bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Postnatal Exposure to Isoflurane Disrupts Oligodendrocyte Development and Myelin Formation in the Mouse Hippocampus
Authors: Li Qun , Mathena Reilley P. , Xu Jing , Eregha O’Rukevwe N. , Wen Jieqiong , Mintz Cyrus D. 
Published: August 2019

Abstract

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Background
Early postnatal exposure to general anesthetics may interfere with brain development. We tested the hypothesis that isoflurane causes a lasting disruption in myelin development via actions on the mammalian target of rapamycin pathway.

Methods
Mice were exposed to 1.5% isoflurane for 4 h at postnatal day 7. The mammalian target of rapamycin inhibitor, rapamycin, or the promyelination drug, clemastine, were administered on days 21 to 35. Mice underwent Y-maze and novel object position recognition tests (n = 12 per group) on days 56 to 62 or were euthanized for either immunohistochemistry (n = 8 per group) or Western blotting (n = 8 per group) at day 35 or were euthanized for electron microscopy at day 63.

Results
Isoflurane exposure increased the percentage of phospho-S6–positive oligodendrocytes in fimbria of hippocampus from 22 ± 7% to 51 ± 6% (P < 0.0001). In Y-maze testing, isoflurane-exposed mice did not discriminate normally between old and novel arms, spending equal time in both (50 ± 5% old:50 ± 5% novel; P = 0.999), indicating impaired spatial learning. Treatment with clemastine restored discrimination, as evidenced by increased time spent in the novel arm (43 ± 6% old:57 ± 6% novel; P < 0.001), and rapamycin had a similar effect (44 ± 8% old:56 ± 8% novel; P < 0.001). Electron microscopy shows a reduction in myelin thickness as measured by an increase in g-ratio from 0.76 ± 0.06 for controls to 0.79 ± 0.06 for the isoflurane group (P < 0.001). Isoflurane exposure followed by rapamycin treatment resulted in a g-ratio (0.75 ± 0.05) that did not differ significantly from the control value (P = 0.426). Immunohistochemistry and Western blotting show that isoflurane acts on oligodendrocyte precursor cells to inhibit both proliferation and differentiation. DNA methylation and expression of a DNA methyl transferase 1 are reduced in oligodendrocyte precursor cells after isoflurane treatment. Effects of isoflurane on oligodendrocyte precursor cells were abolished by treatment with rapamycin.

Conclusions
Early postnatal exposure to isoflurane in mice causes lasting disruptions of oligodendrocyte development in the hippocampus via actions on the mammalian target of rapamycin pathway.
Macrophages and cadherins in fibrosis and systemic sclerosis
Authors: To Sarah , Agarwal Sandeep K. 
Published: August 2019

Purpose of review
Macrophages are key players in systemic sclerosis (SSc) and fibrosis. The mechanism by which macrophages regulate fibrogenesis is unclear and understanding the origin and function of macrophages is critical to developing effective therapeutics. Novel targets on macrophages are under investigation and recently, cadherins have emerged as a potential therapeutic target on macrophages. The current review will discuss the importance of macrophages in SSc and fibrosis and summarize recent studies on the role of cadherin-11 (Cdh11) on macrophages and fibrosis.

Recent findings
Genome-wide expression studies demonstrate the importance of macrophages in SSc and fibrosis. Although M2 macrophages are associated with fibrosis, the presence of a mixed M1/M2 phenotype in fibrosis has recently been reported. Several studies aiming to identify macrophage subsets involved in fibrogenesis suggest that monocyte-derived alveolar macrophages are key players in the development of murine lung fibrosis. Recent functional studies show that Cdh11 regulates macrophages, fibroblast invasion, and adhesion of macrophages to myofibroblasts.

Summary
Macrophages play an important role in SSc and fibrosis. New insights into the mechanisms by which macrophages regulate fibrogenesis have been discovered on the basis of Cdh11 studies and suggest that targeting Cdh11 may be an effective target to treat fibrosis.
Role of dose-dense chemotherapy in high-risk early breast cancer
Authors: Blondeaux Eva , Poggio Francesca , Del Mastro Lucia 
Published: August 2019

Purpose of review
Adjuvant chemotherapy for breast cancer significantly reduces the risk of recurrence and improves overall survival (OS). The purpose of the current article is to review available evidence on dose-dense chemotherapy, also focusing on special population, including premenopausal women and those with HER2-positive disease.

