bluuebunny/crossref_metadata_2025 huggingface dataset:
Keeping the Nurse in the Nurse Practitioner
Authors: Wood Sylvia K.
Published: January 2020

Nurse practitioners are a vital and growing body of primary healthcare providers. The ever-changing advancements in science and technology and the increasing complexities in health care delivery are significant factors culminating in the expanding role of nurse practitioner-led care. Nurse educators are striving to develop nurse practitioner curricula to keep pace with the increasingly sophisticated knowledge and competencies nurse practitioners must possess to render safe quality care as independent primary health care providers. However, nursing theory is losing its place as a formative foundation in nurse practitioner curricula. Multiple factors such as content-laden, competency-based, medically focused education have caused a diminishing presence of nursing theory, shrinking the philosophical basis for nursing in nurse practitioner education. The loss of the central unifying focus of the discipline and discipline-specific knowledge (nursology) risks losing the very identity that forms the basis and relevance for nurse practitioner practice. Moreover, the loss of the nurse in the nurse practitioner unmoors nurse practitioner practice from its theoretical and scientific basis, losing discipline-specific attributes that lead to higher levels of patient satisfaction and improved patient outcomes. Keeping the nurse in the nurse practitioner is a moral imperative in nurses' ethical and social contract with society. This article discusses relevant literature and offers recommendations to keep the nurse in the nurse practitioner.
Reported Prevalence of Maternal Hepatitis C Virus Infection in the United States
Authors: Rossi Robert M. , Wolfe Christopher , Brokamp Richard , McAllister Jennifer M. , Wexelblatt Scott , Warshak Carri R. , Hall Eric S.
Published: January 2020

OBJECTIVE:

To quantify the reported prevalence and trend of maternal hepatitis C virus (HCV) infection in the United States (2009–2017) and identify maternal characteristics and obstetric outcomes associated with HCV infection during pregnancy.

METHODS:

We conducted a population-based retrospective cohort study of all live births in the United States for the period 2009 through 2017 using National Center for Health Statistics birth records. We estimated reported prevalence and trends over this time period for the United States. We also evaluated demographic factors and pregnancy outcomes associated with maternal HCV infection for a contemporary U.S. cohort (2014–2017).

RESULTS:

During the 9-year study period, there were 94,824 reported cases of maternal HCV infection among 31,207,898 (0.30%) live births in the United States. The rate of maternal HCV infection increased from 1.8 cases per 1,000 live births to 4.7 cases per 1,000 live births (relative risk [RR] 2.7, 95% CI 2.6–2.8) in the United States. After adjusting for various confounders in the contemporary U.S. cohort (2014–2017), demographic characteristics associated with HCV infection included non-Hispanic white race (adjusted RR 2.8, 95% CI 2.7–2.8), Medicaid insurance (adjusted RR 3.3, CI 3.2–3.3), and cigarette smoking (adjusted RR 11.1, CI 10.9–11.3). Co-infection during pregnancy with hepatitis B (adjusted RR 19.2, CI 18.1–20.3), gonorrhea, chlamydia, or syphilis were also associated with maternal HCV infection. Obstetric and neonatal outcomes associated with maternal HCV infection included cesarean delivery, preterm birth, maternal intensive care unit admission, blood transfusion, having small-for-gestational-age neonates (less than the 10th percentile) birth weight, neonatal intensive care unit admission, need for assisted neonatal ventilation, and neonatal death.

CONCLUSION:

The reported prevalence of maternal HCV infection has increased 161% from 2009 to 2017.
Severe Maternal Morbidity and Mortality Among Indigenous Women in the United States
Authors: Kozhimannil Katy B. , Interrante Julia D. , Tofte Alena N. , Admon Lindsay K.
Published: January 2020

OBJECTIVE:

To describe delivery-related severe maternal morbidity and mortality among indigenous women compared with non-Hispanic white (white) women, distinguishing rural and urban residents.

METHODS:

We used 2012–2015 maternal hospital discharge data from the National Inpatient Sample to conduct a pooled, cross-sectional analysis of indigenous and white patients who gave birth. We used weighted multivariable logistic regression and predictive population margins to measure health conditions and severe maternal morbidity and mortality (identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure codes) among indigenous and white patients, to test for differences across both groups, and to test for differences between rural and urban residents within each racial category.

RESULTS:

We identified an estimated 7,561,729 (unweighted n=1,417,500) childbirth hospitalizations that were included in the analyses. Of those, an estimated 101,493 (unweighted n=19,080) were among indigenous women, and an estimated 7,460,236 (unweighted n=1,398,420) were among white women. The incidence of severe maternal morbidity and mortality was greater among indigenous women compared with white women (2.0% vs 1.1%, respectively; relative risk [RR] 1.8, 95% CI 1.6–2.0). Within each group, incidence was higher among rural compared with urban residents (2.3% for rural indigenous women vs 1.8% for urban indigenous women [RR 1.3, 95% CI 1.0–1.6]; 1.3% for rural white women vs 1.2% for urban white women [RR 1.1, 95% CI 1.1–1.2]).

