bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-conductance Ca
2+
- and voltage-gated K
+
channels form and break interactions with membrane lipids during each gating cycle
Authors: Tian Yutao , Heinemann Stefan H. , Hoshi Toshinori
Published: April 2019

Significance

Ion channels mediating electrical excitability reside within membrane lipids; however, the nature of the interactions remains obscure. This study shows that specific positive amino acid residues of the Ca
2+
- and voltage-gated K
+
[big potassium (BK)] channel, a negative-feedback component in cell excitability, form interactions with negative lipid oxygen atoms when the ion conduction gate is open. When the gate is closed, the same positive residues interact with negative residues within the protein. This lipid-dependent gating cycle may explain how cell-signaling molecules and pharmacological modulators of the BK channel work, advancing the fundamental understanding of ion channel function and facilitating therapeutic drug development.
A general characterization method for nonlinearities in superconducting circuits
Authors: Weißl T , Jolin S W , Borgani R , Forchheimer D , Haviland D B
Published: April 2019

Detailed knowledge of nonlinearity in superconducting microwave circuits is required for the optimal control of their quantum state. We present a general method to precisely characterize this nonlinearity to very high order. Our method is based on intermodulation spectroscopy at microwave frequencies and does not require DC-connection or DC-measurement of an on-chip reference structure. We give a theoretical derivation of the method and we validate it by reconstructing a known nonlinearity from simulated data. We experimentally demonstrate the reconstruction of the unknown nonlinear current-phase relation of a microwave resonator with superconducting nanowires.
Limits of flexural wave absorption by open lossy resonators: reflection and transmission problems
Authors: Leng J , Gautier F , Pelat A , Picó R , Groby J-P , Romero-García V
Published: April 2019

The limits of flexural wave absorption by open lossy resonators are analytically and numerically reported in this work for both the reflection and transmission problems. An experimental validation for the reflection problem is presented. The reflection and transmission of flexural waves in 1D resonant thin beams are analyzed by means of the transfer matrix method. The hypotheses, on which the analytical model relies, are validated by experimental results. The open lossy resonator, consisting of a finite length beam thinner than the main beam, presents both energy leakage due to the aperture of the resonators to the main beam and inherent losses due to the viscoelastic damping. Wave absorption is found to be limited by the balance between the energy leakage and the inherent losses of the open lossy resonator. The perfect compensation of these two elements is known as the critical coupling condition and can be easily tuned by the geometry of the resonator. On the one hand, the scattering in the reflection problem is represented by the reflection coefficient. A single symmetry of the resonance is used to obtain the critical coupling condition. Therefore the perfect absorption can be obtained in this case. On the other hand, the transmission problem is represented by two eigenvalues of the scattering matrix, representing the symmetric and anti-symmetric parts of the full scattering problem. In the geometry analyzed in this work, only one kind of symmetry can be critically coupled, and therefore, the maximal absorption in the transmission problem is limited to 0.5. The results shown in this work pave the way to the design of resonators for efficient flexural wave absorption.
Tissue-engineered nerve grafts using a scaffold-independent and injectable drug delivery system: a novel design with translational advantages
Authors: Liu Yanxi , Yu Shuangjiang , Gu Xiaosong , Cao Rangjuan , Cui Shusen
Published: April 2019

Objective. Currently commercially available nerve conduits have demonstrated suboptimal clinical efficacy in repairing peripheral nerve defects. Although tissue-engineered nerve grafts (TENGs) with sustained release of neurotrophic factors (NTFs) are experimentally proved to be more effective than these blank conduits, there remains a lack of clinical translation. NTFs are typically immobilized onto scaffold materials of the conduit via adsorption, specific binding or other incorporation techniques. These scaffold-based delivery strategies increase complexity and cost of conduit fabrication and lack flexibility in choosing different drugs. Therefore, to facilitate clinical translation and commercialization, we construct a TENG using a scaffold-independent drug delivery system (DDS). Approach. This study adopted a scaffold-independent DDS based on methoxy-poly (ethylene glycol)-b-poly(γ-ethyl-L-glutamate) (mPEG-PELG) thermosensitive hydrogels that undergo sol-to-gel transition at body temperature. In addition, TENG, a chitosan scaffold filled with nerve growth factor (NGF)-loaded mPEG-PELG that gel in the lumen upon injection during surgery and function as a drug-releasing conduit-filler, was designed. Subsequently, the efficacy of DDS and therapeutic effects of TENG were assessed. Main results. The results demonstrated that NGF-loaded mPEG-PELG controllably and sustainably released bioactive NGF for 28 d. When bridging a 10 mm rat sciatic nerve gap, the morphological, electrophysiological, and functional analyses revealed that NGF-releasing TENG (Scaffold  +  NGF/mPEG-PELG) achieved superior regenerative outcomes compared to plain scaffolds and those combined with systemic delivery of NGF (daily intramuscular injection (IM)), and its effects were relatively similar to autografts. Significance. This study has proposed a TENG using thermosensitive hydrogels as an injectable implant to controllably release NGF, which has promising therapeutic potential and translatability. Such TENGs obviate the need for conduit modification, complex preloading or binding mediators, therefore they allow the ease of drug switching in clinical practice and greatly simplify the manufacturing process due to the independent preparation of drug delivery system.
The carrot or the stick? Drivers of California farmer support for varying groundwater management policies
Authors: Niles Meredith T , Hammond Wagner Courtney R
Published: April 2019

