bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rack1 function in intestinal epithelia: regulating crypt cell proliferation and regeneration and promoting differentiation and apoptosis
Authors: Cheng Zhuan-Fen , Pai Reetesh K. , Cartwright Christine A. 
Published: September 2017

Previously, we showed that receptor for activated C kinase 1 (Rack1) regulates growth of colon cells in vitro, partly by suppressing Src kinase activity at key cell cycle checkpoints, in apoptotic and cell survival pathways and at cell-cell adhesions. Here, we generated mouse models of Rack1 deficiency to assess Rack1’s function in intestinal epithelia in vivo. Intestinal Rack1 deficiency resulted in proliferation of crypt cells, diminished differentiation of crypt cells into enterocyte, goblet, and enteroendocrine cell lineages, and expansion of Paneth cell populations. Following radiation injury, the morphology of Rack1-deleted small bowel was strikingly abnormal with development of large polypoid structures that contained many partly formed villi, numerous back-to-back elongated and regenerating crypts, and high-grade dysplasia in surface epithelia. These abnormalities were not observed in Rack1-expressing areas of intestine or in control mice. Following irradiation, apoptosis of enterocytes was strikingly reduced in Rack1-deleted epithelia. These novel findings reveal key functions for Rack1 in regulating growth of intestinal epithelia: suppressing crypt cell proliferation and regeneration, promoting differentiation and apoptosis, and repressing development of neoplasia. NEW & NOTEWORTHY Our findings reveal novel functions for receptor for activated C kinase 1 (Rack1) in regulating growth of intestinal epithelia: suppressing crypt cell proliferation and regeneration, promoting differentiation and apoptosis, and repressing development of neoplasia.
Effects of expiratory muscle activation via high-frequency spinal cord stimulation
Authors: Kowalski K. E. , Romaniuk J. R. , Kowalski T. , DiMarco A. F. 
Published: September 2017

In persons with spinal cord injury, lower thoracic low-frequency spinal cord stimulation (LF-SCS; 50 Hz, 15 mA) is a useful method to restore an effective cough. Unfortunately, the high-stimulus-amplitude requirements and potential activation of pain fibers significantly limit this application in persons with intact sensation. In this study, the mechanism of the expiratory muscle activation, via high-frequency SCS (HF-SCS; 500 Hz, 1 mA) was evaluated in dogs. In group 1, the effects of electrode placement on airway pressure generation (P) was evaluated. Maximal P occurred at the T9–T10 level with progressive decrements in P at more rostral and caudal levels for both LF-SCS and HF-SCS. In group 2, electromyographic (EMG) latencies of internal intercostal muscle (II) activation were evaluated before and after spinal root section and during direct motor root stimulation. Onset time of II EMG activity during HF-SCS was significantly longer (3.84 ± 1.16 ms) than obtained during direct motor root activation (1.61 ± 0.10 ms). In group 3, P and external oblique (EO) EMG activity, before and after sequential spinal section at the T11–T12 level, were evaluated. Bilateral dorsal column section significantly reduced EO EMG activity below the section and resulted in a substantial fall in P. Subsequent lateral funiculi section completely abolished those activities and resulted in further reductions in P. We conclude that 1) activation of the expiratory muscles via HF-SCS is dependent entirely on synaptic spinal cord pathways, and 2) HF-SCS at the T9 level produces a comparable level of muscle activation with that achieved with LF-SCS but with much lower stimulus amplitudes. NEW & NOTEWORTHY The findings in the present study suggest that lower thoracic high-frequency spinal cord stimulation with low stimulus currents results in sufficient activation of the expiratory muscles via spinal circuitry to produce large positive airway pressures sufficient to generate an effective cough mechanism. This method, therefore, may be applied in patient populations with intact sensation such as stroke and amyotrophic lateral sclerosis to restore an effective cough.
Are You What You Eat or What Your Mother Ate or Both?
Authors: Freedland Stephen J. 
Published: September 2017

