bluuebunny/crossref_metadata_2025 huggingface dataset:
High Prevalence of Lipid Abnormalities and Insulin Resistance Among Antiretroviral Naïve HIV-infected Children in India
Authors: Padmapriyadarsini C. , Shet Anita , Srinivasan R. , Ramachandran Geetha , Sanjeeva G. N. , Devi Poornaganga , Ramesh K. , Bhavani Perumal K. , Reddy Devaraj , Suresh E. , Chandrasekhar C. , Wanke Christine , Swaminathan Soumya
Published: November 2017

Background:

As large numbers of children are accessing antiretroviral therapy (ART) in India, we evaluated the dietary intake, growth pattern and risk of metabolic complications like dyslipidemia and insulin resistance among ART-naïve HIV-infected children (CLHIV).

Methods:

CLHIV 2–12 years of age, at the time of initiating ART in Chennai and Bangalore, were assessed for their dietary intake, anthropometry, blood CD4 cell count, HIV-1 viral load, fasting serum lipids, glucose and insulin. Homeostatic model assessment-insulin resistance was derived.

Results:

Three hundred and ninety CLHIV (mean age [SD]: 8 [3] yrs; median viral load: 141,000 [25,876–436,000] copies/mL) were started on non-nucleoside reverse transcriptase inhibitor-based ART. Perinatal infection was documented among 97%. Sixty percent of children were in stage 3 or 4 of World Health Organization clinical staging of HIV/AIDS. Food insecurity was seen in 40% of households. A total of 204 children (52.4%) were stunted and 224 (57.6%) were underweight. Stunting seemed to be more prevalent with increasing age (0–4 years: 48%; >9 years: 60%). Mean intakes of calories, iron, folate and calcium were significantly less than recommended dietary allowances across all age groups. Dyslipidemia, in terms of any abnormal triglycerides or total cholesterol or low-density lipoprotein cholesterol (excluding high-density lipoprotein cholesterol), was seen in approximately 40% of children; insulin resistance in 17%; and C-reactive protein in risk range of metabolic syndrome in 24% of children.

Conclusions:

In the background of high food insecurity and malnutrition, cardiometabolic abnormalities were seen in 20%–35% of ART-naïve CLHIV in India emphasizing close monitoring of these children for long-term cardiovascular morbidities after initiation of ART.
Moyamoya Syndrome in a Child With HIV-1 Infection
Authors: Jindal Ankur Kumar , Bhattad Sagar , Suri Deepti , Singhal Manphool , Gupta Aman , Singh Paramjeet
Published: November 2017

Neurologic manifestations of HIV infection are not uncommon. However, stroke secondary to Moyamoya syndrome has rarely been described in children with HIV infection. We report a 10-year-old boy with perinatally acquired HIV-1 infection, who presented with recurrent strokes while on antiretroviral therapy.
Implementation of a Routine Health Literacy Assessment at an Academic Medical Center
Authors: Warring Carrie D. , Pinkney Jacqueline R. , Delvo-Favre Elaine D. , Rener Michelle Robinson , Lyon Jennifer A. , Jax Betty , Alexaitis Irene , Cassel Kari , Ealy Kacy , Hagen Melanie Gross , Wright Erin M. , Chang Myron , Radhakrishnan Nila S. , Leverence Robert R.
Published: November 2017

Limited health literacy is a common but often unrecognized problem associated with poor health outcomes. Well-validated screening tools are available to identify and provide the opportunity to intervene for at-risk patients in a resource-efficient manner. This is a multimethod study describing the implementation of a hospital-wide routine health literacy assessment at an academic medical center initiated by nurses in April 2014 and applied to all adult inpatients. Results were documented in the electronic health record, which then generated care plans and alerts for patients who screened positive. A nursing survey showed good ease of use and adequate patient acceptance of the screening process. Six months after hospital-wide implementation, retrospective chart abstraction of 1,455 patients showed that 84% were screened. We conclude that a routine health literacy assessment can be feasibly and successfully implemented into the nursing workflow and electronic health record of a major academic medical center.
Lung ultrasound in diagnosing pneumonia in the emergency department: a systematic review and meta-analysis
Authors: Orso Daniele , Guglielmo Nicola , Copetti Roberto
Published: November 2017

Community-acquired pneumonia (CAP) is one of the most widespread and severe infectious diseases worldwide. In the emergency department (ED), there is still a need for a rapid and accurate tool that can diagnose CAP. Lung ultrasound (LUS) is a recent tool that is increasingly being for this purpose. So far, the LUS has been evaluated on a wide range of patients, but not yet on the specific population in the ED through a meta-analysis. Our aim was to assess the accuracy of the LUS in diagnosing CAP in this setting through a systematic review and a meta-analysis. A systematic research of literature was carried out for all published studies comparing the diagnostic accuracy of the LUS against chest radiography or computerized tomography scan in patients older than 18 years of age with clinical criteria for CAP assessed in the ED. We extracted the descriptive and quantitative data from eligible studies, and calculated the pooled sensitivity, specificity, and diagnostic odds ratio. We defined the summary receiver operating characteristic curve. Our initial search strategy yielded 10 377 studies, of which 17 (0.2%) were eligible. These studies provided a combined sample size of 5108 participants. The general risk of bias of the considered studies was quite low, but some concerns were highlighted. The diagnostic odds ratio was around 181 (I
2: 27%). The pooled area under the curve, sensitivity, and specificity were, respectively, 97, 92, and 93%. The LUS was found to be an accurate tool in diagnosing CAP in adult patients in the ED. More methodologically rigorous trials are needed.
Precision medicine in pediatric oncology
Authors: Forrest Suzanne J. , Geoerger Birgit , Janeway Katherine A.
Published: November 2017

Purpose of review

The current review describes recent advances and unique challenges in precision medicine for pediatric cancers and highlights clinical trials assessing the clinical impact of targeted therapy matched to molecular alterations identified by tumor profiling.