CONCLUSION:

Severe maternal morbidity and mortality is elevated among indigenous women compared with white women. Incidence is highest among rural indigenous residents. Efforts to improve maternal health should focus on populations at greatest risk, including rural indigenous populations.
Sexual and Reproductive Health Characteristics of Women in Substance Use Treatment in Michigan
Authors: MacAfee Lauren K. , Harfmann Roxanne F. , Cannon Lindsay M. , Kolenic Giselle , Kusunoki Yasamin , Terplan Mishka , Dalton Vanessa K.
Published: January 2020

OBJECTIVE:

To evaluate the sexual and reproductive health characteristics of women in treatment for opioid use disorder in Michigan and explore services provided and desired.

METHODS:

We conducted a cross-sectional study of female patients aged 18–50 years who accessed opioid use disorder treatment at 22 randomly selected facilities in Michigan from December 2015 to May 2017. Computer-assisted self-interviews were completed using online survey management software to assess prior substance use and use disorder treatment, sexual and reproductive health history, and sexual and reproductive health services received in the previous 12 months through a treatment program, and desire for and barriers to sexual and reproductive health services within substance use disorder treatment. Descriptive statistics were calculated.

RESULTS:

The final sample consisted of 260 participants. About half (51.5%) had ever had an abnormal Pap test result, and 57.3% had ever tested positive for a sexually transmitted infection. Unintended pregnancy was common (61.2%), as was substance use during pregnancy (74.2%). Nearly half (46.5%) were not currently using a method of contraception, and only 28.5% were using a highly effective method. Common barriers to accessing reproductive health services included fear of being treated poorly or judged because of substance use, fear of child protective services, and structural barriers such as cost and lack of transportation. Most participants (80.4%) indicated interest in receiving sexual and reproductive health services on site or by referral from their substance use disorder treatment programs.

CONCLUSION:

Women in treatment for opioid use disorder in Michigan have high rates of adverse sexual and reproductive health experiences and face barriers to accessing care.
Selection of Distal Fusion Level for Lenke 5 Curve
Authors: Shu Shibin , Bao Hongda , Zhang Yuancheng , Gu Qi , Zhang Tianyuan , Jing Wenting , Liu Zhen , Qiu Yong , Zhu Zezhang
Published: January 2020

Study Design.

A retrospective analysis.

Objective.

To evaluate whether the rotation of the presumed lower instrumented vertebra (LIV) on baseline convex side-bending (SB) radiographs leads to distal adding-on in Lenke 5C adolescent idiopathic scoliosis (AIS) patients.

Summary of Background Data.

In Lenke 1A patients, derotation of the presumed LIV on baseline bending films is important owing to the association between LIV rotation and postoperative distal adding-on. However, the relationship between distal adding-on and derotation of the presumed LIV in Lenke 5C patients remains unknown.

Methods.

Eighty-five Lenke 5C patients with a minimum of 2-year follow-up for posterior fusion were enrolled. L3 was selected as the LIV in all patients. Patients were divided into the presumed LIV derotation (DR group) and nonderotation (NDR group) groups according to derotation of the presumed LIV on SB films. Radiographic parameters, including Cobb angle, coronal balance, lower disc angle of LIV, LIV tilt, and LIV translation, were measured pre- and postoperatively.

Results.

Distal adding-on occurred in 16 patients (18.8%) at the final follow-up: 2 patients (10%) in the DR group and 14 patients (21.5%) in the NDR group (P = 0.248). Distal adding-on incidence was not greatly reduced with derotation of the presumed LIV on SB films at baseline. In the NDR group, the immediately postoperative lower disc angle of the LIV, LIV tilt, and LIV translation were significantly smaller in patients without than in those with distal adding-on (all P < 0.05). Logistic regression analysis revealed that the immediately postoperative LIV tilt and LIV translation were significant predictors of distal adding-on.

Conclusion.

Derotation of the presumed LIV on SB films may hint less risk of distal adding-on in Lenke 5C patients. Nevertheless, horizontalization of the LIV and minimizing LIV translation during correction could reduce the risk of distal adding-on despite the presence of LIV rotation at baseline.

Level of Evidence: 4
Choice of the Open Side in Unilateral Open-Door Laminoplasty for Cervical Ossification of the Posterior Longitudinal Ligament
Authors: Tang Yifan , Zhou Shengyuan , Wang Zhiwei , Huang Wenmao , Jia Lianshun , Chen Xiongsheng
Published: January 2020

Study Design.

Retrospective study.

Objective.

To determine the optimal open side in unilateral open-door laminoplasty (UODL) for lateral cervical ossification of posterior longitudinal ligament (OPLL).

Summary of Background Data.

No literature has reported which side of the vertebral arch should be chosen as the open side in UODL for lateral cervical OPLL.

Methods.

Patients with lateral cervical OPLL who were treated with UODL between 2013 and 2018 were retrospectively analyzed in two groups: Group A, where the open side was contralateral to the ectopic bone, and Group B, where the open side was ipsilateral to the ectopic bone. The Japanese Orthopaedic Association (JOA) Score, JOA recovery rate, spinal canal enlargement rate, cervical range of motion (ROM), and spinal cord area (SCA) were measured to evaluate and compare the clinical outcomes between the two groups. Statistical analysis was performed by t test and Hotelling T2 test.

Results.

There was no significant difference in patient demographics and major complications between the two groups. The postoperative JOA Score and JOA recovery rate in Group A were significantly higher than those in Group B. There was no significant difference in cervical ROM within or between the two groups during the 2-year follow-up period, nor was there significant difference in spinal canal enlargement between the two groups. However, both postoperative SCA and increased SCA in Group A were significantly higher than those in Group B.

Conclusion.