Growing demand for groundwater, coupled with the projected threats to groundwater supplies and impacts, has led to an increased focus on policy options for groundwater management. Globally, agriculture is the largest human-use of water, making farmers a critical stakeholder for policy engagement. In California, the Sustainable Groundwater Management Act (SGMA), a comprehensive groundwater policy, was signed into law in 2014. Here we explore farmer perspectives of groundwater availability and groundwater management policy preferences through a mail survey of farmers (n = 137) in Yolo County, California, implemented in 2017. Overall, farmers expressed widespread concern for the five applicable ‘undesirable results’ considered under SGMA and the majority of farmers felt that these conditions were either occurring now or were likely to occur in the next ten years. The majority of farmers were supportive of individual or incentive-based policy options to address groundwater concerns (e.g. voluntary adoption of water management practices). However, a sizable group of farmers were also supportive of regulatory-based policy options (e.g. moratorium on drilling new wells). Multivariate regression models suggest that for both kinds of policies, individual support for SGMA positively predicts groundwater management policy support. However, for regulatory-based policies, subjective norms - a farmers’ belief that the majority of other farmers support SGMA—is also an important predictor of regulatory policy approaches along with a number of other factors. These results suggest that, should regulatory approaches for SGMA implementation be necessary, fostering subjective norms among farmers may be an important mechanism to achieving farmer support.
Electronic features of vacancy, nitrogen, and phosphorus defects in nanodiamonds
Authors: Hertkorn Jens , Fyta Maria
Published: April 2019

Defective nanostructures with a surface termination are the focus of this work. In order to elucidate the influence of the defect on the properties of nanomaterials, we take hydrogen terminated nanodiamonds. Various vacancy defect centers are separately embedded in a nanodiamond at different positions. These include some of the known defects, such as the charged nitrogen-vacancy (NV−), the silicon-vacancy (SiV0), the germanium-vacancy (GeV0), the phosphorous-nitrogen (PN), and the nickel-vacancy (NiV−). For these defective nanodiamonds, we probe the influence of the defect type, its position, as well as the size of the nanodiamond through their structural and electronic features. A detailed and comparative analysis is provided here, based on quantum mechanical simulations. Our results shed light into the inherent differences of these defects in nanodiamonds, allowing for a better understanding of defective nanostructures. In the end, we discuss the potential of tuning their characteristics in view of novel nanotechnological applications.
Serum Sodium and Pulse Pressure in SPRINT
Authors: Nowak Kristen L , Chonchol Michel , Jovanovich Anna , You Zhiying , Bates Jeffrey , Foy Capri , Glasser Stephen , Killeen Anthony A , Kostis John , Rodriguez Carlos J , Segal Mark , Simmons Debra L , Taylor Addison , Lovato Laura C , Ambrosius Walter T , Supiano Mark A ,   SPRINT Research Group
Published: April 2019

BACKGROUND

High dietary sodium intake may induce a small, yet physiologically relevant rise in serum sodium concentration, which associates with increased systolic blood pressure. Cellular data suggest that this association is mediated by increased endothelial cell stiffness. We hypothesized that higher serum sodium levels were associated with greater arterial stiffness in participants in the Systolic Blood Pressure Intervention Trial (SPRINT).

METHODS

Multivariable linear regression was used to examine the association between baseline serum sodium level and (i) pulse pressure (PP; n = 8,813; a surrogate measure of arterial stiffness) and (ii) carotid–femoral pulse wave velocity (CFPWV; n = 591 in an ancillary study to SPRINT).

RESULTS

Baseline mean ± SD age was 68 ± 9 years and serum sodium level was 140 ± 2 mmol/L. In the PP analysis, higher serum sodium was associated with increased baseline PP in the fully adjusted model (tertile 3 [≥141 mmol] vs. tertile 2 [139–140 mmol]; β = 0.87, 95% CI = 0.32 to 1.43). Results were similar in those with and without chronic kidney disease. In the ancillary study, higher baseline serum sodium was not associated with increased baseline CFPWV in the fully adjusted model (β = 0.35, 95% CI = –0.14 to 0.84).

CONCLUSIONS

Among adults at high risk for cardiovascular events but free from diabetes, higher serum sodium was independently associated with baseline arterial stiffness in SPRINT, as measured by PP, but not by CFPWV. These results suggest that high serum sodium may be a marker of risk for increased PP, a surrogate index of arterial stiffness.
Alcoholic Hepatitis: A Review
Authors: Hosseini Nooshin , Shor Julia , Szabo Gyongyi
Published: April 2019

Alcoholic liver disease (ALD) represents a spectrum of injury, ranging from simple steatosis to alcoholic hepatitis to cirrhosis. Regular alcohol use results in fatty changes in the liver which can develop into inflammation, fibrosis and ultimately cirrhosis with continued, excessive drinking. Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality that can occur in patients with steatosis or underlying cirrhosis. The pathogenesis of ALD is multifactorial and in addition to genetic factors, alcohol-induced hepatocyte damage, reactive oxygen species, gut-derived microbial components result in steatosis and inflammatory cell (macrophage and neutrophil leukocyte) recruitment and activation in the liver. Continued alcohol and pro-inflammatory cytokines induce stellate cell activation and result in progressive fibrosis. Other than cessation of alcohol use, medical therapy of AH is limited to prednisolone in a subset of patients. Given the high mortality of AH and the progressive nature of ALD, there is a major need for new therapeutic intervention for this underserved patient population.
Report on Current Experience of ASAPS Membership and Management of Cosmetic Tourism Complications
Authors: Qureshi Ali A , Gould Daniel J , Stevens W Grant , Fernau James
Published: April 2019

Background

Cosmetic tourism is an expanding industry with increasing scrutiny in the public domain of complications and patient safety issues. The health and financial implications for patients are large and deserve further investigation.

