bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Hypothermia After Cardiac Arrest: Involvement of the Risk Pathway in Mitochondrial PTP-Mediated Neuroprotection
Authors: Jahandiez Vincent , Cour Martin , Abrial Maryline , Loufouat Joseph , Ovize Michel , Argaud Laurent 
Published: July 2018

ABSTRACT
Therapeutic hypothermia is neuroprotective after cardiac arrest (CA) via poorly understood mechanisms. It may prevent mitochondrial permeability transition pore (PTP) opening, an event which plays a pivotal role in ischemia-reperfusion injury. PTP is the main end-effector of the reperfusion injury salvage kinase (RISK) signaling pathway. We hypothesized that therapeutic hypothermia activates the RISK pathway, thereby preventing PTP opening and its deleterious neurological consequences after CA. Four groups of New Zealand White rabbits were subjected to 15 min of CA and 120 min of reperfusion: Control, HT (hypothermia at 32°–34°C), NIM (specific PTP inhibition with N-methyl-4-isoleucine-cyclosporine at the onset of reperfusion), and HT+NIM. A Sham group only underwent surgery. The following measurements were taken: pupillary reflexes and brain damage biomarkers (NSE and S100β), RISK pathway activation in brain cortex (total and phosphorylated forms of both protein kinase B [Akt] and extracellular signal-regulated kinase [ERK]) and PTP opening in isolated brain mitochondria. Therapeutic hypothermia and pharmacological PTP inhibition preserved the pupillary reflexes and prevented the increase in both NSE and S100β (P < 0.05 vs. controls). These two interventions also enhanced (P < 0.05 vs. controls) the phospho-Akt/Akt ratio to a similar extent while preventing a CA-induced increase in phospho-ERK/ERK ratio. This Akt activation in the HT and NIM groups was associated with an attenuation of CA-induced PTP opening. In this model, therapeutic hypothermia promoted the activation of the RISK signaling pathway via Akt and limited CA-induced brain injury by preventing PTP opening.
The Effects of the Duration of Aortic Balloon Occlusion on Outcomes of Traumatic Cardiac Arrest in a Porcine Model
Authors: Xu Jiefeng , Shen Peng , Gao Yuzhi , Xia Senlin , Liu Shaoyun , Li Zilong , Zhou Guangju , Xu Yongan , Zhang Mao 
Published: July 2018

ABSTRACT
Aortic balloon occlusion (ABO) facilitates the success of cardiopulmonary resuscitation (CPR) in non-traumatic cardiac arrest, and is also effective in controlling traumatic hemorrhage; however, a prolonged occlusion results in irreversible organ injury and death. In this study, we investigated the effects of ABO on CPR outcomes and its optimal duration for post-resuscitation organ protection in a porcine model of traumatic cardiac arrest (TCA).
Twenty-seven male domestic pigs weighing 33 ± 4 kg were utilized. Forty percent of estimated blood volume was removed within 20 min. The animals were then subjected to 5 min of untreated ventricular fibrillation and 5 min of CPR. Coincident with the start of CPR, the animals were randomized to receive either 30-min ABO (n = 7), 60-min ABO (n = 8) or control (n = 12). Meanwhile, fluid resuscitation was initiated by the infusion of normal saline with 1.5 times of hemorrhage volume in 1 h, and finished by the reinfusion of 50% of the shed blood in another 1 h. The resuscitated animals were monitored for 6 h and observed for an additional 18 h.
During CPR, coronary perfusion pressure was significantly increased followed by a higher rate of resuscitation success in the 30 and 60-min ABO groups compared with the control group. However, post-resuscitation cardiac, neurologic dysfunction, and injuries were significantly milder accompanied with less renal and intestinal injuries in the 30-min ABO group than in the other two groups.
In conclusion, ABO augmented the efficacy of CPR after TCA, and furthermore a 30-min ABO improved post-resuscitation cardiac and neurologic outcomes without exacerbating the injuries of kidney and intestine.
Medial Thigh Anatomy in Female Cadavers: Clinical Applications to the Transobturator Midurethral Sling
Authors: Shah Nemi M. , Jackson Lindsey A. , Phelan John N. , Corton Marlene M. 
Published: July 2018

Background
Mesh resection for refractory pain after transobturator midurethral sling may require exploration of structures different than those involved in insertion. Our objective was to describe the muscular and neurovascular anatomy of the medial thigh compartment.