The contralateral open side approach is preferable to the ipsilateral open side approach in UODL for lateral cervical OPLL.Level of Evidence: 3
Percutaneous Plate Osteosynthesis of Ulnar Shaft Fractures: A Surgical Technique and Case Series
Authors: Clark DesRaj M. , Napora Joshua K. , Eglseder Andrew
Published: January 2020

Treatment of ulnar diaphyseal fractures can range broadly from nonoperative with immobilization to surgical intervention with a variety of implants or approaches. At a Level 1 trauma center, a series of ulnar shaft fractures have been treated using a percutaneous plating technique that is base beneath the extensor carpi ulnaris. This technique description illustrates relevant anatomy, important patient and injury characteristics, implant considerations, and potential outcomes and complications. The described treatment option provides an effective way of spanning comminuted fracture patterns without disrupting the surrounding biology while providing stable fixation. An associated patient series is included which enumerates associated injuries and describes limited follow-up. In the multiply injured trauma patient, such a fixation method also had potential benefits for their overall care and rehabilitation.
Successful immune checkpoint inhibition in an EGFR-mutant lung cancer patient refractory to epidermal growth factor receptor tyrosine kinase inhibitor treatment
Authors: Hochmair Maximilian Johannes , Weinlinger Christoph , Prosch Helmut
Published: January 2020

It is widely assumed that immune checkpoint inhibition does not give rise to clinical benefits in patients with lung cancer and activating epidermal growth factor receptor (EGFR) mutations. Clinical trial data have predominantly demonstrated low activity of immunotherapy in this patient group, although some evidence has been obtained that implies outcome improvement with checkpoint inhibitors even in EGFR-positive disease. The case presented here demonstrates excellent activity of the PD-L1 inhibitor atezolizumab and the PD-1 inhibitor pembrolizumab as the sixth- and seventh-line treatments in a patient with EGFR-mutant metastatic non–small-cell lung cancer who had not responded to EGFR-targeted agents. Chemotherapy had led to partial remission, and immunotherapy was initiated as a last-line option. The patient achieved complete remission with both atezolizumab for 1 year, and pembrolizumab after progression on atezolizumab. At present, the patient is receiving pembrolizumab and shows stable remission. Later-line immunotherapy might be particularly suitable for patients with EGFR-mutant tumors who did not respond to EGFR tyrosine kinase inhibition therapy. Although further studies are necessary, for patients who are in need of effective treatment, checkpoint inhibition should not be avoided just because EGFR mutations are present.
Predictors of outcome in elderly patients with metastatic colorectal cancer: the final results of a prospective phase II study of bevacizumab in combination with capecitabine as first-line treatment
Authors: Omrčen Tomislav , Katić Andrija , Tomić Snježana , Eterović Davor , Vrdoljak Eduard
Published: January 2020

In 2011, we demonstrated that bevacizumab in combination with capecitabine as first-line treatment is effective in elderly patients with metastatic colorectal cancer (mCRC). We present the final results of the study with data on tumor molecular biology, sidedness and postprogression therapy. Forty patients with mCRC aged ≥70 years, initially treated with bevacizumab and capecitabine, were followed from the start of the treatment of metastatic disease to death. Tumor tissue samples were retrospectively analyzed for RAS, BRAF and microsatellite status. After a median follow-up time of 20.5 months, the median progression-free survival (PFS) and overall survival (OS) were 9.8 and 20.5 months, respectively and the objective response rate (ORR) was 65%. Twelve patients had mutation in RAS and four patients in BRAF gene, which coexisted with MSI in two cases. Patients with the right-sided tumor had apparently, but not statistically significantly lower PFS (8.6 vs. 13 months, P = 0.14) and statistically significantly lower OS (13 vs. 23.1 months, P = 0.046). Twelve patients with one or more postprogression therapy lines had significantly better ORR (12/12 = 100% vs. 14/28 = 50%, P = 0.003), median PFS (17.2 vs. 8.5 months, P < 0.001) and median OS (42 vs. 13 months, P < 0.001) than patients who received just first-line study treatment. Elderly patients with mCRC responded favorably to bevacizumab and capecitabine, especially the subgroup with the left-sided primary tumor. In the further subset of this group, characterized by RAS/BRAF wild-type and MSS tumors, the application of postprogression therapies was feasible and resulted in significant prolongation of survival.
Effects of oxycodone on sensitivity to reinforcement magnitude: implications for effects of opioids on impulsive and risky choice
Authors: Hunt Katelyn H. , Hughes Christine E. , Pitts Raymond C.
Published: January 2020

Opioid addiction/dependence is associated with impulsive and risky behavior. Moreover, opioids can increase impulsive choice in preclinical studies with nonhumans. The objective of this study was to investigate a potential behavioral mechanism of opioids: a change in the impact of reinforcement magnitude on choice. Rats (n = 7) chose between smaller and larger reinforcers under a continuous-choice (concurrent-chains) procedure. The levers associated with the smaller and larger reinforcers alternated every five sessions. During baseline under this procedure, rats showed a reliable preference for the larger reinforcer. Effects of several doses (0.1–1.7 mg/kg, s.c.) of the prescription opioid, oxycodone, were examined on preference based upon reinforcement magnitude. Oxycodone dose-dependently decreased preference for the larger reinforcer (i.e. decreased sensitivity to reinforcement magnitude). The decrease in sensitivity to reinforcement magnitude was selective in that the intermediate doses did not affect, or had minimal impact on, other measures of performance (e.g. on general motivation to respond). These data suggest that a decrease in the sensitivity to reinforcement magnitude is a reliable outcome of μ-opioid administration, an effect that has important implications for the impact of these drugs on both impulsive and risky behavior.
HYPERAUTOFLUORESCENT SPOTS IN ACUTE OCULAR TOXOPLASMOSIS
Authors: Mathis Thibaud , Delaunay Benoit , Favard Catherine , Denis Philippe , Kodjikian Laurent
Published: January 2020

Purpose:

The aim of this study was to describe the fundus autofluorescence patterns in acute ocular toxoplasmosis (OT) and to correlate these findings with other imaging.

