bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoplasmic Reticulum Stress Contributes to Nociception via Neuroinflammation in a Murine Bone Cancer Pain Model
Authors: Mao Yanting , Wang Chenchen , Tian Xinyu , Huang Yulin , Zhang Ying , Wu Hao , Yang Shuai , Xu Ke , Liu Yue , Zhang Wei , Gu Xiaoping , Ma Zhengliang 
Published: December 2019

Abstract

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background
Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development.

Methods
The authors used a male mouse model of bone cancer pain. The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414. The nociceptive behaviors, endoplasmic reticulum stress markers, and inflammatory mediators were assessed.

Results
Increased expression of the p-RNA-dependent protein kinase-like endoplasmic reticulum kinase and p-eukaryotic initiation factor 2α were found in the spinal neurons during bone cancer pain, along with upregulation of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6). Intrathecal administration of TNF-α or lipopolysaccharide increased the expression of endoplasmic reticulum stress markers in control mice. Inhibition of endoplasmic reticulum stress by intrathecal administration of 4-PBA (baseline vs. 3 h: 0.34 ± 0.16 g vs. 1.65 ± 0.40 g in paw withdrawal mechanical threshold, 8.00 ± 1.20 times per 2 min vs. 0.88 ± 0.64 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) or GSK2606414 (baseline vs. 3 h: 0.37 ± 0.08 g vs. 1.38 ± 0.11 g in paw withdrawal mechanical threshold, 8.00 ± 0.93 times per 2 min vs. 3.25 ± 1.04 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) showed time- and dose-dependent antinociception. Meanwhile, decreased expression of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6), as well as decreased activation of astrocytes in the spinal cord, were found after 4-PBA or GSK2606414 treatment.

Conclusions
Inhibition of inflammatory mediator–triggered endoplasmic reticulum stress in spinal neurons attenuates bone cancer pain via modulation of neuroinflammation, which suggests new approaches to pain relief.
The Role of MRI in Children With Congenital Limb Deficiencies With Associated Scoliosis
Authors: Gettys Franklin K. , Carpenter Ashley , Stasikelis Peter J. 
Published: December 2019

Background:
The association of scoliosis and congenital limb deficiency has been well described. However, the incidence of neural axis abnormalities in this population is not known. The ability to assess the neural axis by physical examination may be limited in patients with a limb deficiency. Although mobility of the spine is important for all children, it can be especially so in children with a limb deficiency. As spinal fusion in children with limb deficiency potentially has more functional impact, detecting reversible forms of scoliosis seems particularly important.

Methods:
Retrospective review of children treated at 1 institution between 1990 and 2017 with both a diagnosis of a congenital limb deficiency, upper or lower, and scoliosis. Children were excluded if they had any neurological difference on history or physical examination, if they had sacral agenesis or spina bifida, or if their limb deficiency was related to trauma or early amniotic rupture sequence.

Results:
Twenty-four children were identified, 11 with lower extremity deficiency, 14 with upper extremity deficiency with 1 having both. Fifteen children demonstrated neural axis abnormalities, 6 (40%) required neurosurgery. Five (45%) of 11 lower extremity deficiency children had MRI findings, 3 of these needing neurosurgery. Of the 14 upper extremity deficiency children, 10 had MRI changes, and 3 required neurosurgery. Eight children with congenital scoliosis, 5 had MRI findings, with 4 children requiring neurosurgery. The other 16 children had scoliosis without vertebral abnormalities, 10 had MRI findings, and 2 required neurosurgery.

Conclusions:
There is a high incidence of neural axis abnormalities (63%) in children with congenital limb deficiencies and scoliosis. A large portion of these require neurosurgical intervention. MRI should be considered soon after presentation in this population of children.

Level of Evidence:
Level IV.

Design:
Retrospective cohort.
Mortality Prediction in Rural Kenya: A Cohort Study of Mechanical Ventilation in Critically Ill Patients
Authors: Parker Robert K. , Mwachiro Elizabeth B. , Mwachiro Michael M. , Pletcher Jocelyn , Parker Andrea S. , Many Heath R. 
Published: December 2019

Importance:
Critical care is expanding in low- and middle-income countries. Yet, due to factors such as missing data and different disease patterns, predictive scores often fail to adequately predict the high rates of mortality observed.

