bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytomegalovirus Evades TRAIL-Mediated Innate Lymphoid Cell 1 Defenses
Authors: Picarda Gaelle , Ghosh Raima , McDonald Bryan , Verma Shilpi , Thiault Nicolas , El Morabiti Rachid , Griffith Thomas S. , Benedict Chris A.
Published: May 2019

Cytomegalovirus (a betaherpesvirus) is a master at manipulating immune responses to promote its lifelong persistence, a result of millions of years of coevolution with its host. Using a one-of-a-kind MCMV mutant unable to restrict expression of the TNF-related apoptosis-inducing ligand death receptors (TRAIL-DR), we show that TRAIL-DR signaling significantly restricts both early and persistent viral replication. Our results also reveal that these defenses are employed by TRAIL-expressing innate lymphoid type I cells (ILC1) but not conventional NK cells. Overall, our results are significant because they show the key importance of viral counterstrategies specifically neutralizing TRAIL effector functions mediated by a specific, tissue-resident subset of group I ILCs.
Titrating Gene Function in the Human Fungal Pathogen Candida albicans through Poly-Adenosine Tract Insertion
Authors: Tournu Helene , Butts Arielle , Palmer Glen E.
Published: May 2019

Investigating a protein’s functional importance at the whole-organism level usually involves altering its expression level or its specific activity and observing the consequences with respect to physiology or phenotype. Several approaches designed to partially or completely abolish the function of a gene, including its deletion from the genome and the use of systems that facilitate conditional expression, have been widely applied. However, each has significant limitations that are especially problematic in pathogenic microbes when it is desirable to determine if a particular gene is required for infection in an animal model. In this study, we sought to determine if an alternative approach—the insertion of poly-A repeats within the coding sequence of the gene—is sufficient to modulate its function in the prevalent human fungal pathogen
C. albicans
. Our results confirm that this approach enables us to predictably and gradually titrate the expression level of a protein and thus to investigate the phenotypic consequences of various levels of gene/protein function.
Ultrasound elastography correlations between anthropometrical parameters in kidney transplant recipients
Authors: Järv Leelo , Kull Ingrid , Riispere Zivile , Kuudeberg Anne , Lember Margus , Ots-Rosenberg Mai
Published: May 2019

Ultrasound elastography (USE) is a method to assess the stiffness of parenchymatous organs. Shear wave elastography (SWE) is considered to be the most suitable elastography method for the non-invasive kidney transplant (KTx) elasticity assessment. The aim of this study was to assess the implementability of SWE for the evaluation of kidney transplant elasticity measurement depending on the depth of an allograft, body mass index (BMI) and donor age. Secondly, to investigate the associations between SWE stiffness measurements and the clinical parameters. This cross-sectional prospective study involved consecutive 100 KTx patients were grouped according to time from transplantation and their BMI (in BMI<25 group the mean was 22.1±2.4, n=42 and in BMI≥25 group the mean BMI was 29.9±3.3, n=58). Mean estimated glomerular filtration rate was almost similar in both groups: <25 group 54.3 and ≥25 group 53.4 mL/min. Mean elastography results were found statistically different (p=0.006) BMI<25 (8.95±5.84 kPa) and BMI≥25 (5.95±3.16 kPa) groups. Significant correlation was found between SWE and the depth of the measurement (r=−0.4, p<0.05). The variations in USE stiffness values were smallest in patients group with lower BMI. In conclusion, we demonstrated that the non-invasive USE measurement stiffness result depends on a patient's BMI, the depth of renal allograft and donor age.
Endovascular treatment of tandem occlusions in vertebrobasilar stroke: technical aspects and outcome compared with isolated basilar artery occlusion
Authors: Piechowiak Eike I , Kaesmacher Johannes , Zibold Felix , Dobrocky Tomas , Mosimann Pascal J , Jung Simon , Fischer Urs , Arnold Marcel , Bellwald Sebastian , Heldner Mirjam R , Gralla Jan , Mordasini Pasquale
Published: May 2019

Background and purpose

Acute basilar artery occlusion (BAO) is a devastating disease with a high rate of mortality and morbidity, and early recanalization is crucial to achieve a good prognosis. The best treatment strategy for BAO combined with a proximal stenosis (tandem occlusion) is not yet clear. Our study aimed to evaluate whether and how vertebrobasilar tandem occlusions can be treated effectively and safely compared with isolated BAO.

Materials and methods

Fifty-two patients with acute vertebrobasilar occlusive stroke treated with mechanical thrombectomy were identified in a prospective database from March 2010 to September 2016. We retrospectively analysed the clinical, technical, and functional outcomes of the patients.

Results

Of the 52 patients, 15 presented with a tandem occlusion, 14 with a single intracranial occlusion due to an underlying stenosis, and 23 with a single embolic BAO. Successful recanalization was achieved in all of the patients with tandem occlusions (modified Thrombolysis in Cranial Infarction 2b/3) and in 35 of 37 patients with a single BAO (with and without stenosis). A favourable outcome was achieved (modified Rankin Scale ≤2) in 8 of the 15 patients with a tandem occlusion compared with 4 of the 14 patients with a single BAO with underlying stenosis and 5 of the 23 patients with isolated embolic BAO (p=0.18).