Recent findings
A recent patient-level meta-analysis showed that the use of dose-dense chemotherapy is associated with significant reduction in disease recurrence, breast cancer mortality and improvement in OS. The benefit of dose-dense chemotherapy is irrespective from HER2 status, although women with HER2-positive disease enrolled in trials included in the meta-analysis did not receive the current standard of treatment with anti-HER2 agents. Among premenopausal women, dose-dense chemotherapy improved OS, and thus should be considered standard of care for them.

Summary
In conclusion, high-risk early stage breast cancer patients should be treated with (neo)adjuvant dose-dense anthracycline-based chemotherapy followed by paclitaxel. In the era of trastuzumab, the benefit of dose-dense chemotherapy is still unclear for patients with HER2-positive breast cancer.
Optical Coherence Tomography Angiography in Pinguecula and Pterygium
Authors: Zhao Fengping , Cai Sijie , Huang Zhu , Ding Peisheng , Du Chixin 
Published: August 2019

Purpose:
To investigate the density of conjunctival blood vessels in normal eyes and in eyes with pinguecula or pterygium.

Methods:
In this cross-sectional study, the conjunctival blood vessel density of 15 normal eyes, 15 pinguecula eyes, and 15 pterygium eyes of 43 healthy adults was assessed using optical coherence tomography angiography with an anterior segment lens adapter. The nasal surface of each eye (3 × 3 mm) was scanned 3 times to a depth of 800 μm. Conjunctival vessel density was defined as the percent of the scanned volume occupied by vessels in which blood flow was measured.

Results:
The high reliability of data measurement was supported by good coefficients of repeatability (<10%) of the image quality score and high intraclass correlation coefficients (>0.9). The vessel density in normal conjunctivas, 52.2 ± 4.1%, was similar to that in pinguecula conjunctivas, 50.5 ± 4.7% (P = 0.3006). However, the vessel density in conjunctivas with pterygium, 63.6 ± 3.7%, was greater than that in either normal (P < 0.0001) or pinguecula (P < 0.0001) conjunctivas.

Conclusions:
Using optical coherence tomography angiography with an anterior segment lens adapter, the ocular surface blood vessel density was imaged and assessed with good repeatability and reliability. The blood vessel density of conjunctivas with pterygium was significantly greater than that in either normal or pinguecula conjunctivas. This suggests that, in contrast to pinguecula development, pterygium development includes angiogenesis and neovascularization.
Laying the Foundation for the National TeleNursing Center: Integration of the Quality-Caring Model Into TeleSANE Practice
Authors: Meunier-Sham Joan , Preiss Rachel M. , Petricone Randi , Re Cheryl , Gillen Leah 
Published: August 2019

ABSTRACT
In 2012, the Massachusetts Department of Public Health Sexual Assault Nurse Examiner (SANE) Program was awarded a grant from the Department of Justice, Office for Victims of Crime, to pilot the use of telemedicine technology to extend the reach of SANE expertise to six diverse communities across the United States. To meet the goals of this project, the National TeleNursing Center (NTC) developed a three-phase professional practice model integrating the Quality-Caring Model (QCM) to support the delivery of NTC teleSANE services. Using the QCM as a foundation for teleSANE practice ensures that patients experiencing a recent sexual assault who participate in teleSANE encounters receive quality forensic nursing care. In this article, we briefly review elements of the QCM, describe the application of the model to the NTC Professional Practice Model, and detail how teleSANEs integrate the QCM Caring Behaviors into all three phases of its model. The NTC Professional Practice Model provides a quality-based teleSANE model that may be translatable to other areas of telenursing practice.
Hypertriglyceridemia and Intravenous Lipid Titration During Routine Parenteral Nutrition in Small Preterm Infants
Authors: Correani Alessio , Giretti Ilaria , Antognoli Luca , Monachesi Chiara , Cogo Paola , D'Ascenzo Rita , Biagetti Chiara , Carnielli Virgilio P. 
Published: August 2019

