bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fifty Years Since the Discovery of PKA
Authors: Taylor Susan S. , Kim Choel W. , Cheng Cecilia Y. , Kannan Natarajan , Sastri Mira , Eggers Christopher W. , Wu Jian 
Published: January 2018

In 1968, after Sutherland's discovery of cAMP, Krebs discovered cAMP‐dependent Protein Kinase (PKA), thus establishing the major paradigm for cAMP signaling in mammalian cells. The protein kinases, one of the largest gene families, are associated with many diseases, and PKA serves as a prototype for general protein kinase structure and function. While the structure of PKA first defined the conserved protein kinase fold, the recent solution of inhibited complexes of the catalytic (C) and regulatory (R) subunits have defined not only the molecular basis for inhibition but also the mechanisms for activation by cAMP. In addition, they show the dramatic flexibility that is embedded within the R‐subunit as it releases cAMP and wraps itself around the large lobe of the C‐subunit. In contrast, the C‐subunit functions as a stable scaffold that binds to many proteins. In addition to the R‐subunit isoforms and PKI, the C‐subunit docks to other proteins such as the A Kinase Interacting Protein (AKIP‐1), which contributes to its nuclear localization. The R‐ and C‐subunits do not typically exist as isolated entities in the cell but instead are part of large complexes assembled in part through A Kinase Anchoring Proteins (AKAPs). Localization and trafficking are an essential part of kinase function, and the challenge for the next decade will be to understand how these large PKA‐mediated signaling complexes assemble and integrate highly regulated functional responses. It is a challenge that requires the concerted integration of structural biology, cell biology, pharmacology and physiology.(Funded by grants from the NIH to SST and fellowships from the American Cancer Society to CK and CWE, and NIH Training Grant GM08326 to CYC.)
Laughter Is the Best Medicine: Teaching to Teach Using Standardized Patients
Authors: Kaylor Sara K. , Strickland Haley P. , Sartain Andrea F. 
Published: January 2018

Abstract
This article describes an innovative approach to patient teaching using standardized patients, humor, and therapeutic communication. The strategy was designed for baccalaureate students enrolled in a fundamentals nursing course. Students, divided into small groups, were assigned a patient education topic to provide to the standardized patient. Student and faculty feedback indicated positive responses to this instructional strategy. Utilization of this learner-centered teaching environment to promote therapeutic communication during a complex patient-teaching scenario was found to be beneficial for novice nursing students.
Effects of Ambient Temperature and Forced-air Warming on Intraoperative Core Temperature
Authors: Pei Lijian , Huang Yuguang , Xu Yiyao , Zheng Yongchang , Sang Xinting , Zhou Xiaoyun , Li Shanqing , Mao Guangmei , Mascha Edward J. , Sessler Daniel I. 
Published: January 2018

Abstract

Background
The effect of ambient temperature, with and without active warming, on intraoperative core temperature remains poorly characterized. The authors determined the effect of ambient temperature on core temperature changes with and without forced-air warming.

Methods
In this unblinded three-by-two factorial trial, 292 adults were randomized to ambient temperatures 19°, 21°, or 23°C, and to passive insulation or forced-air warming. The primary outcome was core temperature change between 1 and 3 h after induction. Linear mixed-effects models assessed the effects of ambient temperature, warming method, and their interaction.

Results
A 1°C increase in ambient temperature attenuated the negative slope of core temperature change 1 to 3 h after anesthesia induction by 0.03 (98.3% CI, 0.01 to 0.06) °Ccore/(h.°Cambient) (P < 0.001), for patients who received passive insulation, but not for those warmed with forced-air (–0.01 [98.3% CI, –0.03 to 0.01] °Ccore/[h.°Cambient]; P = 0.40). Final core temperature at the end of surgery increased 0.13°C (98.3% CI, 0.07 to 0.20; P < 0.01) per degree increase in ambient temperature with passive insulation, but was unaffected by ambient temperature during forced-air warming (0.02 [98.3% CI, –0.04 to 0.09] °Ccore/°Cambient; P = 0.40). After an average of 3.4 h of surgery, core temperature was 36.3° ± 0.5°C in each of the forced-air groups, and ranged from 35.6° to 36.1°C in passively insulated patients.

Conclusions
Ambient intraoperative temperature has a negligible effect on core temperature when patients are warmed with forced air. The effect is larger when patients are passively insulated, but the magnitude remains small. Ambient temperature can thus be set to comfortable levels for staff in patients who are actively warmed.
Antifungal Susceptibility and Clinical Outcome in Neonatal Candidiasis
Authors: Autmizguine Julie , Tan Sylvia , Cohen-Wolkowiez Michael , Cotten C. Michael , Wiederhold Nathan , Goldberg Ronald N. , Adams-Chapman Ira , Stoll Barbara J. , Smith P. Brian , Benjamin Daniel K. 
Published: January 2018

Background:
Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI.