Objectives

The aim of this study was to understand the experience of the American Society for Aesthetic Plastic Surgery (ASAPS) members treating medical tourism patients with complications who returned to the United States for secondary management.

Methods

A 20-question survey was administered electronically in August 2018 to ASAPS members with voluntary participation. Questions about surgeon experience, the nature of complications, type of initial surgery, and subsequent management were asked. Responses were tabulated and percentages of response choices were calculated and reported.

Results

Ninety-three responses were received from the 1611 physician ASAPS members (5.8% response rate). More than half of respondents had seen 2 to 5 patients in the last 12 months with a complication from cosmetic tourism. The most common procedure that patients had done abroad was abdominoplasty. The most common complication was infection caused by Gram-positive organisms, managed on an outpatient basis without surgical intervention. Involvement of an ASAPS member led to successful resolution of complications in the vast majority of patients. Estimated costs out of pocket for management of complications were most commonly between $1001 and 5000.

Conclusions

While the experience of ASAPS members is as varied as the complications faced by cosmetic tourism patients, the vast majority of complications is infectious and can be managed on an outpatient basis successfully with the involvement of an ASAPS member. Further collaborative efforts both domestically and internationally can help improve patient safety for cosmetic tourism patients.
IsoformSwitchAnalyzeR: analysis of changes in genome-wide patterns of alternative splicing and its functional consequences
Authors: Vitting-Seerup Kristoffer , Sandelin Albin
Published: April 2019

Alternative splicing is an important mechanism involved in health and disease. Recent work highlights the importance of investigating genome-wide changes in splicing patterns and the subsequent functional consequences. Current computational methods only support such analysis on a gene-by-gene basis. Therefore, we extended IsoformSwitchAnalyzeR R library to enable analysis of genome-wide changes in specific types of alternative splicing and predicted functional consequences of the resulting isoform switches. As a case study, we analyzed RNA-seq data from The Cancer Genome Atlas and found systematic changes in alternative splicing and the consequences of the associated isoform switches.

Availability and implementation

Windows, Linux and Mac OS: http://bioconductor.org/packages/IsoformSwitchAnalyzeR.

Supplementary information

Supplementary data are available at Bioinformatics online.
Restraint stress of male mice induces apoptosis in spermatozoa and spermatogenic cells: role of the FasL/Fas system†
Authors: Xiao Bin , Li Xiao , Feng Xiu-Yun , Gong Shuai , Li Zhi-Bin , Zhang Jie , Yuan Hong-Jie , Tan Jing-He
Published: April 2019

The mechanisms by which psychological stress impairs semen quality are largely unknown. By using a restraint-stressed mouse model, we studied the role of the FasL/Fas system in psychological stress-induced apoptosis of spermatozoa and spermatogenic cells. Male mice were restrained for 48 h before examination for sperm fertilizing potential and for apoptosis and FasL/Fas expression in spermatozoa, spermatogenetic cells/seminiferous tubules, and caudae epididymides. The results showed that the male restraint reduced motility, fertilization rates, and mitochondrial membrane potential while increasing apoptosis and Fas expression in spermatozoa. Restraint also facilitated apoptosis and FasL/Fas expression in spermatogenic cells/seminiferous tubules and caudae epididymides. The restraint-induced apoptosis in spermatozoa and spermatogenic cells was significantly ameliorated in gld mice that harbor a loss-of-function mutation in FasL. However, incubation with FasL did not affect sperm motility and apoptosis, while incubation with tumor necrosis factor (TNF)-α did. The epididymis of the gld mice produced significantly less TNF-α and TNF-related apoptosis-inducing ligand (TRAIL) than that of wild-type mice did after male restraint. Thus, the results confirmed that the FasL/Fas system played an important role in the psychological stress-induced apoptosis of spermatozoa and spermatogenic cells and that FasL triggered sperm apoptosis in epididymis dependently through promoting TNF-α and TRAIL secretion.
A Comprehensive Analysis of 2D&3D Video Watching of EEG Signals by Increasing PLSR and SVM Classification Results
Authors: Manshouri Negin , Kayikcioglu Temel
Published: April 2019