Objectives:
We evaluated multiple prognostic models for the outcome of mortality in critically ill, mechanically ventilated patients in rural Kenya and examined factors contributing to mortality in our setting.

Design, Setting, and Participants:
A prospective cohort study was conducted on mechanically ventilated patients in rural Kenya. Consecutive patients 16 years old and older initiated on mechanical ventilation between January 1, 2016, and April 30, 2017, at Tenwek Hospital were included. Demographic data, clinical characteristics, and patient outcomes were collected during routine clinical care.

Main Outcomes and Measures:
We assessed the discrimination and calibration of multiple previously-described models for mortality: Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, quick Sequential Organ Failure Assessment, Simplified Acute Physiology Score II, Modified Early Warning Score, Tropical Intensive Care Score, Rwanda-Mortality Predictive Model, Vitals score (validated in Tanzania), and Vitals score for sepsis (validated in Uganda). Factors most associated with mortality were analyzed in our cohort utilizing stepwise regression.

Results:
Among the final cohort of 300 patients, the overall mortality rate was 60.7%, the average age was 39.9 years, 65% were male, and 33% were seen at an outside facility prior to admission to the critical care unit. Missing variables occurred in patients for numerous models but were complete in most adapted to resource-limited settings. Models displayed moderate prediction of mortality and variable discrimination area under the receiver operating characteristic curves (and Hosmer-Lemeshow chi-square statistic) of 0.77 (22.4) for Acute Physiology and Chronic Health Evaluation II, 0.70 (3.4) for Modified Early Warning Score, 0.65 (0.16) for quick Sequential Organ Failure Assessment, 0.55 (18.4) for Simplified Acute Physiology Score II and 0.74 (9.2) for Rwanda-Mortality Predictive Model, 0.72 (0.12) for Vitals Tanzania, 0.68 (14.7) for Vitals Uganda, and 0.65 (13.9) for Tropical Intensive Care Score. Variables associated with increased mortality in our population were hypotension, infection, traumatic brain injury, and hematocrit.

Conclusions and Relevance:
Overall, survival for critically ill patients in rural Kenya was poor, but predictable with contributing factors. Models designed for resource-constrained settings had favorable discrimination and better calibration for mortality prediction than high-resource models in our population of mechanically ventilated, critically ill patients in rural Kenya.
Community Experience With Acute Respiratory Distress Syndrome in the Prone Position
Authors: Khan Fahmida , Fistler Christa R. , Mixell Jefferson , Caplan Richard , Vest Michael T. 
Published: December 2019

Objectives:
Mechanical ventilation in the prone position has been shown to improve outcomes in randomized trials of patients with moderate to severe acute respiratory distress syndrome and is recommended in clinical practice guidelines. However, data is lacking on the results of attempts to implement this practice in the community outside of clinical trials. To describe our early outcomes implementing mechanical ventilation in the prone position.

Design:
Retrospective cohort study.

Setting:
Medical intensive care unit of a large community-based teaching hospital.

Participants:
All patients ventilated in the prone position between June 2013 and October 2016.

Measurements and Main Results:
We describe patient characteristics, mortality, and frequency of complications (such as skin breakdown and accidental extubation) at our center. Eighty-one patients with a mean age of 55 years underwent mechanical ventilation in the prone position during the study period. Most patients also received vasopressors, neuromuscular blockade, and steroids. Overall mortality was 43%. The duration of the first proning session ranged from 1.5 to 40.5 hours. Mortality was lower (34%) in those ventilated in the prone position for more than 16 hours during the first session. In the 50 patients without treatment limitations, only 14% expired. There were no accidental extubations during prone positioning. Most of those who died had limitations placed on treatment prior to death.

Conclusions:
Overall mortality was higher in our cohort than in the randomized trial. However, differences such as lack of stabilization period, different cultures impacting end-of-life decisions, and timing of enrollment in the course of illness limit interpretation of this comparison. This exercise allows identification of areas for future quality improvement efforts such as increasing the duration of some proning sessions. Complications of prone positioning were uncommon.
Clinico-neuropathological features of isocitrate dehydrogenase 2 gene mutations in lower-grade gliomas
Authors: Wang Lei-Ming , Li Zhuo , Piao Yue-Shan , Cai Yan-Ning , Zhang Li-Yan , Ge Hai-Jing , Xu Wei-Wei , Lu De-Hong 
Published: December 2019

Abstract

Background:
Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lower-grade gliomas that carry IDH2 mutations.

