bluuebunny/crossref_metadata_2025 huggingface dataset:
Gout
Authors: Dalbeth Nicola
Published: May 2018

Gout is a common and treatable disorder of purine metabolism. Gout typically presents as recurrent self-limiting episodes of severe inflammatory arthritis affecting the foot. In the presence of persistent hyperuricaemia, tophi, chronic synovitis, and joint damage may develop. Diagnosis of gout is confirmed by identification of monosodium urate (MSU) crystals using polarizing light microscopy. Hyperuricaemia is the central biochemical cause of gout. Genetic variants in certain renal tubular urate transporters including SLC2A9 and ABCG2, and dietary factors including intake of high-purine meats and seafood, beer, and fructose, contribute to development of hyperuricaemia and gout. Gout treatment includes: (1) management of the acute attack using non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or low-dose colchicine; (2) prophylaxis against gout attacks when commencing urate-lowering therapy (ULT), with NSAIDs or colchicine; and (3) long-term ULT to achieve a target serum urate of less than 0.36 mmol/litre. Interleukin (IL)-1β‎‎ is a central mediator of acute gouty inflammation and anti-IL-1β‎‎ therapies show promise for treatment of acute attacks and prophylaxis. The mainstay of ULT remains allopurinol. However, old ULT agents such as probenecid and benzbromarone and newer agents such as febuxostat and pegloticase are also effective, and should be considered in patients in whom allopurinol is ineffective or poorly tolerated. Management of gout should be considered in the context of medical conditions that frequently coexist with gout, including type 2 diabetes, hypertension, dyslipidaemia, and chronic kidney disease. Patient education is essential to ensure that acute gout attacks are promptly and safely managed, and long-term ULT is maintained.
Paget’s disease of bone
Authors: Ralston Stuart H.
Published: May 2018

Paget’s disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal abnormalities of bone remodelling which disrupt normal bone architecture, leading to expansion and reduced mechanical strength of affected bones. This can lead to various complications including deformity, fracture, nerve compression syndromes, and osteoarthritis, although many patients are asymptomatic. Genetic factors play a key role in the pathogenesis of PDB. This seems to be mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which increase susceptibility to environmental triggers. Environmental factors which have been suggested to predispose to PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are helpful in defining disease extent. Serum alkaline phosphatase levels can be used as a measure of disease activity. Inhibitors of bone resorption are the mainstay of medical management for PDB and bisphosphonates are regarded as the treatment of choice. Bisphosphonates are highly effective at reducing bone turnover in PDB and have been found to heal osteolytic lesions, and normalize bone histology. Although bisphosphonates can improving bone pain caused by elevated bone turnover, most patients require additional therapy to deal with symptoms associated with disease complications. It is currently unclear whether bisphosphonate therapy is effective at preventing complications of PDB.
Disorders of bone mineralization—osteomalacia
Authors: Jadon Deepak R. , Ahmed Tehseen , Bhalla Ashok K.
Published: May 2018

Disorders of bone mineralization cause rickets in children and osteomalacia in adults. Both remain common in developing countries. Incidence in Western countries had declined since the fortification of foodstuffs, but appears to be increasing again. Calcium and inorganic phosphate are the key precursors for bone mineralization and growth. The commonest aetiology of osteomalacia is vitamin D deficiency, primarily due to low dietary intake and inadequate sun exposure. In the last decade gene mutations have been identified that are responsible for inherited rickets and osteomalacia, particularly those that result in phosphate deficiency, hypophosphatasia, and vitamin D receptor or metabolizing enzyme mutations. Additionally, the pathogenesis of tumour-induced osteomalacia is becoming better understood. Osteomalacia may present as bone pain and tenderness, muscle pain and weakness, and skeletal deformity or fracture. Key investigations include biochemical assessment and plain radiographs. Radioisotope bone scans and bone biopsy may be considered in selected cases. Differential diagnoses include osteoporosis, seronegative arthritides, and localized soft tissue disorders. Treatment, guided by the underlying aetiology, aims to reduce symptoms, fracture risk, bone deformity and sequelae. Vitamin D deficient patients require vitamin D and calcium replacement.
Foot and ankle
Authors: Redmond Anthony C. , Helliwell Philip S.
Published: May 2018

Foot and ankle problems have been the subject of major advances in the rheumatology in recent years. This chapter reviews the anatomy of the foot and covers the manifestations of foot pathology for the major conditions: rheumatoid arthritis, osteoarthritis, the seronegative arthritides, connective tissue disease, crystal diseases, and miscellaneous conditions including hypermobility syndrome. Relevant local conditions including plantar fasciitis, tendinopathy, and neuroma are addressed separately. The principles of assessing and treating the foot and ankle in rheumatology are covered, along with the relevant specific approaches best suited to dealing with problems associated with the major conditions.
Childhood regional conditions
Authors: Houghton Kristin
Published: May 2018

Musculoskeletal (MSK) complaints are common in childhood. The majority of causes are benign and self-limiting, but MSK symptoms may be the presenting feature of serious life-threatening illness or chronic disease. Pain is often attributed to minor trauma, and atraumatic causes including infectious, inflammatory, and oncologic conditions, amplified musculoskeletal pain syndromes, and normal skeletal growth variants need to be considered. The age of the child helps identify the possible developmental conditions unique to the growing paediatric skeleton. Evaluation and management requires a thorough history and physical examination, and understanding of normal development.
This chapter reviews common MSK regional conditions in childhood.
Paper integration: The structural constraints and consequences of the US refugee resettlement program
Authors: Fee Molly
Published: May 2018