Methods
Dissections were performed in unembalmed female cadavers. Relationships of medial thigh structures were evaluated relative to the midpubic arch and obturator nerve. An out-to-in transobturator tape was passed in a subset of cadavers, and its relationships to the obturator nerve and adductor muscles were examined. Descriptive statistics were used for analyses.

Results
Sixteen cadavers were examined. The adductor longus muscle was a median of 37 mm (26–50) from the midpubic arch with tendon length of 26 mm (12–53) and width of 16 mm (14–29). The gracilis was 21 mm (17–26) from the midpubic arch with tendon length of 28 mm (15–56) and width of 45 mm (31–68). The obturator nerve was 58 mm (51–63) from the midpubic arch with width of 5 mm (4–7). No differences between measurements in the supine and lithotomy positions were noted. The transobturator tape was 42 mm (30–47) from the midpubic arch, 36 mm (30–44) from the obturator nerve, and 20 mm (5–31) from the closest obturator nerve branch. The transobturator sling passed through the gracilis muscle in all specimens with variable passage through the adductors longus (75%) and brevis (25%).

Conclusions
Familiarity with the medial thigh is essential for surgeons utilizing transobturator midurethral slings. Risks of mesh excision should be weighed against benefits before extensive thigh dissection for pain-related indications.
Spontaneous Transvaginal Sigmoid Colon Evisceration and Sepsis From Complete Procidentia
Authors: Schefter Alexandra M. , Fischer John , Erickson Britt K. 
Published: July 2018

Background
Transvaginal bowel evisceration is an exceptionally rare event. Most reported cases are of small bowel evisceration in postmenopausal women who have undergone hysterectomy.

Case
Here, we report an isolated case of complete procidentia and spontaneous sigmoid colon evisceration leading to sepsis in an 89-year-old woman with no surgical history.

Conclusions
We highlight the risk factors, clinical presentation, and treatment options for this unique multidisciplinary emergency.
Interventions to Reduce High-Risk Medication Use in the Geriatric Population
Authors: Stuckey Nathan , Henriksen Brian , Singh Hamdeep , Dawson Amy , Waterson Zachary 
Published: July 2018

Background:
The Beers List is a guideline for health care workers to prescribe medications that are safe in the elderly. Using Beers List guidelines in the primary care setting, morbidity and mortality secondary to adverse effects, drug-drug interactions, and falls can be reduced significantly.

Objective:
To improve the quality and decrease the number of high-risk medications prescribed to the geriatric population through an interprofessional appointment approach.

Methods:
A prospective quality improvement project was completed over a 3-month period from August 2016 to November 2016 at a residency training outpatient family medicine clinic. Data on Medicare patients with 1 or more high-risk medication were obtained from the electronic health record (Allscripts NQF 0022). Participants were older than 65 years, with one or more high-risk medication as defined by Medicare. Patients were contacted for medication review appointments via phone and mail. The appointment was scheduled for a total of 60 minutes, with the initial 40 minutes spent with the pharmacy team for a comprehensive, medication reconciliation, and an assessment of their health literacy. Health literacy was assessed with the Short Assessment of Health Literacy. Recommendations for interventions by the interprofessional team were discussed and implemented during the last 20 minutes. Descriptive statistics and 2-sided dependent t tests were used to evaluate the data.

Results:
Thirty-four participants had a mean age of 74 years, 53% were male, 74% Caucasian, 24% African, and 2% Native Americans. Health literacy was good with only 20% below functional. The total high-risk medications dropped from 42 to 28, resulting in a 33% reduction of high-risk medications (P = .0005). There were 6 possible interventions with an average of 2 interventions per participant. The interventions were medication discontinuation for 11.39% (n = 8), changing medications for 7.25% (n = 5), medication reduced for 24.64% (n = 17), patients unwilling to change medications for 5.79% (n = 4), physicians deemed medication necessary for 14.5% (n = 10), and patient education for 36% (n = 25).
Variable Surface Training and Fall Risk in the Older Adult
Authors: Kogler Katherine , Howard Natalie , Schumacher Margaret , Knight Heather 
Published: July 2018

Context:
Variable surface balance training is frequently used as a rehabilitative intervention.

