bluuebunny/crossref_metadata_2025 huggingface dataset:
Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis*
Authors: Emrath Elizabeth T. , Fortenberry James D. , Travers Curtis , McCracken Courtney E. , Hebbar Kiran B.
Published: April 2017

Objective:

To evaluate outcomes in patients receiving balanced fluids for resuscitation in pediatric severe sepsis.

Design:

Observational cohort review of prospectively collected data from a large administrative database.

Setting:

PICUs from 43 children’s hospitals.

Patients:

PICU patients diagnosed with severe sepsis.

Interventions:

None.

Measurements and Main Results:

We reviewed data from the Pediatric Health Information System database from 2004 to 2012. Children with pediatric severe sepsis receiving balanced fluids for resuscitation in the first 24 and 72 hours of treatment were compared to those receiving unbalanced fluids. Thirty-six thousand nine hundred eight patients met entry criteria for analysis. Two thousand three hundred ninety-eight patients received exclusively balanced fluids at 24 hours and 1,641 at 72 hours. After propensity matching, the 72-hour balanced fluids group had lower mortality (12.5% vs 15.9%; p = 0.007; odds ratio, 0.76; 95% CI, 0.62–0.93), lower prevalence of acute kidney injury (16.0% vs 19.2%; p = 0.028; odds ratio, 0.82; 95% CI, 0.68–0.98), and fewer vasoactive infusion days (3.0 vs 3.3 d; p < 0.001) when compared with the unbalanced fluids group.

Conclusions:

In this retrospective analysis carried out by propensity matching, exclusive use of balanced fluids in pediatric severe sepsis patients for the first 72 hours of resuscitation was associated with improved survival, decreased prevalence of acute kidney injury, and shorter duration of vasoactive infusions when compared with exclusive use of unbalanced fluids.
NPY Impairs Cell Viability and Mitochondrial Membrane Potential Through Ca2+ and p38 Signaling Pathways in Neonatal Rat Cardiomyocytes
Authors: Hu Jun , Xu Xuehua , Zuo Yuanyi , Gao Xiangting , Wang Yun , Xiong Cunquan , Zhou Hongcheng , Zhu Shaohua
Published: April 2017

NPY is involved in stress cardiomyopathy. However, the associated mechanism for NPY-induced stress cardiomyopathy remains unclear. In this study, we aimed to explore potential cell signaling pathways that are related to NPY-mediated cell viability in neonatal rat cardiomyocytes. We found that NPY induced cell viability suppression in cultured cardiomyocytes in a dose-dependent manner. After NPY treatment, expression of CaN and p-CAMKII increased significantly, and phosphorylation of p38 but not ERK and JNK was changed. Moreover, NPY treatment significantly increased PGC-1α (the key factor of mitochondrial biogenesis and energy metabolism) expression but decreased mitochondrial membrane potential in cultured cardiomyocytes. More importantly, the blockage of CaN, CAMKII, and p38 signaling pathways by their inhibitors could rescue the reduced cell viability and mitochondrial membrane potential in NPY-treated cardiomyocytes. Collectively, our data demonstrated that NPY mediated cell viability and mitochondrial membrane potential in cardiomyocytes through CaN, CAMKII, and p38 signaling pathways.
Inhibition of Mid-chain HETEs Protects Against Angiotensin II–induced Cardiac Hypertrophy
Authors: Elkhatali Samya , Maayah Zaid H. , El-Sherbeni Ahmed A. , Elshenawy Osama H. , Abdelhamid Ghada , Shoieb Sherif M. , El-Kadi Ayman O. S.
Published: April 2017

Recent data demonstrated the role of CYP1B1 in cardiovascular disease. It was, therefore, necessary to examine whether the inhibition of CYP1B1 and hence inhibiting the formation of its metabolites, using 2,4,3′,5′-tetramethoxystilbene (TMS), would have a cardioprotective effect against angiotensin II (Ang II)-induced cardiac hypertrophy. For this purpose, male Sprague Dawley rats were treated with Ang II with or without TMS (300 μg/kg every third day i.p.). Thereafter, cardiac hypertrophy and the formation of mid-chain HETEs and arachidonic acid were assessed. In vitro, RL-14 cells were treated with Ang II (10 μM) in the presence and absence of TMS (0.5 μM). Then, reactive oxygen species, mitogen-activated protein kinase phosphorylation levels, and nuclear factor-kappa B–binding activity were determined. Our results demonstrated that TMS protects against Ang II-induced cardiac hypertrophy as indicated by the improvement in cardiac functions shown by the echocardiography as well as by reversing the increase in heart weight to tibial length ratio caused by Ang II. In addition, the cardioprotective effect of TMS was associated with a significant decrease in cardiac mid-chain HETEs levels. Mechanistically, TMS inhibited reactive oxygen species formation, the phosphorylation of ERK1/2, p38 mitogen-activated protein kinase, and the binding of p65 NF-κB.
Pharmacodynamic and -kinetic Behavior of Low-, Intermediate-, and High-Dose Landiolol During Long-Term Infusion in Whites
Authors: Krumpl Günther , Ulč Ivan , Trebs Michaela , Kadlecová Pavla , Hodisch Juri , Maurer Gabriele , Husch Bernhard
Published: April 2017