The migration literature contends that, unlike other immigrants, refugees resettled in the US benefit from a federal program of integration. These claims do not consider the barriers that may complicate the implementation of resettlement policy. Based on 16 months of ethnographic fieldwork at a refugee resettlement agency in California, I argue that the organizational structure of the US Resettlement Program shapes how caseworkers provide resettlement services on a daily basis. The financial insecurity of Resettlement Agencies coupled with high stakes government oversight creates an organizational culture of vulnerability where caseworkers rely on discretion as they put resettlement policy into practice. Caseworkers develop coping mechanisms to get by as they simultaneously attend to the demands of their funders and their refugee clients. Given these structural constraints and limited resources, caseworkers instrumentalize paperwork as a discretionary tool. When files and documents are privileged over the quality and extent of resettlement services, caseworkers creatively utilize paperwork to separate policy from practice in order to protect themselves and appease their refugee clients. This policy of integration instead becomes a practice of paper integration, which problematizes prior theories and assumptions about US refugee resettlement. This practice of paper integration ultimately affects the services that arriving refugees receive and the degree to which they benefit from this ostensible program of integration.
Endoscopic Endonasal Transclival Approach to the Ventral Brainstem: Anatomic Study of the Safe Entry Zones Combining Fiber Dissection Technique with 7 Tesla Magnetic Resonance Guided Neuronavigation
Authors: Weiss Alessandro , Perrini Paolo , De Notaris Matteo , Soria Guadalupe , Carlos Alarcon , Castagna Maura , Lutzemberger Lodovico , Santonocito Orazio Santo , Catapano Giuseppe , Kassam Amin , Prats-Galino Alberto
Published: May 2018

BACKGROUND

Treatment of intrinsic lesions of the ventral brainstem is a surgical challenge that requires complex skull base antero- and posterolateral approaches. More recently, endoscopic endonasal transclival approach (EETA) has been reported in the treatment of selected ventral brainstem lesions.

OBJECTIVE

In this study we explored the endoscopic ventral brainstem anatomy with the aim to describe the degree of exposure of the ventral safe entry zones. In addition, we used a newly developed method combining traditional white matter dissection with high-resolution 7T magnetic resonance imaging (MRI) of the same specimen coregistered using a neuronavigation system.

METHODS

Eight fresh-frozen latex-injected cadaver heads underwent EETA. Additional 8 formalin-fixed brainstems were dissected using Klingler technique guided by ultra-high resolution MRI.

RESULTS

The EETA allows a wide exposure of different safe entry zones located on the ventral brainstem: the exposure of perioculomotor zone requires pituitary transposition and can be hindered by superior cerebellar artery. The peritrigeminal zone was barely visible and its exposure required an extradural anterior petrosectomy. The anterolateral sulcus of the medulla was visible in most of specimens, although its close relationship with the corticospinal tract makes it suboptimal as an entry point for intrinsic lesions. In all cases, the use of 7T-MRI allowed the identification of tiny fiber bundles, improving the quality of the dissection.

CONCLUSION

Exposure of the ventral brainstem with EETA requires mastering surgical maneuvers, including pituitary transposition and extradural petrosectomy. The correlation of fiber dissection with 7T-MRI neuronavigation significantly improves the understanding of the brainstem anatomy.
Video Head Impulse Test to Preoperatively Identify the Nerve of Origin of Vestibular Schwannomas
Authors: Constanzo Felipe , Sens Patricia , Teixeira Bernardo Corrêa de Almeida , Ramina Ricardo
Published: May 2018

BACKGROUND

Identification of the nerve of origin in vestibular schwannoma (VS) is an important prognostic factor for hearing preservation surgery. Thus far, vestibular functional tests and magnetic resonance imaging have not yielded reliable results to preoperatively evaluate this information. The development of the video head impulse test (vHIT) has allowed a precise evaluation of each semicircular canal, and its localizing value has been tested for some peripheral vestibular diseases, but not for VS.

OBJECTIVE

To correlate patterns of semicircular canal alteration on vHIT to intraoperative identification of the nerve of origin of VSs.

METHODS

A total 31 patients with sporadic VSs were preoperatively evaluated with vHIT (gain of vestibule-ocular reflex, overt and covert saccades on each semicircular canal) and then the nerve of origin was surgically identified during surgical resection via retrosigmoid approach. vHIT results were classified as normal, isolated superior vestibular nerve (SVN) pattern, isolated inferior vestibular nerve (IVN) pattern, predominant SVN pattern, and predominant IVN pattern. Hannover classification, cystic component, and distance between the tumor and the end of the internal auditory canal were also considered for analysis.

RESULTS

Three patients had a normal vHIT, 12 had an isolated SVN pattern, 5 had an isolated IVN pattern, 7 had a predominant SVN pattern, and 4 had a predominant IVN pattern. vHIT was able to correctly identify the nerve of origin in 89.7% of cases (100% of altered exams).