Abstract
A high-fat high-sugar (HF-HS) diet promotes cancer development and progression. However, does the timing of diet matter? This is an important question with profound public health relevance. By exposing mice to a HF-HS diet either through feeding to a pregnant mother or nursing mother or after weaning and then chemically inducing breast cancer, the authors found the most crucial time for breast cancer risk was after weaning, while a HF-HS in utero diet actually slowed tumor development. Understanding early-life events provides valuable insight for later life events and proves it is never too early to start preventing disease. Cancer Prev Res; 10(10); 551–2. ©2017 AACR.
See related article by Lambertz, p. 553–62.
Sympathomimetic Effects of Acute E‐Cigarette Use: Role of Nicotine and Non‐Nicotine Constituents
Authors: Moheimani Roya S. , Bhetraratana May , Peters Kacey M. , Yang Benjamin K. , Yin Fen , Gornbein Jeffrey , Araujo Jesus A. , Middlekauff Holly R. 
Published: September 2017

Background
Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non‐nicotine constituents in e‐cigarette emissions in causing these pathologies in otherwise healthy humans.

Methods and Results

Thirty‐three healthy volunteers who were not current e‐cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e‐cigarette with nicotine, an e‐cigarette without nicotine, or a sham control. Cardiac
sympathetic nerve activity
was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e‐cigarette with nicotine, but not to the e‐cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high‐frequency component and the increases in the low‐frequency component and the
low‐frequency
to
high‐frequency
ratio were significantly greater following exposure to the e‐cigarette with nicotine compared with exposure to the e‐cigarette without nicotine or to sham control. Oxidative stress, as estimated by
plasma paraoxonase,
did not increase following any of the 3 exposures.

Conclusions

The acute sympathomimetic effect of e‐cigarettes is attributable to the inhaled nicotine, not to non‐nicotine constituents in e‐cigarette aerosol, recapitulating the same
heart rate variability
pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by
plasma paraoxonase
activity, was not uncovered following acute e‐cigarette exposure.
Effects of Physical Activity on Poststroke Cognitive Function
Authors: Oberlin Lauren E. , Waiwood Aashna M. , Cumming Toby B. , Marsland Anna L. , Bernhardt Julie , Erickson Kirk I. 
Published: September 2017

Background and Purpose—
Despite the social, health, and economic burdens associated with cognitive impairment poststroke, there is considerable uncertainty about the types of interventions that might preserve or restore cognitive abilities. The objective of this systematic review and meta-analysis was to evaluate the effects of physical activity (PA) training on cognitive function poststroke and identify intervention and sample characteristics that may moderate treatment effects.

Methods—
Randomized controlled trials examining the association between structured PA training and cognitive performance poststroke were identified using electronic databases EMBASE and MEDLINE. Intervention effects were represented by Hedges’ g and combined into pooled effect sizes using random- and mixed-effects models. Effect sizes were subjected to moderation analyses using the between-group heterogeneity test.

Results—

Fourteen studies met inclusion criteria, representing data from 736 participants. The primary analysis yielded a positive overall effect of PA training on cognitive performance (Hedges’ g [95% confidence interval]=0.304 [0.14–0.47]). Mixed-effects analyses demonstrated that combined aerobic and strength training programs generated the largest cognitive gains and that improvements in cognitive performance were achieved even in the chronic stroke phase (mean=2.6 years poststroke). Positive moderate treatment effects were found for attention/processing speed measures (Hedges’ g [confidence interval]=0.37 [0.10–0.63]), while the executive function and working memory domains did not reach significance (
P
>0.05).

Conclusions—
We found a significant positive effect of PA training on cognition poststroke with small to moderate treatment effects that are apparent even in the chronic stroke phase. Our findings support the use of PA training as a treatment strategy to promote cognitive recovery in stroke survivors.
Minimal Clinically Important Difference for Safe and Simple Novel Acute Ischemic Stroke Therapies
Authors: Cranston Jessica S. , Kaplan Brett D. , Saver Jeffrey L. 
Published: September 2017

Background and Purpose—
Determining the minimal clinically important difference (MCID) is essential for evaluating novel therapies. For acute ischemic stroke, expert surveys have yielded MCIDs that are substantially higher than the MCIDs observed in actual expert behavior in guideline writing and clinical practice, potentially because of anchoring bias.

Methods—
We administered a structured, internet-based survey to a cross-section of academic stroke neurologists in the United States. Survey responses assessed demographic and clinical experience, and expert judgment of the MCID of the absolute increase needed in the proportion of patients achieving functional independence at 3 months to consider a novel, safe neuroprotective agent as clinically worthwhile. To mitigate anchoring bias, the survey response framework used a base 1000 rather than base 100 patient framework.