Pharmacokinetics, pharmacodynamics, safety, and tolerability of long-term administration of landiolol, a fast-acting cardioselective β-blocker, were investigated for the first time in white subjects in a prospective clinical trial. Blood concentrations of landiolol and its metabolites, heart rate (HR), blood pressure (BP), and electrocardiogram parameters were studied in 12 healthy volunteers receiving continuous infusions of a new 12-mg/mL formulation of landiolol using a dose-escalation regimen (10 μg/kg BW/min for 2 hours, 20 μg/kg BW/min for 2 hours, 40 μg/kg BW/min for 20 hours, 6 hours follow-up). Landiolol blood concentrations were dose proportional. Time until steady state decreased with increasing doses. Pharmacokinetic parameters were t1/2 = 4.5 minutes, VD = 366 mL/kg, and total body clearance = 53 mL·kg−1·min−1. Maximal blood concentrations of the inactive main metabolite M1 were 10-fold higher than those of landiolol, with t1/2 = 126 minutes, VD = 811 mL/kg, and total body clearance = 4.5 mL·kg−1·min−1. HR reduction from baseline was fast (significant after 16 minutes) and sustained throughout the administration period. Systolic and diastolic BP reductions and electrocardiogram parameter changes were less pronounced and became significant only occasionally. Recovery after discontinuation of infusion was fast with little (HR) or no (BP) rebound. The new formulation showed excellent local and general tolerability.
Inhibition of Rho-kinase Attenuates Left Ventricular Remodeling Caused by Chronic Intermittent Hypoxia in Rats via Suppressing Myocardial Inflammation and Apoptosis
Authors: Wang Zhi-hua , Zhu Die , Xie Sheng , Deng Yan , Pan Yueying , Ren Jie , Liu Hui-guo
Published: April 2017

Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact mechanisms are not fully elucidated. This study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms. Adult male Sprague-Dawley rats suffered from CIH or normoxia stimulus and were intervened with vehicle or fasudil (10 mg·kg−1·d−1, intraperitoneal injection) for 6 weeks. In this study, treatment with fasudil significantly reversed intermittent hypoxia-induced histopathological transformations and ultrastructural changes in rat myocardium. Moreover, fasudil downregulated the protein levels of RhoA and phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1), thus effectively inhibited the activation of RhoA/ROCK signaling pathway. Simultaneously, activity of nuclear factor (NF)-kB was suppressed by fasudil, which was accompanied by reduced NF-kB downstream inflammatory genes including interleukin-6, tumor necrosis factor-a and monocyte chemotactic protein-1, and apoptosis. These results suggest that fasudil attenuates myocardial remodeling in CIH rats, at least partly by suppressing activation of NF-kB. Inhibition of the RhoA/ROCK pathway could become an important therapeutic target in the prevention of OSAS-related cardiomyopathy.
β-adrenergic Receptor-stimulated Cardiac Myocyte Apoptosis: Role of Cytochrome P450 ω-hydroxylase
Authors: Jiang Shan , Huo Dan , Wang Xueying , Zhao Huan , Tan Jiang , Zeng Qinghua , O'Rourke Stephen T. , Sun Chengwen
Published: April 2017

Prolonged or excessive β-adrenergic activation leads to cardiac myocyte loss and heart dysfunction; however, the underlying cellular mechanisms are still unclear. Therefore, we first confirmed the effect of isoproterenol (ISO), a β-adrenergic receptor agonist, on cardiac toxicity using TUNEL and caspase activity assays in cultured rat cardiomyocytes. ISO treatment significantly increased cardiomyocyte apoptosis. Persistent ISO stimulation of cardiomyocytes also increased the expression of CYP4A3, a major CYP450 ω-hydroxylase that produces 20-hydroxyeicosatetraenoic acid (20-HETE) in a time-dependent manner. Next, we examined the effect of ISO and 20-HETE on cardiomyocyte apoptosis using annexin V and propidium iodide staining. Treatment with either 20-HETE or ISO significantly increased cardiomyocyte apoptosis, and inhibition of 20-HETE production using 17-ODYA, a CYP450 ω-hydroxylase inhibitor, dramatically attenuated ISO-induced cardiomyocyte apoptosis. To determine the apoptotic pathway involved, the mitochondrial membrane potential (ΔΨm) was measured by detecting the ratio of JC-1 green/red emission intensity. The results demonstrated that 17-ODYA significantly abolished ISO-induced disruption of ΔΨm and that 20-HETE alone induced a marked disruptive effect on ΔΨm in cardiomyocytes. In addition, 20-HETE–induced disruption of ΔΨm and apoptosis was significantly attenuated by KN93, a CaMKII inhibitor. Taken together, these results demonstrate that 20-HETE treatment induces significant apoptosis via mitochondrial-dependent pathways, and that inhibition of 20-HETE production using 17-ODYA attenuates ISO-induced cardiomyocyte apoptosis.
Pyoderma Gangrenosum after Deep Inferior Epigastric Perforator Breast Reconstruction: Systematic Review and Case Report
Authors: Zelones Justin T. , Nigriny John F.
Published: April 2017

Background:

Pyoderma gangrenosum (PG) is a rare skin disorder of the neutrophilic dermatoses spectrum that can mimic wound infections in surgical patients. PG after breast surgery has been reported but in limited amounts in autologous breast reconstruction patients. We present the first case of PG after a delayed bilateral deep inferior epigastric perforator flap breast reconstruction in the setting of systemic disease along with a systematic review.

Methods:

PubMed, Ovid, and Web of Science were systematically searched to obtain cases of PG after autologous breast reconstruction. Sixty articles were identified but only 16 were relevant to this study.