ABSTRACTObjectives:In case of hypertriglyceridemia (HiTG) during parenteral nutrition (PN), the 2018 European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an intravenous (IV) lipid titration, but its consequences in small preterm infants are largely unknown. We compared macronutrient and energy intakes, growth, diseases associated with prematurity, and neurodevelopment in small preterm infants on PN who developed (cases) or did not develop HiTG (controls, CNTR).Methods:We retrospectively reviewed data of preterm infants with a birth weight (BW) <1250 g consecutively admitted to our neonatal intensive care unit (2004–2016) who received routine PN. HiTG infants were defined by at least 1 triglyceride (TG) measurement >250 mg/dL during the first 10 days of life. Patients with and without HiTG were match‐paired for BW and gestational age.Results:A total of 658 infants were analyzed and 196 (30%) had HiTG. One hundred thirty‐six HiTG patients were matched with 136 CNTR. In the first 10 days of life, IV lipid, non‐protein energy and total energy intakes, but not IV amino acids and carbohydrates, were significantly lower in HiTG infants. We found no differences between groups in diseases associated with prematurity. Anthropometry at 36 weeks (W), anthropometry at 2‐year (Y) corrected age (CA), and neurodevelopment at 2Y CA were not different.Conclusions:Growth, diseases associated with prematurity, and neurodevelopment at 2Y CA in HiTG infants were similar to CNTR. This occurred despite a statistically significant albeit small reduction in IV lipid and non‐protein energy intakes due to a strict TG monitoring and IV lipid titration at TG levels >250 mg/dL.
The Effect of Stroke on Middle Cerebral Artery Blood Flow Velocity Dynamics During Exercise
Authors: Kempf Katie S. , Whitaker Alicen A. , Lui Yumei , Witte Emily , Perdomo Sophy J. , Ward Jaimie L. , Eickmeyer Sarah , Ledbetter Luke , Abraham Michael , Billinger Sandra A. 
Published: August 2019

Background and Purpose:
Previous work demonstrates that older adults have a lower response in the middle cerebral artery velocity (MCAv) to an acute bout of moderate-intensity exercise when compared with young adults. However, no information exists regarding MCAv response to exercise after stroke. We tested whether MCAv response to an acute bout of moderate-intensity exercise differed between participants 3 months after stroke and an age- and sex-matched control group of older adults (CON). A secondary objective was to compare MCAv response between the stroke- and non-stroke-affected MCAv.

Methods:
Using transcranial Doppler ultrasound, we recorded MCAv during a 90-second baseline (BL) followed by a 6-minute moderate-intensity exercise bout using a recumbent stepper. Heart rate (HR), end-tidal CO2 (PETCO2), and beat-to-beat mean arterial blood pressure (MAP) were additional variables of interest. The MCAv response measures included BL, peak response amplitude (Amp), time delay (TD), and time constant (τ).

Results:
The Amp was significantly lower in the stroke-affected MCAv compared with CON (P < 0.01) and in the nonaffected MCAv compared with CON (P = 0.03). No between-group differences were found between TD and τ. No significant differences were found during exercise for PETCO2 and MAP while HR was lower in participants with stroke (P < 0.01). Within the group of participants with stroke, no differences were found between the stroke-affected and non-stroke-affected sides for any measures.

Discussion and Conclusions:
Resolution of the dynamic response profile has the potential to increase our understanding of the cerebrovascular control mechanisms and test cerebrovascular response to physical therapy–driven interventions such as exercise.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A284).
A History of the Frenchay Hospital Plastic Surgery Unit, Bristol, United Kingdom
Authors: Davies Alex J. , Pleat Jonathon M. , Wilson Sherif M. 
Published: August 2019

Abstract
Frenchay Hospital has long since been established as the center for plastic surgery in Bristol, providing care to the city and its surrounding catchment area. From humble origins in the Second World War when the site took on the role of a large military hospital providing reconstructive surgery for the victims of war to a busy modern-day National Health Service establishment, the plastic surgery unit at Frenchay Hospital has grown and developed through in parallel with the genesis and development of the specialty. Recent centralization of care in Bristol has seen a massive reorganization of services, and with it the closure of Frenchay Hospital. Because the plastic surgery unit establishes a new home at Southmead Hospital, this review documents the foundations of reconstructive surgery in Bristol and the South West United Kingdom.
Cytoplasmic Cyclin E Expression Predicts for Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Karakas Cansu , Francis Ashleigh M. , Ha Min Jin , Wingate Hannah F. , Meena Richard A. , Yi Min , Rasaputra Komal S. , Barrera Angelica M. Gutierrez , Arun Banu , Do Kim-Anh , Sahin Aysegul , Keyomarsi Khandan , Hunt Kelly K. 
Published: August 2019

Background:
Pathologic complete response (pCR) has been shown to be associated with favorable outcomes in breast cancer. Predictors of pCR could be useful in guiding treatment decisions regarding neoadjuvant therapy. The objective of this study was to evaluate cyclin E as a predictor of response to neoadjuvant chemotherapy in breast cancer.

