bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a Multidisciplinary Infection Prevention Initiative on Central Line and Urinary Catheter Utilization in a Long-term Acute Care Hospital
Authors: Chandramohan Suganya , Navalkele Bhagyashri , Mushtaq Ammara , Krishna Amar , Kacir John , Chopra Teena
Published: July 2018

Background

Prolonged central line (CL) and urinary catheter (UC) use can increase risk of central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI).

Methods

This interventional study conducted in a 76-bed long-term acute care hospital (LTACH) in Southeast Michigan was divided into 3 periods: pre-intervention (January 2015–June 2015), intervention (July–November 2015), and postintervention (December 2015–March 2017). During the intervention period, a multidisciplinary infection prevention team (MIPT) made weekly recommendations to remove unnecessary CL/UC or switch to alternate urinary/intravenous access. Device utilization ratios (DURs) and infection rates were compared between the study periods. Interrupted time series (ITS) and 0-inflated poisson (ZIP) regression were used to analyze DUR and CLABSI/CAUTI data, respectively.

Results

UC-DUR was 31% in the pre- and postintervention periods and 21% in the intervention period. CL-DUR decreased from 46% (pre-intervention) to 39% (intervention) to 37% (postintervention). The results of ITS analysis indicated nonsignificant decrease and increase in level/trend in DURs coinciding with our intervention. The CAUTI rate per catheter-days did not decrease during intervention (4.36) compared with pre- (2.49) and postintervention (1.93). The CLABSI rate per catheter-days decreased by 73% during intervention (0.39) compared with pre-intervention (1.45). Rates again quadrupled postintervention (1.58). ZIP analysis indicated a beneficial effect of intervention on infection rates without reaching statistical significance.

Conclusions

We demonstrated that a workable MIPT initiative focusing on removal of unnecessary CL and UC can be easily implemented in an LTACH requiring minimal time and resources. A rebound increase in UC-DURs to pre-intervention levels after intervention end indicates that continued vigilance is required to maintain performance.
Twenty-Year Secular Trends in Infective Endocarditis in a Teaching Hospital
Authors: Cuervo Guillermo , Rombauts Alexander , Caballero Queralt , Grau Immaculada , Pujol Miquel , Ardanuy Carmen , Berbel Dámaris , Gudiol Carlota , Sánchez-Salado Jose Carlos , Ruiz-Majoral Alejandro , Sbraga Fabrizio , Gracia-Sánchez Laura , Peña Carmen , Carratalà Jordi
Published: July 2018

Background

The purpose of this study was to analyze the secular trends of infective endocarditis in a teaching hospital between January 1996 and December 2015.

Methods

We report on a single-center retrospective study of patients with left-side valve infective endocarditis. We performed an analysis of secular trends in the main epidemiological and etiological aspects, as well as clinical outcomes, in 5 successive 4-year periods (P1 to P5).

Results

In total, 595 episodes of infective endocarditis were included, of which 76% were community-acquired and 31.3% involved prosthetic valves. Among the cases, 70% occurred in men, and the mean age (SD) was 64.1 (14.3) years. A significant increase in older patients (age ≥70 years) between P1 (15.332%) and P5 (51.9%; P < .001) was observed. The rate of infective endocarditis on biological prostheses also increased in the prosthetic group, accounting for 30% in P1 and 67.3% in P5 (P < .001). By contrast, there were significant decreases in vascular and immunological phenomena over the study period, with decreases in the presence of moderate to severe valvular insufficiency (75.9% in P1 to 52.6% in P5; P < .001) and valvular surgery (43% in P1 vs 29.6% in P5; P = .006). Finally, overall mortality was 23.9%, and although it was highest in P1, it subsequently remained stable through P2 to P5 (38% in P1 to 20% in P5; P = .004).

Conclusions

There has been a significant increase in infective endocarditis in older patients. The decrease in moderate to severe valve regurgitation at diagnosis could explain the stable mortality despite the increase in the mean age of patients over time.
The Shadows of Sunlight: Why Disclosure Should Not Be a Priority in Addressing Conflicts of Interest
Authors: Goldberg Daniel S
Published: July 2018

This article argues that positioning disclosure as a primary remedy in addressing the ethical problems posed by conflicts of interest (‘COIs’) in medicine and health is an error. Instead, bioethical resources should be devoted to the problems associated with sequestration, defined as the elimination of relationships between commercial industries and health professionals in all cases where it is remotely feasible. The argument begins by arguing that adopting Andrew Stark’s conceptual framework for COIs leads to advantages in understanding COIs and in ordering priorities for intervention. The article then draws on prior work establishing that COIs are, under ordinary epidemiologic standards, properly regarded as population health hazards. This justifies attention to possible remedies, of which disclosure generates by far the most analysis. Such primacy is unwarranted given the extensive evidence suggesting that disclosure as a remedy for COIs is at best ineffective. ‘At best’ is justified because the evidence also shows that disclosure may have a perverse effect, intensifying biased behaviors. Expending significant attention on an ineffective or even deleterious intervention is unjustified and also crowds out devotion of resources to the real problems that attend sequestration. Therefore, disclosure ought to be regarded as a lower priority among possible COI interventions.
Growth-inhibiting Fungicides Affect Detection of Phytophthora ramorum from Infected Foliage and Roots
Authors: Shishkoff Nina
Published: July 2018