Results:

Systemic disease was present in 2 patients (13%). Wound onset occurred typically 5 days after surgery. Fever and/or leukocytosis was observed in 10 patients (63%). Wound cultures were positive in 2 patients (13%). Donor-site wounds were present in 9 patients (56%). Bilateral breast wounds were present in 67% of bilateral cases. Debridement was performed in 10 cases (63%). Skin graft or substitute was performed in 6 cases (38%). Resection of autologous flap was performed in 3 cases (19%). All patients were treated with systemic steroids (81%) and/or immunosuppressive medications (50%). Complete wound healing occurred by 4 months on average.

Conclusion:

If early ulcerative wounds develop at multiple sites after autologous breast reconstruction with worsening after debridement and antibiotic therapy, then PG should be considered. It is imperative that an early diagnosis and subsequent treatment with steroids and/or immunosuppressive medications be initiated so further surgical procedures, flap loss, and scarring can be minimized.
Prediction of Skin Necrosis after Mastectomy for Breast Cancer Using Indocyanine Green Angiography Imaging
Authors: Gorai Katsuya , Inoue Keita , Saegusa Noriko , Shimamoto Ryo , Takeishi Meisei , Okazaki Mutsumi , Nakagawa Masahiro
Published: April 2017

Background:

In immediate tissue expander reconstruction following total mastectomy for breast cancer, indocyanine green angiography (ICGA)–guided skin trimming is useful for the prevention of complications. However, instances of unclear ICGA contrast can occur with this method, which are difficult to judge as to whether preventive trimming is warranted. To further improve the mastectomy flap necrosis rate, more accurate objective parameters are necessary.

Methods:

The degree of clinical improvement was compared between 81 patients trimmed according to the surgeon’s judgment (non-ICGA group) and 100 patients with ICGA-guided trimming (ICGA group). We then retrospectively measured 3 parameters [relative perfusion (RP); time (T) to reach RPmax; and slope (S = RP/T) reflecting the rate of increase to RPmax] by using region of interest analysis software and examined their relationships with skin necrosis.

Results:

The rate of grade III necrosis (reaching the subcutaneous fat layer) was significantly lower in the ICGA group (4.8%) than in the non-ICGA group (17.8%; P < 0.05). The specificity of RP for the diagnosis of skin necrosis was high (98.5%; cutoff value, 34). However, the sensitivities of slope parameters were higher than RP.

Conclusions:

ICGA-guided trimming decreased the rate of deep skin necrosis requiring additional surgical treatment. Region of interest analysis indicated that a relatively low percentage luminescence (RP < 34) was indicative of the need for skin trimming, combined with a slow increase in the perfusion of the mastectomy skin flaps.
Effectiveness of Emollient Therapy in Pediatric Patients With Atopic Dermatitis
Authors: Barfield Amanda , Brown Hope , Pernell Paige , Woodard Jessica
Published: April 2017

Background and Purpose

Atopic dermatitis is a chronic inflammatory skin disease that can develop in early childhood and affects 15%–30% of children. The purposes of this research were to review the literature and critique the evidence to better understand the use of emollient therapy in atopic dermatitis.

Methods

A literature review was performed using the databases CINAHL, Cochrane, and MEDLINE and the clinical decision-making resource UptoDate.

Findings

Recent specialty research has begun to focus on the multifactorial triggers that predispose a child to develop atopic dermatitis and subsequent burden of sequelae later in life. Evidence is beginning to show that long-term control of atopic conditions is better achieved using primary prevention measures.

Conclusions

Emollient therapy is a low-risk primary prevention intervention that has been shown to have a steroid-sparing effect. Effective emollient therapy may also prevent the development of atopic dermatitis in at-risk populations. An algorithm or clinical tool is needed to assist primary care providers in the selection of an emollient, how to apply an emollient when used concurrently with a topical rescue medication, and how to adequately educate parents of the importance of primary prevention in the long-term management of atopic dermatitis.
Breast-Feeding Analgesia in Infants
Authors: Benoit Britney , Martin-Misener Ruth , Latimer Margot , Campbell-Yeo Marsha
Published: April 2017

To provide an updated synthesis of the current state of the evidence for the effectiveness of breast-feeding and expressed breast milk feeding in reducing procedural pain in preterm and full-term born infants. A systematic search of key electronic databases (PubMed, CINAHL, EMBASE) was completed. Of the 1032 abstracts screened, 21 were found eligible for inclusion. Fifteen studies reported on the use of breast-feeding or expressed breast milk in full-term infants and 6 reported on preterm infants. Direct breast-feeding was more effective than maternal holding, maternal skin-to-skin contact, topical anesthetics, and music therapy, and was as or more effective than sweet tasting solutions in full-term infants. Expressed breast milk was not consistently found to reduce pain response in full-term or preterm infants. Studies generally had moderate to high risk of bias. There is sufficient evidence to recommend direct breast-feeding for procedural pain management in full-term infants. Based on current evidence, expressed breast milk alone should not be considered an adequate intervention.
Pain Management During Newborn Screening
Authors: Harrison Denise , Reszel Jessica , Dagg Bill , Aubertin Cheryl , Bueno Mariana , Dunn Sandra , Fuller Ann , Harrold JoAnn , Larocque Catherine , Nicholls Stuart , Sampson Margaret
Published: April 2017