Despite the development of two- and three-dimensional (2D&3D) technology, it has attracted the attention of researchers in recent years. This research is done to reveal the detailed effects of 2D in comparison with 3D technology on the human brain waves. The impact of 2D&3D video watching using electroencephalography (EEG) brain signals is studied. A group of eight healthy volunteers with the average age of 31 ± 3.06 years old participated in this three-stage test. EEG signal recording consisted of three stages: After a bit of relaxation (a), a 2D video was displayed (b), the recording of the signal continued for a short period of time as rest (c), and finally the trial ended. Exactly the same steps were repeated for the 3D video. Power spectrum density (PSD) based on short time Fourier transform (STFT) was used to analyze the brain signals of 2D&3D video viewers. After testing all the EEG frequency bands, delta and theta were extracted as the features. Partial least squares regression (PLSR) and Support vector machine (SVM) classification algorithms were considered in order to classify EEG signals obtained as the result of 2D&3D video watching. Successful classification results were obtained by selecting the correct combinations of effective channels representing the brain regions.
Clinical utility of the 2016 ASE/EACVI recommendations for the evaluation of left ventricular diastolic function in the stratification of post-discharge prognosis in patients with acute heart failure
Authors: Machino-Ohtsuka Tomoko , Seo Yoshihiro , Ishizu Tomoko , Hamada-Harimura Yoshie , Yamamoto Masayoshi , Sato Kimi , Sai Seika , Sugano Akinori , Obara Kenichi , Yoshida Ikuo , Nishi Isao , Aonuma Kazutaka , Ieda Masaki
Published: April 2019

Aims

Left ventricular diastolic dysfunction (LVDD) has prognostic significance in heart failure (HF). We aimed to assess the impact of LVDD grade stratified by the updated 2016 echocardiographic algorithm (DD2016) on post-discharge outcomes in patients admitted for acute HF and compare with the previous 2009 algorithm (DD2009).

Methods and results

The study included 481 patients hospitalized for acute decompensated HF. Comprehensive echocardiography and LVDD evaluation were performed just before hospital discharge. The primary endpoint was a composite of cardiovascular death and readmission for HF. The concordance between DD2016 and DD2009 was moderate (κ = 0.44, P < 0.001); the reclassification rate was 39%. During the follow-up (median: 15 months), 127 (26%) patients experienced the primary endpoint. In the Kaplan–Meier analysis, Grade III in DD2016 showed a lower event-free survival rate than Grades I and II (log rank, P < 0.001 and P = 0.048, respectively) and was independently associated with a higher incidence of the primary endpoint than Grade I [hazard ratio 1.89; 95% confidence interval (CI) 1.17–3.04; P = 0.009]. Grade II or III in DD2016, reflecting elevation of left ventricular (LV) filling pressure, added an incremental predictive value of the primary endpoint to clinical variables irrespective of LV ejection fraction. DD2016 was comparable to DD2009 in predicting the endpoint (net reclassification improvement = 11%; 95% CI −7% to 30%, P = 0.23).

Conclusion

Despite simplification of the algorithm for LVDD evaluation, the prognostic value of DD2016 for post-discharge cardiovascular events in HF patients was maintained and not compromised in comparison with DD2009.
Long-term blood pressure trajectories and incident atrial fibrillation in women and men: the Tromsø Study
Authors: Sharashova Ekaterina , Wilsgaard Tom , Ball Jocasta , Morseth Bente , Gerdts Eva , Hopstock Laila A , Mathiesen Ellisiv B , Schirmer Henrik , Løchen Maja-Lisa
Published: April 2019

Aims

To explore sex-specific associations between long-term individual blood pressure (BP) patterns and risk of incident atrial fibrillation (AF) in the general population.

Methods and results

Blood pressure was measured in 8376 women and 7670 men who attended at least two of the three population-based Tromsø Study surveys conducted in 1986–87, 1994–95, and 2001. Participants were followed for incident AF throughout 2013. Latent mixed modelling was used to identify long-term trajectories of systolic BP and hypertension. Cox regression was used to estimate associations between the identified trajectories and incident AF. Elevated systolic BP throughout the exposure period (1986–2001) independently and differentially increased risk of AF in women and men. In women, having elevated systolic BP trajectories doubled AF risk compared to having persistently low levels, irrespective of whether systolic BP increased, decreased, or was persistently high over time, with hazard ratios of 1.88 (95% confidence interval 1.37–2.58), 2.32 (1.61–3.35), and 1.94 (1.28–2.94), respectively. In men, those with elevated systolic BP that continued to increase over time had a 50% increased AF risk: 1.51 (1.09–2.10). When compared to those persistently normotensive, women developing hypertension during the exposure period, and women and men with hypertension throughout the exposure period had 1.40 (1.06–1.86), 2.75 (1.99–3.80), and 1.36 (1.10–1.68) times increased risk of AF, respectively.

Conclusion

Long-term BP and hypertension trajectories were associated with increased incidence of AF in both women and men, but the associations were stronger in women.
Developing a Short Multidimensional Measure of Pain Self-efficacy: The Chronic Pain Self-efficacy Scale-Short Form
Authors: Cheng Sheung-Tak , Chen Phoon Ping , Chow Yu Fat , Chung Joanne W Y , Law Alexander C B , Lee Jenny S W , Leung Edward M F , Tam Cindy W C
Published: April 2019

Background and Objectives

The 22-item Chronic Pain Self-efficacy Scale (CPSS) measures three domains of pain self-efficacy: pain management, physical functioning, and coping with symptoms. This study aims to develop a short form (CPSS-SF) that retains the multidimensional structure of the instrument.

Research Design and Methods

Six hundred sixty-four community-dwelling Chinese older adults aged 60–95 years with chronic pain completed a survey. Confirmatory factor analysis (CFA) was conducted on the 22-item CPSS. Regression analyses were performed to examine the items’ correlations with criterion variables. After CPSS-SF items were selected, the performance of CPSS-SF subscales in terms of accounting for pain-related outcomes was compared with the full version.