CONCLUSION

The pattern of semicircular canal dysfunction on vHIT has a localizing value to identify the nerve of origin in VSs.
Preparing BSN Students for Engagement in Interprofessional Learning
Authors: Wall Cynthia L.
Published: May 2018

Interprofessional education in the undergraduate nursing curriculum is an important element for successful interprofessional collaboration and quality outcomes for patients. A correlational study was conducted to determine if professional nursing values were related to attitudes toward interprofessional learning. Results from a cross-sectional survey of 117 nursing students, using the revised Nurse Professional Values Scale and the revised Readiness for Interprofessional Learning Scale, demonstrated a significant correlation between subscales from both instruments (p < .05). Further research is warranted. Nurse educators are encouraged to develop professional values content with consideration for preparing students for their interprofessional roles.
Effects of Cancer Genetic Panel Testing on at-Risk Individuals
Authors: Frost Anja S. , Toaff Miriam , Biagi Tara , Stark Elizabeth , McHenry Allison , Kaltman Rebecca
Published: May 2018

OBJECTIVE:

To evaluate the role of screening patients at increased risk for hereditary cancer syndromes with an extended panel of cancer predisposition genes to identify actionable genetic mutations.

METHODS:

A retrospective chart review was conducted of all patients presenting to a multidisciplinary cancer program for genetic counseling and testing from January 2015 to December 2016. Individuals presenting to the program were identified as at-risk by a personal or family history of cancer, by their health care provider, or by self-referral. All participants met current National Comprehensive Cancer Network criteria for genetic risk evaluation for hereditary cancer. The results of testing and its implications for management, based on National Comprehensive Cancer Network guidelines, were recorded.

RESULTS:

Of 670 at-risk patients who underwent genetic testing, 66 (9.9%) had BRCA-limited testing; of these, 26 of 670 (3.9%) had a deleterious or likely pathogenic mutation. Expanded panel testing was done for 560 of the 670 patients (83.4%), and abnormal results were found in 65 of 670 (9.7%); non-BRCA mutations (predominantly CHEK2) were found in 49 of the 65 (75%). Abnormal genetic testing was associated with increased surveillance in 96% of those with deleterious mutations, whereas negative testing for a known familial mutation in 45 patients was associated with a downgrade of their risk and reduction of subsequent surveillance and management.

CONCLUSION:

Guideline-based management is frequently altered by genetic testing, including panel testing, in patients at risk for cancer. We recommend that obstetrics and gynecology providers routinely refer at-risk patients for genetic counseling and testing when clinically appropriate.
Satisfaction With the Intrauterine Device Insertion Procedure Among Adolescent and Young Adult Women
Authors: Akers Aletha Y. , Harding Jennifer , Perriera Lisa K. , Schreiber Courtney , Garcia-Espana J. Felipe , Sonalkar Sarita
Published: May 2018

OBJECTIVE:

To evaluate satisfaction with intrauterine device (IUD) insertion procedures among adolescent and young adult women.

METHODS:

This secondary analysis of data from a multisite, single-blind, sham-controlled randomized trial of women having a levonorgestrel 13.5-mg IUD inserted enrolled participants from March 2015 through July 2016 at three family planning clinics in Philadelphia, Pennsylvania. Eligible participants were 14–22 years of age, nulliparous, not pregnant, and English-speaking. Randomization was computer-generated allocation in block sizes of four to a 1% lidocaine paracervical or sham block. Only patients were blinded. Satisfaction was measured with three items that assessed overall satisfaction with the procedure, whether participants would recommend the IUD to a friend, and the perception that the IUD was worth the discomfort. Predictors included demographics, sexual and reproductive history, pain after IUD insertion, and treatment group.

RESULTS:

Ninety-five women enrolled; 93 (97.9%) were included in the analysis. Forty-five (47.4%) were white, 34 (36.0%) were black, 62 (66.0%) were privately insured, and 75 (79.0%) had used contraception previously. Most (n=73 [76.8%]) reported high overall satisfaction with the procedure, 64 (67.4%) would recommend an IUD to a friend, and 79 (83.2%) perceived the IUD was worth the discomfort. The odds of reporting high overall satisfaction were lower among adolescents compared with young adults (odds ratio [OR] 0.07, 95% CI 0.008–0.68); those who never had a gynecologic examination compared with those who had (OR 0.26, 95% CI 0.07–0.99); and decreased as pain score increased (OR 0.96, 95% CI 0.94–0.99). Higher pain scores were negatively correlated with the odds of recommending an IUD to a friend and perceiving the IUD was worth the discomfort.

CONCLUSION:

Adolescent and young adult women report high levels of satisfaction after the IUD insertion procedure. Young age, lack of experience with gynecologic examinations, and high pain were inversely related to satisfaction.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02352714.
The concept of oligometastases in colorectal cancer: from the clinical evidences to new therapeutic strategies
Authors: Massaut Edouard , Bohlok Ali , Lucidi Valerio , Hendlisz Alain , Klastersky Jean A. , Donckier Vincent
Published: May 2018

Purpose of review

The concept of oligometastases, defining cancers with limited metastatic capacity and attaining a limited number of secondary sites, is now widely accepted, particularly in colorectal cancer. Currently, however, accurate predictive markers for oligometastatic tumors are still lacking. For this reason, it remains challenging to translate this concept into clinical recommendations. In the present work, we review recent publications on oligometastases in colorectal cancer, showing the evidences for such presentation and underlying the need for the identification of biomarkers, necessary to further develop new therapeutic strategies.