To assess the reach, acceptability, and effect of the BSweet2Babies video showing breast-feeding, skin-to-skin care, and sucrose during blood sampling on intention to recommend the video or advocate for use of the interventions. In July 2014, the video and an electronic survey were produced and posted. After 1 year, the online viewer survey responses and YouTube analytics were analyzed. One year after posting, the BSweet2Babies video had 10 879 views from 125 countries and 187 (1.7%) viewers completed the survey. Most respondents were aware of the analgesic effects of breast-feeding, skin-to-skin care, and sucrose. Nearly all respondents (n = 158, 92%) found the BSweet2Babies video to be a helpful resource and 146 (84%) answered that they would recommend the video to others. After viewing the video, 183 (98%) respondents answered that they would advocate for 1 or more of the interventions. The BSweet2Babies video showing effective pain treatment during blood sampling had a large reach but a very small response rate for the survey. Therefore, analysis of acceptability and effect on intention to recommend the video and advocate for the interventions depicted are limited. Further research is warranted to explore how to best evaluate videos delivered through social media and to determine the effect of the video to promote knowledge translation into clinical practice.
Effectiveness of ShotBlocker for Immunization Pain in Full-Term Neonates
Authors: Caglar Seda , Büyükyılmaz Funda , Coşansu Gülhan , Çağlayan Sabiha
Published: April 2017

Nonpharmacologic strategies exist to manage procedural pain in healthy newborn infants. The aim of this prospective randomized controlled trial (RCT) was to examine the efficacy of ShotBlocker for managing injection pain associated with the first intramuscular hepatitis B vaccine given to healthy full-term neonates. This randomized controlled trial study was conducted in a private university hospital in Istanbul, Turkey, in which 100 healthy term neonates were randomly assigned to either a ShotBlocker (n = 50) or control group (n = 50). The Neonatal Infant Pain Scale scores of the neonates in the ShotBlocker and control groups were compared before, during, and after the injections, and the physiological parameters were compared before and after the procedure. The pain scores of the neonates during (ShotBlocker group: 1.64 ± 0.80; control group: 2.96 ± 0.73) and after (ShotBlocker group: 0.74 ± 0.66; control group: 1.42 ± 0.76) the injection procedure were lower in the ShotBlocker group than in the control group (P = .000). The postinjection heart rate in the infants in the ShotBlocker group (145.02 ± 13.50) was found to be lower than in those for whom ShotBlocker was not used (150.24 ± 13.36) (P = .05). The use of ShotBlocker during the hepatitis B vaccine in term neonates is effective in reducing the acute pain.
Quality of Antiepileptic Treatment Among Older Medicare Beneficiaries With Epilepsy
Authors: Pisu Maria , Richman Joshua , Piper Kendra , Martin Roy , Funkhouser Ellen , Dai Chen , Juarez Lucia , Szaflarski Jerzy P. , Faught Edward
Published: April 2017

Background:

Enzyme-inducing antiepileptic drugs (EI-AEDs) are not recommended for older adults with epilepsy. Quality Indicator for Epilepsy Treatment 9 (QUIET-9) states that new patients should not receive EI-AEDs as first line of treatment. In light of reported racial/ethnic disparities in epilepsy care, we investigated EI-AED use and QUIET-9 concordance across major racial/ethnic groups of Medicare beneficiaries.

Research Design:

Retrospective analyses of 2008–2010 Medicare claims for a 5% random sample of beneficiaries 67 years old and above in 2009 augmented for minority representation. Logistic regressions examined QUIET-9 concordance differences by race/ethnicity adjusting for individual, socioeconomic, and geography factors.

Subjects:

Epilepsy prevalent (≥1 International Classification of Disease-version 9 code 345.x or ≥2 International Classification of Disease-version 9 code 780.3x, ≥1 AED), and new (same as prevalent+no seizure/epilepsy events nor AEDs in 365 d before index event) cases.

Measures:

Use of EI-AEDs and QUIET-9 concordance (no EI-AEDs for the first 2 AEDs).

Results:

Cases were 21% white, 58% African American, 12% Hispanic, 6% Asian, 2% American Indian/Alaskan Native. About 65% of prevalent, 43.6% of new cases, used EI-AEDs. QUIET-9 concordance was found for 71% Asian, 65% white, 61% Hispanic, 57% African American, 55% American Indian/Alaskan new cases: racial/ethnic differences were not significant in adjusted model. Beneficiaries without neurology care, in deductible drug benefit phase, or in high poverty areas were less likely to have QUIET-9 concordant care.

Conclusions:

EI-AED use is high, and concordance with recommendations low, among all racial/ethnic groups of older adults with epilepsy. Potential socioeconomic disparities and drug coverage plans may affect treatment quality and opportunities to live well with epilepsy.
Long non-coding RNAs in leukemia: biology and clinical impact
Authors: Lammens Tim , Durinck Kaat , Wallaert Annelynn , Speleman Frank , Van Vlierberghe Pieter
Published: April 2017

Purpose of review

Over the last years, long non-coding RNAs (lncRNAs) have emerged as putative regulators of malignant hematopoietic development. Here, we review recent literature on the involvement of lncRNAs in leukemia, including their role in driving or sustaining disease and their potential impact on diagnosis, classification, and prognosis.

Recent findings

Leukemogenesis is a complex process resulting from the accumulation of multiple genetic alterations. Over the last years, advances in high-throughput sequencing and transcriptome profiling have enabled the identification of lncRNAs involved in leukemia development. lncRNAs are able to distinguish different subtypes of human leukemia and several reports have identified specific patterns of lncRNA expression associated with clinical patient characteristics. Although functional studies on the actual role of these lncRNAs during transformation remain scarce, emerging evidence suggests that complex interactions between coding and non-coding transcript are truly involved in leukemia development.