Methods:
Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.

Results:
Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively).

Conclusions:

IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.
Latest clinical evidence of maintenance therapy in ovarian cancer
Authors: Walsh Christine S. 
Published: December 2019

Purpose of review
To summarize the data supporting the use of maintenance therapy in ovarian cancer treatment.

Recent findings
Since December 2016, the United States Food and Drug Administration has approved four drugs for six different ovarian cancer maintenance indications based on the results of clinical trials demonstrating efficacy and tolerability. These include antiangiogenesis and poly (adenosine diphosphate-ribose) inhibitors (PARP inhibitors). Four drugs are approved for use in maintenance therapy for recurrent ovarian cancer, including bevacizumab (GOG-0213 and OCEANS), niraparib (NOVA), olaparib (Study 19 and SOLO2) and rucaparib (ARIEL3). Two drugs are approved for use in maintenance therapy in newly diagnosed ovarian cancer, including bevacizumab (GOG-0218) and olaparib (SOLO1). New data were reported at the European Society for Medical Oncology Congress in October 2019 that may lead to the approval of additional strategies in front-line maintenance, including the use of niraparib (PRIMA), veliparib (VELIA) and bevacizumab + olaparib (PAOLA).

Summary
The landscape of maintenance treatment options for ovarian cancer has been rapidly expanding and continues to evolve as new data emerge. Currently approved strategies include antiangiogenesis and PARP inhibitor treatments.
IMPAIRED DARK ADAPTATION ASSOCIATED WITH A DISEASED BRUCH MEMBRANE IN PSEUDOXANTHOMA ELASTICUM
Authors: Hess Kristina , Gliem Martin , Birtel Johannes , Müller Philipp , Hendig Doris , Andrews Colm , Murray Ian J. , Holz Frank G. , Charbel Issa Peter 
Published: December 2019

Purpose:
To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane.

Methods:
In this prospective case–control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life.

Results:
Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation.

Conclusion:
Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.
DEVELOPMENT OF MACULAR ATROPHY AFTER PARS PLANA VITRECTOMY FOR MYOPIC TRACTION MACULOPATHY AND MACULAR HOLE RETINAL DETACHMENT IN PATHOLOGIC MYOPIA
Authors: Fang Yuxin , Yokoi Tae , Shimada Noriaki , Du Ran , Shinohara Kosei , Takahashi Hiroyuki , Uramoto Kengo , Ohno-Matsui Kyoko 
Published: December 2019

Purpose:
To determine the incidence and long-term outcome of macular atrophy (MA) after pars plana vitrectomy (PPV) in pathologic myopia.

Methods:
Highly myopic patients who underwent PPV for myopic traction maculopathy and macular hole retinal detachment at Tokyo Medical and Dental University between 2012 and 2016 were studied. Fundus photographs and/or optical coherence tomography were examined before and after PPV at every visit.

Results:
A total of 133 eyes were followed for 39 months with the mean age of 62.8 years and the mean axial length of 30.0 mm. Postoperatively, 14 eyes (10.5%) developed fovea-centered MA, observed initially as a small, isolated, whitish lesion at the center of fovea at 3.5 months after PPV. The appearance of the MA was distinctly different from the choroidal neovascularization–related MA or patchy atrophy–related MA. With time, the lesions enlarged circumferentially. In these 14 eyes, the final best-corrected visual acuity was worse than the baseline, although the difference was not significant. The occurrence of MA was significantly associated with the preoperative foveal status.

Conclusion:
The development of MA can occur in 11% of highly myopic eyes after PPV for myopic traction maculopathy and macular hole retinal detachment. This postoperative MA might be a new complication of pathologic myopia.
Stroke Templates and Trainee Education are Associated With Improved Data Capture in an Academic Hospital
Authors: Toumbs Randi , Dao Thanh , Zhu Liang , McCullough Louise , Savitz Sean , Cossey TC 
Published: December 2019

ABSTRACT

Background:
Effective medical record documentation is required to support accurate capture of diagnoses, patient acuity (case mix index [CMI]), and justify resource utilization for reimbursement. Billing code complexity and a lack of formal documentation education in training programs have created a need for academic medical centers to incorporate training for trainees (residents, fellows, and new nurse practitioners). We hypothesized that standardized stroke note templates, trainee education, and feedback from chart audits would improve documentation accuracy.