Recent findings

This review of recently published series confirms that long-term survival and cure could be obtained in patients undergoing surgical resection for colorectal metastases, particularly in the cases of liver metastases. Similar results are observed in other secondary sites such as in pulmonary metastases. Furthermore, in patients with unresectable metastases, significant survival benefit could be still obtained using nonresectional targeted approaches, as thermal ablation or stereotactic radiotherapy. Although these clinical evidences could now serve as proof-of-concept for the existence of an oligometastatic phenotype in colorectal cancer, neither clinical characteristics nor biological biomarkers have been established to be able to prospectively define the patients that will benefit from such therapeutic approaches targeting the metastatic sites. This emphasizes the need for further studies aiming at better defining early clinical and biological characteristics of these patients. As, currently, the reliable identification of the oligometastatic patients could only rely on the demonstration of favorable long-term outcomes after metastases-directed therapies, we propose that retrospective studies will be pivotal to analyze this question.

Extensive research is undergoing to define biologically the oligometastatic phenotype in colorectal cancer. Currently, the selection of the patients for potentially curative metastasectomy remains mostly empirical.
Dual-Frequency Ultrasound as a New Treatment Modality for Refractory Rosacea: A Retrospective Study
Authors: Park Jun Yeong , Ahn Min Kyun , Cho Eun Byul , Park Eun Joo , Kim Kwang Ho
Published: May 2018

BACKGROUND

Dual-frequency ultrasound (DFU) has emerged as a new treatment modality for improving inflammatory skin disorders. Although there have been few pilot studies, there are a limited number of studies that investigated efficacy of DFU on refractory rosacea.

OBJECTIVE

This study investigated the effect of DFU on patients with refractory rosacea.

MATERIALS AND METHODS

The authors retrospectively analyzed medical records of 42 patients with refractory rosacea (erythematotelangiectatic rosacea [ETR], n = 26; papulopustular rosacea [PPR], n = 14, mixed, n = 2). The patients were treated with DFU twice per week for the 1st week, and then once per week thereafter. Efficacy was assessed using erythema index (EI), transepithelial water loss (TEWL), and patient self-assessment (PSA).

RESULTS

Treatment with DFU resulted in significant decrease in EI, TEWL, and PSA. No significant difference was noted between ETR and PPR.

CONCLUSION

Application of DFU in patients with refractory rosacea resulted in improvement in persistent erythema, barrier dysfunction, and patient-reported symptoms. Dual-frequency ultrasound may be an additional treatment option for rosacea that is resistant to other treatments.
ZEB Proteins in Leukemia: Friends, Foes, or Friendly Foes?
Authors: Soen Bieke , Vandamme Niels , Berx Geert , Schwaller Jürg , Van Vlierberghe Pieter , Goossens Steven
Published: May 2018

ZEB1 and ZEB2 play pivotal roles in solid cancer metastasis by allowing cancer cells to invade and disseminate through the transcriptional regulation of epithelial‐to‐mesenchymal transition. ZEB expression is also associated with the acquisition of cancer stem cell properties and therapy resistance. Consequently, expression levels of ZEB1/2 and of their direct target genes are widely seen as reliable prognostic markers for solid tumor aggressiveness and cancer patient outcome.

Recent loss‐of‐function mouse models demonstrated that both ZEBs are also essential hematopoietic transcription factors governing blood lineage commitment and fidelity. Interestingly, both gain‐ and loss‐of‐function mutations have been reported in multiple hematological malignancies. Combined with emerging functional studies, these data suggest that ZEB1 and ZEB2 can act as tumor suppressors and/or oncogenes in blood borne malignancies, depending on the cellular context. Here, we review these novel insights and discuss how balanced expression of ZEB proteins may be essential to safeguard the functionality of the immune system and prevent leukemia.
FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA
Authors: Onishi Yuka , Yokoi Tae , Kasahara Kaori , Yoshida Takeshi , Nagaoka Natsuko , Shinohara Kosei , Kaneko Yuichiro , Suga Mitsuki , Uramoto Kengo , Ohno-Tanaka Akiko , Ohno-Matsui Kyoko
Published: May 2018

Purpose:

To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV).

Method:

We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis.

Results:

The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy.

Conclusion:

Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.
Effect of Diabetes Mellitus and Metformin on Central Corneal Endothelial Cell Density in Eye Bank Eyes
Authors: Chocron Isaac M. , Rai Dinesh K. , Kwon Ji-Won , Bernstein Nicole , Hu Jimmy , Heo Moonseong , Lee Jimmy K. , Gore Patrick K. , McCartney Mitchell D. , Chuck Roy S.
Published: May 2018

Purpose:

To determine whether metformin use and diabetes mellitus (DM) affect central corneal endothelial cell density (ECD) by examining an eye bank corneal donor database.