Methods:

A retrospective multicenter case series of 27 eyes from 27 patients with acute onset of posterior OT was conducted. Multimodal imaging including fundus autofluorescence was performed at diagnosis and during follow-up.

Results:

All OT lesions were hypoautofluorescent on fundus autofluorescence imaging. Fourteen patients (51.8%) also had hyperautofluorescent spots around the active foci that disappeared after retinal photobleaching. Although these spots were not seen on early phase of indocyanine green angiography, they become hypofluorescent in the late phase without choriocapillaris flow impairment on optical coherence tomography angiography. On B-scan spectral domain optical coherence tomography, spots corresponded to outer retinal alterations in all cases. All hyperautofluorescent spots disappeared during follow-up as acute OT resolved. Younger patients and those with more posterior inflammatory symptoms (vasculitis and/or papillitis) were more frequent with the presence of hyperautofluorescent spots.

Conclusion:

Ocular toxoplasmosis may trigger a transient outer retinal disruption in eyes with marked inflammatory symptoms of the younger patients.
Radial Forearm Free Flap for Cochlear Implant Coverage in a Post-Irradiated Field
Authors: Dewyer Nicholas A. , Sethi Rosh K. , Yamasaki Alisa , Lee Daniel J.
Published: January 2020

Objective:

To describe a novel use of a radial forearm free flap (RFFF) for soft tissue coverage over a cochlear implant (CI) in a post-irradiated field.

Patients:

Single patient case report of a woman with a history of radiation therapy for brainstem astrocytoma who suffered from repeated CI extrusion despite tympanomastoid obliteration and locoregional pedicled flap soft tissue coverage.

Intervention(s):

Sequential bilateral, single-staged revision cochlear implantation with RFFF soft tissue coverage.

Main Outcome Measure(s):

Postoperative wound healing complications including infection or device extrusion.

Results:

There have been no further issues with wound healing, infection, or device extrusion with a follow up period of 3 years on one side and 8 months on the second side. Both CIs are functioning well with the flaps being sufficiently thin to allow for the use of typical external processor magnets.

Conclusions:

A RFFF can be used to provide robust soft tissue coverage over a CI in a post-irradiated field. The RFFF and CI may safely be performed in a single operation.
Use of IL-5 Inhibitor Benralizumab as a Novel Therapy for Eosinophilic Otitis Media: Clinical Capsule and Review of Literature
Authors: Chow Kevin , Cosetti Maura K.
Published: January 2020

Objective:

We report a case of recurrent eosinophilic otitis media (EOM) successfully treated with the novel monoclonal IL-5 inhibitor benralizumab. We also review literature relevant to EOM diagnosis and potential for biologic treatment.

Patient:

A 24-year-old woman with bilateral otitis media with effusion unresponsive to standard treatment.

Intervention(s):

Multidisciplinary treatment using subcutaneous benralizumab after diagnosis of EOM.

Main Outcome Measure(s):

Behavioral audiometry, peripheral serology, otomicroscopy, and eosinophilic otitis media symptom severity.

Results:

Recalcitrant otitis media with effusion (OME) in the setting of nasal polyposis and asthma prompted clinical suspicion for EOM, which was confirmed by pathologic examination of middle ear effusion and soft tissue biopsy. Treatment with benralizumab was initiated by pulmonology and well-tolerated. Within 2 months of treatment onset there was a cessation of EOM symptoms, a reduction of peripheral eosinophil levels, and an improvement in conductive hearing loss.

Conclusions:

Monoclonal antibodies such as benralizumab may be an effective treatment option for EOM. A high level of clinical suspicion in patients with bronchial asthma, nasal polyposis, and recalcitrant OME may allow early diagnosis of EOM. Awareness of emerging biologic treatment options is important in the management of this challenging entity and may prevent long-term sequelae.
American Organization of Nurse Executives 2nd Compensation Survey
Authors: Kittner Alyse , Thrall Terese Hudson
Published: January 2020

The American Organization of Nurse Executives conducted its 2nd salary and compensation survey of nursing leaders in 2016. Annual salaries from responding nurse leaders vary largely, with half falling between $90000 and $149999. Two-thirds of the respondents are eligible for an incentive. Overall job satisfaction was high among nurse leaders.
Progression of Subclinical Vascular Damage in People Living With HIV Is Not Predicted by Current Cardiovascular Risk Scores: A Prospective 3-Year Study
Authors: Kapelios Chris J. , Argyris Antonios A. , Protogerou Athanase D. , Katsarolis Ioannis , Arida Aikaterini , Papadopoulou Martha , Ntaroutsou Eirini , Kitas George , Sfikakis Petros P. , Psichogiou Mina
Published: January 2020

Background:

People living with HIV (PLWH) are at high cardiovascular disease (CVD) risk. Traditional CVD risk scores do not accurately reflect their CVD risk. Noninvasive subclinical vascular damage (SVD) biomarkers are valid surrogates of CVD and able to stratify CVD risk.

