bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secochiliolide ester derivatives: Preparation and evaluation of their antitrypanosomal and antimalarial efficacy
Authors: Ronchi Romina J. , Beaufay Claire , Bero Joanne , Robirosa Juan B. , Mazzuca Marcia , Palermo Jorge A. , Quetin‐Leclercq Joëlle , Sánchez Marianela 
Published: September 2018

AbstractIn the present study, a series of new esters of secochiliolide acid (SA), a diterpene isolated from Nardophyllum bryoides, were synthesized in good yield. All compounds were evaluated for their in vitro antiparasitic properties (on Plasmodium falciparum and Trypanosoma brucei brucei) and cytotoxicity (on WI38, normal mammalian cells). They displayed moderate antitrypanosomal activity with IC50 values between 2.55 and 18.14 μm, with selectivity indices >10, and low antiplasmodial effects with IC50 > 29 μm. The only exception was the n‐hexyl ester of SA, which showed a strong and selective antiplasmodial activity (IC50 = 1.99 μm and selectivity index = 117.0). The in vivo antimalarial efficacy of this compound was then assessed according to the 4‐day suppressive test of Peters in mice. An intraperitoneal treatment at 50 mg kg−1 day−1 induced a slight parasitaemia reduction by 56% which was statistically significant on day 4 post‐infection and an increase in the survival time.
Technetium‐99m radiolabeling and biological study of epirubicin for in vivo imaging of multi‐drug‐resistant Staphylococcus aureus infections via single photon emission computed tomography
Authors: Khan Naeem‐Ul‐Haq , Naqvi Syed Ali Raza , Roohi Samina , Sherazi Tauqir A. , Khan Zulfiqar Ali , Zahoor Ameer Fawad 
Published: September 2018

AbstractThe development of functional imaging is a promising strategy for diagnosis and treatment of infectious and cancerous diseases. In this study, epirubicin was developed as a [99mTc]‐labeled radiopharmaceutical for the imaging of multi‐drug‐resistant Staphylococcus aureus infections. The labeling was carried out using sodium pertechnetate (Na99mTcO4; ~370 MBq). The other parameters such as amount of ligand, reducing agent (SnCl2.2H2O), and pH were optimized. The highest labeling yield ≥96.98% was achieved when 0.3 mg epirubicin, 13 μg SnCl2.2H2O, and ~370 MBq Na99mTcO4 were incubated at pH 7 for 15 min in the presence of ascorbic acid at room temperature. Radiochemical purity, stability, charge, and glomerular filtration rate were studied to evaluate the biological compatibility for in vivo administration. Biodistribution investigations showed radiotracer uptake (13.89 ± 1.56% ID/gm organ) by liver and 7.79 ± 0.38% ID/gm organ by kidneys at 30 min post‐injection which promisingly wash out at 24 hr post‐injection. Scintigraphy study showed selective uptake in S. aureus‐infected tissues in contrast to turpentine oil‐induced inflamed tissues. Target‐to‐non‐target ratio (6.7 ± 0.05) was calculated at 1 hr post‐injection using SPECT gamma camera. The results of this study reveal that the [99mTc]‐epirubicin can be a choice of imaging and monitoring the treatment process of multi‐drug resistant S. aureus bacterial infections.
A propeller‐like small molecule as a novel G‐quadruplex DNA binder: The study of fluorescent sensing property and preferential interactions with human telo21 structure
Authors: Sun Ning , Li Dongli , Hou Jinqiang , Long Wei , Guo Qi , Lu Yujing , Zhang Kun , Yuan Wenchang , Wong Wing‐Leung 
Published: September 2018

AbstractA new propeller‐like small molecule was synthesized with three terminal amino side groups. The molecule was found to be a selective nucleic acid binder towards telo21 G‐quadruplex DNA compared with other representative nucleic acids including single‐stranded DNA (dA21), duplex DNA (ds26) and RNA. The fluorescent signal of the molecule upon interaction with telo21 G‐quadruplex structure shows remarkable enhancement (Fmax/F0 = 17.9) while interaction with other nucleic acids shows the signal enhancement which is less than 2.1. In addition, a good linear relationship of binding signal correlated with the concentration of telo21 DNA was obtained. Molecular docking study was also performed to acquire the binding behaviour and its interaction modes of the molecule with the structure of human telomeric DNA G‐quadruplex. The modelling results show that the three conjugated terminal units (dimethylaminobenzyl groups) associated through the ethylene bridges with the central methylated pyridine ring formed a co‐planar conformation upon stacking onto the G‐quartets via pi‐pi stacking interactions. This could be the key reason that the molecule shows excellent fluorescent signal of binding towards telo21 G‐quadruplex DNA rather than other types of nucleic acids.
Biophysical screening methods for extracellular domain peptide receptors, application to natriuretic peptide receptor C ligands
Authors: Conole Daniel , Myers Samuel H. , Mota Filipa , Hobbs Adrian J. , Selwood David L. 
Published: September 2018