Results—
Survey responses were received from 122 of 333 academic stroke neurologists, there were 23% women, 72.8% had ≥6 years of practice experience, and neurovascular disease accounted for more than half of practice time in >70%. Responder–nonresponder and continuum of resistance tests indicated that responders were representative of the full expert population. Among respondents, the median MCID was 1.3% (interquartile range, 0.8% to >2%).

Conclusions—
Stroke expert responses to MCID surveys are affected by anchoring and centrality bias. When survey design takes these into account, the expert-derived MCID for a safe acute ischemic stroke treatment is 1.1% to 1.5%, in accord with actual physician behavior in guideline writing and clinical practice. This revised MCID value can guide clinical trial design and grant-funding and regulatory agency decisions.
Normobaric Hyperoxia Reduces Blood Occludin Fragments in Rats and Patients With Acute Ischemic Stroke
Authors: Shi Shuhai , Qi Zhifeng , Ma Qingfeng , Pan Rong , Timmins Graham S. , Zhao Yongmei , Shi Wenjuan , Zhang Yunzhou , Ji Xunming , Liu Ke Jian 
Published: September 2017

Background and Purpose—
Damage of the blood–brain barrier (BBB) increases the incidence of neurovascular complications, especially for cerebral hemorrhage after tPA (tissue-type plasminogen activator) therapy. Currently, there is no effective method to evaluate the extent of BBB damage to guide tPA use. Herein, we investigated whether blood levels of tight junction proteins could serve as biomarker of BBB damages in acute ischemic stroke (AIS) in both rats and patients. We examined whether this biomarker could reflect the extent of BBB permeability during cerebral ischemia/reperfusion and the effects of normobaric hyperoxia (NBO) on BBB damage.

Methods—

Rats were exposed to NBO (100% O
2
) or normoxia (21% O
2
) during middle cerebral artery occlusion. BBB permeability was determined. Occludin and claudin-5 in blood and cerebromicrovessels were measured. Patients with AIS were assigned to oxygen therapy or room air for 4 hours, and blood occludin and claudin-5 were measured at different time points after stroke.

Results—
Cerebral ischemia/reperfusion resulted in the degradation of occludin and claudin-5 in microvessels, leading to increased BBB permeability in rats. In blood samples, occludin increased with 4-hour ischemia and remained elevated during reperfusion, correlating well with its loss from ischemic cerebral microvessels. NBO treatment both prevented occludin degradation in microvessels and reduced occludin levels in blood, leading to improved neurological functions in rats. In patients with AIS receiving intravenous tPA thrombolysis, the blood occludin was already elevated when patients arrived at hospital (within 4.5 hours since symptoms appeared) and remained at a high level for 72 hours. NBO significantly lowered the level of blood occludin and improved neurological functions in patients with AIS.

Conclusions—
Blood occludin may be a clinically viable biomarker for evaluating BBB damage during ischemia/reperfusion. NBO therapy has the potential to reduce blood occludin, protect BBB, and improve outcome in AIS patients with intravenous tPA thrombolysis.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02974283.
New fossil taxa of Ischalia Pascoe (Coleoptera: Ischaliidae) from Eocene Baltic amber
Authors: ALEKSEEV VITALII I. , BUKEJS ANDRIS 
Published: September 2017

Two new fossil species of false fire-colored beetles (Coleoptera: Ischaliidae), Ischalia dohnaturris sp. nov. and I. danieli sp. nov., are described and illustrated from Eocene Baltic amber. The fossil species I. dohnaturris sp. nov. is considered to be the first macropterous representative of the subgenus Eupleurida LeConte. The second species, I. danieli sp. nov., is placed in the newly described subgenus Telnovia subgen. nov. The subgeneric characters of Ischalia are briefly discussed. A key to fossil species of Ischalia is also provided.
Evaluation of modified risk claim advertising formats for Camel Snus
Authors: Fix Brian V , Adkison Sarah E , O’Connor Richard J , Bansal-Travers Maansi , Cummings K Michael , Rees Vaughan W , Hatsukami Dorothy K 
Published: September 2017