Purpose:
To improve the accurate/complete capture of expected (E) length of stay (LOS) and CMI by designing/implementing ischemic and hemorrhagic stroke templates containing high-frequency complication and comorbidity diagnoses with the greatest impact on stroke populations, combined with trainee education and chart audits.

Methods:
Descriptive statistics were used for outcomes before/after implementation of the templates. Primary outcomes include ELOS and CMI. Wilcoxon rank-sum test or chi-square test was used for group comparison.

Results:
The post-template group demonstrated a significant improvement in ELOS from 5.84 to 8.27 days (p < .0001). Case mix index increased (1.73–1.75; p < .0001) in the post-template group.

Conclusions:
Stroke-specific templates, trainee education, and chart audits were associated with significant improvement in documentation accuracy and an improved business model of stroke care in our hospital.
Leadership Competencies for Physical Therapists: A Delphi Determination
Authors: Sebelski Chris A , Green-Wilson Jennifer , Zeigler Stacey , Clark Diane , Tschoepe Barbara 
Published: December 2019

Introduction.
Leadership is linked to patient experience and quality of care. Some health care professions have identified leadership competencies to guide curriculum design. Yet, the physical therapy profession lacks explicit leadership competencies for the point-of-care professional. The academic community is inconsistent including leadership development within Doctor of Physical Therapy entry-level education or residency/fellowship training. This project aimed to fill this knowledge gap and inform the conversation on leadership competencies essential for new graduate physical therapists while clarifying whether expectations differ for those physical therapists with additional experience who do not hold formal leadership positions.

Subjects.
Delphi panel of physical therapists with content expertise in leadership

Methods.
A collated document of leadership competencies was circulated electronically to the Delphi panelists for 2 rounds of structured review. Each panelist rated each competency for level of importance for new graduate physical therapists and the more experienced physical therapists. Consensus threshold was set priori at 0.80.

Results.
The Delphi panel consisted of 14 content experts. Ten completed 2 rounds of review. Of the 76 potential leadership competencies, 37 were deemed as “very important” and 1 as “somewhat” important for all physical therapists regardless of years postlicensure. Three were “not important” for new graduate physical therapists. Consensus was not reached on 35 leadership competencies.

Conclusions.
Identification of leadership competencies for physical therapists is essential for role identity and to impact quality of care and the overall patient experience in physical therapy. Results of this paper provide a foundation for discussions on the adoption of a set of leadership competencies within the profession to guide leadership development within curricula for entry-level and professional development activities.
Impact of DPT Student Coordination of a Physical Therapy Pro Bono Clinic: A Qualitative Investigation
Authors: Stickler Laurie , Hoogenboom Barbara J. , Ozga Karen 
Published: December 2019

Introduction.
Pro bono physical therapy clinics provide a beneficial service to the community. Studies have identified a positive impact of student volunteerism in pro bono clinics. However, little is known about the immediate and long-term impact on those who serve as student coordinators of such clinics. Thus, the purpose of this study was to explore current and past pro bono clinic coordinators' perceptions of the professional and personal impact of serving as leaders of a pro bono physical therapy clinic.

Methods.
Current and past coordinators were recruited to participate in focus groups and individual interviews, respectively. All interviews were voice recorded, and the 4-step method for analyzing phenomenological data as described by Giorgi was used for data analysis.

Results.
Nine past coordinators agreed to participate in individual phone interviews, and 2 focus groups were conducted with a total of 8 current student coordinators. Three main themes emerged from the data: Essential Skills and Behaviors, Professional Development, and Personal Development.

Discussion and Conclusion.
Serving as a pro bono coordinator was an eye-opening multidimensional experience that transformed students on personal and professional levels. The results of this paper provide support for the development of leadership characteristics through participation as a student coordinator of a pro bono clinic. Such characteristics are highly desirable in the physical therapy profession.