Introduction of lncRNAs as an additional layer of complexity in human leukemia might provide new molecular genetic insights in the biology of this disease and could create unique opportunities for the identification of novel drug targets and diagnostic or prognostic biomarkers.
Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma
Authors: Dupéré-Richer Daphné , Licht Jonathan D.
Published: April 2017

Purpose of review

Next generation sequencing and large-scale analysis of patient specimens has created a more complete picture of multiple myeloma (MM) revealing that epigenetic deregulation is a prominent factor in MM pathogenesis.

Recent findings

Over half of MM patients have mutations in genes encoding epigenetic modifier enzymes. The DNA methylation profile of MM is related to the stage of the disease and certain classes of mutations in epigenetic modifiers are more prevalent upon disease relapse, suggesting a role in disease progression. Many small molecules targeting regulators of epigenetic machinery have been developed and clinical trials are underway for some of these in MM.

Recent findings suggest that epigenetic targeting drugs could be an important strategy to cure MM. Combining these agents along with other strategies to affect the MM cell such as immunomodulatory drugs and proteasome inhibitors may enhance efficacy of combination regimens in MM.
Do triglyceride-lowering drugs decrease risk of cardiovascular disease?
Authors: Maki Kevin C. , Dicklin Mary R.
Published: April 2017

Purpose of review

This review summarizes the evidence supporting a relationship between lowering triglycerides (TGs) and TG-rich lipoprotein cholesterol (TGRL-C) levels and reduced atherosclerotic cardiovascular disease (ASCVD) event risk.

Recent findings

Data from observational investigations, including studies of genetic variants, provide evidence consistent with a causal relationship between elevations in TG and TGRL-C and greater risk for ASCVD. Randomized controlled trial evidence of ASCVD risk reduction with therapies that substantially lower TG and TGRL-C is limited by the fact that no large-scale trial results have been published from a study that enrolled subjects selected specifically on the basis of TG or TGRL-C elevation, although three such trials are underway or in the planning stages. Subgroup analyses from randomized controlled trials are suggestive of a reduction in coronary heart disease and ASCVD event rates with statins, fibrates, omega-3 fatty acid concentrates, and niacin in subjects with elevated TGs, particularly if accompanied by low high-density lipoprotein-cholesterol. Mechanistic studies also support the biologic plausibility of this relationship.

In conclusion, the available data are suggestive of a benefit of ASCVD reduction with therapies that lower TG and TGRL-C; results from ongoing outcomes trials are expected to provide definitive evidence of this relationship.
Clarifying complex inheritance: apolipoprotein C3 and atherosclerosis
Authors: Galton David J.
Published: April 2017

Purpose of review

To describe some steps in the progress in the molecular biology of a peptide, apolipoprotein C3; its gene mutations that render individuals susceptible or resistant to developing hyperlipidaemia and atherosclerosis.

Recent findings

Data that lead to the development of a new therapeutic agent volanesorsen.

The agent blocks the function of the mRNA of apolipoprotein C3 and successfully treats severe hypertriglyceridaemia in phase 3 trials (Ionis Pharmaceuticals).
Behcet Disease Initially Presenting as Deep Venous Thrombosis: A Case Report
Authors: Gurunathan Arun , T. Teachey David , Chikwava Kudakwashe R. , Witmer Char , Desai Ami V.
Published: April 2017

Behcet disease is a potentially life-threatening multisystemic vasculitis with thrombotic tendency. Mucocutaneous ulcers, arthritis, and uveitis are the most recognizable features, but may be absent at the time of medical evaluation. We report a case in which a 8-year old patient presented with spontaneous bilateral lower extremity deep venous thromboses, and screening for rheumatologic symptoms led to diagnosing Behcet. This case demonstrates that deep venous thromboses can be the initial event bringing a patient with Behcet to medical attention, highlighting the importance of screening for underlying rheumatologic diseases in pediatric patients who present with unprovoked thrombosis.
Current advances in urban leptospirosis diagnosis
Authors: Sayyed Mousavi Mir Naser , Sadeghi Javid , Aghazadeh Mohammad , Asgharzadeh Mohammad , Samadi Kafil Hossein
Published: April 2017

Leptospirosis is generally significant zoonotic disease and an important public health problem in developing countries. Because of primary antibiotic treatment importance in this disease, early diagnosis is essential for appropriate managing. Laboratory tests for the early diagnosis of disease are necessary. PCR is not sole useful for diagnosis, as it is unavailable in most developing countries. Microscopic agglutination test and the ELISA are not suitable leptospirosis tests for early diagnosis, but they can be taken as gold standard methods for leptospirosis diagnosis, especially as complementary tests in a corelation with molecular methods. Leptospirosis detection rate is increased by combining antibody and DNA detection, providing a new tool for timely diagnosis and confirmation of infection.
Impact of Ultrasound on Short Peripheral Intravenous Catheter Placement on Vein Thrombosis Risk
Authors: Holder Max R. , Stutzman Sonja E. , Olson DaiWai M.
Published: April 2017