Conclusions

We suggest that endovascular treatment of vertebrobasilar tandem occlusions is safe and feasible, with a high rate of good outcome.
Reaction cross section calculations via second beta decay using the activation method for the p-process
Authors: Tantoğlu Ezgi , Özkan Nalan , Güray R. Taygun
Published: May 2019

There are 35 proton-rich isotopes between 74Se and 196Hg that cannot be synthesized through neutron captures and β− decays (s- and r-processes). A third process is therefore required for the production of these nuclei, the so-called p-process. The abundance and the origin of the p-nuclei are still not fully understood even though significant experimental and theoretical efforts in astrophysical modeling have been expended in the last two decades. The experimental studies with the activation method to measure cross sections of the relevant reactions have some limitations: the reaction product must be radioactive, should have an appropriate half-life, and its decay should be followed by proper γ-radiations. If the cross section cannot be calculated with the radiation followed by the first beta decay of the product, it can be measured using the second beta decay as an alternative method. In this study, the method and candidate reactions for the cross-section measurements via the second beta decay of the reaction product using the activation method are discussed.
Computational investigation of the valid valence state contribution in calculating the electronic stopping power of a proton in bulk Al within the linear response approach
Authors: Shukri Abdullah Atef , Al-Qawasmeh Ahmad , Al Shorman M.M. , Alsaad A.
Published: May 2019

The electronic stopping power is a fundamental quantity to many technological fields that use ion irradiation. Here we investigate the validity of using a fully ab initio computational scheme based on linear response time-dependent density functional theory to predict the random electronic stopping power (RESP) of a proton in bulk aluminum. We verify the power of using the extrapolation scheme to overcome the expected convergence issue of the RESP calculations. We show that the calculated RESP of valence electrons compares well with experimental data for low proton velocity only when at full convergence and including the exchange-correlation effect. We demonstrate that the inclusion of valence states only is sufficient for calculating the electronic stopping power up to the stopping maximum.
Effects of a non-Hermitian potential on the Landau quantization
Authors: Ramos B. F. , Pedrosa I. A. , Bakke K.
Published: May 2019

In this work, we solve the time-independent Schrödinger equation for a Landau system modulated by a non-Hermitian Hamiltonian. The system consists of a spinless particle in a uniform magnetic field submitted to action of a non-[Formula: see text] symmetric complex potential. Although the Hamiltonian is neither Hermitian nor [Formula: see text]-symmetric, we find that the Landau problem under study exhibits an entirely real energy spectrum.
Global well-posedness and scattering for the defocusing cubic Schrödinger equation on waveguide ℝ2 × 𝕋2
Authors: Zhao Zehua
Published: May 2019

We consider the problem of large data scattering for the defocusing cubic nonlinear Schrödinger equation on [Formula: see text]. This equation is critical both at the level of energy and mass. The key ingredients are global-in-time Stricharz estimate, resonant system approximation, profile decomposition and energy induction method. Assuming the large data scattering for the 2d cubic resonant system, we prove the large data scattering for this problem. This problem is the cubic analogue of a problem studied by Hani and Pausader.
Diffusion limit of a Boltzmann–Poisson system with nonlinear equilibrium state
Authors: Addala Lanoir , Tayeb Mohamed Lazhar
Published: May 2019

The diffusion approximation for a Boltzmann–Poisson system is studied. Nonlinear relaxation type collision operator is considered. A relative entropy is used to prove useful [Formula: see text]-estimates for the weak solutions of the scaled Boltzmann equation (coupled to Poisson) and to prove the convergence of the solution toward the solution of a nonlinear diffusion equation coupled to Poisson. In one dimension, a hybrid Hilbert expansion and the contraction property of the operator allow to exhibit a convergence rate.
Stochastic dynamics of the delayed chemostat with Lévy noises
Authors: Zhao Dianli , Yuan Sanling , Liu Haidong
Published: May 2019

This paper formulates and studies a delayed chemostat with Lévy noises. Existence of the globally positive solution is proved first by establishing suitable Lyapunov functions, and a further result on exact Lyapunov exponent shows the growth of the total concentration in the chemostat. Then, we prove existence of the uniquely ergodic stationary distribution for a subsystem of the nutrient, based on this, a unique threshold is identified, which completely determines persistence or not of the microorganism in the chemostat. Besides, recurrence is studied under special conditions in case that the microorganism persists. Results indicate that all the noises have negative effects on persistence of the microorganism, and the time delay has almost no effects on the sample Lyapunov exponent and the threshold value of the chemostat.
Protective effects of maresin 1 against inflammation in experimentally induced acute pancreatitis and related lung injury
Authors: Munir Fahad , Jamshed Muhammad Babar , Shahid Numan , Muhammad Syed Aun , Bhandari Adheesh , Zhang QiYu
Published: May 2019

Severe acute pancreatitis (SAP) is an inflammatory disorder that progresses with local and systemic difficulties accompanied by a relatively high mortality rate. In recent years, maresin 1 (MaR1) has been shown to be a macrophage mediator with effective proresolving and anti-inflammatory properties that prevents the occurrence of various inflammatory conditions. The purpose of this study was to investigate the role of MaR1 in SAP and related lung injury. Experimental SAP was induced in mice with a combination of cerulean and lipopolysaccharide. MaR1 was administered 30 min before the primary injection of cerulean. Biochemical markers and histological injury scores were used to evaluate the severity of acute pancreatitis. To determine the degree of inflammation, serum cytokines and myeloperoxidase activity in pancreas and lung tissues were measured. Western blot analysis detected the activation of NF-κB. After MaR1 pretreatment, the activities of amylase, lipase, TNF-α, IL-1β, and IL-6 were decreased in serum, and the myeloperoxidase activity both in pancreas and in lung tissues significantly decreased, whereas the activity of anti-inflammatory cytokine IL-10 in serum was increased. MaR1-pretreated mice reduced the activation of pancreatic NF-κB and decreased the severity of pancreatic and lung-related injuries. These results confirm that MaR1 alleviated inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimentally induced acute pancreatitis and exerted anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of SAP.