Recent findings

Multiple prospective clinical sequencing studies in pediatric oncology have been reported in the last 2 years. These studies demonstrated feasibility of sequencing in the clinic and revealed a rate of actionable variants that justifies the development of precision trials for childhood cancer. A number of precision medicine trials are recently completed, underway or in development and these will be reviewed herein, with a focus on highlighting aspects of precision medicine trial design relevant to pediatric oncology.

The primary results of the first round of pediatric precision oncology clinical trials will provide us with a greater understanding of the clinical impact of linking tumor profiling to selection of targeted therapies. The aggregation of sequencing and clinical data from these trials and the results of biologic investigations linked to these trials will drive further discoveries and broaden opportunities for precision medicine for children with cancer.
Acute Myeloid Leukemia With Central Nervous System Involvement in Children: Experience From the French Protocol Analysis ELAM02
Authors: Felix Arthur , Leblanc Thierry , Petit Arnaud , Nelkem Brigitte , Bertrand Yves , Gandemer Virginie , Sirvent Anne , Paillard Catherine , Schmitt Claudine , Rohrlich Pierre Simon , Fenneteau Odile , Ragu Christine , Michel Gerard , Auvrignon Anne , Baruchel André , Leverger Guy
Published: November 2017

Central nervous system (CNS) involvement at diagnosis of pediatric acute myeloid leukemia (AML) is not considered as an independent prognostic factor. This study describes the prognostic value of pediatric AML with CNS involvement at diagnosis. Pediatric patients were treated for de novo AML in the French multicenter trial ELAM02. Lumbar puncture was carried out in the first week, and the treatment was adapted to the CNS status. No patient received CNS radiotherapy. The patients were classified into 2 groups: CNS+ and CNS−. Of the 438 patients, 16% (n=70) had CNS involvement at diagnosis, and 29% showed clinical signs. The patients with CNS disease were younger (40% were below 2 y old), had a higher white blood cell count (median of 45 vs. 13 G/L), and had M4 and M5 morphologies. The complete remission rate was similar at 92.8% for CNS+ and 88.5% for CNS−. There was no significant difference between the CNS+ and the CNS− group in overall survival (76% and 71%, respectively) and event-free survival (57% and 52%, respectively). Regarding the occurrence of first relapse, the CNS+ group had a higher combined relapse rate of 26.1% compared with 10% for the CNS− group. The results indicate that CNS involvement at diagnosis of pediatric AML is not an independent prognostic factor. Triple intrathecal chemotherapy combined with high-dose intravenous cytarabine should be the first-line treatment for CNS disease.
Extraneuraxial Hemangioblastoma: Clinicopathologic Features and Review of the Literature
Authors: Bisceglia Michele , Muscarella Lucia A. , Galliani Carlos A. , Zidar Nina , Ben-Dor David , Pasquinelli Gianandrea , la Torre Annamaria , Sparaneo Angelo , Fanburg-Smith Julie C. , Lamovec Janez , Michal Michal , Bacchi Carlos E.
Published: November 2017

Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures, somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD) or in sporadic cases. TheVHLgene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed. The clinical criteria for the diagnosis of VHLD are summarized, with emphasis on the distinction of sporadic hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD). The world literature on the topic of extraneuraxial hemangioblastomas has been comprehensively reviewed with ∼200 cases reported to date: up to 140 paraneuraxial, mostly of proximal spinal nerve roots, and 65 peripheral, 15 of soft tissue, 6 peripheral nerve, 5 bone, and 39 of internal viscera, including 26 renal and 13 nonrenal. A handful of possible yet uncertain cases from older literature are not included in this review. The clinicopathologic features of extraneuraxial hemangioblastoma are selectively presented by anatomic site of origin, and the differential diagnosis is emphasized in these subsets. Reference is made also to 10 of the authors’ personal cases of extraneuraxial hemangioblastomas, which include 4 paraneuraxial and 6 peripheral (2 soft tissue hemangioblastoma and 4 renal).
Indicators for Evaluating Community- and Societal-Level Risk and Protective Factors for Violence Prevention: Findings From a Review of the Literature
Authors: Armstead Theresa L. , Wilkins Natalie , Doreson Amanda
Published: November 2017