Results

CFA supported a modified 3-factor model of the CPSS. On the basis of factor loadings on the 3 dimensions and the items’ correlations with pain intensity and pain disability, 11 items were selected for the CPSS-SF, which correlated at .97 with the full version. Regression analyses showed that the associations of the CPSS-SF subscales with pain intensity, pain disability, depressive symptoms, instrumental activities of daily living, and physical and mental health-related quality of life, were indistinguishable from their full-version counterparts.

Discussion and Implications

The CPSS-SF is a valid instrument that can be used in lieu of the full scale. Its availability will facilitate the assessment of pain self-efficacy in research and clinical settings due to its brevity but strong psychometric properties. However, the current evidence is limited to Chinese older adults; more research is needed to ascertain its validity in other age and cultural groups.
Shades of Blue and Gray: A Comparison of the Center for Epidemiologic Studies Depression Scale and the Composite International Diagnostic Interview for Assessment of Depression Syndrome in Later Life
Authors: Dang Linh , Dong Liming , Mezuk Briana
Published: April 2019

Background and Objectives

Psychiatric research lacks the equivalent of a thermometer, that is, a tool that accurately measures mental disorder regardless of context. Instead, the psychometric properties of scales that purport to assess psychopathology must be continuously evaluated. To that end, this study evaluated the diagnostic agreement between the eight-item Center for Epidemiologic Studies Depression Scale (CESD-8) and the Composite International Diagnostic Interview—short form (CIDI-SF) in the Health and Retirement Study (HRS).

Research Design and Methods

Data come from 17,613 respondents aged >50 from the 2014 wave of the HRS. Kappa coefficients were used to assess the agreement between the 2 instruments on depression classification across a range of thresholds for identifying case status, including variation across subgroups defined by age, race/ethnicity, and gender.

Results

The point prevalence of depression syndrome estimated by the CESD was higher than that estimated by the CIDI-SF (CESD: 9.9%–19.5% depending on the cutoff applied to the CESD vs CIDI-SF: 7.7%). Assuming CIDI-SF as the gold standard, the CESD yielded a sensitivity of 56.2%–70.2% and specificity of 84.7%–94.0% across the range of cutoffs. The agreement on depression classification was weak (κ = 0.32–0.44).

Discussion and Implications

Depression cases identified by the CESD have poor agreement with those identified by the CIDI-SF. Conceptually, psychological distress as measured by the CESD is not interchangeable with depression syndrome as measured by the CIDI-SF. Population estimates of depression among older adults based on the CESD should be interpreted with caution.
Regeneration-Competent and -Incompetent Murids Differ in Neutrophil Quantity and Function
Authors: Cyr Jennifer L , Gawriluk Thomas R , Kimani John M , Rada Balázs , Watford Wendy T , Kiama Stephen G , Seifert Ashley W , Ezenwa Vanessa O
Published: April 2019

Regeneration is rare in mammals, but spiny mice (Acomys spp.) naturally regenerate skin and ear holes. Inflammation is thought to inhibit regeneration during wound healing, but aspects of inflammation contribute to both regeneration and pathogen defense. We compared neutrophil traits among uninjured, regeneration-competent (Acomys: A. cahirinus, A. kempi, A. percivali) and -incompetent (Mus musculus: Swiss Webster, wild-caught strains) murids to test for constitutive differences in neutrophil quantity and function between these groups. Neutrophil quantity differed significantly among species. In blood, Acomys had lower percentages of circulating neutrophils than Mus; and in bone marrow, Acomys had higher percentages of band neutrophils and lower percentages of segmented neutrophils. Functionally, Acomys and Mus neutrophils did not differ in their ability to migrate or produce reactive oxygen species, but Acomys neutrophils phagocytosed more fungal zymosan. Despite this enhanced phagocytosis activity, Acomys neutrophils were not more effective than Mus neutrophils at killing Escherichia coli. Interestingly, whole blood bacteria killing was dominated by serum in Acomys versus neutrophils only or neutrophils and serum in Mus, suggesting that Acomys primarily rely on serum to kill bacteria whereas Mus do not. These subtle differences in neutrophil traits may allow regeneration-competent species to offset damaging effects of inflammation without compromising pathogen defense.
An implicit class of continuous dynamical system with data-sample outputs: a robust approach
Authors: Juarez Raymundo , Azhmyakov Vadim , Espinoza A Tadeo , Salas Francisco G
Published: April 2019

This paper addresses the problem of robust control for a class of nonlinear dynamical systems in the continuous time domain. We deal with nonlinear models described by differential-algebraic equations (DAEs) in the presence of bounded uncertainties. The full model of the control system under consideration is completed by linear sampling-type outputs. The linear feedback control design proposed in this manuscript is created by application of an extended version of the conventional invariant ellipsoid method. Moreover, we also apply some specific Lyapunov-based descriptor techniques from the stability theory of continuous systems. The above combination of the modified invariant ellipsoid approach and descriptor method makes it possible to obtain the robustness of the designed control and to establish some well-known stability properties of dynamical systems under consideration. Finally, the applicability of the proposed method is illustrated by a computational example. A brief discussion on the main implementation issue is also included.
Rv1075c of Mycobacterium tuberculosis is a GDSL-Like Esterase and Is Important for Intracellular Survival
Authors: Yang Dong , He Xiaoping , Li Shaoji , Liu Jiawang , Stabenow Jennifer , Zalduondo Lillian , White Stephen , Kong Ying
Published: April 2019