NEW & NOTEWORTHY These results provided us evidence to confirm that maresin 1 (MaR1) can alleviate inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimental induced acute pancreatitis and exerts certain anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of severe acute pancreatitis.
Human recombinant relaxin-2 does not attenuate hypertension or renal injury but exacerbates vascular dysfunction in a female mouse model of SLE
Authors: Wolf Victoria L. , Phillips Taylor L. , Taylor Erin B. , Sasser Jennifer M. , Ryan Michael J.
Published: May 2019

Systemic lupus erythematosus (SLE) is an autoimmune disease that disproportionately affects women of reproductive age and increases their risk for developing hypertension, vascular, and renal disease. Relaxin has potential beneficial therapeutic effects in cardiovascular disease through direct actions on the vasculature. The potential therapeutic benefit of relaxin on SLE-associated cardiovascular and renal risk factors like hypertension has not previously been tested. We hypothesized that relaxin would attenuate hypertension, renal injury, and vascular dysfunction in an established female mouse model of SLE (NZBWF1 mice). Serelaxin (human recombinant relaxin-2, 0.5 mg·kg−1·day−1) or vehicle was administered via osmotic mini-pump for 4 wk in female control (NZW) or SLE mice between 28 and 31 wk of age. Serelaxin treatment increased uterine weights in both groups, suggesting that the Serelaxin was bioactive. Mean arterial pressure, measured by carotid artery catheter, was significantly increased in vehicle-treated SLE mice compared with vehicle-treated controls, but was not changed by Serelaxin treatment. Albumin excretion rate, measured by ELISA, was similar between vehicle- and Serelaxin-treated SLE mice and between vehicle- and Serelaxin-treated control mice. Wire myography was performed using isolated carotid arteries to assess endothelial-independent and -dependent vasodilation, and data confirm that SLE mice have impaired endothelium-independent and -dependent relaxation compared with control mice. Serelaxin treatment did not affect endothelium-independent vasodilation, but exacerbated the endothelium-dependent dysfunction. These data suggest that, contrary to our hypothesis, Serelaxin infusion does not attenuate hypertension, renal injury, or vascular dysfunction in SLE, but worsens underlying vascular endothelial dysfunction in this experimental model of SLE. These data do not support the use of human recombinant relaxin-2 as an antihypertensive in the SLE patient population.

NEW & NOTEWORTHY Relaxin is a peptide hormone commonly known for its role in pregnancy and for its use in recent clinical trials for the treatment of heart failure. Evidence suggests that relaxin has immunomodulatory effects; however, the potential therapeutic impact of relaxin in chronic immune mediated disease is unclear. This study tests whether recombinant human relaxin (Serelaxin) attenuates the progression of autoimmunity, and the associated cardiovascular consequences, in an experimental model of systemic lupus erythematosus.
Dietary Calanus oil recovers metabolic flexibility and rescues postischemic cardiac function in obese female mice
Authors: Jansen Kirsten M. , Moreno Sonia , Garcia-Roves Pablo M. , Larsen Terje S.
Published: May 2019

The aim of this study was to find out whether dietary supplementation with Calanus oil (a novel marine oil) or infusion of exenatide (an incretin mimetic) could counteract obesity-induced alterations in myocardial metabolism and improve postischemic recovery of left ventricular (LV) function. Female C57bl/6J mice received high-fat diet (HFD, 45% energy from fat) for 12 wk followed by 8-wk feeding with nonsupplemented HFD, HFD supplemented with 2% Calanus oil, or HFD plus exenatide infusion (10 µg·kg−1·day−1). A lean control group was included, receiving normal chow throughout the whole period. Fatty acid and glucose oxidation was measured in ex vivo perfused hearts during baseline conditions, while LV function was assessed with an intraventricular fluid-filled balloon before and after 20 min of global ischemia. HFD-fed mice receiving Calanus oil or exenatide showed less intra-abdominal fat deposition than mice receiving nonsupplemented HFD. Both treatments prevented the HFD-induced decline in myocardial glucose oxidation. Somewhat surprising, recovery of LV function was apparently better in hearts from mice fed nonsupplemented HFD relative to hearts from mice fed normal chow. More importantly however, postischemic recovery of hearts from mice receiving HFD with Calanus oil was superior to that of mice receiving nonsupplemented HFD and mice receiving HFD with exenatide, as expressed by better pressure development, contractility, and relaxation properties. In summary, dietary Calanus oil and administration of exenatide counteracted obesity-induced derangements of myocardial metabolism. Calanus oil also protected the heart from ischemia, which could have implications for the prevention of obesity-related cardiac disease.

NEW & NOTEWORTHY This article describes for the first time that dietary supplementation with a low amount (2%) of a novel marine oil (Calanus oil) in mice is able to prevent the overreliance of fatty acid oxidation for energy production during obesity. The same effect was observed with infusion of the incretin mimetic, exanatide. The improvement in myocardial metabolism in Calanus oil-treated mice was accompanied by a significantly better recovery of cardiac performance following ischemia-reperfusion.

Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/dietary-calanus-oil-energy-metabolism-and-cardiac-function/ .
Quantitative trait loci associated with angiotensin II and high-salt diet induced acute decompensated heart failure in Balb/CJ mice
Authors: Becirovic-Agic Mediha , Jönsson Sofia , Hultström Michael
Published: May 2019

Genetic background of different mouse strains determines their susceptibility to disease. We have previously shown that Balb/CJ and C57BL/6J mice develop cardiac hypertrophy to the same degree when treated with a combination of angiotensin II and high-salt diet (ANG II+Salt), but only Balb/CJ show impaired cardiac function associated with edema development and substantial mortality. We hypothesized that the different response to ANG II+Salt is due to the different genetic backgrounds of Balb/CJ and C57BL/6J. To address this we performed quantitative trait locus (QTL) mapping of second filial generation (F2) of mice derived from a backcross between Balb/CJ and first filial generation (F1) of mice. Cardiac function was measured with echocardiography, glomerular filtration rate using FITC-inulin clearance, fluid and electrolyte balance in metabolic cages, and blood pressure with tail-cuff at baseline and on the fourth day of treatment with ANG II+Salt. A total of nine QTLs were found to be linked to different phenotypes in ANG II+Salt-treated F2 mice. A QTL on chromosome 3 was linked to cardiac output, and a QTL on chromosome 12 was linked to isovolumic relaxation time. QTLs on chromosome 2 and 3 were linked to urine excretion and sodium excretion. Eight genes located at the different QTLs contained coding nonsynonymous SNPs published in the mouse genome database that differ between Balb/CJ and C57BL/6J. In conclusion, ANG II+Salt-induced acute decompensation in Balb/CJ is genetically linked to several QTLs, indicating a multifaceted phenotype. The present study identified potential candidate genes that may represent important pathways in acute decompensated heart failure.
Creation of the 5-hydroxytryptamine receptor 7 knockout rat as a tool for cardiovascular research
Authors: Demireva Elena Y. , Xie Huirong , Flood Emma D. , Thompson Janice M. , Seitz Bridget M. , Watts Stephanie W.
Published: May 2019

Using CRISPR-Cas9 technology, we created a 5-HT7 receptor global knockout (KO) rat, on a Sprague-Dawley background, for use in cardiovascular physiology studies focused on blood pressure regulation. A stable line carrying indels in exons 1 and 2 of the rat Htr7 locus was established and validated. Surprisingly, 5-HT7 receptor mRNA was still present in the KO rat. However, extensive cDNA and genomic sequencing of KO tissues confirmed an 11 bp deletion in exon 1 and 4 bp deletion in exon 2. The exon 1 deletion resulted in a frameshifted mRNA sequence coding for a nonfunctional protein. While the Htr1B locus was a potential off-target for the guide RNAs designed for exon 2 of Htr7, there were no off-target sequence changes at this locus in the originating founder. When the F2 generation of KO was compared with wild-type (WT) counterparts, neither the male nor female KO rats were different in body size, fat weights, or mass of organs (kidney, heart, and brain) important to blood pressure. Females were smaller in mass than their counterpart males. Clinical measures of plasma from nonfasted rats revealed largely similar values, comparing WT and KO, of glucose, blood urea nitrogen, creatinine, phosphate, calcium, and albumin to name a few. Loss of a functional 5-HT7 receptor was validated by the complete loss of relaxation to the 5-HT1/7 receptor agonist 5-carboxamidotryptamine in the isolated abdominal vena cava. This newly created 5-HT7 receptor KO rat will be of use to investigate the importance of the 5-HT7 receptor in blood pressure regulation.
Analysis of Haematological Parameters as Predictors of Malaria Infection Using a Logistic Regression Model: A Case Study of a Hospital in the Ashanti Region of Ghana
Authors: Paintsil Ellis Kobina , Omari-Sasu Akoto Yaw , Addo Matthew Glover , Boateng Maxwell Akwasi
Published: May 2019

Malaria is the leading cause of morbidity in Ghana representing 40-60% of outpatient hospital attendance with about 10% ending up on admission. Microscopic examination of peripheral blood film remains the most preferred and reliable method for malaria diagnosis worldwide. But the level of skills required for microscopic examination of peripheral blood film is often lacking in Ghana. This study looked at determining the extent to which haematological parameters and demographic characteristics of patients could be used to predict malaria infection using logistic regression. The overall prevalence of malaria in the study area was determined to be 25.96%; nonetheless, 45.30% of children between the ages of 5 and 14 tested positive. The binary logistic model developed for this study identified age, haemoglobin, platelet, and lymphocyte as the most significant predictors. The sensitivity and specificity of the model were 77.4% and 75.7%, respectively, with a PPV and NPV of 52.72% and 90.51%, respectively. Similar to RDT this logistic model when used will reduce the waiting time and improve the diagnosis of malaria.
Comparative Genomic Analysis ofTrichinella spiralisReveals Potential Mechanisms of Adaptive Evolution
Authors: Qu Zigang , Li Wenhui , Zhang Nianzhang , Li Li , Yan Hongbin , Li Tingting , Cui Jianmin , Yang Yang , Jia Wanzhong , Fu Baoquan
Published: May 2019