Programs geared toward preventing violence before it occurs at the community and societal levels of the social ecology are particularly challenging to evaluate. These programs are often focused on impacting the antecedents (or risk and protective factors) to violence, making it difficult to determine program success when solely relying on measures of violence reduction. The goal of this literature review is to identify indicators to measure risk and protective factors for violence that are accessible and measured at the community level. Indicators of community- and societal-level risk and protective factors from 116 articles are identified. These indicators strengthen violence prevention researchers' and practitioners' ability to detect proximal effects of violence prevention programs, practices, and policies, and provide timely feedback on the impact of their work. Thus, opportunities exist for violence prevention researchers to further study the associations between various indicators and different violent outcomes and to inform practitioner, evaluator, and funder developed logic models that include indicators of relevant risk and protective factors for crosscutting violence prevention measures and outcomes.
Does a Rehabilitation Program of Aerobic and Progressive Resisted Exercises Influence HIV-Induced Distal Neuropathic Pain?
Authors: Maharaj Sonill S. , Yakasai Abdulsalam M.
Published: November 2017

Objective

Distal symmetrical polyneuropathy is a common neurological sequela after HIV, which leads to neuropathic pain and functional limitations. Rehabilitation programs with exercises are used to augment pharmacological therapy to relieve pain but appropriate and effective exercises are unknown. This study explored the safety and effect of moderate-intensity aerobic exercises and progressive resisted exercises for HIV-induced distal symmetrical polyneuropathy neuropathic pain.

Design

A randomized pretest, posttest of 12 wks of aerobic exercise or progressive resisted exercise compared with a control. Outcome measures were assessed using the subjective periphery neuropathy, brief peripheral neuropathy screening, and numeric pain rating scale. Pain was assessed at baseline, 6 and 12 wks. Data between groups were compared using Kruskal-Wallis, Mann-Whitney U test, and within-groups Friedman and Wilcoxon signed rank tests.

Results

There were 136 participants (mean [SD] age = 36.79 [8.23] yrs) and the exercise groups completed the protocols without any adverse effects. Pain scores within and between aerobic exercise and progressive resisted exercise groups showed significant improvement (P < 0.05) from baseline to 6 and 12 wks compared with the control (P > 0.05).

Conclusions

This study supports a rehabilitation program of moderate-intensity aerobic exercise and progressive resisted exercise being safe and effective for reducing neuropathic pain and is beneficial with analgesics for HIV-induced distal symmetrical polyneuropathy.
The Pancreatic Cancer Microenvironment
Authors: Dougan Stephanie K.
Published: November 2017

Pancreatic ductal adenocarcinoma (PDAC) is composed of a minority of malignant cells within a microenvironment of extracellular matrix, fibroblasts, endothelial cells, and immune cells. Therapeutic failures of chemotherapy, targeted therapy, and immunotherapy have all been attributed to the PDAC microenvironment. In this review, we dissect the components of the microenvironment and explain how each cell type contributes to form a highly immunosuppressive, hypoxic, and desmoplastic cancer. New efforts in single-cell profiling will enable a better understanding of the composition of the microenvironment in primary and metastatic PDAC, as well as an understanding of how the microenvironment may respond to novel therapeutic approaches.
Targeting Reflux-Free Veins with a Vein Visualizer to Identify the Ideal Recipient Vein Preoperatively for Optimal Lymphaticovenous Anastomosis in Treating Lymphedema
Authors: Yang Johnson Chia-Shen , Wu Shao-Chun , Chiang Min-Hsien , Lin Wei-Che
Published: November 2017

Lymphaticovenous anastomosis is one of the main surgical treatments nowadays for alleviating lymphedema. A successful lymphaticovenous anastomosis relies on being able to identify “functional” lymphatic collecting vessels that are still capable of transporting lymph, and a nearby vein that is, ideally, reflux-free. This is a retrospective study. A total of 28 lymphedema patients were enrolled from October of 2016 to March of 2017 in Kaohsiung Chang Gung Hospital, Kaohsiung, Taiwan. A noninvasive vein visualizer was used to preselect reflux-free veins for lymphaticovenous anastomosis from five female patients. As a control, the total number of veins used for lymphaticovenous anastomoses without the use of a vein visualizer from 23 consecutive lymphedema patients was also recorded and compared. In the experimental group, a total of 12 of 13 veins (92 percent sensitivity) preselected by using the VeinViewer were confirmed to be reflux-free intraoperatively during lymphaticovenous anastomosis. In the control group, 21 of 56 veins (37.5 percent sensitivity) showed no venous reflux. Statistical analysis with the chi-square test showed a value of p < 0.001 (number needed to treat = 2.706). The odds of identifying reflux-free veins can be increased significantly with the use of a vein visualizer.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Diagnostic, II.
Assessing Patients' Perceptions of Safety Culture in the Hospital Setting: Development and Initial Evaluation of the Patients' Perceptions of Safety Culture Scale
Authors: Monaca Clara , Bestmann Beate , Kattein Martina , Langner Daria , Müller Hardy , Manser Tanja
Published: November 2017

Objectives

Both patient satisfaction and hospital safety culture have been recognized as key characteristics of healthcare quality and patient safety. Thus, both characteristics are measured widely to support quality and safety improvement efforts. However, because safety culture surveys focus exclusively on the perspective of hospital staff, the complimentary information to be gained from patients' perceptions of safety culture has received little research attention so far. We aimed to develop a measure explicitly focusing on patients' perceptions of safety culture in the hospital setting and perform an initial evaluation of its measurement properties.