AbstractEndothelium‐derived C‐type natriuretic peptide possesses cytoprotective and anti‐atherogenic functions that regulate vascular homeostasis. The vasoprotective effects of C‐type natriuretic peptide are somewhat mediated by the natriuretic peptide receptor C, suggesting that this receptor represents a novel therapeutic target for the treatment of cardiovascular diseases. In order to facilitate our drug discovery efforts, we have optimized an array of biophysical methods including surface plasmon resonance, fluorescence polarization and thermal shift assays to aid in the design, assessment and characterization of small molecule agonist interactions with natriuretic peptide receptors. Assay conditions are investigated to explore the feasibility and dynamic range of each method, and peptide‐based agonists and antagonists are used as controls to validate these conditions. Once established, each technique was compared and contrasted with respect to their drug discovery utility. We foresee that such techniques will facilitate the discovery and development of potential therapeutic agents for NPR‐C and other large extracellular domain membrane receptors.
Novel synthetic chalcone‐coumarin hybrid for Aβ aggregation reduction, antioxidation, and neuroprotection
Authors: Lee Shin‐Ying , Chiu Ya‐Jen , Yang Shu‐Mei , Chen Chiung‐Mei , Huang Chin‐Chang , Lee‐Chen Guey‐Jen , Lin Wenwei , Chang Kuo‐Hsuan 
Published: September 2018

AbstractBackgroundAggregation of misfolded amyloid β (Aβ) in senile plaques causes oxidative stress and neuronal death in Alzheimer's disease (AD). Compounds possessing antiaggregation and antioxidant properties are promising candidate compounds for AD treatment.MethodsWe examined the potential of synthetic derivatives of licochalcone A and coumarin for inhibiting Aβ aggregation, scavenging reactive oxygen species (ROS), and providing neuroprotection by using biochemical assays and Tet‐On Aβ‐GFP 293/SH‐SY5Y cell models for AD.ResultsAmong test compounds, LM‐031, a novel chalcone‐coumarin hybrid, inhibited Aβ aggregation and scavenged free oxygen radicals. LM‐031 markedly reduced Aβ misfolding and ROS as well as promoted neurite outgrowth and inhibited acetylcholinesterase in Tet‐On Aβ‐GFP 293/SH‐SY5Y cells. Mechanistic studies showed upregulation of the HSPB1 chaperone, NRF2/NQO1/GCLC pathway, and CREB/BDNF/BCL2 pathway. Decreased neurite outgrowth upon the induction of Aβ‐GFP was rescued by LM‐031, which was counteracted by knockdown of HSPB1, NRF2, or CREB.ConclusionTaken together, these findings demonstrate that LM‐031 exhibited antiaggregation, antioxidant, and neuroprotective effects against Aβ toxicity by enhancing HSPB1 and the NRF2‐related antioxidant pathway as well as by activating the CREB‐dependent survival and antiapoptosis pathway. These results imply that LM‐031 may be a new therapeutic compound for AD.
Survival differences in nasopharyngeal carcinoma among racial and ethnic minority groups in the United States: A retrospective cohort study
Authors: Challapalli Sai D. , Simpson Matthew C. , Adjei Boakye Eric , Walker Ronald J. , Antisdel Jastin L. , Ward Greg M. , Osazuwa‐Peters Nosayaba 
Published: September 2018