Mycobacterium tuberculosis lipid metabolism pathways facilitate access to carbon and energy sources during infection. M. tuberculosis gene Rv1075c was annotated as a conserved hypothetical protein. We identified that Rv1075c amino acid sequence shares similarities with other bacterial lipase/esterases and we demonstrated that it has esterase activity, with preference for short-chain fatty acids, particularly acetate, with highest activity at 45°C, pH 9. Site-direct mutagenesis revealed its activity triad as Ser80, Asp244, and His247. We further determined that rRv1075c hydrolyzed triacetin and tributyrin, and it was mainly distributed in cell wall and membrane. Its expression was induced at pH 4.5, mimicking the acidic phagosome of macrophages. Mutation of Rv1075c led to reduced bacterial growth in THP-1 cells and human peripheral blood mononuclear cell-derived macrophages, and attenuated M. tuberculosis infection in mice. Our data suggest that Rv1075c is involved in ester and fatty acid metabolism inside host cells.
Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings
Authors: Ueno Naomi , Banno Shigeo , Endo Yutaka , Tamura Motoko , Sugaya Katsuko , Hashigaki Satoshi , Ohki Emiko , Yoshimura Akinobu , Gemma Akihiko
Published: April 2019

Objective

Post-marketing surveillance (PMS) was performed in Japan to obtain information on the safety and efficacy of crizotinib.

Methods

Target patients included almost all patients with anaplastic lymphoma kinase-positive non-small cell lung cancer who were administered crizotinib. The observation period was 52 weeks. In the present study, we focused on the treatment status and safety of crizotinib therapy and analyzed the real-world data obtained by this PMS (ClinicalTrials.gov: NCT01597258).

Results

The safety analysis set included 2028 Japanese patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of adverse drug reactions (ADRs) was 91.6%, and common ADRs (incidence ≥15%) were nausea (32.2%), diarrhea (24.3%), photopsia (18.9%), vomiting (17.5%) and dysgeusia (16.8%). Many patients (623 patients) discontinued treatment of crizotinib because of adverse events within 12 weeks after therapy initiation, which tended to frequently occur in the following cases: (1) elderly, (2) body weight <40 kg, (3) body surface area <1.2 m2 (4) ECOG PS 2–4, (5) higher Brinkman index and (6) history of occupational/environmental exposure such as asbestos/pneumoconiosis. The proportions of patients remaining on crizotinib therapy were 68.2% for 3 months, 55.2% for 6 months and 36.1% for 12 months, with a median duration of 7.9 months. Multivariate analysis with a Cox proportional hazard model identified 10 statistically significant patient background factors influencing the duration of crizotinib therapy.

Conclusions

No new safety concerns were observed in this PMS study. Our results provide useful information regarding the status of crizotinib therapy in the clinical setting.
Safety Comparison of Two Enterovirus 71 (EV71) Inactivated Vaccines in Yiwu, China
Authors: Luo Shuying , Wu Fei , Ye Xiaojun , Fu Tao , Tao Jingbo , Luo Weibiao , Wang Ying , Jia Jianwei , Lou Lingqiao
Published: April 2019

The safety of two kinds of post-marketing enterovirus 71 (EV71) vaccine in China was evaluated in this study. Fourteen vaccination clinics were randomly assigned in a 1:1 ratio, and both children in two groups were administered according to a two-dose schedule (on a 0 and 28 day schedule). Written informed consent was obtained, and recipients in this study were observed for 30 min after inoculation in the clinic, and then followed via phone or on-site follow-up at day 3 and 30. No severe EV71-associated adverse event was reported. No significant difference was noticed between Group Sinovac and Group CAMS (χz = 0.346, p = 0.556). There was no significant difference in the occurrence of adverse events among recipients aged less than 24 months; however, the proportion of adverse events was higher in Group CAMS than in Group Sinovac among the subjects aged 24–35 months (5.3% vs. 2.5%, p < 0.001). The two kinds of EV71 vaccines showed satisfactory safety. Adverse events after vaccination were normal and acceptable.
Glucose-6-phosphate dehydrogenase deficiency genotypes and allele frequencies in the Kavango and Zambezi regions of northern Namibia
Authors: Haiyambo Daniel H , Ilunga Alex , Nangombe Ruth , Ababio Grace , Hatuikulipi Toini , Aleksenko Larysa , Misihairabgwi Jane , Uusiku Petrina , Pernica Jeffrey M , Greco Beatrice , Quaye Isaac K
Published: April 2019

Background

Namibia has made significant gains in the fight against malaria, with a target of elimination by 2023. We examined the genotype and allele frequencies of glucose-6-phosphate dehydrogenase (G6PD) deficiency to inform decisions on primaquine use, as we recently detected clusters of Plasmodium ovale curtisi in Kavango.

Methods

A multistaged cross-sectional sampling method was used to enrol 212 children 2–9 y of age from schools and clinics in the Okavango and Zambezi regions of northern Namibia. Genotypes for the 202 G→A and 376 A→G mutations were assigned by polymerase chain reaction restriction fragment length polymorphism.