Trichinellosis caused by parasitic nematodes of the genusTrichinellamay result in human morbidity and mortality worldwide. Deciphering processes that drive species diversity and adaptation are key to understanding parasitism and developing effective control strategies. Our goal was to identify genes that are under positive selection and possible mechanisms of adaptive evolution ofTrichinella spiralisgenes using a comparative genomic analysis with the genomes ofBrugia malayi,Trichuris suis,Ancylostoma ceylanicum,andCaenorhabditis elegans. The CODEML program derived from the PAML package was used to deduce the most probable dN/dS ratio, a measurement to detect genes/proteins undergoing adaptation. For each pair of sequences, those with a dN/dS ratio > 1 were considered positively selected genes (PSGs). Altogether, 986 genes were positively selected (p-value < 0.01). Genes involved in metabolic pathways, signaling pathways, and cytosolic DNA-sensing pathways were significantly enriched among the PSGs. Several PSGs are associated with exploitation of the host: modification of the host’s metabolism, creation of new parasite-specific morphological structures betweenT. spiralisand the host interface, xenobiotic metabolism to combat low oxygen concentrations and host toxicity, muscle cell transformation, cell cycle arrest, DNA repair processes during nurse cell formation, antiapoptotic factors, immunomodulation, and regulation of epigenetic processes. Some of theT. spiralisPSGs haveC. elegansorthologs that confer severe or lethal RNAi phenotypes. Fifty-seven PSGs inT. spiraliswere analyzed to encode differentially expressed proteins. The present study utilized an overall comparative genomic analysis to discover PSGs withinT. spiralisand their relationships with biological function and organism fitness. This analysis adds to our understanding of the possible mechanism that contributes toT. spiralisparasitism and biological adaptation within the host, and thus these identified genes may be potential targets for drug and vaccine development.
Development of a Sensitive Chemiluminescence Immunoassay for the Quantification of Folic Acid in Human Serum
Authors: Chen Xiang , Zhou Qiyang , Zhang Ting , Wang ChunXin , Yu Zheng , Ahamada Hadji , Bai Zhonghu , Huang Xuan
Published: May 2019

Folic acid (FA) is an important vitamin for human growth, especially for pregnant women. FA deficiency is associated with megaloblastic anemia, neural tube defects, cardiovascular diseases, irritability, diarrhea, and psychiatric disorders. Normally, FA molecules bind to folate-binding protein (FBP) in the serum as complex. Before quantify the FA concentration, a releasing procedure should be conducted. Alkaline condition and tris(2-carboxyethyl)phosphine (TCEP) are used to release binding FA to freeing state. In this work, a chemiluminescence immunoassay (CLIA) for human serum FA was established by competition model. Streptavidin (SA) was labeled to magnetic beads by an 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDAC/NHS) method. Activated biotin molecules were labeled to FBP molecules purified from milk. FA was labeled to horseradish peroxidase (HRP) by EDAC to activate the FA molecules. The pretreated samples or standards were added into the reaction tube with biotin-FBP and FA-horseradish peroxidase (HRP), FA in the sample compete with FA-HRP for binding to biotin-FBP, the signal is inversely proportional to the FA concentration. The method established shows good thermostability and performance. The limitation of detection (LOD) is 0.44 ng/mL. The intra-assay coefficient of variation (CV) is 3.6%–7.1%, the interassay CV is 4.2%–7.5%, and the recovery rate is 92.1%–103.5%. Cross reactivity (CR) was remarkably low with aminopterin, folinic acid, and methotrexate. The method shows good correlation with the FA CLIA product from Beckman Coulter; the equation is y = 0.9618x−0.1434 while the R2 value is 0.9224. The established method is sensitive, rapid, and accurate which can fully satisfy for the clinical requirement.
Risk Factors of Gout in MDR-TB Patients in Eritrea: A Case-Control Study
Authors: Russom Mulugeta , Tesfaselassie Hager , Goitom Rozina , Ghirmai Tadese , Weldedhawariat Freweini , Berhe Abiel , Tesfai Dawit , Debesai Merhawi , Berhane Tesfit , Woldu Henok G.
Published: May 2019

Though the incidence of gout in general population is less than 5% (globally), a study conducted in Eritrea among patients with multidrug resistant tuberculosis (MDR-TB) revealed a higher incidence (25%). Other similar studies conducted elsewhere, however, did not report gout as an adverse effect. It is unknown why a higher incidence of gout is being reported in Eritrea compared to similar studies from other countries. The objective of this study is therefore to explore risk factors for the increased risk of incident gout among MDR-TB patients in Eritrea. A case-control study was conducted in Merhano MDR-TB National Referral Hospital in Eritrea. All MDR-TB patients diagnosed with gout between June 2011 and June 2018 were considered as cases. Controls matched by age, sex, and cumulative drug exposure time were selected from the same study population (1:1 ratio). A total of 84 MDR-TB patients, 42 cases and 42 controls, were included in this study. No patient from the control group has comorbidities, while six patients from the case group have diabetes (χ2 = 6.46, df=1, p=0.026). Patients having tachycardia (OR=3.26, 95% CI=1.28, 8.27), alopecia (OR=3.11, 95% CI=1.00, 9.67), and gastrointestinal upset (OR=3.17, 95% CI=1.26, 7.96) as adverse effects and being on prolonged use of propranolol (OR=3.26, 95% CI=1.28, 8.27) were found to be more likely to develop incident gout compared to their controls. In conclusion, MDR-TB patients with diabetes mellitus, tachycardia, alopecia, and gastrointestinal upset and on prolonged use of propranolol tablet had increased risk of incident gout.
BCMA-Targeted CAR T-cell Therapy plus Radiotherapy for the Treatment of Refractory Myeloma Reveals Potential Synergy
Authors: Smith Eric L. , Mailankody Sham , Staehr Mette , Wang Xiuyan , Senechal Brigitte , Purdon Terence J. , Daniyan Anthony F. , Geyer Mark B. , Goldberg Aaron D. , Mead Elena , Santomasso Bianca D. , Landa Jonathan , Rimner Andreas , Riviere Isabelle , Landgren Ola , Brentjens Renier J.
Published: May 2019