ObjectiveThe literature on nasopharyngeal carcinoma survival in the United States has focused mostly on Whites or Asians and not much is known about survivorship in other minority racial and ethnic groups. We aimed to determine the disease‐specific survival rate and prognostic factors for nasopharyngeal carcinoma survival across the minority United States population.DesignA retrospective cohort study.SettingThe Surveillance, Epidemiology and End Results (SEER) 13 database from 1992 to 2014 was queried for adult cases of nasopharyngeal carcinoma (n = 2549).ParticipantsEligible cases were Blacks, Hispanics, Asians/Pacific Islanders, American Indians/Alaska Natives; White patients were excluded.Main Outcomes MeasureA multivariable competing risk survival analysis yielded hazard ratios (HR) for competing mortality and was used to identify independent prognostic factors for survival.ResultsNon‐Hispanic American Indians/Alaska Natives consistently had the worst cause‐specific survival of any group and that non‐Hispanic Asians/Pacific Islanders consistently had the best survival (P < 0.001). Even after adjusting for other poor prognostic factors in the study, including older age, keratinising histology, and lack of radiation treatment, non‐Hispanic American Indians/Alaska Natives had more than double hazards of death from nasopharyngeal cancer compared with non‐Hispanic Asians/Pacific Islanders (aHR = 2.63, 95% CI 1.67, 4.13).ConclusionsThere are disparities in nasopharyngeal carcinoma survival among racial and ethnic minority groups in the United States, with American Indians/Alaskan Natives faring worst. It is critical that future research focuses on nasopharyngeal carcinoma among this population to improve survivorship and mitigate cancer‐related health disparities.
Benign paroxysmal positional vertigo in children
Authors: Yao Qingxiu , Song Qiang , Wang Hui , Shi Haibo , Yu Dongzhen 
Published: September 2018

ObjectiveTo describe the clinical features of benign paroxysmal positional vertigo (BPPV) in children.DesignA retrospective study.SettingSix children diagnosed with BPPV between March 2014 and March 2015 were retrospectively evaluated. BPPV was diagnosed using the Dix‐Hallpike and supine roll tests and treated with either the modified Epley particle repositioning procedure or Lempert or Gufoni manoeuvre. Follow‐up was performed at 1‐week intervals until vertigo and nystagmus disappeared during positional testing.ParticipantsA total of six children were followed up for a period of 10‐22 months.Main outcome measuresClinical features such as history, nystagmus and symptoms of vertigo, dizziness and nausea.ResultsSix children were diagnosed with BPPV using positional testing and treated with the modified Epley or Lempert/Gufoni particle repositioning procedures. Four children were diagnosed with posterior canal BPPV, while the remaining two were diagnosed with horizontal canal BPPV. One girl reported a history of head trauma, one girl had a family history of vertigo, and one boy reported hearing loss in the same ear as that affected by BPPV. Overall, 83.33% of children (5/6) were completely relieved of vertigo following one treatment session. The remaining child was asymptomatic after two sessions. No child reported relapse of vertigo during the follow‐up period.ConclusionsBPPV can be diagnosed accurately by taking a detailed medical history and by use of positional testing. BPPV in children can be successfully identified and treated.
Outcomes for individuals turned down for living kidney donation
Authors: Reese Peter P. , Allen Matthew B. , Carney Caroline , Leidy Daniel , Levsky Simona , Pendse Ruchita , Mussell Adam S. , Bermudez Francisca , Keddem Shimrit , Thiessen Carrie , Rodrigue James R. , Emanuel Ezekiel J. 
Published: September 2018

AbstractBackgroundA better understanding of the consequences of being turned down for living kidney donation could help transplant professionals to counsel individuals considering donation.MethodsIn this exploratory study, we used survey instruments and qualitative interviews to characterize nonmedical outcomes among individuals turned down for living kidney donation between July 1, 2010 and December 31, 2013. We assembled a comparator group of kidney donors.ResultsAmong 83 turned‐down donors with contact information at a single center, 43 (52%) participated in the study (median age 53 years; 53% female; 19% black). Quality of life, depression, financial stress, and provider empathy scores were similar between individuals turned down for donation (n = 43) and donors (n = 128). Participants selected a discrete choice response to a statement about the overall quality of their lives; 32% of turned‐down donors versus 7% of donors (P < 0.01) assessed that their lives were worse after the center's decision about whether they could donate a kidney. Among turned‐down donors who reported that life had worsened, 77% had an intended recipient who was never transplanted, versus 36% among individuals who assessed life as the same or better (P = 0.02). In interviews, the majority of turned‐down donors reported emotional impact, including empathy, stress, and other challenges, related to having someone in their lives with end‐stage kidney disease.ConclusionsGeneric instruments measuring quality of life, depression, financial stress, and provider empathy revealed no significant differences between kidney donors and turned‐down donors. However, qualitative interviews revealed preliminary evidence that some turned‐down donors experienced emotional consequences. These findings warrant confirmation in larger studies.
Dentofacial traumatic injuries: A survey of knowledge and attitudes among emergency medicine physicians in Turkey
Authors: Yigit Yavuz , Helvacioglu‐Yigit Dilek , Kan Bahadir , Ilgen Cansu , Yilmaz Serkan 
Published: September 2018