Results

Of the 212 subjects enrolled, genotypes were available for 210, made up of 61 males and 149 females. G6PD-deficient males (hemizygotes) and females (homozygotes) constituted 3.27% (2/61) and 0.0% (0/149), respectively. Female heterozygotes (AA− and BA−) constituted 10.07% (15/149), while G6PD wild-type males (with A or B haplotype) and females (with AA, BB or AB haplotypes) consisted of 96.72% (59/61) and 89.93% (134/149), respectively. The A−, A and B allele frequencies were 0.0474, 0.3036 and 0.6490, respectively. Hardy–Weinberg equilibrium tests for female genotype frequencies did not show deviation (p=0.29).

Conclusions

The frequency of G6PD deficiency alleles in males in the Kavango and Zambezi regions of northern Namibia constitute 3.27%, a first report to inform policy on primaquine role out.
A systematic approach to describing fractures
Authors: Bolander Sarah
Published: April 2019

Clinicians, including practitioners in primary care and across numerous specialties, are essential to the interpretation of imaging for correlating clinical presentation with fracture identification on plain radiographs. A comprehensive review of radiographs lets clinicians document findings accurately and communicate these findings to colleagues, specialists, and patients. This article reviews fracture terminology that clinicians need to provide better understanding of the injury and direct appropriate management.
Dynamic 3D Reconstruction of Thoracic Cage and Abdomen in Children and Adolescents With Scoliosis: Preliminary Results of Optical Reflective Motion Analysis Assessment
Authors: Xun FuXing , Canavese Federico , Xu HongWen , Kaelin André , Li YiQiang , Dimeglio Alain
Published: April 2019

Background:

In patients with untreated scoliosis or in those with posterior spinal instrumented fusion (PSF), the movements of neither the thoracic cage (ThC) nor the abdomen (ABD) during quiet and deep breathing have been well defined in the literature. The purpose of this study was to evaluate kinematic variations in the ThC and ABD during quiet and deep breathing by optical reflective motion analysis (ORMA) in children with scoliosis.

Methods:

The study included 6 healthy children (group A), 7 subjects with untreated scoliosis over 50 degrees (group B), and 8 patients with scoliosis treated by PSF (group C). After anthropometric measurements (standing height, sitting height, arm span, chest perimeter, body weight, body mass index, T1-T12, and L1-L5 length) were obtained, the movements of subjects during quiet and deep breathing were measured with a 10-camera 3-dimensional ORMA system (82 markers) with the subjects in a standard standing position.

Results:

No significant differences were observed in sex, age, weight, height, or arm span (P>0.05). Significant differences were observed in the chest perimeter, Cobb angle, and body mass index (P<0.05). ThC and ABD movements during quiet and deep breathing decreased significantly in group B and C when compared with group A (P<0.05). Group B showed decreased expansion of the ThC (−52.4% to −58.3%) and relatively increased motion of the ABD compared with groups A and C (P<0.001). However, ABD expansion remained lower in group B than in groups A and C (−32.8% and −5.7%). PSF does not completely eliminate transverse plane kinematics, although a greater reduction was observed at instrumented than noninstrumented levels (−60.8% vs. −35.1%; P<0.05).

Conclusions:

ORMA is a useful tool for assessing alterations in the kinematics of the ThC and ABD caused by severe scoliosis and/or PSF. Compared with normal subjects, patients with severe scoliosis had poorer and less effective kinematics of the ThC and ABD. In contrast, operated subjects had better and more effective kinematics of the ThC and ABD, breathing curves, thoracic expansion, and abdominal movements closer to normal compared with patients with severe, untreated deformity.

Level of Evidence:

Level III.
Pediatric Septic Arthritis of the Knee: Predictors of Septic Hip Do Not Apply
Authors: Obey Mitchell R. , Minaie Arya , Schipper Jaclyn A. , Hosseinzadeh Pooya
Published: April 2019

Background:

The early diagnosis of pediatric septic arthritis is paramount to the prevention of long-term sequela. The purpose of this study is to investigate if the commonly used criteria developed by Kocher and colleagues for hip septic arthritis can be used for screening children with suspected septic knee.

Methods:

We retrospectively reviewed the charts of patients under the age of 19, between June 2002 to June 2017, who presented to a major tertiary-care children’s hospital with septic knee. Diagnostic criteria included either a positive synovial culture from the knee, synovial white blood cell (WBC)>50,000 cells/mm3, or synovial WBC count >25,000 cells/mm3 and clinical agreement of diagnosis from Infectious Disease and Orthopaedic colleagues. Collected data included the initial criteria described by Kocher and colleagues: history of fever, non–weight-bearing, erythrocyte sedimentation rate, and serum WBC as well as a recently modified criterion: C-reactive protein. Univariate analysis was used to determine the quality of these variables in ruling out septic knee.

Results:

One hundred four patient charts were found to meet our inclusion criteria demonstrating C-reactive protein>20 mg/L (75%), fever (65%), non–weight-bearing status (64%), erythrocyte sedimentation rate>40 mm/h (60%), and WBC>12,000 cells/mm3 (49%). With the 25 different combinations of these predictors adjusted for, in an escalating manner, 0 predictors suggested a sensitivity of 0.02, 1 predictor a sensitivity of 0.06, 2 predictors a sensitivity of 0.2, 3 predictors a sensitivity of 0.32, 4 predictors a sensitivity of 0.3, and 5 predictors a sensitivity of 0.11.