Methods

We employed a multistep development approach including (a) literature review of survey instruments for patient experience and safety culture and (b) item categorization and selection. We evaluated the measurement properties of the final item set focusing on factor structure, internal consistency, item difficulty, and discrimination. Data were collected from June to December 2015 via an online patient survey conducted routinely by a health insurer.

Results

Overall, 112,814 insured persons participated in the online survey (response rate = 19.7%). The final 11-item set formed a single scale that was named Patients' Perceptions of Safety Culture scale. Its measurement properties were deemed satisfactory based on this initial evaluation.

Conclusions

The Patients' Perceptions of Safety Culture scale contributes to both a more comprehensive view of patients' experience of healthcare and a more balanced approach to safety culture measurement in healthcare. It contributes to an increased recognition of patients' views on safety-relevant aspects of their care that provide important inputs to patient safety improvement.
Evaluation of a Broad-Spectrum Partially Automated Adverse Event Surveillance System: A Potential Tool for Patient Safety Improvement in Hospitals With Limited Resources
Authors: Saikali Melody , Tanios Alain , Saab Antoine
Published: November 2017

Objective

The aim of the study was to evaluate the sensitivity and resource efficiency of a partially automated adverse event (AE) surveillance system for routine patient safety efforts in hospitals with limited resources.

Methods

Twenty-eight automated triggers from the hospital information system’s clinical and administrative databases identified cases that were then filtered by exclusion criteria per trigger and then reviewed by an interdisciplinary team. The system, developed and implemented using in-house resources, was applied for 45 days of surveillance, for all hospital inpatient admissions (N = 1107). Each trigger was evaluated for its positive predictive value (PPV). Furthermore, the sensitivity of the surveillance system (overall and by AE category) was estimated relative to incidence ranges in the literature.

Results

The surveillance system identified a total of 123 AEs among 283 reviewed medical records, yielding an overall PPV of 52%. The tool showed variable levels of sensitivity across and within AE categories when compared with the literature, with a relatively low overall sensitivity estimated between 21% and 44%. Adverse events were detected in 23 of the 36 AE categories defined by an established harm classification system. Furthermore, none of the detected AEs were voluntarily reported.

Conclusions

The surveillance system showed variable sensitivity levels across a broad range of AE categories with an acceptable PPV, overcoming certain limitations associated with other harm detection methods. The number of cases captured was substantial, and none had been previously detected or voluntarily reported. For hospitals with limited resources, this methodology provides valuable safety information from which interventions for quality improvement can be formulated.
Augmented Quadruple-Phase Contrast Media Administration and Triphasic Scan Protocol Increases Image Quality at Reduced Radiation Dose During Computed Tomography Urography
Authors: Saade Charbel , Mohamad May , Kerek Racha , Hamieh Nadine , Alsheikh Deeb Ibrahim , El-Achkar Bassam , Tamim Hani , Abdul Razzak Farah , Haddad Maurice , Abi-Ghanem Alain S. , El-Merhi Fadi
Published: November 2017

Purpose

The aim of this article was to investigate the opacification of the renal vasculature and the urogenital system during computed tomography urography by using a quadruple-phase contrast media in a triphasic scan protocol.

Materials and Methods

A total of 200 patients with possible urinary tract abnormalities were equally divided between 2 protocols. Protocol A used the conventional single bolus and quadruple-phase scan protocol (pre, arterial, venous, and delayed), retrospectively. Protocol B included a quadruple-phase contrast media injection with a triphasic scan protocol (pre, arterial and combined venous, and delayed), prospectively. Each protocol used 100 mL contrast and saline at a flow rate of 4.5 mL. Attenuation profiles and contrast-to-noise ratio of the renal arteries, veins, and urogenital tract were measured. Effective radiation dose calculation, data analysis by independent sample t test, receiver operating characteristic, and visual grading characteristic analyses were performed.

Results

In arterial circulation, only the inferior interlobular arteries in both protocols showed a statistical significance (P < 0.05). Venously, the inferior vena cava, proximal and distal renal veins demonstrated a significant opacification reduction in protocol B than in protocol A (P < 0.001). Protocol B showed a significantly higher mean contrast-to-noise ratio than protocol A (protocol B: 22.68 ± 13.72; protocol A: 14.75 ± 5.76; P < 0.001). Radiation dose was significantly reduced in protocol B (7.38 ± 2.22 mSv) than in protocol A (12.28 ± 2.72 mSv) (P < 0.001). Visual grading characteristic (P < 0.027) and receiver operating characteristic (P < 0.0001) analyses demonstrated a significant preference for protocol B.

Conclusions

In computed tomography urography, augmented quadruple-phase contrast media and triphasic scan protocol usage increases the image quality at a reduced radiation dose.
Correlation Between Semen Analysis Parameters and Diffusion-Weighted Magnetic Resonance Imaging of the Testicles in Patients With Varicocele: A Pilot Study
Authors: Çekiç Bülent , Kiliç Koray Kaya , Toslak Iclal Erdem , Şükun Abdullah , Sağlik Semih , Savaş Murat , Köroğlu Mert
Published: November 2017

Purpose

The aims of this study were to evaluate using testicle apparent diffusion coefficient (ADC) values in patients with varicocele and compare them with those of healthy individuals, to identify an optimal ADC threshold level to predict abnormal semen analysis using diffusion-weighted imaging.