We present a case of a patient with multiply relapsed, refractory myeloma whose clinical course showed evidence of a synergistic abscopal-like response to chimeric antigen receptor (CAR) T-cell therapy and localized radiotherapy (XRT). Shortly after receiving B-cell maturation antigen (BCMA)–targeted CAR T-cell therapy, the patient required urgent high-dose steroids and XRT for spinal cord compression. Despite the steroids, the patient had a durable systemic response that could not be attributed to XRT alone. Post-XRT findings included a second wave of fever and increased CRP and IL6, beginning 21 days after CAR T cells, which is late for cytokine-release syndrome from CAR T-cell therapy alone on this trial. Given this response, which resembled cytokine-release syndrome, immediately following XRT, we investigated changes in the patient's T-cell receptor (TCR) repertoire over 10 serial time points. Comparing T-cell diversity via Morisita's overlap indices (CD), we discovered that, although the diversity was initially stable after CAR T-cell therapy compared with baseline (CD = 0.89–0.97, baseline vs. 4 time points after CAR T cells), T-cell diversity changed after the conclusion of XRT, with >30% newly expanded TCRs (CD = 0.56–0.69, baseline vs. 4 time points after XRT). These findings suggest potential synergy between radiation and CAR T-cell therapies resulting in an abscopal-like response.
Proteomic Profiling of Signaling Networks Modulated by G-CSF/Plerixafor/Busulfan-Fludarabine Conditioning in Acute Myeloid Leukemia Patients in Remission or with Active Disease prior to Allogeneic Stem Cell Transplantation
Authors: Zeng Zhihong , Liu Wenbin , Benton Christopher B. , Konoplev Sergej , Lu Hongbo , Wang Rui-Yu  , Chen Julianne , Shpall Elizabeth , Baggerly Keith A. , Champlin Richard  , Konopleva Marina
Published: May 2019

To characterize intracellular signaling in peripheral blood (PB) cells of acute myeloid leukemia (AML) patients undergoing pretransplant conditioning with CXCR4 inhibitor plerixafor, granulocyte colony-stimulating factor (G-CSF), and busulfan plus fludarabine (Bu+Flu) chemotherapy, we profiled 153 proteins in 33 functional groups using reverse phase protein array. CXCR4 inhibition mobilized AML progenitors and clonal AML cells, and this was associated with molecular markers of cell cycle progression. G-CSF/plerixafor and G-CSF/plerixafor/Bu+Flu modulated distinct signaling networks in AML blasts of patients undergoing conditioning with active disease compared to nonleukemic PB cells of patients in remission. We identified AML-specific proteins that remained aberrantly expressed after chemotherapy, representing putative chemoresistance markers in AML.
Mitochondrial DNA 3,860-bp Deletion Increases with Aging in the Auditory Nervous System of C57BL/6J Mice
Authors: Du Zheng-De , He Lu , Tu Chunmei , Guo Xiao-An , Yu Shukui , Liu Ke , Gong Shusheng
Published: May 2019

Background/Aims: Mitochondrial DNA (mtDNA) is sensitive to oxidative damage during aging, which can result in mtDNA mutations. A previous study reported that a 3,860-bp mtDNA deletion, similar to a 4,977-bp mtDNA deletion in humans, is also common occurrence in murine tissues, and increases in the brain and liver with aging. However, no previous study evaluated both topics in the murine auditory nervous system. Methods: We compared mtDNA oxidative damage, mitochondrial ultrastructural changes, and the frequency of the 3,860-bp deletion in the peripheral (spiral ganglion, SG) and central (auditory cortex, AC) auditory nervous system of C57BL/6J mice aged 2, 12, and 18 months. Results: We found that the threshold of auditory brainstem response increased with age along with the signal of 8-hydroxy-2′-deoxyguanosine – a marker of DNA oxidative damage – in the mitochondria of SG and AC neurons. The mitochondrial ultrastructural damage also increased with aging in the SG and AC neurons. Moreover, the relative amount of mtDNA 3,860-bp deletion in 12- and 18-month-old mice was significantly higher in the SG and AC as compared to 2-month-old mice. Conclusion: These results suggest that the mtDNA 3,860-bp deletion is common in the auditory nervous system of mice and increases with age and may contribute to age-related hearing loss.
Suppressed Expression but Not Activity of Collagenases MMP-1 and MMP-13 in Human Renal Carcinoma
Authors: Młynarczyk Grzegorz , Kudelski Jacek , Darewicz Barbara , Bruczko-Goralewska Marta , Romanowicz Lech
Published: May 2019

Background: Collagenases are enzymes starting collagen degradation. The role of collagenases in renal carcinoma development is not well understood. Objective: Evaluation of collagen content and collagenase expression and activity in human kidney cancers. Methods: Collagen content was measured by the hydroxyproline assay. The expression and the content of collagenases were evaluated by Western blotting and ELISA. Fluorogenic substrate was used to measure enzyme activity. Results: Collagen content significantly decreases with the progression of kidney cancer. Both collagenases are first present in high molecular complexes in both control and cancer tissue. The healthy part of the kidney contains similar amounts of both collagenases. Collagenase content decreased significantly in tumor tissue with increasing cancer stage. MMP-13 activity is much higher than that of MMP-1 in all tissues investigated. We observed increasing collagenase activity (MMP-1 and MMP-13) with increasing renal cancer grade. Conclusions: The lower content and higher activity of the collagenases investigated in cancer tissue indicate that most of these enzymes are in active form in renal carcinoma. The lower collagen content in cancer tissue can be explained at least in part by increased collagenase activity.
The Short-Term Safety Evaluation of Corneal Crosslinking Agent-Genipin
Authors: Song Wenjing , Tang Yun , Qiao Jing , Li Haili , Rong Bei , Yang Songlin , Wu Yuan , Yan Xiaoming
Published: May 2019