Growth-inhibiting fungicides are used routinely to control common and regulated Oomycete pathogens. This study investigated whether such fungicides could affect detection of Phytophthora ramorum from plant tissue, both foliage and roots. Whole plants of Rhododendron × ‘Cunningham's White’ were inoculated with P. ramorum and treated 3 days later with fosetyl-Al, mefenoxam, or propamocarb. The foliage was sampled over time to see if fungicides prevented successful culturing of the pathogen from infected leaf tissue or interfered with detection using real-time PCR or ELISA. Mefenoxam significantly reduced the ability to culture the pathogen from leaves for the first 6 weeks while recovery from leaves treated with other fungicides did not differ from water-treated controls; detection using PCR or ELISA was not affected by fungicide application. The roots of Viburnum cuttings were inoculated with P. ramorum and then treated 4 days later with fosetyl-Al, mefenoxam, or propamocarb. The amount of inoculum in flow through water samples taken weekly for 5 weeks was quantified and percent root colonization determined at the end of the experiment. Propamocarb had no effect on inoculum production or root infection, while viable inoculum production was significantly decreased in fosetyl-Al- or mefenoxam-treated plants over 5 weeks, and root colonization was significantly decreased.

Accepted for publication 23 January 2014. Published 18 March 2014.
Getting a Notch closer to renal dysfunction: activated Notch suppresses expression of the adaptor protein Disabled‐2 in tubular epithelial cells
Authors: Schütte-Nütgen Katharina , Edeling Maria , Mendl Gudrun , Krahn Michael P. , Edemir Bayram , Weide Thomas , Kremerskothen Joachim , Michgehl Ulf , Pavenstädt Hermann
Published: July 2018

Reactivation of Notch signaling in kidneys of animal models and patients with chronic kidney disease (CKD) has been shown to contribute to epithelial injury and fibrosis development. Here, we investigated the mechanisms of Notch‐induced injury in renal epithelial cells. We performed genome‐wide transcriptome analysis to identify Notch target genes using an in vitro system of cultured tubular epithelial cells expressing the intracellular domain of Notch1. One of the top downregulated genes was Disabled‐2 (Dabi). With the use of Drosophila nephrocytes as a model system, we found that Dab (the Drosophila homolog of Dab2) knockdown resulted in a significant filtration defect, indicating that loss of Dab2 plays a functional role in kidney disease development. We showed that Dab2 expression in cultured tubular epithelial cells is involved in endocytic regulation and that it also protects cells from TGF‐β‐induced epithelial‐to‐mesenchymal transition. In vivo correlation studies indicated its additional role in renal ischemia‐induced injury. Together, these data suggest that Dab2 plays a versatile role in the kidney and may impact on acute and CKDs.—Schütte‐Nütgen, K., Edeling, M., Mendl, G., Krahn, M. P., Edemir, B., Weide, T., Kremerskothen, J., Michgehl, U., Pavenstädt, H., Getting a Notch closer to renal dysfunction: activated Notch suppresses expression of the adaptor protein Disabled‐2 in tubular epithelial cells. FASEB J. 33, 821–832 (2019). www.fasebj.org
Transient p53 inhibition sensitizes aged white adipose tissue for beige adipocyte recruitment by blocking mitophagy
Authors: Fu Wenyan , Liu Yang , Sun Christina , Yin Hang
Published: July 2018

Aging of white adipose tissue (WAT) is associated with reduced insulin sensitivity, which contributes to whole‐body glucose intolerance. WAT aging in mice impairs cold‐induced beige adipocyte recruitment (beiging), which has been attributed to the senescence of adipose progenitor cells. Tumor suppressor p53 has also been implicated in WAT aging. However, whether p53‐related cellular aging in mature white adipocytes is causative of age‐impaired WAT beiging remains unknown. It is also unclear whether transient p53 inhibition can rescue WAT beiging. Herein, we report that p53 increased in adipose tissues of 28‐wk‐old (aged) mice with impaired beiging capability. Cold exposure decreased p53 in beiging WAT of young mice but not in aged mice. In aged mice, inducible p53 ablation in differentiated adipocytes restored cold‐induced WAT beiging and augmented whole‐body energy expenditure and insulin sensitivity. Transient pharmacological inhibition of p53 led to the same beneficial effects. Mechanistically, cold exposure repressed autophagy in beiging WAT of young mice yet increased autophagy in aged WAT. p53‐ablation reduced microtubule‐associated protein light chain 3‐mediated mitochondria clearance (mitophagy) and hence facilitated the increase of mitochondria during beiging. These findings suggest that p53‐induced mitophagy in aged white adipocytes impedes WAT beiging and may be therapeutically targeted to improve insulin sensitivity in aged WAT.—Fu, W., Liu, Y., Sun, C., Yin, H. Transient p53 inhibition sensitizes aged white adipose tissue for beige adipocyte recruitment by blocking mitophagy. FASEB J. 33, 844–856 (2019). www.fasebj.org
Smartphone imaging for the ophthalmic examination in primary care
Authors: Bifolck Eric , Fink Andrew , Pedersen Daniel , Gregory Tanya
Published: July 2018