Methods:
Patients (n = 285) with stage II–III breast cancer were enrolled in a prospective study and received neoadjuvant chemotherapy with anthracyclines, taxanes, or combination of the two. Pretreatment biopsies from 190 patients and surgical specimens following chemotherapy from 192 patients were available for immunohistochemical analysis. Clinical and pathologic responses were recorded and associated with presence of tumor infiltrating lymphocytes, cyclin E, adipophilin, programmed cell death-ligand 1, and elastase staining and other patient, tumor and treatment characteristics.

Results:
The pCR rate was significantly lower in patients with cytoplasmic cyclin E staining compared with those who had no cyclin E expression (16.1% vs 38.9%, P = 0.0005). In multivariable logistic regression analysis, the odds of pCR for patients who had cytoplasmic negative tumors was 9.35 times (P value < 0.0001) that compared with patients with cytoplasmic positive tumors after adjusting for ER, PR, and HER2 status. Cytoplasmic cyclin E expression also predicts long-term outcome and is associated with reduced disease free, recurrence free, and overall survival rates, independent of increased pretreatment tumor infiltrating lymphocytes.

Conclusions:
Cyclin E independently predicted response to neoadjuvant chemotherapy. Hence, its routine immunohistochemical analysis could be used clinically to identify those breast cancer patients expected to have a poor response to anthracycline/taxane-based chemotherapy.
Laparoscopic to Open Cholecystectomy: The Risk Factors and the Reasons; A Retrospective Analysis of 1950 Cases of a Single Tertiary Center
Authors: Kara Yasin , Kalayci Mustafa U. 
Published: August 2019

Purpose:
We investigated the reasons, rates, and risk factors for the conversion to open cholecystectomies (CTOC) by statistical analysis with the demographic properties.

Materials and Methods:
Demographic properties (age and sex), abdominal operations, and intraoperative and postoperative reasons for cholecystectomies were analyzed in 1950 patients.

Results:
The patients included 1540 (79%) women and 410 (21%) men (F/M=3.8); of these 115 (5.9%) had CTOC in early or late period. The rate of CTOC in men was significantly high (P= 0.009). There was no mortality. The reasons for CTOC were: significant inflammation (n=53, 46%), inadequate dissection of Calot triangle due to fibrotic adhesions (n=31, 27%), adhesions of previous surgery (n=9, 7.8%), uncontrollable bleeding (n=5, 4.3%), technical insufficiency (n=5, 4.3%), bile duct injury (n=5, 4.3%), anatomical variations (n=3, 2.6%), iatrogenic visceral injury (n=2, 1.7%), isolated right posterior bile duct injury (strasberg type-C) (n=1, 0.9%), and common hepatic duct partial injury (n=1, 0.9%).

Conclusions:
Significant inflammation, inadequate dissection of Calot triangle due to fibrotic adhesions, and adhesions due to previous surgery were the 3 main reasons for conversion. Men and elderly patients were associated with significantly high rate of conversion.
The impact of reactive mass vaccination campaigns on measles outbreaks in the Katanga region, Democratic Republic of Congo
Authors: Funk Sebastian , Takahashi Saki , Hellewell Joel , Gadroen Kartini , Carrion-Martin Isidro , van Lenthe Marit , Rivette Katiana , Dietrich Sebastian , Edmunds W. John , Siddiqui Ruby , Rao V. Bhargavi 
Published: August 2019