Conclusions:

According to the Kocher criteria of the hip, at 3 or more criteria the probability of septic arthritis becomes 93% with a sensitivity of 0.84 provoking many physicians to use this cutoff in their assessment of hip pain. This study suggests that if these criteria were applied to the knee, 52% of septic knee cases could be missed. There is a need for further investigation of specific criteria of the knee as the markers of the hip septic arthritis are not necessarily applicable in the knee.

Level of Evidence:

Level III.
Simulation Training of Orthopaedic Residents for Distal Radius Fracture Reductions Improves Radiographic Outcomes
Authors: Jackson Taylor J. , Shah Apurva S. , Buczek Matthew J. , Lawrence John Todd R.
Published: April 2019

Background:

Most distal radius fractures can be treated with closed reduction and casting in pediatric patients. These skills are traditionally developed treating real patients, however, there is growing interest in the use of simulation training to supplement traditional learning strategies.

Methods:

Seventy-eight children with distal radius fractures that underwent closed reduction and casting by novice orthopaedic surgery residents were retrospectively reviewed. Radiographic measures of patients treated by simulation-trained residents were compared with patients treated by residents without simulation training.

Results:

Patients treated by simulation-trained residents had less residual angulation in the anteroposterior radiograph (3.7 vs. 6.3 degrees, P=0.006) and translation on the lateral (14% vs. 21%, P=0.040) and anteroposterior radiograph (10% vs. 16%, P=0.029). Patients treated by simulation-trained residents also had lower rates of redisplacement (50% vs. 79%, P=0.016).

Conclusions:

Loss of reduction is common, particularly when novice trainees perform their first independent reductions. Residents who underwent simulation training had lower rates of loss of reduction, thus simulation training has potential as a supplement to the traditional apprentice model of medical education.

Level of Evidence:

Level III.
Long-term Results of Spine Stapling for AIS to Skeletal Maturity and Beyond
Authors: Haber Lawrence L. , Adams Tyler M. , Briski David C. , Celestre Paul C. , Robbins Daniel J. , Waldron Sean R.
Published: April 2019

Background:

We looked at long-term follow-up of spine stapling with Nitinol Staples. This was a cohort of all adolescent idiopathic scoliosis (AIS) patients with curves at high risk to progress based on curve magnitude, premenarchal status in all females, failure of brace treatment, and skeletal immaturity.

Methods:

This is a single surgeon retrospective review of consecutive AIS patients treated with Nitinol staples for progressive scoliosis. Fourteen patients, 16 curves from 2005 to 2008 were eligible. Minimum curve for stapling was 30 degrees. Standard preoperative, intraoperative, and postoperative data were collected. All patients were followed for a minimum of 36 months and to skeletal maturity. Three groups were: improved (group 1), correction of any amount; minimal progression (group 2), progression ≤10 degrees; and failure (group 3), ≥10 degrees of progression.

Results:

A total of 13 thoracic curves and 2 compensatory lumbar curves met the inclusion criteria (94%). Average follow-up was 61 months. The mean preoperative main thoracic curve was 35 degrees. All but 1 patients progressed at least 9 degrees in a brace prior to stapling. Females were all premenarchal, 10 patients were Risser 0 and 3 Risser 1. The average number of vertebrae stapled per curve was 6. Group 1 included 6 curves (40%). Group 2, 5 curves (33%). Group 3, 4 curves (27%). Three patients went on to uncomplicated fusion. Final curve measurement at the end of follow-up or before fusion (P=0.0037), curve progression (P≤0.001), and percentage of coronal correction on first postoperative standing radiograph (P=0.042) were the significant differences between groups 1+2 (successful) versus group 3 (failures). In total, 73% of this group either progressed ≤10 degrees or improved.

Conclusions:

This is the first study that follows AIS patients treated with spine stapling to skeletal maturity. Staples likely changed natural history in some of our patients. Initial percentage of correction on first standing postoperative PA x-rays was the only predictor of success. Stapling was safe without any long-term complications.

Level of Evidence:

Level III—retrospective study.
Hormone therapy is not associated with the risk of sudden sensorineural hearing loss in postmenopausal women: a 10-year nationwide population-based study
Authors: Chen Po-Jun , Chung Chi-Hsiang , Chien Wu-Chien , Chen Hsin-Chien
Published: April 2019

Objective:

The association between hormone therapy (HT) and the risk for sudden sensorineural hearing loss (SSNHL) in postmenopausal women has been described only in case reports. No large study has further evaluated the association between HT and the risk of SSNHL in postmenopausal women. The objective of our study was to investigate whether postmenopausal women with HT exhibit a risk of SSNHL.

Methods:

This matched cohort study enrolled 13,112 postmenopausal women 45 to 79 years of age who used HT between 2000 and 2010; they were selected from the National Health Insurance Research Database of Taiwan, and 39,336 participants without HT use were enrolled as controls matched by age and index year at a 1:3 ratio.

Results:

We used a Cox proportional hazards regression model to identify the risk of SSNHL during 10 years of follow-up, and the results indicated no significant increase in the proportion of postmenopausal women with HT use (P = 0.814) who developed SSNHL compared with those without HT use (1.14%, 150/13, 112 vs 1.12%, 439/39, 336). After adjustment for age and other variables, the adjusted hazard ratio was 0.78 (95% CI, 0.308-1.025, P = 0.762) and showed no association between HT use and SSNHL development in postmenopausal women.

Conclusions:

Our results showed that HT was not associated with the risk of SSNHL in postmenopausal women over a 10-year follow-up study.