Direct ophthalmoscopy is an integral part of the physical examination and is the most widely used technique to assess the fundus, especially in primary care. The gold standard slit-lamp technique is used in specialty clinics and in some EDs. Most medical professionals own smartphones, and a smartphone ophthalmoscope could bring the quality of a slit-lamp examination into primary care. Imaging techniques with smartphones are easy to learn and use, providing a significant step toward reversing the lack of confidence that students and clinicians have in traditional methods. Current evidence supports the potential of smartphone imaging to replace direct ophthalmoscopy in primary care settings.
Health Care Policy Update: New Medicaid Work Requirements, Preexisting Conditions at Risk, the Drug Cost Crisis
Authors: Molyneux Jacob
Published: July 2018

High-stakes debates about access and affordability as midterm elections approach.
Nursing Practice and Particulate Matter Exposure
Authors: Castner Jessica , Polivka Barbara J.
Published: July 2018

Environmental factors underlie more than one-fifth of deaths and disability worldwide. Globally, both indoor and outdoor particulate matter pollution are leading risk factors for reduced quality of life and death. Nurses are in a key position to assess particulate matter exposure and to intervene, providing population, community, family, and individual risk reduction and care. This article presents a case study describing one patient's experiences with asthma and multiple comorbidities, an overview of particulate matter exposure and health, and management strategies for practice.
Youth Hospitalizations for Suicidal Ideation and Attempts Have Steadily Increased
Authors: Rosenberg Karen , Mechatie Elizabeth
Published: July 2018

According to this study:

ED presentation, observation stays, and hospitalizations for suicidal ideation and attempts among children and adolescents more than doubled over a seven-year study period.

More than half of these encounters led to hospitalization.
Multidrug-Resistant Organisms and Contact Precautions
Authors: Todd Betsy
Published: July 2018

Most nurses know when to start precautions, but for how long should they continue?
The Crazy Aunt or the Nurse
Authors: Padgett Tonja
Published: July 2018

After a nephew's overdose, the author finds little refuge in her professional identity.
Progress and Control of Myopia by Light Environments
Authors: Jiang Xiaoyan , Kurihara Toshihide , Torii Hidemasa , Tsubota Kazuo
Published: July 2018

During the past 30 years, the prevalence rate of myopia has been increased dramatically. Myopia has become one of the leading causes of vision loss in some countries, whereas the mechanism of the main pathological change in myopia is still largely unknown. Although several studies showed genetic background influences the phenotype of myopia to some extent, the sudden increase of morbidity cannot be explained by genetics only. The change in lifestyle results in tremendous change in the light environment, which can be considered to play an important role in the onset and progression of myopia. The difference between indoor and outdoor light environments such as intensity and wavelength of modern electronic lighting equipment may be a cue for myopia control as environmental factors. In this review, we discuss the relationship between myopia and light environment focusing on the basic and clinical studies.
Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in Postpenetrating Keratoplasty Steroid-induced Glaucoma: A Case Report
Authors: Nazarali Samir , Cote Stephanie L. , Gooi Patrick
Published: July 2018

Glaucoma following penetrating keratoplasty (PKP) remains the leading cause of blindness following PKP. Patients with post-PKP glaucoma can be managed medically and surgically. Evidence studying glaucoma surgical techniques following PKP is limited, but suggests the possibility for high-risk complications, including graft failure. Minimally invasive glaucoma surgeries offer an alternative. We report the first case of post-PKP glaucoma managed with gonioscopy-assisted transluminal trabeculotomy (GATT). The patient was a 33-year-old man with a history of keratoconus who underwent PKP in his right eye. On presentation, his visual acuity was 20/60 and intraocular pressure was 48 mm Hg OD. He underwent GATT and cataract phacoemulsification. Following 22 months of follow-up, the patient’s visual acuity was 20/30 and intraocular pressure 13 mm Hg, off all glaucoma medications. This case demonstrates GATT may be a good surgical option for post-PKP glaucoma, given the ability to perform future incisional surgery and avoidance of high-risk complications associated with traditional glaucoma surgeries.
The impact of age on thyroid cancer staging
Authors: Kazaure Hadiza S. , Roman Sanziana A. , Sosa Julie A.
Published: July 2018

Purpose of review

Patient age at diagnosis is a well established prognostic factor for thyroid cancer survival; it is included in the American Joint Committee on Cancer (AJCC) thyroid cancer-staging system. This review provides an update on the epidemiology, risk stratification, and staging of differentiated thyroid cancer (DTC), in the context of patient age.

Recent findings

In the eighth edition AJCC staging system for DTC, the age cut-point was increased from 45 to 55 years. The appropriate age-cut point remains a subject of debate, as some studies have found a linear association of age and survival, and therefore, questioned the use of an age cut-point in the DTC staging system altogether. Emerging data on the additive role of molecular markers in the compromised survival of older patients with DTC raise the prospect of eventual inclusion of genetic markers in the management of patients and risk-stratification systems.