Approximately 90% of hospitalized patients have a short peripheral intravenous catheter (SPC) placed. Methods of inserting the catheter have evolved over time and now include the use of ultrasound (US)-guided procedures for placement. Little is known about the impact that US-guided procedures have on the vein. This study compared the rate of venous thrombosis in patients with and without US-guided catheter placement. This prospective, single-blind, observational study assessed for venous thrombosis in 153 veins from 135 patients. Veins were evaluated by a research nurse blinded to the method of placement between 48 and 72 hours after the SPC was placed. The Fisher exact test showed a significant difference between vessel compressibility and catheter insertion method (P = .0012). The proportion of noncompressible veins was significantly greater when US was used in comparison with freehand SPC insertion. The Mantel-Haenszel chi-square value of 10.34 (P = .0013) showed that US insertion technique is associated with a higher likelihood of noncompressible veins. This pilot study provides compelling evidence that the use of US to assist with catheter placement is associated with a higher rate of noncompressible veins at day 2 or 3. Further studies are needed with a larger sample to determine the generalizability of the results from this pilot study.
Dilator Use After Vaginal Brachytherapy for Endometrial Cancer
Authors: Hanlon Alexandra , Small William , Strauss Jonathan , Lin Lilie L. , Hanisch Laura , Huang Liming , Bai Jinbing , Wells Jessica , Bruner Deborah Watkins
Published: April 2017

Background:

Vaginal brachytherapy, a common treatment of endometrial cancer, is associated with high rates of vaginal stenosis. Recommendations for vaginal dilator use to minimize stenosis generally include 3 times per week for approximately 10 minutes per use. However, adherence rates range widely and are generally well less than 50%.

Objectives:

The aims of this study were to assess feasibility of recruitment to a study of dilator use and test a theoretically driven enhanced educational program (EEP) to increase adherence.

Methods:

Eligibility included women treated with postoperative vaginal brachytherapy for stage I to IIIc endometrial cancer. Patients were randomized to either nurse-delivered standard institutional instruction or EEP.

Results:

Of eligible patients, 76% consented, 42 were randomized, and 69% completed the 6-month assessment. Mean age was 58.2 years; 48% were sexually active. There was no difference in adherence between arms. Overall, 20% and 8.3% were adherent to the prescribed use of 3 times per week, and 64% and 16% were adherent to use at least once per week at 6 weeks and 6 months, respectively. Adherence was greater among those motivated by vaginal health and having lower body mass index. Nonadherence was significantly higher among those who are college educated, in the EEP group, and with higher weight.

Conclusions:

Feasibility of recruitment into a study of vaginal dilator use was high. Adherence was low, and there was no difference between groups. Adherence to vaginal dilator use requires novel interventions to test.

Implications for Practice:

Nursing education that includes how dilators may maintain vaginal health may improve use because it was a motivator for adherence in this study.
Reconstructing the Gigabase Plant Genome ofSolanum pennelliiusing Nanopore Sequencing
Authors: Schmidt Maximilian H.-W. , Vogel Alxander , Denton Alisandra K. , Istace Benjamin , Wormit Alexandra , van de Geest Henri , Bolger Marie E. , Alseekh Saleh , Maβ Janina , Pfaff Christian , Schurr Ulrich , Chetelat Roger , Maumus Florian , Aury Jean-Marc , Fernie Alisdair R. , Zamir Dani , Bolger Anthony M. , Usadel Bjöern
Published: April 2017

Recent updates in sequencing technology have made it possible to obtain Gigabases of sequence data from one single flowcell. Prior to this update, the nanopore sequencing technology was mainly used to analyze and assemble microbial samples1-3. Here, we describe the generation of a comprehensive nanopore sequencing dataset with a median fragment size of 11,979 bp for the wild tomato speciesSolanum pennelliifeaturing an estimated genome size of ca 1.0 to 1.1 Gbases. We describe its genome assembly to a contig N50 of 2.5 MB using a pipeline comprising a Canu4pre-processing and a subsequent assembly using SMARTdenovo. We show that the obtained nanopore basedde novogenome reconstruction is structurally highly similar to that of the referenceS. pennelliiLA7165genome but has a high error rate caused mostly by deletions in homopolymers. After polishing the assembly with Illumina short read data we obtained an error rate of <0.02 % when assessed versus the same Illumina data. More importantly however we obtained a gene completeness of 96.53% which even slightly surpasses that of the referenceS. pennelliigenome5. Taken together our data indicate such long read sequencing data can be used to affordably sequence and assemble Gbase sized diploid plant genomes.

Raw data is available athttp://www.plabipd.de/portal/solanum-pennelliiand has been deposited as PRJEB19787.
Amygdala input differentially influences prefrontal local field potential and single neuron encoding of reward-based decisions
Authors: Stoll Frederic M. , Mosher Clayton P. , Tamang Sarita , Murray Elisabeth A. , Rudebeck Peter H.
Published: April 2017

Reward-guided behaviors require functional interaction between amygdala, orbital (OFC), and medial (MFC) divisions of prefrontal cortex, but the neural mechanisms underlying these interactions are unclear. Here, we used a decoding approach to analyze local field potentials (LFPs) recorded from OFC and MFC of monkeys engaged in a stimulus-choice task, before and after excitotoxic amygdala lesions. Whereas OFC LFP responses were strongly modulated by the amount of reward associated with each stimulus, MFC responses best represented which stimulus subjects decided to choose. This was counter to what we observed in the level of single neurons where their activity was closely associated with the value of the stimuli presented on each trial. After lesions of the amygdala, stimulus-reward value and choice encoding were reduced in OFC and MFC, respectively. However, while the lesion-induced decrease in OFC LFP encoding of stimulus-reward value mirrored changes in single neuron activity, reduced choice encoding in MFC LFPs was distinct from changes in single neuron activity. Thus, LFPs and single neurons represent different information required for decision-making in OFC and MFC. At the circuit-level, amygdala input to these two areas play a distinct role in stimulus-reward encoding in OFC and choice encoding in MFC.
How does mixed reality affect quiet stance?
Authors: Kong Gaiqing , Wei Kunlin , Kording Konrad P.
Published: April 2017