Objectives: The US Food and Drug Administration (FDA) has regulatory authority for modified risk tobacco product advertising claims. To guide future regulatory efforts, we investigated how variations in modified risk claim advertisements influence consumer perceptions of product risk claims for Camel Snus. Methods: Young people and adults (15–65), including current, never, and former smokers, were randomised to view one of five Camel Snus print advertisements as part of a web-based survey. Four of the advertisements presented information related to nitrosamine content of snus using four formats: (1) text, (2) a bar chart, (3) a text/testimonial and (4) a bar chart/testimonial. The fifth format, used as a control, was a current advertisement for Camel Snus without the explicit claims made about nitrosamine content. After viewing advertisements for all products, participants were asked which product they would be most interested in trying. Results: Participants exposed to advertisements that contained an explicit reduced risk message agreed the advertising claim for that product posed fewer health risks than cigarettes. However, advertisements containing the reduced risk messages were also viewed as containing less truthful information and respondents were more sceptical of the information presented. Advertisement claim format was not associated with selecting snus over the other tobacco products, nor was it associated with purchase intentions. Conclusion: The results of this research indicate that consumers respond to reduced risk messages, though perhaps not in the direct way anticipated. We found no significant differences by advertisement format (numerical, graphical, testimonial).
Dual Antiplatelet Therapy Is Associated With Coagulopathy Detectable by Thrombelastography in Acute Stroke
Authors: McDonald Mark M. , Almaghrabi Tareq S. , Saenz Daniel M. , Cai Chunyan , Rahbar Mohammad H. , Choi H. Alex , Lee Kiwon , Grotta James C. , Chang Tiffany R. 
Published: September 2017

Background: Thrombelastography (TEG) provides a global, dynamic measure of coagulation. We examined the effect of antiplatelet (AP) medications on coagulation in patients with acute stroke as measured by TEG. Methods: We reviewed prospectively collected data on patients presenting with acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH) between 2009 and 2014. Patient demographics and baseline TEG values were compared among 4 different drug use groups: aspirin only, clopidogrel only, both aspirin and clopidogrel, and no AP. Multivariable regression models were conducted to compare the differences in TEG components. Results: A total of 202 patients were included, 139 with AIS and 63 with ICH. Forty-eight (24%) patients were taking aspirin alone, 12 (6%) were taking clopidogrel, 16 (8%) dual AP, and 126 (62%) no AP. Dual AP use was associated with prolonged mean R (time to initiate clotting) of 5.5 minutes as compared to no AP use (4.6 minutes, P = .04). Additionally, mean maximal amplitude (MA; final clot strength) and angle (rate of clot formation) were decreased in the dual AP group (MA = 59.3 mm, angle = 57.8°) as compared to the no AP group (MA = 64.5 mm, angle = 64.5°; P = .04 and P = .01, respectively). Patients on single AP therapy (either aspirin or clopidogrel) did not differ from those on no AP therapy in any TEG parameters measured. Conclusion: Dual AP therapy is associated with a detectable coagulopathy which may have implications in the management of patients with AIS and hemorrhagic stroke. The effects of single AP therapy may not be demonstrated by TEG.
Prolonged Intensive Care Unit Stay Following Transcatheter Aortic Valve Replacement
Authors: Higuchi Ryosuke , Takayama Morimasa , Hagiya Kenichi , Saji Mike , Mahara Keitaro , Takamisawa Itaru , Shimizu Jun , Tobaru Tetsuya , Iguchi Nobuo , Takanashi Shuichiro 
Published: September 2017