Setting:

We tested whether 4 widely applied CVD risk scores [Framingham (FRS), Atherosclerotic CVD, Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D), and Greek-specific European Society of Cardiology (ESC) risk scores] are associated with or detect the presence, incidence, and progression of arteriosclerosis, atheromatosis, and arterial hypertrophy in PLWH and uninfected individuals.

Methods:

We prospectively examined (at baseline and 3-year follow-up) 10 different arterial sites applying 5 different noninvasive vascular biomarkers and measured all 4 CVD risk scores at baseline.

Results:

In both PLWH (n = 138) and uninfected (n = 664) individuals, the CVD risk scores (except the ESC) performed differently but reasonably well in identifying the presence of SVD, but all scores failed to predict the incidence/progression of overall SVD. The most clinically useful biomarkers (carotid plaque/atheromatosis) revealed that in PLWH, only the FRS was able to stratify the progression (11% of the low-risk, 33.3% of the medium-risk, and 0% of the high-risk group).

Conclusions:

This extensive vascular phenotyping study demonstrated the clear need to incorporate vascular imaging in CVD risk stratification, in addition to designing more accurate HIV-specific CVD risk models. The use of FRS would further enable treatment optimization and CVD prevention strategies in PLWH at medium CVD risk because one-third of carotid atheromatosis progresses within 3 years.
The Free Serratus-Rib Flap for Orbital Floor Reconstruction After Oncologic Resection
Authors: Kraft Casey T. , Hanasono Matthew M. , Skoracki Roman J.
Published: January 2020

Introduction

Maxillary cancer is relatively rare but devastating for those affected with the disease. For patients who require suprastructural or total maxillectomy for oncologic resection, the resection of the orbital floor can be challenging to reconstruct. The serratus-rib flap is a well-known and useful method of head and neck reconstruction, albeit infrequently used. However, the serratus-rib flap has not previously been described for reconstruction of the orbital floor and has the potential to provide excellent globe support after orbital floor resection in patients after undergoing maxillectomy.

Methods

We retrospectively reviewed all patients who had undergone orbital floor reconstruction using the serratus-rib osteomyofascial free flap by the senior author throughout their career. Surgical technique, postoperative course, complications, and additional required procedures were evaluated.

Results

Six patients were found to have undergone the serratus-rib osteomyofascial free flap for orbital floor reconstruction. Average follow-up was 26.7 months from initial surgery. Fifty percent of patients had later minor revision surgery such as fat grafting or scar revision. No patients had any significant complications, and all patients were noted to have good ocular function without diplopia postoperatively.

Conclusion

The serratus-rib osteomyofascial free flap is an efficacious method for reconstruction of the orbital floor after oncologic resection. Surgeons should consider this flap when performing orbital floor reconstruction, particularly when dead space also needs to be filled with the use of a free flap.
Correction of the type strain of Aeromonas punctata (Zimmermann 1890) Snieszko 1957 and of A. punctata subsp. punctata from ATCC 15468T to NCMB 74T (=NCIMB 74T= ATCC 23309T)
Authors: Holmes Barry , Farmer III J. Jim
Published: January 2020

Under Rule 23a (Note 4) of the Bacteriological Code we ask the Judicial Commission to issue an opinion that will correct two errors that were made on the original 1980 Approved Lists of Bacterial Names. We request that the type strain designations for

Aeromonas punctata

and

Aeromonas punctata

subsp.

punctata

be corrected from ATCC 15468T to NCMB 74T. We also ask that the opinion state the ‘correct’ or best way to write the author citations for several other

Aeromonas

names in order to avoid future instability in nomenclature when the citations are given.
Quality characteristics of Kujippong (Cudrania tricuspidata) vinegar fermented by various acetic acid bacteria
Authors: Lee Su Jeong , Kim Sun Hee , Kim So Young , Yeo Soo-Hwan
Published: January 2020

In this study was we investigated the optimum conditions for the fermentation of Kujippong (Cudrania tricuspidata) vinegar by various acetic acid bacteria (Acetobacter pasteurianus A26, A37, B7) and its quality characteristics. Fermentation at various initial acidities (pH 2, 3, and 4) and temperatures (20℃, 30℃, and 35℃) revealed that A. pasteurianus A37 and B7 produced the most acetic acid when fermented at pH 4 and 20℃. The acidities of the Kujippong fermented vinegars prepared with the A37 and B7 strains increased by 6.3% and 6.1%, to pH 2.45 and pH 2.43, respectively. Meanwhile, the vinegar produced by the A26 strain showed low acidity under all conditions. At the end of fermentation period, the acetic acid content of the main organic acid had increased by a factor of ten from day 0, to values of 37.34 mg/mL for A. pasteurianus A37 and 39.34 mg/mL for B7. The A37 and B7 strains produced 37.5% and 59.2% volatile components, respectively, which were mainly acetic acid and its ethyl ester, among a relatively diverse range of volatile compounds produced. Therefore, the good aceitc acid production of farm-made Kujippong-fermented vinegar is expected to promote the consumption of local agricultural products and and increase in farm income.
Physiochemical characteristics of Platycodon grandiflorum flower ethanolic extracts
Authors: Kang Jae Ran , Kang Min Jung , Cho A Ro , Shin Jung Hye
Published: January 2020