AbstractBackground/AimEmergency department (ED) visits for dental issues are mostly related to traumatic injuries. The knowledge of ED physicians about the diagnosis and treatment of dentofacial injuries is crucial for prognosis. The aim of this study was to evaluate the attitude and knowledge as well as education and self‐confidence levels of emergency medicine physicians in ED regarding the diagnosis and treatment of dentofacial traumatic injuries.Material and methodsA total of 109 emergency medicine physicians participated in the study. Participants were residents and specialists who attended a national emergency medicine symposium held in Turkey. A questionnaire was distributed during the symposium relating to general data about physicians, their attitudes, basic knowledge, and confidence levels which were believed to be indicative of their capabilities in managing of traumatic dental and maxillofacial injuries.ResultsThe questionnaire was answered by 109 physicians who were general practitioners (11%), emergency medicine residents (56.8%), and emergency medicine specialists (32.2%). The most experienced group of physicians were emergency medicine specialists. Regardless of the physicians’ titles, dentofacial trauma knowledge levels of ED physicians were found to be insufficient. Having a dentist in the family (P < 0.01), the duration of emergency service experience (P = 0.04), and the age of the physicians (P < 0.001) were significantly related to the knowledge level.ConclusionsThe majority of ED physicians had low knowledge regarding the diagnosis and treatment of dentofacial traumatic injuries. There is a need for education during and after medical training for ED physicians to provide appropriate primary management of dentofacial trauma.
Chronic nicotine administration restores brain region specific upregulation of oxytocin receptor binding levels in a G72 mouse model of schizophrenia
Authors: Zanos Panos , Keyworth Helen , Georgiou Polymnia , Hambsch Boris , Otte David M. , Kitchen Ian , Zimmer Andreas , Bailey Alexis 
Published: September 2018

AbstractNicotine dependence and schizophrenia are two mental health disorders with remarkably high comorbidity. Cigarette smoking is particularly prevalent amongst schizophrenic patients and it is hypothesised to comprise a form of self‐medication for relieving cognitive deficits in these patients. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin in the modulation of drug addiction, as well as schizophrenia symptomology; however, the underlying mechanism remains unclear. Therefore, we sought to investigate the effects of chronic nicotine administration on oxytocin receptor (OTR) binding in the brain of a transgenic mouse model of schizophrenia that carries a bacterial artificial chromosome of the human G72/G30 locus (G72Tg). Female wild‐type (WT) and heterozygous G72 transgenic CD‐1 mice were treated with a chronic nicotine regimen (24 mg/kg/day, osmotic minipumps for 14 days) and quantitative autoradiographic mapping of oxytocin receptors was carried out in brains of these animals. OTR binding levels were higher in the cingulate cortex (CgCx), nucleus accumbens (Acb), and central amygdala (CeA) of saline treated G72Tg mice compared to WT control mice. Chronic nicotine administration reversed this upregulation in the CgCx and CeA. Interestingly, chronic nicotine administration induced an increase in OTR binding in the CeA of solely WT mice. These results indicate that nicotine administration normalises the dysregulated central oxytocinergic system of this mouse model of schizophrenia and may contribute towards nicotine's ability to modulate cognitive deficits which are common symptoms of schizophrenia.
Nonequivalent lethal equivalents: Models and inbreeding metrics for unbiased estimation of inbreeding load
Authors: Nietlisbach Pirmin , Muff Stefanie , Reid Jane M. , Whitlock Michael C. , Keller Lukas F. 
Published: September 2018