DTC staging is evolving. The pathogenesis of the compromised survival of older patients with DTC is complex, multifactorial, and not well understood. Recent advances in molecular testing are promising. More studies are needed prior to the formal inclusion of molecular markers in the staging system of DTC.
Quality of Life in Patients With Progressive Familial Intrahepatic Cholestasis
Authors: Wassman Sonja , Pfister Eva‐Doreen , Kuebler Joachim F. , Ure Benno M. , Goldschmidt Imeke , Dingemann Jens , Baumann Ulrich , Schukfeh Nagoud
Published: July 2018

Objectives:

In patients with progressive familial intrahepatic cholestasis (PFIC), partial external biliary diversion (PEBD), which is associated with a permanent stoma, is recommended as first‐line therapy, whereas primary liver transplantation (LTx) is restricted to those with cirrhosis. Our aim was to quantify the health‐related quality of life (HRQOL) in patients with PFIC and to evaluate whether there is a difference in their HRQOL depending on the surgical approach.

Methods:

A prospective HRQOL study on a consecutive series of PFIC was conducted using Pediatric Quality of Life Inventory 4.0 child‐self and parent‐proxy reports. Patients with PFIC after PEBD who still lived with their native livers were compared to those after LTx. Both groups were compared to healthy children.

Results:

A total of 32 patients (53% girls) patients with a mean age of 17.7 ± 7.3 years were studied. Twenty‐two had undergone LTx at a mean age of 7.8 ± 3.8 years and 10 had undergone PEBD at a mean age of 4.1 ± 3.9 years. At the time of HRQOL assessment, the mean age was 18.9 ± 7.5 years in the LTx group and 15.3 ± 6.5 years in the PEBD group. Child‐self and parent‐proxy reports showed no significant difference in HRQOL between patients with PFIC after LTx and those after PEBD except for marginal difference in physical functioning/health (P = 0.07). Except for a lower score in patient school functioning of patients after LTx (P = 0.01), HRQOL‐results showed no difference from healthy children in any group.

Conclusions:

The HRQOL of patients with PFIC after PEBD was similar to those after LTx. The HRQOL in both groups was also similar to that of healthy children. Thus, our data support the current policy of PEBD as primary surgical treatment for patients with PFIC without cirrhosis.
Carbapenem and colistin resistance in Enterobacteriaceae: worldwide spread and future perspectives
Authors: Ghasemian Abdolmajid , Shafiei Morvarid , Hasanvand Fatemeh , Shokouhi Mostafavi Seyyed K.
Published: July 2018

Carbapenems and colistin antibiotics are the major weapons against multidrug-resistant (MDR) and extensively drug-resistant Gram-negative bacteria. Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacea, Klebsiella oxytoca, Proteus mirabilis, Citrobacter freundii, Citrobacter koseri, Serratia spp., Morganella morganii and Salmonella spp. have been reported as carbapenemase-producing Enterobacteriaceae members. Carbapenem resistance mostly occurs by means of some enzymes such as classes A, B and D carbapenemases. New Delhi metallo-β-lactamases, K. pneumoniae carbapenemase, imipenemase metallo-β-lactamase, Verona integron-encoded metallo-β-lactamase and OXA-48-like subtypes have been reported worldwide with some epidemiological differences. Plasmid-mediated transmission has facilitated their spread. In addition, colistin resistance by means of either chromosomal mutation in one of the three genes involved in the biosynthesis of LipA, LpxA, LpxC and LpxD cell wall components or via extrachromosomal elements (plasmid-mediated mcr genes) has recently reported in some species worldwide. MDR and extensively drug-resistant strains have become nonsusceptible to last-line antibiotics, thus consideration of effective ways such as the implementation of appropriate infection control strategies, separation of patients infected with MDR strains from others, public education, containment of antibiotic consumption in livestock industry, accurate antibiotic susceptibility testing and prescription and the proper implementation of antibiotic surveillance in hospitals are necessary. In addition, the use of last-line antibiotics in livestock and food animals must be restricted or banned.
Psychological Safety in Nursing Simulation
Authors: Kang Sook Jung , Min Hae Young
Published: July 2018

Background

Although nursing students enjoy and learn from simulation practice, some experience negative feelings that may hamper their learning outcomes.

Purpose

The purpose of this study was to understand nursing students' perceptions of psychological safety in simulation practice to provide a foundation for a safe and effective simulation learning environment.

Methods

A convenient sample of 15 undergraduate nursing students was included in this study. Focus group interviews and inductive content analysis were used for this study.

Results

Four themes extracted from the study included feeling unready, anxious about having students' mistakes exposed, worry about damaging teamwork, and fear of evaluation.

Conclusions

Findings indicated that providing prebriefing and considering students' level of simulation experience in sharing their recorded video may help ensure a psychologically safe environment. An instrument measuring psychological safety and evidence-based guidelines to ensure a safe learning environment needs to be developed.
Successful Modeling of Factors Related to Recruitment and Retention of Prenursing Students
Authors: Stankus Jo-Ann , Hamner Mark , Stankey Michael , Mancuso Peggy
Published: July 2018

Background

The traditional admission methodology used by many schools of nursing is the second-tier admission based on specified criteria. This method has been associated with a student body that is predominately female, white, and English speaking.

Problem

Rational judgment modeling (points assigned to criteria) used to evaluate applicants for admission into prenursing programs potentially overlooks students who do not fit into the traditional model.

Approach

This study compared predictive logistic regression with traditional rational judgment models to classify potential nursing school applicants.

Outcomes

A higher number of Hispanic and black prenursing students were identified for potential upper-level nursing program admission.