AbstractThe Katanga region in the Democratic Republic of Congo (DRC) has been struck by repeated epidemics of measles, with large outbreaks occurring in 2010–13 and 2015. In many of the affected health zones, reactive mass vaccination campaigns were conducted in response to the outbreaks. Here, we attempted to determine how effective the vaccination campaigns in 2015 were in curtailing the ongoing outbreak. We further sought to establish whether the risk of large measles outbreaks in different health zones could have been determined in advance to help prioritise areas for vaccination campaign and speed up the response. In doing so, we first attempted to identify factors that could have been used in 2015 to predict in which health zones the greatest outbreaks would occur. Administrative vaccination coverage was not a good predictor of the size of outbreaks in different health zones. Vaccination coverage derived from surveys, on the other hand, appeared to give more reliable estimates of health zones of low vaccination coverage and, consequently, large outbreaks. On a coarser geographical scale, the provinces most affected in 2015 could be predicted from the outbreak sizes in 2010–13. This, combined with the fact that the vast majority of reported cases were in under-5 year olds, would suggest that there are systematic issues of undervaccination. If this was to continue, outbreaks would be expected to continue to occur in the affected health zones at regular intervals, mostly concentrated in under-5 year olds. We further used a model of measles transmission to estimate the impact of the vaccination campaigns, by first fitting a model to the data including the campaigns and then re-running this without vaccination. We estimated the reactive campaigns to have reduced the size of the overall outbreak by approximately 21,000 (IQR: 16,000–27,000; 95% CI: 8300–38,000) cases. There was considerable heterogeneity in the impact of campaigns, with campaigns started earlier after the start of an outbreak being more impactful. Taken together, these findings suggest that while a strong routine vaccination regime remains the most effective means of measles control, it might be possible to improve the effectiveness of reactive campaigns by considering predictive factors to trigger a more targeted vaccination response.
Evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection
Authors: Trotter Alexander J. , Dean Rachael , Whitehouse Celia E. , Mikalsen Jarle , Hill Claire , Brunton-Sim Roxanne , Kay Gemma L. , Shakokhani Majeed , Durst Alexander , Wain John , McNamara Iain , O’Grady Justin 
Published: August 2019

AbstractBackgroundMicrobiological diagnosis of prosthetic joint infection (PJI) relies on culture techniques that are slow and insensitive. Rapid tests are urgently required to improve patient management. Calprotectin is a neutrophil biomarker of inflammation that has been demonstrated to be effective for the diagnosis of PJI. A calprotectin based lateral flow test has been developed for the rapid detection of PJI using synovial fluid samples.MethodsA convenience series of 69 synovial fluid samples from patients at the Norfolk and Norwich University Hospitals (NNUH) were collected intraoperatively from 52 hip and 17 knee revision operations. Calprotectin levels were measured using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone). For all samples, synovial fluid was pipetted onto the lateral flow device and the signal was read using a mobile phone app after 15 minutes incubation at room temperature.ResultsAccording to the Musculoskeletal Infection Society (MSIS) criteria, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test against the MSIS criteria was 75%. The test had a sensitivity and specificity of 75% and 76% respectively with a positive predictive value (PPV) of 62% and a negative predictive value (NPV) of 85%. Discordant results were then reviewed by the clinical team using available patient data to develop an alternative gold standard for defining presence/absence of infection (MSIS+). Compared to MSIS+, the test showed an overall accuracy of 83%, sensitivity and specificity of 95% and 78% respectively, a PPV of 62% and an NPV of 98%. Test accuracy for hip revisions was 77% and for knee revisions was 100%.ConclusionsThis study demonstrates that the calprotectin lateral flow assay is an effective diagnostic test for PJI. Our data suggests that the test is likely to generate false positive results in patients with metallosis and gross osteolysis.
Challenges in Building and Maintaining Rare Disease Patient Registries: Results of a Questionnaire Survey in Japan at 2012
Authors: Morita Mizuki , Ogishima Soichi 
Published: August 2019

AbstractBackgroundResearch infrastructure such as patient registries and biobanks is expected to play important roles by aggregating information and biospecimens to promote research and development for rare diseases. However, both building and maintaining them can be costly. This paper presents results of a survey of patient registries for rare diseases in Japan conducted at the end of 2012, with emphasis on clarifying costs and efforts related to building and maintaining them.ResultsOf 31 patient registries in Japan found by searching a database of research grant reports and by searching the internet, 11 returned valid responses to this survey. Results show that labor and IT system costs are major expenses for developing and maintaining patient registries. Half of the respondent patient registries had no prospect of securing a budget to maintain them. Responders required the following support for patient registries: financial support, motivation of registrants (medical doctors or patients), and improved communication with and visibility to potential data users. These results resemble those reported from another survey conducted almost simultaneously in Europe (EPIRARE survey).ConclusionsSurvey results imply that costs and efforts to build and maintain patient registries for many rare diseases make them unrealistic. Some alternative strategy is necessary to reduce burdens, such as offering a platform that supplies IT infrastructure and basic secretariat functions that can be used commonly among many patient registries.