Methods:

The Lions Eye Institute corneal donor database, which consists of 38,318 corneal samples, was examined. Associations of ECD with metformin use and DM were tested by mixed effects linear models that account for correlations of outcomes between eyes within subjects adjusting for age, intraocular lens status, and glaucoma. Subjects (N = 17,056) with observed ECD counts for both eyes are included for analysis.

Results:

Average donor age was 56.3 (SD = 15.0). ECD was not associated with metformin use (mean ± SE = 2592 ± 11.9 (N = 1014) versus nonuse [2592 ± 3.0 (N = 16,042), P = 0.302]; further analysis showed that ECD was not significantly associated with metformin use in patients with diabetes. However, metformin use was significantly associated with lower ECD among patients with glaucoma: [2658 ± 50.7 (N = 27) for use versus 2789 ± 19.0 (N = 164) for nonuse, P = 0.018]. The presence of DM was significantly associated with lower ECD 2581 ± 5.6 (N = 4766) for DM versus 2595 ± 3.4 (N = 12,290) for non-DM, P = 0.031).

Conclusions:

Lower ECD was associated with DM. Lower ECD was not associated with metformin use except in a subgroup of patients with glaucoma, in which subgroup analysis showed lower ECD. The differences in ECD observed were small and unlikely to affect the suitability for transplantation of donor corneas.
Intravenous Hypertonic Saline to Lower Intraocular Pressure in Ocular Hypertension and Primary Open-angle and Exfoliation Glaucoma
Authors: Inborr Pia Katriina , Harju Mika , Kivelä Tero T.
Published: May 2018

Purpose:

The purpose of this article was to quantitate the effect of intravenous hypertonic saline (IVHTS) on elevated intraocular pressure (IOP) among 3 groups of glaucoma patients or suspects.

Materials and Methods:

Among the forty-four patients with IOP 24 to 30 mm Hg included in this study, 13 had ocular hypertension (OHT), 14 primary open-angle glaucoma (POAG), and 17 exfoliation glaucoma (ExG). Participants received a bolus of 23.4% IVHTS (1.0 mmol/kg) through an antecubital vein. We measured IOP, heart rate, and blood pressure before the bolus, thereafter every minute for 10 minutes, and less frequently for 2 hours.

Results:

The median baseline IOP was 24 mm Hg (range, 24 to 30 mm Hg), 26.5 mm Hg (range, 24 to 30 mm Hg), and 26 mm Hg (range, 24 to 30 mm Hg) in OHT, POAG, and ExG patients, respectively. Sixteen minutes after the bolus, IOP was a median of 9 mm Hg (range, 4 to 12 mm Hg), 10 mm Hg (range, 6 to 12 mm Hg), and 10 mm Hg (range, 4 to 14 mm Hg) lower in OHT, POAG, and ExG groups (P=0.70), respectively. After 1 hour, the median IOP reduction was similar between ExG (9 mm Hg; range, 4 to 14 mm Hg) and POAG patients (9.5 mm Hg; range, 6 to 12 mm Hg) but lower in OHT patients (6 mm Hg; range, 2 to 9 mm Hg; P=0.006). Heart rate decreased by a median of 7 beats/min. Blood pressure increased within 3 minutes (median, mm Hg; 15 systolic; 5 diastolic), but returned to baseline at 10 minutes. Within 1 to 3 minutes of treatment, 36 (82%) patients felt pain in the infusion arm, and 29 (66%) reported a feeling of warmth in their head.

Conclusions:

IVHTS reduced IOP effectively in all groups.
Referral to Low Vision Services for Glaucoma Patients: Referral Criteria and Barriers
Authors: Kaleem Mona A. , West Sheila K. , Im Lily , Swenor Bonnielin K.
Published: May 2018

Purpose:

To determine what criteria are being used by glaucoma specialists to refer patients to low vision services (LVS) and to identify potential barriers to LVS referral.

Methods:

A survey was emailed to members of the American Glaucoma Society (AGS). The number and percentage of responses to each survey question were examined.

Results:

Reported criteria for referral included difficulty performing activities related to vision (78%), degree of visual field loss (63%), and difficulty with orientation and mobility (27%). Reported barriers to LVS referral included patients not expressing difficulty with activities related to vision (34%), not having enough time to counsel patients during clinic visits (32%), and perceiving that patients would not be able to afford LVS even if they were referred (31%).

Conclusions:

Among glaucoma specialists, patient-reported difficulties with vision-related activities were the most common criteria used for LVS referral. Reported barriers to LVS referral, including perceived patient economic restraints and insufficient time to counsel patients during clinic visits, need to be addressed through appropriate interventions.
Endogenous pain modulation in chronic orofacial pain: a systematic review and meta-analysis
Authors: Moana-Filho Estephan J. , Herrero Babiloni Alberto , Theis-Mahon Nicole R.
Published: May 2018