Methods:
This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18–22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III).

Results:
Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed.

Conclusions:
Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.
Orally active Epac inhibitor reverses mechanical allodynia and loss of intraepidermal nerve fibers in a mouse model of chemotherapy-induced peripheral neuropathy
Authors: Singhmar Pooja , Huo XiaoJiao , Li Yan , Dougherty Patrick M. , Mei Fang , Cheng Xiaodong , Heijnen Cobi J. , Kavelaars Annemieke 
Published: January 2018

Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of cancer treatment that significantly compromises quality of life of cancer patients and survivors. Identification of targets for pharmacological intervention to prevent or reverse CIPN is needed. We investigated exchange protein regulated by cAMP (Epac) as a potential target. Epacs are cAMP-binding proteins known to play a pivotal role in mechanical allodynia induced by nerve injury and inflammation. We demonstrate that global Epac1-knockout (Epac1−/−) male and female mice are protected against paclitaxel-induced mechanical allodynia. In addition, spinal cord astrocyte activation and intraepidermal nerve fiber (IENF) loss are significantly reduced in Epac1−/− mice as compared to wild-type mice. Moreover, Epac1−/− mice do not develop the paclitaxel-induced deficits in mitochondrial bioenergetics in the sciatic nerve that are a hallmark of CIPN. Notably, mice with cell-specific deletion of Epac1 in Nav1.8-positive neurons (N-Epac1−/−) also show reduced paclitaxel-induced mechanical allodynia, astrocyte activation, and IENF loss, indicating that CIPN develops downstream of Epac1 activation in nociceptors. The Epac-inhibitor ESI-09 reversed established paclitaxel-induced mechanical allodynia in wild-type mice even when dosing started 10 days after completion of paclitaxel treatment. In addition, oral administration of ESI-09 suppressed spinal cord astrocyte activation in the spinal cord and protected against IENF loss. Ex vivo, ESI-09 blocked paclitaxel-induced abnormal spontaneous discharges in dorsal root ganglion neurons. Collectively, these findings implicate Epac1 in nociceptors as a novel target for treatment of CIPN. This is clinically relevant because ESI-09 has the potential to reverse a debilitating and long-lasting side effect of cancer treatment.
Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain
Authors: Nation Kelsey M. , De Felice Milena , Hernandez Pablo I. , Dodick David W. , Neugebauer Volker , Navratilova Edita , Porreca Frank 
Published: January 2018

Abstract
The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.
Modification Patterns of Urinary Albumin Correlates With Serum Albumin and Outcome in Severe Alcoholic Hepatitis
Authors: Das Sukanta , Hussain Md. Shabir , Maras Jaswinder S. , Kumar Jitendra , Shasthry Saggere M. , Nayak Suman , Arora Vinod , Vijayaraghavan Rajan , Sharma Shvetank , Maiwall Rakhi , Sarin Shiv K. 
Published: January 2018

Background and Aims:
Albumin modifications and deranged functions are well documented in serum of severe alcoholic hepatitis (SAH). We investigated whether urinary albumin (u-Alb) can serve as surrogate marker of circulatory albumin phenotype, functionality, and could predict outcome in SAH patients.

Patients and Methods:
Baseline serum and urine samples from 100 SAH, 20 alcoholic cirrhosis, and 20 healthy controls were subjected to u-Alb, ischemia modified albumin (IMA), IMA to albumin ratio (IMAr), advanced oxidation protein products, advanced glycation end-products, albumin-binding capacity determination. In addition, SAH urinary samples were also analyzed at day 4 and day 7 to predict nonresponse to corticosteroid therapy.

Results:
Urine and serum levels of IMA, advanced oxidation protein products and advanced glycation end-products were higher (P<0.05) in SAH versus alcoholic cirrhosis and healthy controls. IMAr was low in urine but high in serum of SAH (P<0.05). Albumin-binding capacity was lower (P<0.05) in both urinary and serum albumin of SAH. Urinary and serum albumin parameters showed direct correlation, whereas IMAr showed inverse correlation (cc>0.2, P<0.05). Baseline u-Alb level was significantly higher in SAH, and was correlated directly with corticosteroid treatment outcome and 12-month mortality in SAH. Baseline u-Alb showed an area under the receivers operating curve analysis of 0.7 and a hazard ratio of 1.23 for prediction of 12-month mortality in SAH. Baseline u-Alb level >9.0 mg/dL was associated with reduced 12-month survival in SAH (log rank <0.01).