Materials and Methods

Thirty-one patients with the diagnosis of varicocele and 20 healthy controls were enrolled in the study. All subjects underwent testicle diffusion-weighted imaging atbvalues of 0, 400, and 800 s/mm2and semen analysis. Studentttests were used to compare continuous variables between 2 groups. Testicle ADC values were correlated with semen analysis parameters. The relationship between ADC values and impaired semen analysis parameters was evaluated using Pearson correlation coefficient analysis. Receiver operating characteristic curves were formed. Cut-off values for ADC, sensitivity, and specificity values were measured.

Results

There was a negative correlation between mean ADC values and plexus pampiniformis vein diameter (r= −0.467,P< 0.001) and a positive correlation between mean ADC values and sperm count (r= 0.838,P< 0.001) as well as sperm morphology (r= 0.548,P< 0.05). Sensitivity values of 94.3% and 86.6% and specificity values of 87.5% and 43.8% were determined for the best cut-off ADC values in diagnosing the sperm count and morphology, respectively (area under the curve, 0.961 and 0.781).

Conclusions

Decreased testicular ADC values in patients with varicocele are significantly correlated with semen parameters. This method may be used to determine the degree of testicular parenchymal destruction. In addition, testicular ADC cut-off values might be useful in dyspermia patients for the management of patients with varicocele.
Incidental Case of Relapsing Polychondritis Detected by 18F-FDG PET/CT
Authors: Kaida Hayato , Ishii Kazunari , Hanada Soichiro , Tohda Yuji , Murakami Takamichi
Published: November 2017

A 78-year-old man had fever, persistent wheezing, and serum C-reactive protein elevation. Malignant lymphoma was suspected because of mediastinal lymph nodes swelling on CT and soluble interleukin 2 receptor elevation. Symmetric18F-FDG uptake in the tracheobronchial tree and bilateral auricles was observed on PET/CT. He was finally diagnosed as having relapsing polychondritis by auricular cartilage biopsy.18F-FDG PET/CT may have crucial role in evaluating the extent of inflammation and deciding the biopsy site of relapsing polychondritis.
Metastatic Male Breast Cancer With Increased Uptake on 18F-Fluciclovine PET/CT Scan
Authors: Gill Harkanwar S. , Tade Funmilayo , Greenwald David Theodore , Yonover Paul M. , Savir-Baruch Bital
Published: November 2017

Prostate imaging with 18F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC, 18F-fluciclovine) PET/CT scan (Axumin) was recently approved by the US Food and Drug Administration for men with suspected prostate cancer recurrence based on elevated blood prostate-specific antigen levels following prior treatment. We present a rare case of a 77-year-old man with suspected recurrent prostate cancer with an incidental finding of advanced-stage breast cancer showing different degrees of 18F-fluciclovine uptake.
Rapid Anterior Segmental Maxillary Retraction by Compression Osteogenesis
Authors: Hellal Usama Saad , Fayed Nabila , Elsharkawy Rehab , Abdelrahmen Mostafa
Published: November 2017

Maxillary protrusion is one of the deformities of the upper jaw. Orthodontics and orthodontics combined with anterior segmental osteotomy are the common treatment strategies for this deformity. The hypothesis of this study was that the maxillary bone segment could be gradually moved backward safely by using a tooth-borne-specific compression device that causes bone compression at the bony segment interface after performance of surgical bone cuts in cases of anterior maxillary protrusion. Ten patients with skeletal maxillary protrusion were treated by modified subapical maxillary osteotomy. Then the protrusion was gradually set back and fixed in a new position through the use of a compression device. After 8 weeks, the device was removed, and soft and hard tissue was evaluated. The average setback of the anterior maxillary segment was found to be 6.8 mm. The ratio of the upper lip to the maxillary incisor retraction was 0.52:1. The nasolabial angle increased with a change of 13.5°. The mentolabial angle increased with a change of 12.5°. This study is the first clinical study in using compression osteogenesis aided by a modified anterior subapical maxillary osteotomy technique in the management of skeletal maxillary protrusion that considered as an alternative to traditional surgical methods and to avoid its complications. It can be used successfully and safely, leading to rapid maximum setback of the anterior maxillary segment with great contact between bone segment, better and gradual hard and soft tissue remodeling, short treatment duration, and avoid using plates and screws with its complications.
Craniosynostosis Surgery and the Impact of Tranexamic Acid Dosing
Authors: Kurnik Nicole M. , Pflibsen Lacey R. , Do Annie , Bristol Ruth , Singh Davinder J.
Published: November 2017