Conclusions

The use of logistic regression modeling can identify a more diverse student population. Advisors at both high school and university/college levels can use results of this model to help students determine their progress, identify academic weaknesses, and develop individual plans of action to help students successfully complete the prenursing curriculum requirements.
Endometriosis-associated Ovarian Cancer is a Subset With a More Favorable Outcome and Distinct Clinical-pathologic Characteristics
Authors: Bassiouny Dina , El-Baz Mahmoud A. , Gamil Tawakol M. , Shams Nazem , Ismiil Nadia , Dubé Valerie , Han Guangming , Cesari Matthew , Lu Fang-I , Slodkowska Elzbieta , Chiu Hak Fai , Naeim Magda , Li Nim , Nofech-Mozes Sharon , Khalifa Mahmoud A.
Published: July 2018

There is a controversy about whether endometriosis-associated ovarian cancer (EAOC) might represent a different entity from the corresponding ovarian cancer occurring de novo, in the absence of endometriosis. This study investigated the clinical-pathologic characteristics and outcome of EAOC compared with other ovarian carcinomas that are not associated with endometriosis (non-EAOC) in a large cohort. Seven hundred two patients meeting the inclusion criteria were further subclassified as group I when patients had ovarian carcinoma associated with or arising within endometriosis (EAOC) and group II when patients had non-EAOC. Age, gross features, histologic type, International Federation of Gynecology and Obstetrics stage, and disease-free survival (DFS) were compared between the groups. One hundred sixty-eight (23.9%) patients had EAOC, whereas 534 (76.1%) patients had non-EAOC. EAOCs were mostly endometrioid and clear cell type. Patients with EAOC were younger, present early, and had a lower rate of recurrence when compared with patients with non-EAOC, P<0.001. Patients with EAOC had longer DFS time, 51.9 mo (95% confidence interval, 44.9–58.8) versus 30.5 mo (95% confidence interval, 27.7–33.3) in non-EAOC patients. The 5 yr Kaplan-Meier estimate of DFS rate was 70% in 166 patients of group I and was 39.3% in 532 patients of group II, P<0.001. On multivariate analysis, International Federation of Gynecology and Obstetrics staging, histologic type, and treatment were the only significant factors affecting the hazards of recurrence. Patients with tumors associated with endometriosis are usually, younger, present early, have lower rate of recurrence, longer DFS, and their tumors are of lower grade and are more likely endometrioid or clear cell carcinoma.
Microscopic and Macroscopic Fat Embolism: Solving the Puzzle with Case Reports
Authors: Durán Héctor , Cárdenas-Camarena Lázaro , Bayter-Marin Jorge Enrique , Ramos-Gallardo Guillermo , Robles-Cervantes José Antonio
Published: July 2018

Background:

The frequency of fat embolism mortality after liposuction has increased. As the only dependable evidence for this problem is that available in the medical literature, a study of clinical case reports is warranted.

Methods:

The authors reviewed the medical literature by searching for case reports of fat embolism after liposuction in humans who manifested either of the variants of the condition: microscopic fat embolism or macroscopic fat embolism. The authors performed a literature search of the PubMed and PubMed Central databases from the first case of fat embolism syndrome associated with liposuction reported until March of 2017; keywords Fat Embolism (Fat Embolism Syndrome), Liposuction, and Case (((fat embolism) AND liposuction) AND case) were used. A detailed analysis of the data contained in the clinical case reports was conducted.

Results:

In total, 39 and 98 articles were found in PubMed and PubMed Central, respectively, using the keywords (((Fat + Embolism) + AND + Liposuction) + AND + Case). After analysis, only 15 reports corresponded to cases of macroscopic or microscopic fat embolism after liposuction, and the basic statistics of the two proposed variants were examined.

Conclusions:

This work provides relevant information regarding very important characteristics of microscopic and macroscopic fat embolism. Despite the diagnostic difficulty, clinical diagnosis remains the gold standard for identifying microscopic and macroscopic fat embolism. The establishment of a rapid and timely diagnosis is of great help for appropriate treatment.
Assessment of Quantitative Magnetic Resonance Imaging Background Parenchymal Enhancement Parameters to Improve Determination of Individual Breast Cancer Risk
Authors: Lam Diana L. , Hippe Daniel S. , Kitsch Averi E. , Partridge Savannah C. , Rahbar Habib
Published: July 2018

Objectives

The aims of this study were to identify optimal quantitative breast magnetic resonance imaging background parenchymal enhancement (BPE) parameters associated with breast cancer risk and compare performance to qualitative assessments.

Methods

Using a matched case-control cohort of 46 high-risk women who underwent screening magnetic resonance imaging (23 who developed breast cancer matched to 23 who did not), fibroglandular tissue area, BPE area, and intensity metrics (mean, SD, quartiles, skewness, and kurtosis) were quantitatively measured at varying enhancement thresholds. Optimal thresholds for discriminating between cancer and control cohorts were identified for each metric and performance summarized using area under the receiver operating characteristic curve.

Results

Women who developed breast cancer exhibited greater BPE area (adjusted P = 0.004) and higher intensity statistics (adjusted P < 0.004, except skewness and kurtosis with P > 0.99) than did control subjects, with areas under the receiver operating characteristic curve ranging from 0.75 to 0.78 at optimized thresholds.