Objective:
To determine the effects of variable surface training on fall risk in the older adult and begin to explore evidence-based exercise parameters to drive clinical practice.

Study Selection:
A search on PubMed and CINAHL in March 2016 resulted in 8 randomized control trials to include in this literature review.

Results:
All studies reported statistically significant improvements on at least one outcome measure following variable surface training.

Conclusion:
All health care professionals can refer older adults at risk for falls to physical therapy to help prevent falls before they occur.
Organ Donation Attitudes Among Individuals With Stage 5 Chronic Kidney Disease
Authors: Loughery Caitlin , Andrews Ann M. , Zhang Nanhua , Smith Allyce Haney , Resnicow Ken , Chapman Remonia , Riley Holly Jenkins , Stav Sheri , Yee Jerry 
Published: July 2018

Background
The need for transplantable organs drastically outweighs the supply. Misconceptions are a barrier to increasing the rate of donor registration. Individuals with stage 5 chronic kidney disease (CKD) may incorrectly believe they are unable to be donors; however, their attitudes have not been studied. This study aims to explore beliefs of individuals with stage 5 CKD about their ability to donate and test the validity of an organ donation scale.

Methods
We examined the psychometric properties of a new 25-item organ donation scale among 554 patients with stage 5 CKD at 12 dialysis units in southeast Michigan. Patients completed surveys during dialysis treatment with assistance from a program coordinator or social worker.

Results
Two subscales with good psychometric properties were identified: general benefits (α = 0.86) and general barriers (α = 0.80). For both subscales, more positive attitudes were associated with higher intent to sign up on the donor registry, suggesting validity of the scale.

Conclusions
Patients who were older than 60 years, white, or of higher education status reported more positive attitudes. Misconceptions about the ability of patients with stage 5 CKD to donate are common and highlight a need for education about donor eligibility. Individuals with stage 5 CKD may be able to donate organs and tissues.
Pathologies Underlying Longitudinal Cognitive Decline in the Oldest Old
Authors: Nguyen Madeline T. , Mattek Nora , Woltjer Randy , Howieson Diane , Silbert Lisa , Hofer Scott , Kaye Jeffrey , Dodge Hiroko , Erten-Lyons Deniz 
Published: July 2018

Background:
Understanding contributions of different brain pathologies to domain-specific cognitive trajectories in the oldest old is crucial to guide future intervention studies.

Methods:
Two-hundred-twenty Oregon Alzheimer’s Disease Center research participants who were cognitively intact at entry were followed on average for 7.3 years with annual neuropsychological testing until death (mean age, 93.7 y) and autopsy. Mixed effects models examined the relationship between trajectories in memory, verbal fluency, and mini-mental state examination (MMSE) and pathology (neurofibrillary tangles, neuritic plaques, gross infarcts, hippocampal sclerosis, Lewy bodies, APOE genotype, age at death, and years of education). The association between the MMSE trajectory and pathologic variables were examined using a Poisson model with MMSE errors as outcomes given the nonlinear distribution of MMSE scores.

Results:
Memory trajectory was associated with the APOε4 allele (P=0.006). Verbal fluency trajectory was associated with gross infarcts (P=0.008). MMSE trajectory was associated with high Braak scores (P=0.03), gross infarcts (P<0.0001), hippocampal sclerosis (P=0.003), moderate neuritic plaques (P=0.04), and the APOε4 allele (P=0.02).

