality Inventory, Beck Depression Inventory, and Beck Anxiety Inventory. The Wilcoxon test was used to verify the differences after 4 weeks of intervention (12 sessions) and the Mann‐Whitney U test was used to compare the results for the RT group and CG.

Results

The results demonstrated that 4 weeks of RT reduces the impact of FM on quality of life, depression, and anxiety (P < .05). Higher depression and anxiety scores were related to worsening quality of life. The CG did not show significant changes.

Conclusions

RT reduces the impact of FM on the quality of life, and alleviates symptoms in women with FM.

Level of Evidence

II [Correction added on June 21, 2019, after first online publication: Level of Evidence changed from I to II.]
The outcomes of hypoglossal nerve stimulation in the management of OSA: A systematic review and meta‐analysis
Authors: Kompelli Anvesh R. , Ni Jonathan S. , Nguyen Shaun A. , Lentsch Eric J. , Neskey David M. , Meyer Ted A.
Published: September 2018

Objectives

Obstructive sleep apnea (OSA) is a prevalent disease with significant health impacts. While first line therapy is CPAP, long‐term compliance is low and device misuse is common, highlighting the need for alternative therapies. Upper airway surgery is one alternative, but substantial side effects hamper efficacy. A new alternative is an implantable hypoglossal nerve stimulator (HNS). These devices utilize neuromodulation to dilate/reinforce the airway and reduce side effects associated with traditional surgery. Several recent trials investigated the efficacy of these devices. The purpose of this study was to perform meta‐analysis of available HNS studies investigating treatment of OSA to analyze objective and subjective outcomes and side effects.

Methods

A comprehensive literature search of PubMed and Scopus was performed. Two independent reviewers examined clinical trials investigating HNS in treatment of sleep apnea in adults. Studies with objective and subjective endpoints in sleep were included for analysis. Adverse events from trials were also recorded.

Results

Across 16 studies, 381 patients were analyzed. At 6 months (p = 0.008), mean SAQLI improved by 3.1 (95%CI, 2.6–3.7). At 12 months (p < 0.0001), mean AHI was reduced by 21.1 (95%CI, 16.9–25.3), mean ODI was reduced by 15.0 (95%CI, 12.7–17.4), mean ESS was reduced by 5.0 (95%CI, 4.2–5.8), mean FOSQ improved by 3.1 (95%CI, 2.6–3.4). Pain (6.2%:0.7–16.6), tongue abrasion (11.0%:1.2–28.7), and internal (3.0%:0.3–8.4)/external device (5.8%:0.3–17.4) malfunction were common adverse events.

Conclusions

HNS is a safe and effective treatment for CPAP refractory OSA. Further study comparing HNS to other therapies is required.
Characterizing asymptotic randomization in abelian cellular automata
Authors: HELLOUIN DE MENIBUS B. , SALO V. , THEYSSIER G.
Published: September 2018

Abelian cellular automata (CAs) are CAs which are group endomorphisms of the full group shift when endowing the alphabet with an abelian group structure. A CA randomizes an initial probability measure if its iterated images have weak*-convergence towards the uniform Bernoulli measure (the Haar measure in this setting). We are interested in structural phenomena, i.e., randomization for a wide class of initial measures (under some mixing hypotheses). First, we prove that an abelian CA randomizes in Cesàro mean if and only if it has no soliton, i.e., a non-zero finite configuration whose time evolution remains bounded in space. This characterization generalizes previously known sufficient conditions for abelian CAs with scalar or commuting coefficients. Second, we exhibit examples of strong randomizers, i.e., abelian CAs randomizing in simple convergence; this is the first proof of this behaviour to our knowledge. We show, however, that no CA with commuting coefficients can be strongly randomizing. Finally, we show that some abelian CAs achieve partial randomization without being randomizing: the distribution of short finite words tends to the uniform distribution up to some threshold, but this convergence fails for larger words. Again this phenomenon cannot happen for abelian CAs with commuting coefficients.
Arctic Sunrise Arbitration (Netherlands/Russia) (Award on Compensation) (Perm. Ct. Arb.)
Authors: Kill Theodore
Published: September 2018

An ad hoc arbitral tribunal convened pursuant to Article 287 and Annex VII of the United Nations Convention on the Law of the Sea (UNCLOS) delivered its award on compensation on July 10, 2017, in Arctic Sunrise (Netherlands/Russia). The award was unanimous on all holdings and included no separate opinions. The Tribunal awarded the Netherlands just under EUR 5.4 million under four separate heads of damages arising out of Russian violations of its obligations under UNCLOS that were established in the Tribunal's award of August 15, 2015.