Mixed reality (MR) has promise for learning, design, and entertainment, and for use during everyday life. However, when interacting with objects in mixed reality, will moving objects make us fall or perturb our postural stability? To address this question, we recruited participants, instructed them to stand quietly, and measured how much virtual objects presented in mixed reality (Microsoft HoloLens) affected their stance. We analyzed the effects of solid object and text, in both a static and a dynamic setting. Mixed reality events induced some movements, but the effect, while significant, was exceptionally small (< 1mm & < 0.5° perturbations in terms of mean distance and angle rotations). We conclude that induced movement in “real reality” should not be too much of a concern when designing mixed reality applications.
BROCKMAN: Deciphering variance in epigenomic regulators byk-mer factorization
Authors: de Boer Carl G. , Regev Aviv
Published: April 2017

Background

Variation in chromatin organization across single cells can help shed important light on the mechanisms controlling gene expression, but scale, noise, and sparsity pose significant challenges for interpretation of single cell chromatin data. Here, we develop BROCKMAN (Brockman Representation Of Chromatin byK-mers in Mark-Associated Nucleotides), an approach to infer variation in transcription factor (TF) activity across samples through unsupervised analysis of the variation in DNA sequences associated with an epigenomic mark.

Results

BROCKMAN represents each sample as a vector of epigenomic-mark-associated DNA word frequencies, and decomposes the resulting matrix to find hidden structure in the data, followed by unsupervised grouping of samples and identification of the TFs that distinguish groups. Applied to single cell ATAC-seq, BROCKMAN readily distinguished cell types, treatments, batch effects, experimental artifacts, and cycling cells. We show that each variable component in thek-mer landscape reflects a set of co-varying TFs, which are often known to physically interact. For example, in K562 cells, AP-1 TFs were central determinant of variability in chromatin accessibility through their variable expression levels and diverse interactions with other TFs. We provide a theoretical basis for why cooperative TF binding – and any associated epigenomic mark – is inherently more variable than non-cooperative binding.

Conclusions

BROCKMAN and related approaches will help gain a mechanistic understanding of thetransdeterminants of chromatin variability between cells, treatments, and individuals.
Allometric derivation and estimation ofGuadua weberbaueriandG. sarcocarpabiomass in the bamboo-dominated forests of SW Amazonia
Authors: Yavit Noah
Published: April 2017

Bamboo-dominated forests in Southwestern Amazonia encompass an estimated 180,000 km2of nearly contiguous primary, tropical lowland forest. This area, largely composed of two bamboo species,Guadua weberbaueriPilger andG. sarcocarpaLondoño & Peterson, comprises a significant portion of the Amazon Basin and has a potentially important effect on regional carbon storage. Numerous local REDD(+) projects would benefit from the development of allometric models for these species, although there has been just one effort to do so. The aim of this research was to create a set of improved allometric equations relating the above and belowground biomass to the full range of natural size and growth patterns observed. Four variables (DBH, stem length, small branch number and branch number ≥ 2cm diameter) were highly significant predictors of stem biomass (N≤ 278, p< 0.0001 for all predictors,complete modelR2=0.93). A secondaryfield model(containing DBH and branch number > 2cm diameter), proved highly significant as well (N= 278, p< 0.0001 for both predictors, R2=0.84). The belowground biomass was estimated to be 19.2±6.2% of the total dry biomass of the bamboo species examined. To demonstrate the utility of these models in the field and derive stand-level estimates of bamboo biomass, ten 0.36-ha plots were analyzed (N= 3,966 culms), yielding above + belowground biomass values ranging from 4.3–14.5 Mg·ha-1. The results of this research provide novel allometric models and estimates of the contribution ofG. weberbaueriandG. sarcocarpato the total carbon budget of this vast and largely unexplored Amazonian habitat.
Base-specific mutational intolerance near splice-sites clarifies role of non-essential splice nucleotides
Authors: Zhang Sidi , Samocha Kaitlin E. , Rivas Manuel A. , Karczewski Konrad J. , Daly Emma , Schmandt Ben , Neale Benjamin M. , MacArthur Daniel G. , Daly Mark J.
Published: April 2017

Variation in RNA splicing (i.e., alternative splicing) plays an important role in many diseases. Variants near 5′ and 3′ splice sites often affect splicing, but the effects of these variants on splicing and disease have not been fully characterized beyond the 2 “essential” splice nucleotides flanking each exon. Here we provide quantitative measurements of tolerance to mutational disruptions by position and reference allele-alternative allele combination. We show that certain reference alleles are particularly sensitive to mutations, regardless of the alternative alleles into which they are mutated. Using public RNA-seq data, we demonstrate that individuals carrying such variants have significantly lower levels of the correctly spliced transcript compared to individuals without them, and confirm that these specific substitutions are highly enriched for known Mendelian mutations. Our results propose a more refined definition of the “splice region” and offer a new way to prioritize and provide functional interpretation of variants identified in diagnostic sequencing and association studies.
With our powers combined: integrating behavioral and genetic data to estimate mating success and sexual selection
Authors: Gauthey Zoé , Tentelier Cédric , Lepais Olivier , Elosegi Arturo , Royer Laura , Glise Stéphane , Labonne Jacques
Published: April 2017