Conclusions

Elevated quantitative BPE parameters, related to both area and intensity of enhancement, are associated with breast cancer development.
Newly Categorized Seromucinous Tumor of the Ovary: Magnetic Resonance Imaging Findings
Authors: Han Jin Woo , Kim Kyeong Ah , Chang Hye Yoon , Kim Jeong Woo , Park Yang Shin , Lee Jongmee , Choi Jae Woong , Lee Chang Hee , Park Cheol Min
Published: July 2018

Objective

The aim of this study was to describe magnetic resonance imaging findings of newly categorized ovarian seromucinous tumors.

Methods

We retrospectively reviewed the images of 29 patients with seromucinous tumor for the following factors: size, configuration, signal intensity (SI), and accompanying ovarian endometriosis.

Results

Thirty-two tumors (17 benign, 7 borderline, 8 carcinoma) were found on computed tomography or magnetic resonance imaging. Their mean size was 11.4 cm. Benign tumors appeared as unilocular or multilocular cystic masses. Borderline tumors and carcinomas appeared as complex cystic-solid masses. T2-weighted SI of the solid portion was hyperintense in borderline tumors and intermediate in carcinomas. Endometriosis was present in 18 tumors, and hemorrhage (on images) in 20.

Conclusions

The imaging features of seromucinous tumors varied by tumor type. More than half of tumors were accompanied by endometriosis. High T2-weighted SI of the solid portion could be a specific feature of borderline tumors. It is hard to differentiate seromucinous carcinomas from other endometriosis-related carcinomas.
Role of immunotherapy in kidney cancer
Authors: Nazzani Sebastiano , Bazinet Amélie , Karakiewicz Pierre I.
Published: July 2018

Purpose of review

To summarize current knowledge on promising immunotherapeutic agents and to provide a brief outline of current use of immunotherapeutic agents in patients with locally advanced or metastatic renal cell carcinoma (RCC).

Recent findings

Immunotherapy with mAbs directed against programed death cell protein 1, programed death-ligand 1 (PD-L1) and cytotoxic T-Lymphocyte Antigen 4 has become new first-line standard of care for moderate and poor-risk metastatic RCC patients. Similarly, the combination immune-oncology treatment and vascular endothelial growth factor (VEGF) mAbs also showed promising results in first-line therapy despite relative data immaturity. Finally, immune-oncology monotherapy (nivolumab) already represents second or third-line standard of care after tyrosine kinase inhibitor failure.

Combination immune-oncology therapy represents the standard of care for management of intermediate-to-poor risk clear cell metastatic RCC. In addition, combination of immune-oncology and anti-VEGF antibody represents a treatment option across all risk levels in patient with elevated PD-L1 expression. Finally, nivolumab is one of two ideal treatment options in second-line clear cell metastatic RCC patients.
A 20-Year-Old-Trauma Patient With Suspected Malignant Hyperthermia Following Induction With Succinylcholine
Authors: Luckey-Smith Kaitlyn , High Kevin
Published: July 2018

Malignant hyperthermia (MH) is a life-threatening hypermetabolic state that can occur following induction with depolarizing neuromuscular blockade and volatile anesthesia gases. Because succinylcholine is a common choice for prehospital and emergency department inductions, it is important for staff to be able to recognize and effectively treat an MH crisis. This case study highlights a 20-year-old male trauma patient who presented to a Level I trauma center and was intubated for declining mental status. He developed suspected MH following his anesthetic induction with succinylcholine. The following outlines the case, clinical identification of MH, and treatment.
Comparative genomics of Salmonella enterica serovar Montevideo reveals lineage-specific gene differences that may influence ecological niche association
Authors: Nguyen Scott V. , Harhay Dayna M. , Bono James L. , Smith Timothy P. L. , Fields Patricia I. , Dinsmore Blake A. , Santovenia Monica , Wang Rong , Bosilevac Joseph M. , Harhay Gregory P.
Published: July 2018

Salmonella enterica serovar Montevideo has been linked to recent foodborne illness outbreaks resulting from contamination of products such as fruits, vegetables, seeds and spices. Studies have shown that Montevideo also is frequently associated with healthy cattle and can be isolated from ground beef, yet human salmonellosis outbreaks of Montevideo associated with ground beef contamination are rare. This disparity fuelled our interest in characterizing the genomic differences between Montevideo strains isolated from healthy cattle and beef products, and those isolated from human patients and outbreak sources. To that end, we sequenced 13 Montevideo strains to completion, producing high-quality genome assemblies of isolates from human patients (n=8) or from healthy cattle at slaughter (n=5). Comparative analysis of sequence data from this study and publicly available sequences (n=72) shows that Montevideo falls into four previously established clades, differentially occupied by cattle and human strains. The results of these analyses reveal differences in metabolic islands, environmental adhesion determinants and virulence factors within each clade, and suggest explanations for the infrequent association between bovine isolates and human illnesses.
Changing the paradigm for hospital outbreak detection by leading with genomic surveillance of nosocomial pathogens
Authors: Peacock Sharon J. , Parkhill Julian , Brown Nicholas M.
Published: July 2018