The goal of this study was to investigate the physicochemical characteristics of Platycodon grandiflorum flower extracts obtained with different ratios of edible ethanol containing water solutions (10%, 30% and 60% ethanol). The redness and pH values of the extracts increased with increasing ethanol content, whereas the acidity decreased. The total phenol, total flavonoid, and total anthocyanin contents were in the ranges of 105.94-113.79 µg/mL, 11.97-27.13 µg/mL, and 0.01-0.13 µg/mL, respectively, all of which were significantly high and decreased in the order of 60% > 30% > 10% ethanol. The antioxidant activity and cholesterol adsorption activity generally followed the order of 60% > 10% > 30% ethanol, and the α-glucosidase inhibitory activity was significantly higher in the 10% ethanol extract, followed by the 30% > 60% ethanol extract. However, there was no identifiable significant difference in the xanthine oxidase inhibitory activities obtained using the different ethanol addition ratios when the sample concentration was 5 µg/mL. The physiological activities of the ethanol extracts of P. grandiflorum flowers are estimated to be affected by other functional components besides polyphenol compounds and anthocyanins because they were inconsistent with the trends of the total phenol, flavonoid, and anthocyanin contents.
Informative Frailty Indices from Binarized Biomarkers
Authors: Stubbings Garrett , Farrell Spencer , Mitnitski Arnold , Rockwood Kenneth , Rutenberg Andrew
Published: January 2020

Frailty indices (FI) based on continuous valued health data, such as obtained from blood and urine tests, have been shown to be predictive of adverse health outcomes. However, creating FI from such biomarker data requires a binarization treatment that is difficult to standardize across studies. In this work, we explore a “quantile” methodology for the generic treatment of biomarker data that allows us to construct an FI without preexisting medical knowledge (i.e. risk thresholds) of the included biomarkers. We show that our quantile approach performs as well as, or even slightly better than, established methods for the National Health and Nutrition Examination Survey (NHANES) and the Canadian Study of Health and Aging (CSHA) data sets. Furthermore, we show that our approach is robust to cohort effects within studies as compared to other data-based methods. The success of our binarization approaches provides insight into the robustness of the FI as a health measure, the upper limits of the FI observed in various data sets, and highlights general difficulties in obtaining absolute scales for comparing FI between studies.
Assessment of Brain Glucose Metabolism Following Cardiac Arrest by [18F]FDG Positron Emission Tomography
Authors: Zhang Hannah J. , Mitchell Samuel , Fang Yong-Hu , Tsai Hsiu-Ming , Piao Lin , Ousta Alaa , Leoni Lara , Chen Chin-Tu , Sharp Willard W.
Published: January 2020

Background

Cardiac arrest (CA) patients who survived by cardiopulmonary resuscitation (CPR) can present different levels of neurological deficits ranging from minor cognitive impairments to persistent vegetative state and brain death. The pathophysiology of the resulting brain injury is poorly understood and whether changes in post-CA brain metabolism contribute to the injury are unknown. Here we utilized [18F]FDG-PET to studyin vivocerebral glucose metabolism 72 hours following CA in a murine cardiac arrest model.

Methods

Anesthetized and ventilated adult C57BL/6 mice underwent 12-minute KCl-induced CA followed by CPR. Seventy-two hours following cardiac arrest, surviving mice were intraperitoneally injected with [18F]FDG (~186 μCi/200 μL) and imaged on Molecubes preclinical micro PET/CT imaging systems after a 30-minute awake uptake period. Brain [18F]FDG uptake was determined by the VivoQuant software on fused PET/CT images with the 3D brain atlas. Upon completion of PET imaging, remaining [18F]FDG radioactivity in the brain, heart, and liver was determined using a gamma counter.

Results

Global increases in brain [18F]FDG uptake in post-CA mice were observed compared to shams and controls. The median standardized uptake value (SUV) of [18F]FDG for CA animals was 1.79 vs. sham 1.25 (p<0.05) and control animals 0.78 (p<0.01). This increased uptake was consistent throughout the 60-minute imaging period and across all brain regions reaching statistical significance in the midbrain, pons, and medulla. Biodistribution analyses of various key organs yielded similar observations that the median [18F]FDG uptake for brain were 7.04%ID/g tissue for CA mice vs 5.537%ID/g tissue for sham animals, p<0.05).

Conclusions

This study has successfully applied [18F]FDG-PET/CT to measure changes in brain metabolism in a murine model of asystolic CA. Our results demonstrate increased [18F]FDG uptake in the brain 72 hours following CA, suggesting increased metabolic demand in the case of severe neurological injury. Further study is warranted to determine the etiology of these changes.
Mass Spectrometry Imaging of Cocaine, Drug Removal and Methylphenidate Alter Phospholipids in Drosophila Brain
Authors: Philipsen Mai H. , Phan Nhu T. N. , Fletcher John S. , Ewing Andrew G.
Published: January 2020