Consensus does not exist regarding the best dosage regimen for using tranexamic acid (TXA) for patients undergoing open calvarial vault remodeling in craniosynostosis surgery. The purpose of this study was to evaluate 2 dosing protocols, as well as the cost of using TXA. Previously, the institutional protocol was to give patients undergoing open calvarial vault remodeling a loading infusion of TXA (10 mg/kg) at the start of their procedure, after which intravenous TXA (5 mg/kg/h) was given throughout surgery and for 24 hours postoperatively. In July 2015, the protocol changed to a reduced postoperative infusion time of 4 hours. A retrospective review was conducted of records of 30 patients who had surgery before the protocol change (24-hour group) and 23 patients whose surgery occurred after the protocol change (4-hour group). The following data were collected: blood volume transfused, hemoglobin levels, estimated blood loss, and intensive care days; and costs of TXA and blood transfusion. Results showed a 4-hour infusion was as effective as a 24-hour infusion for reducing blood loss in patients undergoing craniosynostosis. Transfusion requirements, hemoglobin and hematocrit levels, and estimated blood loss were not significantly different for the groups. The cost of TXA and transfusion in the 4-hour group was significantly less (P < 0.001) than in the 24-hour group. No significant difference in cost existed for patients who received blood transfusion alone versus patients who received the 4-hour TXA infusion.
Cancer-derived extracellular vesicles: friend and foe of tumour immunosurveillance
Authors: Dörsam Bastian , Reiners Kathrin S. , von Strandmann Elke Pogge
Published: November 2017

Extracellular vesicles (EVs) are important players of intercellular signalling mechanisms, including communication with and among immune cells. EVs can affect the surrounding tissue as well as peripheral cells. Recently, EVs have been identified to be involved in the aetiology of several diseases, including cancer. Tumour cell-released EVs or exosomes have been shown to promote a tumour-supporting environment in non-malignant tissue and, thus, benefit metastasis. The underlying mechanisms are numerous: loss of antigen expression, direct suppression of immune effector cells, exchange of nucleic acids, alteration of the recipient cells' transcription and direct suppression of immune cells. Consequently, tumour cells can subvert the host's immune detection as well as suppress the immune system. On the contrary, recent studies reported the existence of EVs able to activate immune cells, thus promoting the tumour-directed immune response. In this article, the immunosuppressive capabilities of EVs, on the one hand, and their potential use in immunoactivation and therapeutic potential, on the other hand, are discussed.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Organotypic three-dimensional assays based on human leiomyoma–derived matrices
Authors: Salo Tuula , Dourado Mauricio Rocha , Sundquist Elias , Apu Ehsanul Hoque , Alahuhta Ilkka , Tuomainen Katja , Vasara Jenni , Al-Samadi Ahmed
Published: November 2017

Alongside cancer cells, tumours exhibit a complex stroma containing a repertoire of cells, matrix molecules and soluble factors that actively crosstalk between each other. Recognition of this multifaceted concept of the tumour microenvironment (TME) calls for authentic TME mimetics to study cancer
in vitro
. Traditionally, tumourigenesis has been investigated in non-human, three-dimensional rat type I collagen containing organotypic discs or by means of mouse sarcoma-derived gel, such as Matrigel
®
. However, the molecular compositions of these simplified assays do not properly simulate human TME. Here, we review the main properties and benefits of using human leiomyoma discs and their matrix Myogel for
in vitro
assays. Myoma discs are practical for investigating the invasion of cancer cells, as are cocultures of cancer and stromal cells in a stiff, hypoxic TME mimetic. Myoma discs contain soluble factors and matrix molecules commonly present in neoplastic stroma. In Transwell, IncuCyte, spheroid and sandwich assays, cancer cells move faster and form larger colonies in Myogel than in Matrigel
®
. Additionally, Myogel can replace Matrigel
®
in hanging-drop and tube-formation assays. Myogel also suits three-dimensional drug testing and extracellular vesicle interactions. To conclude, we describe the application of our myoma-derived matrices in 3D
in vitro
cancer assays.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Extracellular vesicle-mediated cell–cell communication in haematological neoplasms
Authors: Ohyashiki Junko H. , Umezu Tomohiro , Ohyashiki Kazuma
Published: November 2017

Crosstalk between bone marrow tumour cells and surrounding cells, including bone marrow mesenchymal stromal cells (BM-MSCs), endothelial cells and immune cells, is important for tumour growth in haematological neoplasms. In addition to conventional signalling pathways, extracellular vesicles (EVs), which are endosome-derived vesicles containing proteins, mRNAs, lipids and miRNAs, can facilitate modulation of the bone marrow microenvironment without directly contacting non-tumourous cells. In this review, we discuss the current understanding of EV-mediated cell–cell communication in haematological neoplasms, particularly leukaemia and multiple myeloma. We highlight the actions of tumour and BM-MSC EVs in multiple myeloma. The origin of EVs, their tropism and mechanism of EV transfer are emerging issues that need to be addressed in EV-mediated cell–cell communication in haematological neoplasms.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Diurnal changes in glutamate/glutamine levels of healthy young adults assessed by proton magnetic resonance spectroscopy
Authors: Volk C. , Jaramillo V. , Merki RR. , O’Gorman RL. , Huber R.
Published: November 2017