AbstractInbreeding depression, the deterioration in mean trait value in progeny of related parents, is a fundamental quantity in genetics, evolutionary biology, animal and plant breeding, and conservation biology. The magnitude of inbreeding depression can be quantified by the inbreeding load, typically measured in numbers of lethal equivalents, a population genetic quantity that allows for comparisons between environments, populations or species. However, there is as yet no quantitative assessment of which combinations of statistical models and metrics of inbreeding can yield such estimates. Here, we review statistical models that have been used to estimate inbreeding load and use population genetic simulations to investigate how unbiased estimates can be obtained using genomic and pedigree‐based metrics of inbreeding. We use simulated binary viability data (i.e., dead versus alive) as our example, but the concepts apply to any trait that exhibits inbreeding depression. We show that the increasingly popular generalized linear models with logit link do not provide comparable and unbiased population genetic measures of inbreeding load, independent of the metric of inbreeding used. Runs of homozygosity result in unbiased estimates of inbreeding load, whereas inbreeding measured from pedigrees results in slight overestimates. Due to widespread use of models that do not yield unbiased measures of the inbreeding load, some estimates in the literature cannot be compared meaningfully. We surveyed the literature for reliable estimates of the mean inbreeding load from wild vertebrate populations and found an average of 3.5 haploid lethal equivalents for survival to sexual maturity. To obtain comparable estimates, we encourage researchers to use generalized linear models with logarithmic links or maximum‐likelihood estimation of the exponential equation, and inbreeding coefficients calculated from runs of homozygosity, provided an assembled reference genome of sufficient quality and enough genetic marker data are available.
18F‐sodium fluoride positron emission tomography of the racing Thoroughbred fetlock: Validation and comparison with other imaging modalities in nine horses
Authors: Spriet M. , Espinosa‐Mur P. , Cissell D. D. , Phillips K. L. , Arino‐Estrada G. , Beylin D. , Stepanov P. , Katzman S. A. , Galuppo L. D. , Garcia‐Nolen T. , Murphy B. , Stover S. M. 
Published: September 2018

SummaryBackgroundEarly and accurate detection of stress remodelling in racehorses is of utmost importance to prevent catastrophic injuries. Current imaging techniques have limitations in assessing early changes predisposing to catastrophic breakdowns. Positron emission tomography (PET) using 18F‐sodium fluoride (18F‐NaF) is a sensitive method for the detection of early bone turnover and may improve early recognition of subtle injuries.ObjectivesTo validate the clinical use of 18F‐NaF PET in Thoroughbred racehorses, to assess the value of PET in the detection of bone lesions and to compare PET results with findings of other advanced imaging modalities, clinical examination and pathology.Study designExperimental exploratory study.MethodsTwenty fetlocks from nine Thoroughbred racehorses were imaged using 18F‐NaF PET, computed tomography (CT) and scintigraphy. Five fetlocks were also imaged with magnetic resonance imaging and four fetlocks were also examined histologically. Imaging findings were independently reviewed by three board certified radiologists. Imaging, clinical and histopathological findings were correlated.ResultsPET imaging was well‐tolerated by all horses. PET detected focal areas of 18F‐NaF uptake in instances where other imaging modalities did not identify abnormalities, in particular in the proximal sesamoid bones. Maximal standardised uptake values could be measured to quantify the activity of lesions. Areas of 18F‐NaF uptake corresponded to regions of increased vascularity and increased osteoblastic activity.Main limitationsLimited number of cases.Conclusions18F‐NaF PET imaging of the Thoroughbred fetlock is feasible and compares favourably with other imaging modalities in detecting stress remodelling in Thoroughbred racehorses. PET appears to be a beneficial imaging modality when used for early detection of stress remodelling in an effort to prevent catastrophic musculoskeletal injuries in this population of horses.
Daily Posttraumatic Stress Disorder Symptom Accommodation and Relationship Functioning in Military Couples
Authors: Campbell Sarah B. , Renshaw Keith D. 
Published: September 2018

Romantic partners’ accommodation of trauma survivors’ posttraumatic stress disorder (PTSD) symptoms (e.g., taking on tasks, survivors avoid participating in social withdrawal) is associated with lower relationship satisfaction for both partners and survivors. Little is known about associations of partner accommodation with other aspects of relationship functioning, like intimacy. Sixty‐four male military veterans with at least subclinical PTSD and their partners participated in a 2‐week daily diary study. Veterans completed nightly measures of PTSD symptoms, while female partners completed nightly measures of accommodating behaviors performed that day. Both partners reported feelings of intimacy each night. Multilevel models revealed that accommodation was significantly, negatively associated with feelings of intimacy, with stronger effects for partners (t = −8.70) than for veterans (t = −5.40), and stronger effects when veterans had lower (t = −7.43) rather than higher (t = −5.20) levels of daily PTSD symptoms. Therapists should consider accommodating behaviors as a potential impediment to relationship intimacy, particularly when veterans have less severe symptoms of PTSD. Accommodating behaviors are an ideal treatment target in behavioral couple therapies.