Abnormal endogenous pain modulation was suggested as a potential mechanism for chronic pain, ie, increased pain facilitation and/or impaired pain inhibition underlying symptoms manifestation. Endogenous pain modulation function can be tested using psychophysical methods such as temporal summation of pain (TSP) and conditioned pain modulation (CPM), which assess pain facilitation and inhibition, respectively. Several studies have investigated endogenous pain modulation function in patients with nonparoxysmal orofacial pain (OFP) and reported mixed results. This study aimed to provide, through a qualitative and quantitative synthesis of the available literature, overall estimates for TSP/CPM responses in patients with OFP relative to controls. MEDLINE, Embase, and the Cochrane databases were searched, and references were screened independently by 2 raters. Twenty-six studies were included for qualitative review, and 22 studies were included for meta-analysis. Traditional meta-analysis and robust variance estimation were used to synthesize overall estimates for standardized mean difference. The overall standardized estimate for TSP was 0.30 (95% confidence interval: 0.11-0.49; P = 0.002), with moderate between-study heterogeneity (Q [df = 17] = 41.8, P = 0.001; I2 = 70.2%). Conditioned pain modulation's estimated overall effect size was large but above the significance threshold (estimate = 1.36; 95% confidence interval: −0.09 to 2.81; P = 0.066), with very large heterogeneity (Q [df = 8] = 108.3, P < 0.001; I2 = 98.0%). Sensitivity analyses did not affect the overall estimate for TSP; for CPM, the overall estimate became significant if specific random-effect models were used or if the most influential study was removed. Publication bias was not present for TSP studies, whereas it substantially influenced CPM's overall estimate. These results suggest increased pain facilitation and trend for pain inhibition impairment in patients with nonparoxysmal OFP.
Hemophagocytic Lymphohistiocytosis Associated With Visceral Leishmaniasis
Authors: Özdemir Nihal , Koç Başak , Arslantaş Esra , Odaman Al Işik , Kelleci Çiğdem , Uysalol Ezgi Pasli , Bayram Cengiz , Ayçiçek Ali
Published: May 2018

This is the report of a 2-year-old boy who presented with fever, cytopenia, and splenomegaly. The patient was diagnosed with hemophagocytic lymphohistiocytosis (HLH) and treated with HLH-2004 protocol. Repeated bone marrow aspiration showed amastigotes on follow-up. In endemic countries, visceral leishmaniasis should be considered in the differential diagnosis to avoid chemotherapy toxicity.
An Atypical Case of Atypical Hemolytic Uremic Syndrome
Authors: Francois Tine , Vande Walle Johan , Dhont Evelyn , Keenswijk Werner
Published: May 2018

We present the case of a 2-month-old infant presenting with pallor and laboratory results showing: hemoglobin 5.1 (10 to 1.5) g/dL, MCV 94.7 (75 to 105) fL, leukocytes 17.4 (7 to 15) ×103/μL, platelets 259 (150 to 450) ×103/μL, hyperbilirubinemia and renal dysfunction. A hemolytic anemia with tubular injury secondary to hemoglobinuria was suspected. Hyperhydration and packed cells were given but she deteriorated. Fluid overload with anuria further complicated the course necessating hemodialysis. Atypical hemolytic uremic syndrome was suspected and eculizumab was administered resulting in rapid improvement. Genetic analysis revealed a mutation in the gene encoding complement factor H and atypical hemolytic uremic syndrome was confirmed.
Successful Treatment of Osteosarcoma Without Methotrexate in a 13-Year-Old Boy With Down Syndrome
Authors: Sims Emma , Nath Audrey , Sugalski Aaron
Published: May 2018

Osteosarcoma is the most common primary bone tumor in children, and only 1 article in the literature describes a case of osteosarcoma in a patient with Down syndrome. Although osteosarcoma is generally treated with chemotherapy regimens that include high-dose methotrexate, patients with Down syndrome have heightened sensitivity to the toxicities of methotrexate. The patient from the aforementioned case study died from sepsis soon after treatment with high-dose methotrexate. This case report describes the successful treatment of osteosarcoma in a pediatric patient with Down syndrome without methotrexate.
Implementing Enhanced Recovery After Surgery (ERAS) Program on a Specialty Nursing Unit
Authors: Tezber Kendra , Aviles Cesar , Eller Misty , Cochran Allyson , Iannitti David , Vrochides Dionisios , McClune Garth
Published: May 2018

Implementing Enhanced Recovery After Surgery (ERAS) guidelines is an effective method to standardize patient care, improve patient outcomes, and develop quality improvement projects. Completing the required ERAS Implementation Program provided by the International ERAS Society enabled the hepatopancreaticobiliary surgery team at Carolinas HealthCare System to successfully implement evidence-based practice changes for pancreaticoduodenectomy patients on an acuity-adjustable unit resulting in improved care and cost reduction.
Incidental Detection of Meningioma by 18F-FMAU PET/CT in a Patient With Suspected Prostate Cancer
Authors: Varghese Bino , Velez Erik , Desai Bhushan , Jadvar Hossein
Published: May 2018

We report on an incidental detection of a meningioma on [18F]-2′-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil (18F-FMAU) PET/CT scan that was performed during a prospective investigation of 18F-FMAU PET/CT for targeted biopsy of potential sites of tumor in men with suspected prostate cancer based on elevated prostate-specific antigen level. Neither prostate multiparamteric MRI nor 18F-FMAU PET/CT localized small volume Gleason 3 + 3 tumor deposits. However, an incidental focal high accumulation of 18F-FMAU was observed in high right parietal lobe that displayed characteristics of a meningioma on a subsequent brain MRI.
Unicentric Castleman’s Disease Revealed by 18F-FDG PET/CT and Somatostatin Receptor Scintigraphy With 99mTc-HYNIC-TOC
Authors: Luo Yaping , Wang Ling , Pan Qingqing , Ma Yanru , Li Fang
Published: May 2018