The current paradigm for hospital outbreak detection and investigation is based on methodology first developed over 150 years ago. Daily surveillance to detect patients positive for pathogens of particular importance for nosocomial infection is supported by epidemiological investigation to determine their relationship in time and place, and to identify any other factor that could link them. The antibiotic resistance pattern is commonly used as a surrogate for bacterial relatedness, although this lacks sensitivity and specificity. Typing may be used to define bacterial relatedness, although routine methods lack sufficient discriminatory power to distinguish relatedness beyond the level of bacterial clones. Ultimately, the identification of an outbreak remains a predominately subjective process reliant on the intuition of experienced infection control professionals. Here, we propose a redesign of hospital outbreak detection and investigation in which bacterial species associated with nosocomial transmission and infection undergo routine prospective whole-genome sequencing. Further investigation is based on the probability that isolates are associated with an outbreak, which is based on the degree of genetic relatedness between isolates. Evidence is provided that supports this model based on studies of MRSA (methicillin-resistant Staphylococcus aureus), together with the benefits of a ‘Sequence First’ approach. The feasibility of implementation is discussed, together with residual barriers that need to be overcome prior to implementation.
Structural basis of altered potency and efficacy displayed by a major in vivo metabolite of the anti-diabetic PPARγ drug pioglitazone
Authors: Mosure Sarah A. , Shang Jinsai , Brust Richard , Zheng Jie , Griffin Patrick R. , Kojetin Douglas J.
Published: July 2018

The thiazolidinedione (TZD) pioglitazone (Pio) is an FDA-approved drug for type 2 diabetes mellitus that binds and activates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ). Although TZDs have potent antidiabetic effects, they also display harmful side effects that have necessitated a better understanding of their mechanisms of action. In particular, little is known about the effect of in vivo TZD metabolites on the structure and function of PPARγ. Here, we present a structure-function comparison of Pio and a major in vivo metabolite, 1-hydroxypioglitazone (PioOH). PioOH displayed a lower binding affinity and reduced potency in coregulator recruitment assays compared to Pio. To determine the structural basis of these findings, we solved an X-ray crystal structure of PioOH bound to PPARγ ligand-binding domain (LBD) and compared it to a published Pio-bound crystal structure. PioOH exhibited an altered hydrogen bonding network that could underlie its reduced affinity and potency compared to Pio. Solution-state structural analysis using NMR spectroscopy and hydrogen/deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PioOH stabilizes the PPARγ activation function-2 (AF-2) coactivator binding surface better than Pio. In support of AF-2 stabilization, PioOH displayed stabilized coactivator binding in biochemical assays and better transcriptional efficacy (maximal transactivation response) in a cell-based assay that reports on the activity of the PPARγ LBD. These results, which indicate that Pio hydroxylation affects both its potency and efficacy as a PPARγ agonist, contribute to our understanding of PPARγ-binding drug metabolite interactions and may assist in future PPARγ drug design efforts.
Direct purification of CRISPR/Cas ribonucleoprotein from E. coli in a single step
Authors: Lin Siyu , Qiao Jie , Ma Lixin , Liu Yi
Published: July 2018

CRISPR/Cas ribonucleoprotein (RNP) complexes have been recently used as promising biological tools with plenty of applications, however, there are by far no efficient methods to prepare them at large scale and low cost. Here, we present a simple method to directly produce and purify Cas RNP, including the widely used Cas9 and Cas12a nuclease, from E.coli in a single step using an ultra-high-affinity CL7/Im7 purification system. The prepared Cas RNP shows high stability, solid nuclease activity in vitro, and profound genome editing efficiency in vivo. Our method is convenient, cost-effective, and applicable to prepare other CRISPR associated nucleases.
A novel maize gene,glossy6involved in epicuticular wax deposition and drought tolerance
Authors: Li LI , Du Yicong , He Cheng , Dietrich Charles R. , Li Jiankun , Ma Xiaoli , Wang Rui , Liu Qiang , Liu Sanzhen , Wang Guoying , Schnable Patrick S , Zheng Jun
Published: July 2018

Epicuticular waxes, long-chain hydrocarbon compounds, form the outermost layer of plant surfaces in most terrestrial plants. The presence of epicuticular waxes protects plants from water loss and other environmental stresses. Cloning and characterization of genes involved in the regulation, biosynthesis, and extracellular transport of epicuticular waxes on to the surface of epidermal cells have revealed the molecular basis of epicuticular wax accumulation. However, intracellular trafficking of synthesized waxes to the plasma membrane for cellular secretion is poorly understood. Here, we characterized a maize glossy (gl6) mutant that exhibited decreased epicuticular wax load, increased cuticle permeability, and reduced seedling drought tolerance relative to wild type. We combined an RNA-sequencing based mapping approach (BSR-Seq) and chromosome walking to identify thegl6candidate gene, which was confirmed via the analysis of multiple independent mutant alleles. Thegl6gene represents a novel maize glossy gene containing a conserved, but uncharacterized domain. Functional characterization suggests that the GL6 protein may be involved in the intracellular trafficking of epicuticular waxes, opening a door to elucidating the poorly understood process by which epicuticular wax is transported from its site of biosynthesis to the plasma membrane.