Conclusions:
The association between trajectory of decline in global cognitive scores and multiple brain pathologies highlights the importance of accounting for comorbid pathologies in therapeutic trials aimed at one specific pathology in the oldest old. Only the APOε4 allele showed an association with memory decline, despite accounting for Alzheimer’s disease pathology, suggesting that APOE may be involved in mechanisms beyond amyloid metabolism in its role in memory. Further studies are needed to examine the role of APOE in brain aging.
Composition and consistence of the bacterial microbiome in upper, middle and lower esophagus before and after Lugol’s iodine staining
Authors: Yin Jian , Dong Li , Zhao Jing , Shao Dantong , liu Anqi , Li Juxiao , Yu Aisong , Wei Wenqiang , Chen Wen 
Published: July 2018

ABSTRACTEsophageal bacteria, as the integral composition of human ecosystem, have been reported to be associated with esophageal lesions. However, few studies focus on microbial compositions in different esophageal segments, especially after Lugol’s iodine staining (LIS) in the endoscopic examination for the screening of esophageal cancer. To investigate the composition of the bacterial microbiome in upper, middle and lower esophagus and if LIS would affect the detection of bacteria, 141 fasting samples including the upper, middle and lower esophagus from 27 participants were collected by brushing the mucosal surface of the esophagus before (Eso) and after (Lug) LIS. Bacterial V3-V4 region of 16S rRNA gene was amplified and sequenced by Illumina’s sequencing platform and analyzed using LEfSe system to identify specific microbiota. The top six abundant bacterial phyla taxa among three locations from both Eso and Lug groups were Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and TM7. In terms of genera, the bacterium in three locations from two groups was all characterized by a highest relative abundance of Streptococcus. Bacteria diversity and the relative abundance between Eso and Lug were comparable (P > 0.05). Bacteria diversity was consistent in different esophageal locations for an individual, but it was significantly distinguishing in different subjects (P < 0.05). In Conclusion, the bacterial microbiome in healthy esophagus are highly diverse and consistent even among three physiological stenosis at all clades. Lugol’s iodine staining would not change local microenvironment in term of microbial composition. These finding provide an essential baseline for future studies investigating local and systemic bacterial microbiome and esophageal diseases.
Development and Application of a High-Content Virion Display Human GPCR Array
Authors: Syu Guan-Da , Wang Shih-Chin , Ma Guangzhong , Liu Shuang , Pearce Donna , Prakash Atish , Henson Brandon , Weng Lien-Chun , Ghosh Devlina , Ramos Pedro , Eichinger Daniel , Pino Ignacio , Dong Xinzhong , Xiao Jie , Wang Shaopeng , Tao Nongjian , Kim Kwang Sik , Desai Prashant J. , Zhu Heng 
Published: July 2018

ABSTRACTG protein-coupled receptors (GPCRs) comprise the largest membrane protein family in humans and can respond to a wide variety of ligands and stimuli. Like other multi-pass membrane proteins, the biochemical properties of GPCRs are notoriously difficult to study because they must be embedded in lipid bilayers to maintain their native conformation and function. To enable an unbiased, high-throughput platform to profile biochemical activities of GPCRs in native conformation, we individually displayed 315 human non-odorant GPCRs (>85% coverage) in the envelope of human herpes simplex virus-1 and immobilized on glass to form a high-content Virion Display (VirD) array. Using this array, we found that 50% of the tested commercial anti-GPCR antibodies (mAbs) is ultra-specific, and that the vast majority of those VirD-GPCRs, which failed to be recognized by the commercial mAbs, could bind to their canonical ligands, indicating that they were folded correctly. Next, we used the VirD-GPCR arrays to examine binding specificity of two known peptide ligands and recovered expected interactions, as well as new off-target interactions, three of which were confirmed with real-time kinetics measurements. Finally, we explored the possibility of discovering novel pathogen targets by probing VirD-GPCR arrays with live group B Streptococcus (GBS), a common Gram-positive bacterium causing neonatal meningitis. Using cell invasion assays and a mouse model of hematogenous meningitis, we showed that inhibition of one of the five newly identified GPCRs, CysLTR1, greatly reduced GBS penetration in brain-derived endothelial cells and in mouse brains. Therefore, our work demonstrated that the VirD-GPCR array holds great potential for high-throughput, unbiased screening for small molecule drugs, affinity reagents, and deorphanization.
Genotype-covariate correlation and interaction disentangled by a whole-genome multivariate reaction norm model
Authors: Ni Guiyan , van der Werf Julius , Zhou Xuan , Hyppönen Elina , Wray Naomi R. , Lee Hong 
Published: July 2018