Molecular and electrophysiological studies suggest that sleep ensures efficient functioning of the brain by maintaining synaptic homeostasis. The glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor) is involved in synaptic plasticity processes and it was shown that its expression changes across the sleep wake cycle. Moreover, animal studies have shown that glutamate levels are reduced during non-rapid eye movement (NREM) sleep and that the rate of the decrease is positively correlated with sleep EEG slow wave activity (SWA). In this study, we aimed to assess if proton magnetic resonance spectroscopy (1H-MRS) is sensitive to diurnal changes of glutamate + glutamine (GLX) in healthy young adults and if potential overnight changes of GLX are correlated to SWA. 1H-MRS spectra of 16 adult subjects were measured in the parietal lobe in the evening and in the subsequent morning using a 3T MRI scanner. The night between the scans was recorded with high-density EEG. Our results revealed a significant overnight reduction in GLX levels, whereas other metabolites did not show any significant change. Moreover, the decrease in GLX was positively correlated with the decrease of SWA in the course of the night. Our study demonstrates that quantification of diurnal changes in GLX is possible by means of 1H-MRS and indicates a relationship between changes in GLX and SWA, a marker that is closely linked to the restorative function of sleep. This relationship might be of particular interest in clinical populations in which sleep is disturbed.
Systematic analysis of the molecular architecture of endocytosis reveals a nanoscale actin nucleation template that drives efficient vesicle formation
Authors: Mund Markus , van der Beek Johannes Albertus , Deschamps Joran , Dmitrieff Serge , Monster Jooske Louise , Picco Andrea , Nédélec François , Kaksonen Marko , Ries Jonas
Published: November 2017

Clathrin-mediated endocytosis is an essential cellular function in all eukaryotes that is driven by a self-assembled macromolecular machine of over 50 different proteins in tens to hundreds of copies. How these proteins are organized to produce endocytic vesicles with high precision and efficiency is not understood. Here, we developed high-throughput superresolution microscopy to reconstruct the nanoscale structural organization of 23 endocytic proteins from over 100,000 endocytic sites in yeast. We found that proteins assemble by radially-ordered recruitment according to function. WASP family proteins form a circular nano-scale template on the membrane to spatially control actin nucleation during vesicle formation. Mathematical modeling of actin polymerization showed that this WASP nano-template creates sufficient force for membrane invagination and substantially increases the efficiency of endocytosis. Such nanoscale pre-patterning of actin nucleation may represent a general design principle for directional force generation in membrane remodeling processes such as during cell migration and division.
The Association between Tuberculosis and Diphtheria
Authors: Coleman S.
Published: November 2017

This research investigates the now-forgotten relationship between diphtheria and tuberculosis. Historical medical reports from the 19thcentury are reviewed followed by a statistical regression analysis of the relationship between the two diseases in the early 20thcentury. Historical medical records show a consistent association between diphtheria and tuberculosis that can increase the likelihood and severity of either disease in a co-infection. The statistical analysis uses historical weekly public health data on reported cases in five American cities over a period of several years, finding a modest but statistically significant relationship between the two diseases. No current medical theory explains the association between diphtheria and tuberculosis. Alternative explanations are explored with a focus on how the diseases assimilate iron. In a co-infection, the effectiveness of tuberculosis at assimilating extracellular iron can lead to increased production of diphtheria toxin, worsening that disease, which may in turn exacerbate tuberculosis. Iron-dependent repressor genes connect both diseases.
Rethinking the importance of the structure of ecological networks under an environment-dependent framework
Authors: Cenci Simone , Song Chuliang , Saavedra Serguei
Published: November 2017

A major quest in network and community ecology has been centered on understanding the importance of structural patterns in species interaction networks—the synthesis of who interacts with whom in a given location and time. In the past decades, much effort has been devoted to infer the importance of a particular structure by its capacity to tolerate an external perturbation on its structure or dynamics. Here we demonstrate that such a perspective leads to inconsistent conclusions. That is, the importance of a network structure changes as a function of the external perturbations acting on a community at any given point in time. Thus, we discuss a research agenda to investigate the relative importance of the structure of ecological networks under an environment-dependent framework. We hypothesize that only by studying systematically the link between network structure and community dynamics under an environment-dependent framework, we can uncover the limits at which communities can tolerate environmental changes.

“Variation stands out as the only meaningful reality”

Stephen J. Gould.
Experimental evidence of non-classical brain functions
Authors: Kerskens Christian , Pérez David López
Published: November 2017

Recent proposals in quantum gravity have suggested that unknown systems can mediate entanglement between two known quantum systems, if and only if the mediator itself is non-classical. This approach may be applicable to the brain, where speculations about quantum operations in consciousness and cognition have a long history.

Proton spins of bulk water, which most likely interfere with any brain function, can act as the known quantum systems. If an unknown mediator exists, then NMR methods based on multiple quantum coherence (MQC) can act as entanglement witness. However, there are doubts that today’s NMR signals can contain quantum correlations in general, and specifically in the brain environment. Here, we used a witness protocol based on zero quantum coherence (ZQC) whereby we minimised the classical signals to circumvent the NMR detection limits for quantum correlation. For short repetitive periods, we found evoked signals in most parts of the brain, whereby the temporal appearance resembled heartbeat-evoked potentials (HEPs). We found that those signals had no correlates with any classical NMR contrast. Similar to HEPs, the evoked signal depended on conscious awareness. Consciousness-related or electrophysiological signals are unknown in NMR. Remarkably, these signals only appeared if the local properties of the magnetisation were reduced. Our findings suggest that we may have witnessed entanglement mediated by consciousness-related brain functions. Those brain functions must then operate non-classically, which would mean that consciousness is non-classical.
Comparison of multiple transcriptomes exposes unified and divergent features of quiescent and activated skeletal muscle stem cells
Authors: Pietrosemoli Natalia , Mella Sébastien , Yennek Siham , Baghdadi Meryem B. , Sakai Hiroshi , Sambasivan Ramkumar , Pala Francesca , Di Girolamo Daniela , Tajbakhsh Shahragim
Published: November 2017