Conclusions:
u-Alb modifications are reflective of serum albumin modifications. Further baseline u-Alb levels could be exploited to predict steroid response and mortality in SAH patients.
Diurnal Intraocular Pressure Fluctuations with Self-tonometry in Glaucoma Patients and Suspects: A Clinical Trial
Authors: Huang Jessie , Katalinic Paula , Kalloniatis Michael , Hennessy Michael P. , Zangerl Barbara 
Published: January 2018

SIGNIFICANCE
This article shows that self-tonometry can provide robust measures of diurnal intraocular pressure (IOP) and also detect changes to IOP in response to treatment within a short period of monitoring. These advances in IOP monitoring may contribute to improved management of glaucoma patients and suspects.

PURPOSE
The aim of this study was to prospectively investigate the utility of rebound self-tonometry performed over several weeks for detecting diurnal IOP fluctuations in glaucoma patients and suspects and also initial response to topical treatment in glaucoma patients.

METHODS
Forty patients were recruited following glaucoma-specific examination. Subsequent to successful training with the iCare HOME tonometer, patients were instructed to measure IOP, in a sitting position, four times a day over 4 to 6 weeks. Date, time, laterality, and IOP downloaded from the tonometer and clinical examination data, including applanation IOP and corneal thickness, were analyzed. A user satisfaction survey was also administered at study completion. t Test and analysis of variance were used to compare groups and IOP across days. Pearson correlation was used to compare measurements to Goldmann applanation tonometry and IOP measurements from the first day/s to the overall mean IOP.

RESULTS
Twenty-seven patients (18 suspects and 9 glaucoma patients) completed data collection. Patients self-measured IOP on 118 (±29) occasions for 40 (±7.4) days. Two dominant patterns of fluctuation were revealed: peak IOP upon awakening (n = 11) and at midday (n = 13). Diurnal IOP measured in the first 7 days showed strong correlation to diurnal IOP across the entire study period (r
2 = 0.82, P < .0001). Within 24 hours of treatment commencement (latanoprost 0.005% ophthalmic solution), IOP reduced from 23.9 (±5.2) to 16.1 (±2.6) mmHg. Overall, patients rated the instrument as easy to use, although difficulties with correct alignment were expressed.

CONCLUSIONS
Rebound self-tonometry demonstrated utility for measuring diurnal IOP fluctuations in most patients, hence enhancing management of patient with or at risk of developing glaucoma.
Can Corneal Biomechanical Properties Explain Difference in Tonometric Measurement in Normal Eyes?
Authors: Dey Ashim , David Rathini Lilian , Asokan Rashima , George Ronnie 
Published: January 2018

SIGNIFICANCECorneal biomechanical parameters can affect intraocular pressure (IOP) measurements by different tonometers compared with Goldmann applanation tonometer. This study implies that corneal hysteresis (CH) and corneal resistance factor (CRF) better explain variability in IOP measurements.PURPOSEThe aim of this study was to evaluate the effect of corneal properties on the difference in IOP measured by the Ocular Response Analyzer (ORA), Rebound Tonometer (RBT), Dynamic Contour Tonometer (DCT), and Tono-Pen from the Goldmann applanation tonometer (GAT).METHODSAn observational study was done on healthy participants in a tertiary eye care center. Corneal curvature was measured with a manual keratometer prior to IOP measurements. Intraocular pressure was measured by a single trained examiner with ORA, RBT, DCT, GAT, and Tono-Pen. CH and CRF were measured using the ORA. Central corneal thickness was measured using the ultrasonic pachymeter. Only the right eye was included for analysis. One-way analysis of variance was performed to compare variables, Bland-Altman plots to assess agreement, and regression analyses to study associated factors.RESULTSWe included 82 eyes of 82 participants with a mean age of 40.9 (14.3) years. Mean ± SD DCT IOP (15.22 ± 1.98) mmHg was significantly higher than GAT IOP (13.73 ± 2.42) (P= .01) and ORA Goldmann correlated IOP (13.66 ± 3.16) (P= .003). The limits of agreement between GAT and other tonometers measurements ranged between −5.0 and 2.1 mmHg. With multiple linear regression analyses, CH and CRF were found to be associated with the measured IOP differences between GAT and ORA (corneal compensated IOP and Goldmann correlated IOP) (P< .001) and DCT (P= .014, <.001) whereas differences between GAT and RBT measurements were independently explained by corneal curvature (P= .035) and central corneal thickness (P= .045).CONCLUSIONSThere was good agreement between GAT and other tonometers, but was not good enough for them to be used interchangeably. A combination of CH and CRF may better explain the variability between GAT and tonometers.
Conceptual Considerations for Payment Bundling in Breast Reconstruction
Authors: Sheckter Clifford C. , Razdan Shantanu N. , Disa Joseph J. , Mehrara Babak J. , Matros Evan 
Published: January 2018