Background: Genipin (GP) is a safe method for corneal crosslinking, even for very thin corneas. However, there have been no reports on the optimal GP concentration range to use in vivo for corneal crosslinking. Objectives: To investigate the safety of corneal crosslinking after a 24-h incubation with different concentrations of GP. Methods: Twenty New Zealand white rabbits were divided into a phosphate-buffered saline (PBS) group, 0.2% GP crosslinking (GP-CXL) group, 0.25% GP-CXL group, and 0.3% GP-CXL group. Before and after surgery, the operated eyes of each group were characterized by confocal microscopy, and corneal buttons were excised for endothelium staining and electron microscopy. Results: The keratocyte structures in each GP group appeared to be similar to those in the PBS group. Through the confocal microscopy, the changes in corneal endothelial cell density also did not significantly differ among groups. There was a significant difference in apoptosis between the 0.3% GP-CXL and PBS groups (p < 0.05) and between the 0.3% GP-CXL and 0.25% GP-CXL groups (p < 0.05), but there were no significant differences between the 0.2 and 0.25% GP-CXL groups compared to the PBS group. Transmission electron microscopy showed endothelial cell damage in the 0.3% GP-CXL group, with minimal endothelial cell damage in the other groups. Conclusions: Treatment of rabbit corneas with ≤0.25% GP resulted in minimal toxicity to keratocytes and endothelial cells, suggesting that it is a safe crosslinking agent at those concentrations.
A Comparison of Hemostatic Properties between Monopolar and Bipolar Hysteroscopic Surgery using Rotational Thromboelastometry: A Randomized Trial
Authors: Shin Hyun-Jung , Na Hyo-Seok , Han Ji-Yun , Hwang Jung-Won
Published: May 2019

Objective: Systemic absorption of irrigation fluid can lead to a disturbed coagulation cascade. We compared the changes in hemostatic properties on using nonelectrolyte solution in monopolar hysteroscopic surgery (HS) with that on using isotonic saline in bipolar HS via rotational thromboelastometry (ROTEM) analysis. Methods: A total of 54 patients were randomized into 2 groups: 1 group underwent monopolar HS using a mixture of 2.7% sorbitol and 0.54% mannitol (the HSMP group), whereas the other group underwent bipolar HS using 0.9% isotonic saline (the HSBP group). The effects of these 2 methods on coagulation were assessed via pre and postoperative laboratory tests, including estimation of the international normalized ratio of prothrombin time and activated partial thromboplastin time and ROTEM analysis. In addition, the hemoglobin, hematocrit, and electrolyte levels and the platelet count were analyzed. Results: Patient characteristics, volume of irrigation fluid absorbed, and type of procedure were comparable between the 2 groups. There were no significant differences in the pre and postoperative values of ROTEM parameters between the 2 groups. Most postoperative ROTEM parameters, as compared with preoperative values, changed in both groups; clot formation time was prolonged, and the α-angle and maximum clot firmness were decreased. All ROTEM parameters were maintained within the normal range. Hematological parameters, including hemoglobin and hematocrit levels and platelet count, were significantly decreased postoperatively in both groups compared to the preoperative values. No pre and postoperative hematological and hemostatic parameters were significantly different between the 2 groups. Conclusion: Irrigation fluid absorbed in healthy women during HS caused hypocoagulable changes in the blood, irrespective of the irrigant type, and no significant differences between HS using monopolar and bipolar electrodes were demonstrated.
Efficacy of Vonoprazan for 48-Week Maintenance Therapy of Patients with Healed Reflux Esophagitis
Authors: Mizuno Hideki , Nishino Michiko , Yamada Kazutoshi , Kamiyamamoto Shinji , Hinoue Yoshinobu
Published: May 2019

Aims: We aimed to evaluate the efficacy of vonoprazan (VPZ) as maintenance therapy for healed reflux esophagitis (RE). Methods: We enrolled 74 patients diagnosed with RE with frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) total score ≥8 after at least 8 weeks of treatment with standard proton pump inhibitors (PPIs). These patients were switched to VPZ 20 mg for 4 weeks. We also enrolled 71 patients with no endoscopic evidence of erosive esophagitis who received maintenance therapy with VPZ 10 mg for 48 weeks. The primary end point was the proportion of patients who maintained healed RE refractory to PPIs after 48 weeks of maintenance therapy with on demand 10 mg VPZ. Secondary assessment included the proportion of patients with symptomatic nonrelapse at 48 weeks. Results: Fifty patients successfully completed 48-week maintenance therapy. Maintenance therapy with VPZ 10 mg prevented the relapse of esophageal mucosal breaks in 43 (86.0%) of 50 patients at 48 weeks. During the 48-week maintenance therapy, symptomatic nonrelapse rate for acid reflux-related symptom score of FSSG and acid reflux score of Gastrointestinal Symptom Rating Scale at 48 weeks were 70.0 and 72.0%, respectively. No serious adverse events were reported during the study. Conclusion: VPZ 10 mg is clinically effective for maintenance of healed RE for 48 weeks.
Adherence of Patients with Diabetes to a Lifestyle Advice and Management Plan in Basra, Southern Iraq
Authors: Aladhab Rawnaq Adil , Alabbood Majid Hameed
Published: May 2019