Background

Skeletal muscle stem cells (MuSCs) are quiescent in adult mice and can undergo multiple rounds of proliferation and self-renewal following muscle injury. Several labs have profiled transcripts of myogenic cells during developmental and adult myogenesis with the aim of identifying quiescent markers. Here, we focused on the quiescent cell state and generated new transcriptome profiles that include subfractionations of adult MuSC populations, and an artificially induced prenatal quiescent state, to identify core signatures for quiescent and proliferating MuSCs.

Methods

Comparison of available data offered challenges related to the inherent diversity of datasets and biological conditions. We developed a standardized workflow to homogenize the normalization, filtering, quality control steps for the analysis of gene expression profiles allowing the identification up- and down-regulated genes and the subsequent gene set enrichment analysis. To share the analytical pipeline of this work, we developed Sherpa, an interactive Shiny server that allows multiscale comparisons for extraction of desired gene sets from the analysed datasets. This tool is adaptable to cell populations in other contexts and tissues.

Results

A multiscale analysis comprising eight datasets of quiescent MuSCs had 207 and 542 genes commonly up- and down-regulated, respectively. Shared up-regulated gene sets include an over-representation of the TNFa pathway via NFKb signaling, Il6-Jak-Stat3 signaling, and the apical surface processes, while shared down-regulated gene sets exhibited an over-representation ofMycandE2Ftargets, and genes associated to the G2M checkpoint and oxidative phosphorylation. However, virtually all datasets contained genes that are associated with activation or cell cycle entry, such as the immediate early stress response genesFosandJun. Empirical examination of fixed and isolated MuSCs showed that these and other genes were absentin vivo, but activated during procedural isolation of cells.

Conclusions

Through the systematic comparison and individual analysis of diverse transcriptomic profiles, we identified genes that were consistently differentially expressed among the different datasets and common underlying biological processes key to the quiescent cell state. Our findings provide impetus to define and distinguish transcripts associated with truein vivoquiescence from those that are first responding genes due to disruption of the stem cell niche.
Predator-prey feedback in a gyrfalcon-ptarmigan system?
Authors: Barraquand Frédéric , Nielsen Ólafur K.
Published: November 2017

Specialist predators with oscillating dynamics are often strongly affected by the population dynamics of their prey, yet they do not always participate in a predator-prey cycle. Only those that exert strong population regulation of their prey do so. Inferring the strength and direction of the predator-prey coupling from time series therefore requires contrasting models with top-down versus bottom-up predator-prey dynamics. We examine such population-level coupling using multivariate autoregressive models. The models translate several hypotheses for the joint dynamics of population densities of the Icelandic gyrfalconFalco rusticolus, and its prey, the rock ptarmiganLagopus muta. The dynamics of both species are likely not only linked to each other but also to stochastic weather variables acting as confounding factors on the joint dynamics. The classical MAR(1) model, used most often in ecology, predicts that the times series exhibit predator-prey feedback (i.e., Granger causality): the predator helps to explain prey dynamics and the prey helps to explain predator dynamics. Weather, in the form of spring temperature, influences gyrfalcon population growth but not ptarmigan population growth, despite individual-level evidence that ptarmigan chicks can be strongly affected by weather. MAR(2) models, allowing for species to cycle independently from each other, further suggests alternative scenarios where a cyclic prey influence its predator but not the other way around; such bottom-up models produce a better fit but less realistic cross-correlation patterns. Simulations of MAR(1) and MAR(2) models further demonstrate that the top-down MAR(1) models are most likely to be misidentified as bottom-up dynamics than vice-versa. We therefore conclude that predator-prey feedback in the gyrfalcon-ptarmigan system is very likely, though bottom-up dynamics cannot be excluded with certainty. We finally discuss what sort of information is needed to advance the characterization of joint predator-prey dynamics in birds and other vertebrates.
LSx: Automated reduction of gene-specific lineage evolutionary rate heterogeneity for multi-gene phylogeny inference
Authors: Rivera-Rivera Carlos J. , Montoya-Burgos Juan I.
Published: November 2017

Motivation

LS3 is a recently published algorithm to reduce lineage evolutionary rate heterogeneity, a condition that can produce inference artifacts in molecular phylogenetics. The LS3 scripts are Linux-specific and the criterion to reduce lineage rate heterogeneity can be too stringent in datasets with both very long and very short branches.

Results

LSx is a multi-platform user-friendly R script that performs the LS3 algorithm, and has added features in order to make better lineage rate calculations. In addition, we developed and implemented an alternative version of the algorithm, LS4, which reduces lineage rate heterogeneity not only by detecting branches that are too long but also branches that are too short, resulting in less stringent data filtering.

Availability

The LSx script LSx_v.1.1.R and the user manual are available for download at: https://genev.unige.ch/research/laboratory/Juan-Montoya