The analysis of sexual selection classically relies on the regression of individual phenotypes against the marginal sums of a males × females matrix of pairwise reproductive success, assessed by genetic parentage analysis. When the matrix is binarized, the marginal sums give the individual mating success. Because such analysis treats male and female mating/reproductive success independently, it ignores that the success of a male × female sexual interaction can be attributable to the phenotype of both individuals. Also, because it is based on genetic data only, it is oblivious to costly yet unproductive matings, which may be documented by behavioral observations. To solve these problems, we propose a statistical model which combines matrices of offspring numbers and behavioral observations. It models reproduction on each mating occasion of a mating season as three stochastic and interdependent pairwise processes, each potentially affected by the phenotype of both individuals and by random individual effect: encounter (Bernoulli), concomitant gamete emission (Bernoulli), and offspring production (Poisson). Applied to data from a mating experiment on brown trout, the model yielded different results from the classical regression analysis, with only a limited effect of male body size on the probability of gamete release and a negative effect of female body size on the probability of encounter and gamete release. Because the general structure of the model can be adapted to other partitioning of the reproductive process, it can be used for a variety of biological systems where behavioral and genetic data are available.
Bayesian phylogenetic analysis for diploid and allotetraploid species networks
Authors: Jones Graham
Published: April 2017

Allopolyploid species are formed by genome doubling after hybridization between otherwise intersterile parental species. Allopolyploidy is a common speciation mechanism in land plants. Here we describe and evaluate a Bayesian approach to the phylogenetic analysis of species relationships when both ordinary speciation and allopolyploidy are present. The approach takes incomplete lineage sorting into account using the multi-species coalescent model, and extends this to deal with the extra complications due to allopolyploidy. The number of hybridizations is not assumed, which means that the number of parameters varies and a reversible-jump MCMC algorithm is needed to sample from the posterior. The main restriction is that only diploids and allotetraploids are considered. The model is implemented in the BEAST framework and is an extension of Jones et al. (2013). Simulations show that the topology of the network can be reliably inferred along with estimates of other parameters.
A standardized framework for representation of ancestry data in genomics studies, with application to the NHGRI-EBI GWAS Catalog
Authors: Morales Joannella , Bowler Emily H. , Buniello Annalisa , Cerezo Maria , Hall Peggy , Harris Laura W. , Hastings Emma , Junkins Heather A. , Malangone Cinzia , McMahon Aoife C. , Milano Annalisa , Welter Danielle , Burdett Tony , Cunningham Fiona , Flicek Paul , Parkinson Helen , Hindorff Lucia A. , MacArthur Jacqueline A. L.
Published: April 2017

Background

The accurate description of ancestry is essential to interpret and integrate human genomics data, and to ensure that advances in the field of genomics benefit individuals from all ancestral backgrounds. However, there are no established guidelines for the consistent, unambiguous and standardized description of ancestry. To fill this gap, we provide a framework, designed for the representation of ancestry in GWAS data, but with wider application to studies and resources involving human subjects.

Result

Here we describe our framework and its application to the representation of ancestry data in a widely-used publically available genomics resource, the NHGRI-EBI GWAS Catalog. We present the first analyses of GWAS data using our ancestry categories, demonstrating the validity of the framework to facilitate the tracking of ancestry in big data sets. We exhibit the broader relevance and integration potential of our method by its usage to describe the well-established HapMap and 1000 Genomes reference populations. Finally, to encourage adoption, we outline recommendations for authors to implement when describing samples.

Conclusions

While the known bias towards inclusion of European ancestry individuals in GWA studies persists, African and Hispanic or Latin American ancestry populations contribute a disproportionately high number of associations, suggesting that analyses including these groups may be more effective at identifying new associations. We believe the widespread adoption of our framework will increase standardization of ancestry data, thus enabling improved analysis, interpretation and integration of human genomics data and furthering our understanding of disease.
Rational Design of Evolutionarily Stable Microbial Kill Switches
Authors: Stirling Finn , Bitzan Lisa , Oliver John WK , Way Jeffrey , Silver Pamela A.
Published: April 2017

The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One particularly useful but challenging situation is a switch between life and death depending on environment. Here are presented “essentializer” and “cryodeath” circuits, which act as kill switches inEscherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ rational design and a novel toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. In addition, cryodeath was shown to control the growth environment of a bacterial population, with an escape rate of less than 1 in 105after ten daysin vivo.
Mashona Mole-Rat Automatic Individual Identification Based on the Mating Calls
Authors: Dvorakova Veronika , Ptacek Ladislav , Hrouzkova Ema , Muller Ludek , Sumbera Radim
Published: April 2017

In this study was tested mole-rat vocalization for presence of diverse individually distinctive features. An automatic system based on the GMM-UBM was used for individual recognition. The system distinguishes the recordings of the five mole-rats females. The overall achieved identification accuracy is 76.7%, the lowest 59.2%, and the highest 83.5%. The overall percentage is thus high enough to prove that the mating calls of the Mashona mole-rat can carry information about mole-rat individuality. Our results showed that studied vocal signals in the Mashona mole-rats are individually specific which indicates the possibility of individual vocal recognition in this species.