SIGNIFICANCE STATEMENT

Plant surface waxes provide an essential protective barrier for terrestrial plants. Understanding the composition and physiological functions of surface waxes, as well as the molecular basis underlying wax accumulation on plant surfaces provides opportunities for the genetic optimization of this protective layer. Genetic studies have identified genes involved in wax biosynthesis, extracellular transport, as well as spatial and temporal regulation of wax accumulation. In this study, a maize mutant,gl6was characterized that exhibited reduced wax load on plant surfaces, increased water losses, and reduced seedling drought tolerance compared to wild type controls. Thegl6gene is a novel gene harboring a conserved domain with an unknown function. Quantification and microscopic observation of wax accumulation as well as subcellular localization of the GL6 protein provided evidence thatgl6may be involved in the intracellular trafficking of waxes, opening a door for studying this necessary yet poorly understood process for wax loading on plant surfaces.
Stabilizing Obligatory Non-native Intermediates Along Co-transcriptional Folding Trajectories of SRP RNA Affects Cell Viability
Authors: Fukuda Shingo , Yan Shannon , Komi Yusuke , Sun Mingxuan , Gabizon Ronen , Bustamante Carlos
Published: July 2018

Signal recognition particle (SRP) inEscherichia colicomprises protein Ffh and SRP RNA. Its essential functionality—co-translational protein-targeting/delivery to cellular membranes— hinges on the RNA attaining a native long-hairpin fold that facilitates protein conformational rearrangements within the SRP complex. Since RNA folds co-transcriptionally on RNA polymerase, we use high-resolution optical tweezers to first characterize the mechanical unfolding/refolding of incrementally lengthened RNAs from stalled transcription complexes until reaching the full-length transcript. This analysis allows identification of folding intermediates adopted during the real-time co-transcriptional folding of SRP RNA. The co-transcriptional folding trajectories are surprisingly invariant to transcription rates, and involve formation of an obligatory non-native hairpin intermediate that eventually resolves into the native fold. SRP RNA variants designed to stabilize this non-native intermediate—likely sequestering the SRP ribonucleoprotein complex in an inactive form—greatly reduce cell viability, indicating that the same co-transcriptional folding mechanism operatesin vivoand possible alternative antibiotic strategies.

Highlights

Folding pathway of an essential functional RNA has been resolved co-transcriptionally.

The co-transcriptional folding pathway of SRP RNA is invariant to transcription rates.

Nascent SRP RNA obligatorily forms a non-native intermediate before adopting the native fold.

Modulating transitions from the non-native to native SRP RNA hairpin fold alters cell viability.
Controlled usage of H/D exchange to circumvent concomitant polymorphs of ROY
Authors: Falk Jacqueline , Hofmann Detlef , Merz Klaus
Published: July 2018

The hypothesis that H/D exchange affects the structural formation of organic compounds in the solid state is supported by a deeper understanding of the altering polymorphism of ROY (a substance striking for its high number of polymorphic forms) through deuteration. Therefore, ROY was deuterated at its amine function, which leads to a seemingly small yet effective modification of the hydrogen-bond strength. In contrast to the crystallization of the non-deuterated ROY in methanol or ethanol, which leads to the simultaneous formation of two forms (OP and Y polymorphs), so-called concomitant polymorphs, the crystallization of d
1-ROY leads to the selective formation of the Y polymorph exclusively. The preferred aggregation behavior of the Y form of d
1-ROY is assigned to the weakening of an intramolecular hydrogen bond and a consequently strengthened intermolecular hydrogen bond after deuteration.
The export competitiveness of Italian coffee roasting industry
Authors: Pascucci Federica
Published: July 2018

Purpose

The purpose of this paper is to analyze the competitive position of Italian roasting firms in the international market, thus developing a multidimensional framework for measuring industry export competitiveness.

Design/methodology/approach

Considering that the objective is to evaluate the export competitiveness of Italian roasting firms, the author chooses “positive” and “ex-post” indicators, combined in a multidimensional and a multivariable framework. The two dimensions of competitiveness implemented are competitive performance and competitive potential; the author used four indices to evaluate the first dimension (export market share, net export share, net export index, revealed comparative advantage) and three indices for the second dimension (unit export price, relative quality index, relative export growth).

Findings

The evolution of the international context, with the emergence of new competitors and the spread of coffee consumption worldwide, creates new opportunities but also new challenges for Italian companies. In fact, both competitive performance and competitive potential have been worsening since the second half of the early twenty-first century because of the lack of innovation. A mix of external and internal factors explain this lack.

Practical implications

In order to recover their international competitiveness, firms should leverage on the combination of “traditional elements”–such as Made in Italy effect and the rich technical know-how, depending on their long tradition in the espresso coffee market niche–with “innovative elements,” depending on new marketing skills and competences; these new elements could be developed internally or, most fruitfully, acquired externally, through collaboration with other firms. In this way, Italian businesses could improve the relative quality perceptions of their offering.

Social implications

Coffee roasting industry in Italy is a significant component of the Italian economic system and it contributes to the development of the Made in Italy abroad. Therefore, an improvement of its export competitiveness could be beneficial to the whole domestic market.

Originality/value

This paper constitutes the first attempt to study the evolution of the coffee industry in regards to the international competitive landscape. This is quite surprising, considering that coffee is one of the main segments of the food and beverage industry; it is the second most important commodity exchanged worldwide after oil and the third most popular beverage after water, tea and carbonated beverages. Then, the analysis of export competitiveness is developed combing two main research streams: the industrial organization literature and the strategic management literature. Moreover, this paper offers a methodological framework useful to measure export competitiveness also in other industries and countries.