A 51-year-old woman with a history of hypertension and abdominal pain was found with a retroperitoneal mass. The mass had intense enhancement in contrast-enhanced CT, and it showed a moderate degree of increased FDG uptake in PET/CT. The mass was also positive in somatostatin receptor scintigraphy with 99mTc-HYNIC-TOC, but it was negative in 131I-MIBG scan. The histopathological result after surgical resection of the mass confirmed the diagnosis of Castleman’s disease, the hyaline vascular variant.
Systematic Identification and Analysis of Expression Profiles of mRNAs and Incrnas in Macrophage Inflammatory Response
Authors: Li Lei , Zhang Yimei , Luo Haihua , Huang Chenyang , Li Shan , Liu Aihua , Jiang Yong
Published: May 2018

Long noncoding RNAs (lncRNAs), once thought to be transcriptional noise, have been recently shown to regulate a variety of biological processes. However, their roles in the inflammatory response are largely unexplored. In this study, we performed high-throughput sequencing to identify the profiles of mRNA and lncRNA transcriptomes in response to lipopolysaccharide (LPS) stimulation, followed by a comprehensive bioinformatics analysis. We found a total of 325 lncRNAs and 1,187 mRNAs to be significantly dysregulated in RAW264.7 cells stimulated with LPS (fold change >4.0 or <0.25, false discovery rate <0.01). Further validation with qRT-PCR demonstrated that Cd40 and Traf1 mRNAs were significantly upregulated, whereas Slc43a2 and Ccnd1 were downregulated in RAW264.7 cells treated with LPS. Gene ontology (GO) analysis indicated that the altered mRNAs and lncRNAs were mainly involved in the immune response, inflammation response, chemokine receptor binding, protein binding, and regulation of cytokine production. KEGG pathway analysis showed that altered lncRNAs and mRNAs were significantly enriched in immune- and inflammation-related signaling pathways, such as Herpes simplex infection, cytokine–cytokine receptor interaction, and TNF, PI3K-Akt, MAPK, NF-κB, and JAK-STAT signaling pathways. lncRNA-mRNA network analysis showed that the coexpression network profile for mRNAs and lncRNAs from the immune category consisted of 93 network nodes and 145 connections among 70 differentially expressed mRNAs and 23 dysregulated lncRNAs, suggesting that lncRNAs play an important role in the regulation of functional mRNA expression in LPS-induced inflammation.
Integrative analysis of 5-methyl- and 5-hydroxymethylcytosine indicates a role for 5-hydroxymethylcytosine as a repressive epigenetic mark
Authors: Schlosberg Christopher E. , Edwards John R.
Published: May 2018

Since the discovery of 5-hydroxymethylcytosine (5hmC) as a prominent DNA base modification found in mammalian genomes, an emergent question has been what role this mark plays in gene regulation. 5hmC is hypothesized to function as an intermediate in the demethylation of 5-methylcytosine (5mC) and also in reactivation of silenced regulatory elements, including promoters and enhancers. Further, weak positive correlations have been observed between gene body 5hmC and gene expression. We previously demonstrated that ME-Class, which uses a high-resolution model of whole-genome bisulfite sequencing data, is an effective tool to understand relationships between 5mC and expression. In this work, we present ME-Class2, a machine-learning based tool to perform integrative 5mCG, 5hmCG and expression analysis. Using ME-Class2 we analyze whole-genome single-base resolution 5mC and 5hmC datasets from 20 primary tissue and cell samples to uncover relationships between 5hmC and expression. The addition of 5hmC improves model performance for tissues with high-levels of 5hmC such as the brain. Our analysis further indicates that conversion of 5mC to 5hmC within 2kb of the transcription start site associates with distinct functions depending on the summed level of 5mC + 5hmC. Unchanged levels of 5mC + 5hmC (i.e. conversion from 5mC to stable 5hmC) associate with repression. Meanwhile, decreases in 5mC + 5hmC (i.e. 5hmC-mediated demethylation) associate with gene activation. As more large-scale, genome-wide, differential DNA methylation studies become available, tools such as ME-Class2 will prove invaluable to interpret epigenomic data and guide mechanistic studies into the function of 5hmC.
Modeling gene expression networks to predict interchromosomal organization during human embryonic stem cell differentiation
Authors: Laster Kyle V. , Garza-Gongora Arturo G. , Daley Elizabeth , Terskikh Alexey , Kiskinis Evangelos , Smith Erica D. , Kosak Steven T.
Published: May 2018

Cellular differentiation occurs through the regulation of lineage-specific gene expression networks that are facilitated by the spatial organization of the genome. Although techniques based on the chromatin conformation capture (3C) approach have yielded intrachromosomal genome-wide interaction maps, strategies to identify non-random interchromosomal associations is lacking. Therefore, we modeled the genomic organization of chromosomes based on the regulatory networks involved in the differentiation of pluripotent human embryonic stem cells (hESCs) to committed neuronal precursor cells (cNPCs). Importantly, transcriptional regulation has been demonstrated to be a driving force in non-random genome organization. Thus, we constructed coarse-grainedin siliconetworks using gene expression data to identify potential physical associations among chromosomes occurringin situand then analyzed the three-dimensional (3D) distribution of these chromosomes, assessing how their associations contribute to nuclear organization. Our analysis suggests that coordinate regulation of differentially expressed genes is correlated with the 3D organization of chromosomes in hESC nuclei induced to differentiate to cNPCs.