Cocaine dependence displays a broad impairment in cognitive performance including attention, learning and memory. To obtain a better understanding of the action of cocaine in the nervous system, and the relation between phospholipids and memory, we have investigated whether phospholipids recover in the brain following cocaine removal using the fly model,Drosophila. In addition, the effects of methylphenidate, a substitute medication for cocaine dependence, on fly brain lipids after cocaine abuse are also determined to see if it can rescue the lipid changes caused by cocaine. Time of flight secondary ion mass spectrometry with a (CO2)6000+gas cluster ion beam was used to detect intact phospholipids. We show that cocaine has persistent effects, both increasing and decreasing the levels of specific phosphatidylethanolamines and phosphatidylinositols. These changes remain after cocaine withdrawal and are not rescued by methylphenidate. Cocaine is again shown to generally increase the levels of phosphatidylcholines in the fly brain; however, after drug withdrawal the abundance of these lipids returns to the original level and methylphenidate treatment of the flies following cocaine exposure enhances the reversal of the lipid level reducing them below the original control. The study provides insight into the molecular effects of cocaine and methylphenidate on brain lipids. We suggest that phosphatidylcholine could be a potential target for the treatment of cocaine abuse, as well as be a significant hallmark of cognition and memory loss with cocaine.
A novel cross talk of AtRAV1, an ethylene responsive transcription factor with MAP kinases imparts broad spectrum disease resistance in plants
Authors: Chandan Ravindra Kumar , Kumar Rahul , Swain Durga Madhab , Ghosh Srayan , Bhagat Prakash Kumar , Patel Sunita , Bagler Ganesh , Sinha Alok Krishna , Jha Gopaljee
Published: January 2020

Plant diseases pose a serious threat to sustainable agriculture as controlling them in eco-friendly manner remains a challenge. In this study, we establish RAV1 as a master transcriptional regulator of defense genes in model plant Arabidopsis. The overexpression ofAtRAV1provided disease resistance against necrotrophic fungal pathogen (Rhizoctonia solani)infection inA. thaliana. The transgenic lines exhibited enhanced expression of several defense genes including mitogen associated protein kinases (MAPKs) and the amplitude of their expression was further enhanced upon pathogen infection. Conversely, theatrav1mutant plants were unable to induce the expression of these defense genes and were highly susceptible to infection. Our data suggests that upon pathogen attack, AtRAV1 transcriptionally upregulate the expression ofMAPKs(AtMPK3, AtMPK4andAtMPK6) and AtMPK3 and AtMPK6 are essential for AtRAV1 mediated disease resistance. Further, we demonstrate that AtRAV1 is a phosphorylation target of AtMPK3 (but not AtMPK6) and the phospho-defective variants of AtRAV1 are unable to induce disease resistance inA. thaliana. Considering the presence of AtRAV1 orthologs in diverse plant species, we propose that they can be gainfully deployed to control economically important diseases. In deed we observe that overexpression of tomato ortholog ofAtRAV1(SlRAV1) provides broad spectrum disease resistance against bacterial (Ralstonia solanacearum), fungal (R. solani) and viral (Tomato leaf curl virus) infections in tomato.
COP1 destabilizes DELLA proteins inArabidopsis
Authors: Blanco-Touriñán Noel , Legris Martina , Minguet Eugenio G. , Costigliolo-Rojas Cecilia , Nohales María A. , Iniesto Elisa , García-León Marta , Pacín Manuel , Heucken Nicole , Blomeier Tim , Locascio Antonella , Černý Martin , Esteve-Bruna David , Díez-Díaz Mónica , Brzobohatý Břetislav , Frerigmann Henning , Zurbriggen Matías D. , Kay Steve A. , Rubio Vicente , Blázquez Miguel A. , Casal Jorge J. , Alabadí David
Published: January 2020

DELLA transcriptional regulators are central components in the control of plant body form in response to the environment. This is considered to be mediated by changes in the metabolism of the hormones gibberellins (GAs), which promote the degradation of DELLAs. However, here we show that warm temperature or shade reduced the stability of a GA-insensitive DELLA allele inArabidopsis. Furthermore, the degradation of DELLA induced by the warmth anticipated changes in GA levels and depended on the E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1). COP1 enhanced the degradation of normal and GA-insensitive DELLA alleles when co-expressed inN. benthamiana.DELLA proteins physically interacted with COP1 in yeast, mammalian and plant cells. This interaction was enhanced by the COP1 complex partner SUPRESSOR OFphyA-1051 (SPA1). The level of ubiquitination of DELLA was enhanced by COP1 and COP1 ubiquitinated DELLA proteins in vitro. We propose that DELLAs are destabilized not only by the canonical GA-dependent pathway but also by COP1 and that this control is relevant for growth responses to shade and warm temperature.

Significance

DELLA proteins are plant-specific transcriptional regulators that act as signaling hubs at the interface between the environment and the transcriptional networks that control growth. DELLAs are destabilized by the growth-promoting hormone gibberellin, whose levels are very sensitive to environmental changes. Here we describe an alternative pathway to destabilize these proteins. We show that DELLAs are substrate of COP1, an E3 ubiquitin ligase that increases its nuclear activity to promote growth in response to shade or warmth. Our results also show that the destabilization of DELLAs by COP1 precedes the action of gibberellins, suggesting the existence of a sequential mechanism to control the stability of these proteins.
All-trans retinoic acid (ATRA) reduces proliferative capacity and Brachyury levels in chordoma cells
Authors: Robinson Helena , McFarlane Ramsay J. , Wakeman Jane A.
Published: January 2020