Purpose: Postoperative intensive care unit (ICU) stay after cardiac surgeries has been extensively studied, but little attention has been given to ICU stay following transcatheter aortic valve replacement (TAVR). This study examined ICU stay after TAVR. Methods: Two hundred and forty-five patients who underwent TAVR between April 2010 and October 2016 were studied retrospectively. We investigated the status of ICU stay, the predictors of prolonged ICU stay (PICUS), and its impact on short- and long-term outcomes. Prolonged ICU stay was defined as post-TAVR ICU stay longer than 2 days (day of TAVR + 1 day). Results: Length of ICU stay was 2.6 ± 4.9 days, and PICUS was identified in 14.7% of the patients. The predominant reason for PICUS was congestive heart failure or circulatory failure (41.7%). Pulmonary dysfunction and nontransfemoral approach were independent predictors of PICUS (pulmonary dysfunction: odds ratio = 2.64, 95% confidence interval [CI]: 1.05-7.35; nontransfemoral approach: odds ratio = 2.81, 95% CI: 1.15-6.89). Prolonged ICU stay was associated with higher rate of 30-day combined end point (PICUS vs non-PICUS: 44.4% vs 3.3%, P < .0001), longer postoperative hospital stay (49.9 ± 141.9 days vs 12.0 ± 6.0 days, P < .0001), and lower rate of discharge home (77.8% vs 95.2%, P = .0002). Patients with PICUS had worse long-term survival ( P < .0001), and PICUS was a predictor of mortality (hazard ratio: 4.21, 95% CI: 2.09-8.22). Conclusion: Prolonged ICU stay following TAVR was found in 14.7%, and pulmonary dysfunction and nontransfemoral approach were associated with PICUS. Short- and long-term prognoses were worse in patients with PICUS than those without.
Changes in Radial Artery Pulse Pressure During a Fluid Challenge Cannot Assess Fluid Responsiveness in Patients With Septic Shock
Authors: De la Puente-Diaz de Leon Victor , de Jesus Jaramillo-Rocha Valente , Teboul Jean-Louis , Garcia-Miranda Sofia , Martinez-Guerra Bernardo A. , Dominguez-Cherit Guillermo 
Published: September 2017

Background: Arterial blood pressure is the most common variable used to assess the response to a fluid challenge in routine clinical practice. The aim of this study was to evaluate the accuracy of the change in the radial artery pulse pressure (rPP) to detect the change in cardiac output after a fluid challenge in patients with septic shock. Methods: Prospective observational study including 35 patients with septic shock in which rPP and cardiac output were measured before and after a fluid challenge with 400 mL of crystalloid solution. Cardiac output was measured with intermittent thermodilution technique using a pulmonary artery catheter. Patients were divided between responders (increase >15% of cardiac output after fluid challenge) and nonresponders. The area under the receiver operating characteristic curve (AUROC), Pearson correlation coefficient and paired Student t test were used in statistical analysis. Results: Forty-three percent of the patients were fluid responders. The change in rPP could not neither discriminate between responders and nonresponders (AUROC = 0.52; [95% confidence interval: 0.31-0.72] P = .8) nor correlate ( r = .21, P = .1) with the change in cardiac output after the fluid challenge. Conclusions: The change in rPP neither discriminated between fluid responders and nonresponders nor correlated with the change in cardiac output after a fluid challenge. The change in rPP cannot serve as a surrogate of the change in cardiac output to assess the response to a fluid challenge in patients with septic shock.
Risk of damage and mortality in SLE patients fulfilling the ACR or only the SLICC classification criteria. A 10-year, inception cohort study
Authors: Inês L , Rodrigues M , Jesus D , Fonseca F P , Silva J A P 
Published: September 2017

Objective To compare damage and mortality, from inception up to 10-year follow-up, between SLE patients meeting at baseline the 1997 ACR criteria or only the 2012 SLICC classification criteria. Methods Patients fulfilling the ACR and/or the SLICC classification criteria for SLE were enrolled at inception and followed-up to 10 years at an academic lupus clinic. Damage was defined as SLICC Damage Index (SDI) score ≥1. We assessed with multivariate Cox models the damage and mortality outcomes, according to SLE classification status at inception, adjusting for potential baseline confounders. Results We recruited 192 patients (69.8% fulfilling at inception the ACR criteria and 30.2% only the SLICC criteria). During follow-up, 24.0% of patients accrued organ damage and 4.2% died. Patients meeting ACR criteria compared to those with SLICC criteria alone presented during follow-up with more cases of lupus nephritis (35.1% versus 13.8%, p < 0.01), but less thrombotic antiphospholipid syndrome (4.5% versus 17.2%, p < 0.01). The Cox models showed no significant differences in risk for damage [hazard ratio (HR) (95% CI) 0.991 (0.453–2.167)] or death [hazard ratio (HR) (95% CI) 0.694 (0.107–4.506)] between groups. Conclusion The SLE classification status at inception identified different patterns of clinical phenotype, but did not influence damage accrual or mortality up to 10-year follow-up.