Summary:
Rising health care costs and quality demands have driven both the Centers for Medicare and Medicaid Services and the private sector to seek innovations in health system design by placing institutions at financial risk. Novel care models, such as bundled reimbursement, aim to boost value though quality improvement and cost reduction. The Center for Medicare and Medicaid Innovation is leading the charge in this area with multiple pilots and mandates, including Comprehensive Care for Joint Replacement. Other high-cost and high-volume procedures could be considered for bundling in the future, including breast reconstruction. In this article, conceptual considerations surrounding bundling of breast reconstruction are discussed.
Orthognathic Surgery and Rhinoplasty: Simultaneous or Staged?
Authors: Sun Alexander H. , Steinbacher Derek M. 
Published: January 2018

Background:
Orthognathic surgery can significantly impact the nasolabial envelope, and at times requires an adjunctive rhinoplasty. The purpose of this study was to evaluate nasal morphology in orthognathic patients, focusing on predictive variables, and the need for and timing of definitive rhinoplasty. Based on these data, an algorithm for the implementation of adjunctive rhinoplasty is proposed.

Methods:
A review of cases over a 3-year period was completed. Information regarding demographic, diagnostic, and operative details; nasal morphology; and use of rhinoplasty was compiled. Three-dimensional images were used to quantify anatomical variables.

Results:
Over 589 patients were reviewed during this period. Of these, 163 fulfilled inclusion criteria for this study. The mean age was 23.3 years. In total, 41.7 percent of orthognathic cases underwent adjunctive rhinoplasty. Of these, 82.4 percent were staged and 17.6 percent were simultaneous. The average time between staged procedures was 208 days. When simultaneous, 16.7 percent of the orthognathic procedures had significant maxillary movement (advancement >4 to 5 mm, impaction >2 mm, alar base excisions); in comparison, 92.9 percent of staged cases had significant maxillary movement (p < 0.0001). All patients had self-reported satisfaction with functional and aesthetic results during the follow-up period.

Conclusions:
Nasal and jaw deformities are intricately interlinked. In this series, the authors identified patterns requiring adjunctive rhinoplasty in the setting of orthognathic surgery. The authors present an algorithm to extensively treat the nasomaxillofacial relationship using orthognathic surgery alone, orthognathic surgery in concert with rhinoplasty, or orthognathic surgery followed by staged rhinoplasty.
Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency
Authors: Lyon Sarah M. , Mayampurath Anoop , Song Dongzhe , Ye Jixing , Januszyk Michael , Rogers M. Rose , Ralston Ashley , Frim David M. , He Tong-Chuan , Reid Russell R. 
Published: January 2018

Background:
The pathophysiology of nonsyndromic craniosynostosis remains poorly understood. The authors seek to understand the cause of this condition with a specific focus on how osteoclasts may contribute to craniosynostosis. Here, the authors characterize proteins differentially expressed in patent and fused cranial sutures by comparing their respective proteomes.

Methods:
Fused and patent suture samples were obtained from craniosynostotic patients undergoing surgery at a single academic medical center. Extracted protein from samples was interrogated using mass spectrometry. Differential protein expression was determined using maximum likelihood-based G-test with a q-value cutoffs of 0.5 after correction for multiple hypothesis testing. Immunolocalization of lead protein candidates was performed to validate proteomic findings. In addition, quantitative polymerase chain reaction analysis of corresponding gene expression of proteins of interest was performed.

Results:
Proteins differentially expressed in patent versus fused sutures included collagen 6A1 (Col6A1), fibromodulin, periostin, aggrecan, adipocyte enhancer-binding protein 1, and osteomodulin (OMD). Maximum likelihood-based G-test suggested that Col6A1, fibromodulin, and adipocyte enhancer-binding protein 1 are highly expressed in patent sutures compared with fused sutures, whereas OMD is up-regulated in fused sutures compared with patent sutures. These results were corroborated by immunohistochemistry. Quantitative polymerase chain reaction data point to an inverse relationship in proteins of interest to RNA transcript levels, in prematurely fused and patent sutures that potentially describes a feedback loop mechanism.

Conclusions:
Proteome analysis validated by immunohistochemistry may provide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required.