ABSTRACTThe genomics era has brought useful tools to dissect the genetic architecture of complex traits. We propose a reaction norm model (RNM) to tackle genotype-environment correlation and interaction problems in the context of genome-wide association analyses of complex traits. In our approach, an environmental risk factor affecting the trait of interest can be modeled as dependent on a continuous covariate that is itself regulated by genetic as well as environmental factors. Our multivariate RNM approach allows the joint modelling of the relation between the genotype (G) and the covariate (C), so that both their correlation (association) and interaction (effect modification) can be estimated. Hence we jointly estimate genotype-covariate correlation and interaction (GCCI). We demonstrate using simulation that the proposed multivariate RNM performs better than the current state-of-the-art methods that ignore G-C correlation. We apply the method to data from the UK Biobank (N= 66,281) in analysis of body mass index using smoking quantity as a covariate. We find a highly significant G-C correlation, but a negligible G-C interaction. In contrast, when a conventional G-C interaction analysis is applied (i.e., G-C correlation is not included in the model), highly significant G-C interaction estimates are found. It is also notable that we find a significant heterogeneity in the estimated residual variances across different covariate levels probably due to residual-covariate interaction. Using simulation we also show that the residual variances estimated by genomic restricted maximum likelihood (GREML) or linkage disequilibrium score regression (LDSC) can be inflated in the presence of interactions, implying that the currently reported SNP-heritability estimates from these methods should be interpreted with caution. We conclude that it is essential to correctly account for both interaction and correlation in complex trait analyses and that the failure to do so may lead to substantial biases in inferences relating to genetic architecture of complex traits, including estimated SNP-heritability.
AKT, NOTCH and GSK3β interact to trigger early myogenesis in vertebrate embryos
Authors: Lebrun Diane , Rahal Pamela , Morin Valérie , Marcelle Christophe 
Published: July 2018

ABSTRACTDuring early embryonic development, migrating neural crest cells expressing the NOTCH ligand Delta1 (DLL1) trigger the activation of NOTCH1 signaling in selected epithelial cells within newly formed somites. A key event in this process is a dramatic inhibition of GSK3β activity, initiated by the activation of NOTCH1 and that takes place independent of its transcriptional function. Here, we investigated the mechanism whereby NOTCH1 exerts its non-canonical function in somites. Using the activation of myogenesis as a read-out of the ability of NOTCH receptors to trigger transcription-independent responses in somites, we found that all NOTCH receptors (1-4) activate MYF5 expression and we showed that the RAM (RBPJ-Associated Molecule) domain of the NOTCH Intracellular Domain (NICD) is necessary and sufficient in this process. We then demonstrated that the NOTCH1 Intracellular Domain (NICD1) physically interacts in the cytosol with GSK3β and with the serine threonine protein kinase AKT. Activating AKT triggers myogenesis, likely via the inhibition of GSK3β. We found that AKT, in a dose-dependent manner, decreases the transcriptional activity of NOTCH, suggesting a role in the balance between the canonical and non-canonical functions of NOTCH. Altogether these data strongly support the hypothesis that transcription-independent function of NICD is a central mechanism driving myogenesis in early somites and suggests that, in this tissue, AKT, NOTCH and GSK3β interact in the cytoplasm to trigger a signaling cascade that leads to the formation of the early myotome in vertebrates.
Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex
Authors: Regev Tamar I. , Winawer Jonathan , Gerber Edden M. , Knight Robert T. , Deouell Leon Y. 
Published: July 2018

AbstractMuch of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly non-invasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 sub-dural electrodes, distributed across the posterior cortex of the right hemisphere, for pre-surgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event Related Potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was robust, statistically reliable and spatially localized, very early responses on the bank of the posterior intra-parietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 milliseconds post-stimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for the upper limit of onset times of visual responses across the human cortex.