Author Summary

The cellular commitment and differentiation of stem cells is a hallmark of metazoan development. The ultimate fate of a stem cell is defined by the synergistic modulation of key gene regulatory networks within the nucleus. In our work, we formulate anin silicomodel describing how the similarity in the expression profile of differentially regulated gene networks is correlated with the higher-order organization of chromosomes during differentiation from human embryonic stem cells (hESCs) to committed neuronal precursor cells (cNPCs). Using graph statistics, we observe that the genome networks generated using thein silicomodel exhibit properties similar to real-world networks. In addition to modeling how gene expression relates to dynamic changes in chromosome organization, we test the model by calculating the relative proximity of multiple chromosome pairs using 3D fluorescencein situhybridization (FISH). While various chromosomal properties, including gene density and overall length, have been attributed to chromosome organization, our previous work has identified the emergence of cell-type specific chromosomal topologies related to coordinate gene regulation during cellular differentiation. Here we extend these findings by determining whether ourin silicomodel can predict chromosome association based upon coordinate gene expression. Our work supports the idea that gene co-regulation, in addition to inherent organizational constraints of the nucleus, influences three-dimensional chromosome organization.
Bone remodeling: A tissue-level process emerging from cell-level molecular algorithms
Authors: Arias Clemente F. , Herrero Miguel A. , Echeverri Luis F. , Oleaga Gerardo E. , López José M.
Published: May 2018

Human skeleton undergoes constant remodeling during the whole life. By means of such process, which occurs at a microscopic scale, worn out bone is replaced by new, fully functional one. Multiple bone remodeling events occur simultaneously and independently throughout the body, so the whole skeleton is completely renewed about every ten years.

Bone remodeling is performed by groups of cells called Bone Multicellular Units (BMU). BMUs consist of different cell types; some are specialized in destroying old bone, whereas others produce new bone to replace the former. The whole process is tightly regulated so that the amount of new bone produced exactly balances that of old one removed and bone microscopic structure is maintained.

To date, many regulatory molecules involved in bone remodeling have been identified, but the precise mechanism of BMU operation remains to be fully elucidated. Given the complexity of the signaling pathways already known, the question arises of ascertaining whether such complexity is an inherent requirement of the process, or a consequence of operational redundancy.

In this work we propose a minimal model of BMU function which involves a small number of signals and accounts for fully functional BMU operation. Our main assumptions are i) at any given time, any cell within a BMU can select only one among a reduced choice of decisions: divide, die, migrate or differentiate, ii) such decision is irreversibly determined by depletion of an appropriate internal inhibitor and iii) the dynamics of any such inhibitor is coupled to that of a few external mediators. It is shown that efficient BMU operation then unfolds as an emergent property, which results from individual decisions taken by cells in the BMU unit in the absence of any external planning.

Author summary

Our skeleton is a living organ that is being renewed throughout our life. This task is accomplished by teams of bone cells termed as Bone Multicellular Units (BMUs) that are recruited when and where needed, to operate at places where bone has lost functionality either for an excess of mechanical stress or because loss of activity. Once assembled, BMU remove old bone and replace it by new one, and disband as soon as their mission has been accomplished. No single bone evades BMU screening, so that the whole human skeleton is completely renewed approximately every ten years.

It is natural to wonder how such robust and fascinating process is regulated. Many signaling pathways involved in bone remodeling have been identified so far, but whether all of them are necessary for BMU operation remains unclear. In this work we show that just a reduced number of such signals could suffice for that purpose. This suggests that a large degree of redundancy might have been kept in place, perhaps as a consequence of different convergent strategies developed in the course of evolution.
Temporal dynamics of endogenous attentional modulation without cue awareness
Authors: Osako Yuma , Murai Shota , Shimpaku Jun , Kobayasi Kohta I.
Published: May 2018

Invisible visual stimuli can regulate our broad cognitive performance in the pursuit of current goals. Endogenous spatial attention is an important modulator of cognitive performance, and it can be triggered by unconscious cues. However, how its effect changes with time remains unclear. Here, we show that endogenous attention was triggered by an arrow-cue whose direction participants reported being unaware of but which affected the task performance in a time-dependent manner. Participants were asked to remember the directions of eight Landolt c rings (target memory array) after arrow-cue presentation, which was designed to orient their attention to a certain c ring. Then, we applied a delay, ranging from 83 ms to 1000 ms, between the arrow-cue and the target memory array presentation (the possible delays were equally spaced on a logarithmic scale). The attentional effect was greater for the 83, 183, 250 and 333 ms delays than the other six possible delays. In contrast, its effect was maintained irrespective of the delay when the participants reported being aware of the cue direction. Thus, awareness of arrow-cue direction was necessary to maintain endogenous attentional modulation, and its modulation without arrow-cue direction awareness was limited in a time-dependent manner.