Chordoma is a rare bone cancer for which there are no approved drugs. Surgery is the principle treatment but complete resection can be challenging due to the location of the tumours in the spine and therefore finding an effective drug treatment is a pressing unmet clinical need. A major recent study identified the transcription factor Brachyury as the primary vulnerability and drug target in chordoma. Previously, all-trans retinoic acid (ATRA) has been shown to negatively influence expression of the Brachyury gene,TBXT. Here we extend this finding and demonstrate that ATRA lowers Brachyury protein levels in chordoma cells and reduces proliferation of the chordoma cell line U-CH1 as well as causing a morphological change commensurate with differentiation. ATRA is available as a generic drug and is the first line treatment for acute promyelocytic leukaemia (APL). This study implies ATRA could have therapeutic value if repurposed for chordoma.
The wisdom of stalemates: consensus and clustering as filtering mechanisms for improving collective accuracy
Authors: Winklmayr Claudia , Kao Albert B. , Bak-Coleman Joseph B. , Romanczuk Pawel
Published: January 2020

Groups of organisms, from bacteria to fish schools to human societies, depend on their ability to make accurate decisions in an uncertain world. Most models of collective decision-making assume that groups reach a consensus during a decision-making bout, often through simple majority rule. In many natural and sociological systems, however, groups may fail to reach consensus, resulting in stalemates. Here, we build on opinion dynamics and collective wisdom models to examine how stalemates may affect the wisdom of crowds. For simple environments, where individuals have access to independent sources of information, we find that stalemates improve collective accuracy by selectively filtering out incorrect decisions. In complex environments, where individuals have access to both shared and independent information, this effect is even more pronounced, restoring the wisdom of crowds in regions of parameter space where large groups perform poorly when making decisions using majority rule. We identify network properties that tune the system between consensus and accuracy, providing mechanisms by which animals, or evolution, could dynamically adjust the collective decision-making process in response to the reward structure of the possible outcomes. Overall, these results highlight the adaptive potential ofstalemale filteringfor improving the decision-making abilities of group-living animals.
Modelling bioactivities of combinations of whole extracts of edibles with a simplified theoretical framework reveals the statistical role of molecular diversity and system complexity in their mode of action and their nearly certain safety
Authors: Mayer Pascal
Published: January 2020

Network pharmacology and polypharmacology are emerging as novel drug discovery paradigms. The many discovery, safety and regulatory issues they raise may become tractable with polypharmacological combinations of natural compounds found in whole extracts of edible and mixes thereof. The primary goal of this work is to get general insights underlying the innocuity and the emergence of beneficial and toxic activities of combinations of many compounds in general and of edibles in particular. A simplified model of compounds’ interactions with an organism and of their desired and undesired effects is constructed by considering the departure from equilibrium of interconnected biological features. This model allows to compute the scaling of the probability of significant effects relative to nutritional diversity, organism complexity and synergy resulting from mixing compounds and edibles. It allows also to characterize massive indirect perturbation mode of action drugs as a potential novel multi-compound-multi-target pharmaceutical class, coined Ediceuticals when based on edibles. Their mode of action may readily target differentially organisms’ system robustness as such based on differential complexity for discovering nearly certainly safe novel antimicrobials and anti-cancer treatments. This very general model provides also a theoretical framework to several pharmaceutical and nutritional observations. In particular, it characterizes two classes of undesirable effects of drugs, and may question the interpretation of undesirable effects in healthy subjects. It also formalizes nutritional diversity as such as a novel statistical supra-chemical parameter that may contribute to guide nutritional health intervention. Finally, it is to be noted that a similar formalism may be further applicable to model whole ecosystems in general.
Peritonsillar abscess may not always be a complication of acute tonsillitis: A prospective cohort study
Authors: Sanmark Enni , Wikstén Johanna , Välimaa Hannamari , Aaltonen Leena-Maija , Ilmarinen Taru , Blomgren Karin
Published: January 2020

The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (p<0.001) and older age (p<0.001). We also observed an inverse correlation between S-Amyl and S-CRP levels (AT, r= −0.519; PTA, r= −0.353). Therefore, we observed a group of PTA patients without signs of tonsillar infection who had significantly lower S-CRP levels than other PTA patients. These findings support that PTA may be caused by an etiology other than AT. Variations in the S-Amyl levels and a negative correlation between S-Amyl and S-CRP levels may indicate that minor salivary glands are involved in PTA development.

LEVEL OF EVIDENCE

1b
Optogenetic low-frequency stimulation of dentate granule cells prevents seizure generation in experimental epilepsy
Authors: Paschen E , Elgueta C , Heining K , Vieira DM , Orcinha C , Häussler U , Bartos M , Egert U , Janz P , Haas CA
Published: January 2020

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults and is typically associated with hippocampal sclerosis and drug-resistant seizures. As an alternative to curative epilepsy surgery, brain stimulation evolves as a promising approach for seizure-interference. However, particularly in MTLE with severe hippocampal sclerosis, current stimulation protocols are often not effective. Here, we show that optogenetic low-frequency stimulation (oLFS) of entorhinal afferents exhibits unprecedented anti-ictogenic effects in chronically epileptic mice. Photostimulation at 1 Hz resulted in an almost complete suppression of focal seizures, independent of the degree of hippocampal sclerosis. Furthermore, by performing oLFS for 30 min before a pro-convulsive stimulus, seizure generalization was successfully prevented. Finally, acute slice experiments revealed a decreased excitability upon oLFS, which may partially explain the observed anti-epileptic effects. Taken together, our results suggest that oLFS of entorhinal afferents constitutes a promising approach for seizure control in MTLE.