Background: Poor adherence to treatment regimens is a complex problem, especially for those with chronic illnesses. Noncompliance is believed to be the most common reason for treatment failure in diabetic patients, leading to the absence of metabolic control and accelerating disease-related complications. Data on the adherence of people with diabetes in Iraq are lacking. Objectives: The purpose of this study was to measure the rate of adherence among Iraqi patients with diabetes. Methods: This was a cross-sectional study conducted in the Specialized Endocrine and Diabetes Center in Basra, southern Iraq, during the period from June to August 2018. Data were collected by completing an interviewing questionnaire consisting of 13 questions. Results: A total of 231 patients were included in the study (54.5% were female). Mean age was 51.85 ± 13.55 years. 65.4% of the participants were taking their medications at the right times. The most common reason for not taking their medication (48.8%) was difficulty in remembering the dosage times. 40.7% of the participants were sedentary. Only one-third of the patients followed their doctors’ instructions regarding diet. Conclusions: The rate of adherence to medication regimens and lifestyle advice was unsatisfactory in this study group. The awareness of diabetic patients and their caring physicians about the importance of adherence to therapy, exercise, and diet should be emphasized.
Rare Protein-Truncating Variants in
APOB
, Lower Low-Density Lipoprotein Cholesterol, and Protection Against Coronary Heart Disease
Authors: Peloso Gina M. , Nomura Akihiro , Khera Amit V. , Chaffin Mark , Won Hong-Hee , Ardissino Diego , Danesh John , Schunkert Heribert , Wilson James G. , Samani Nilesh , Erdmann Jeanette , McPherson Ruth , Watkins Hugh , Saleheen Danish , McCarthy Shane , Teslovich Tanya M. , Leader Joseph B. , Lester Kirchner H. , Marrugat Jaume , Nohara Atsushi , Kawashiri Masa-aki , Tada Hayato , Dewey Frederick E. , Carey David J. , Baras Aris , Kathiresan Sekar
Published: May 2019

Background

Familial hypobetalipoproteinemia is a genetic disorder caused by rare protein-truncating variants (PTV) in the gene encoding
APOB
(apolipoprotein B), the major protein component of LDL (low-density lipoprotein) and triglyceride-rich lipoprotein particles. Whether heterozygous
APOB
deficiency is associated with decreased risk for coronary heart disease (CHD) is uncertain. We combined family-based and large scale gene-sequencing to characterize the association of rare PTVs in
APOB
with circulating LDL-C (LDL cholesterol), triglycerides, and risk for CHD.

Methods

We sequenced the
APOB
gene in 29 Japanese hypobetalipoproteinemia families, as well as 57 973 individuals derived from 12 CHD case-control studies—18 442 with early-onset CHD and 39 531 controls. We defined PTVs as variants that lead to a premature stop, disrupt canonical splice-sites, or lead to insertions/deletions that shift reading frame. We tested the association of rare
APOB
PTV carrier status with blood lipid levels and CHD.

Results

Among 29 familial hypobetalipoproteinemia families, 8 families harbored
APOB
PTVs. Carrying 1
APOB
PTV was associated with 55 mg/dL lower LDL-C (
P
=3×10
-5
) and 53% lower triglyceride level (
P
=2×10
-4
). Among 12 case-control studies, an
APOB
PTV was present in 0.038% of CHD cases as compared to 0.092% of controls.
APOB
PTV carrier status was associated with a 43 mg/dL lower LDL-C (
P
=2×10
-7
), a 30% decrease in triglycerides (
P
=5×10
-4
), and a 72% lower risk for CHD (odds ratio, 0.28; 95% CI, 0.12–0.64;
P
=0.002).

Conclusions

Rare PTV mutations in
APOB
which are associated with lower LDL-C and reduced triglycerides also confer protection against CHD.
The Calliphoridae of Namibia (Diptera: Oestroidea)
Authors: KURAHASHI HIROMU , KIRK-SPRIGGS ASHLEY H.
Published: May 2019

The Namibian Calliphoridae fauna is reviewed. Seventy-five nominate species are recorded from the country, based on 7100 specimens housed in the Namibian National Insect Collection. Identification keys to all taxa are provided, together with notes on biology and new biological observations. An annotated checklist of Namibian species is presented, detailing previously published and other known Namibian records, and distributions elsewhere in Africa. Provisional distribution maps are plotted and discussed. Seasonal data, based on specimen label information, are presented in tabular form. The known immature stages of species are reviewed, together with notes on the forensic significance of relevant species. Two new species of the genus Hemigymnochaeta Corti and one new species of Isomyia Walker are described and illustrated, namely: Hemigymnochaeta maraisi Kurahashi and Kirk-Spriggs, sp. nov., Hemigymnochaeta trichaeta Kurahashi and Kirk-Spriggs, sp. nov., and Isomyia hauwangai Kurahashi and Kirk-Spriggs, sp. nov. Rhyncomya zumpti Peris, 1952 stat. rev., formerly synonymised with R. tristis Séguy, 1933, is here reinstated as a valid species. Thirty-four species are new to the Namibian list, namely: Bengalia spinifemorata Villeneuve, Chrysomya ?laxifrons Villeneuve, C. putoria (Wiedemann), Cosmina fuscipennis Robineau-Desvoidy, C. undulata Malloch, Fainia albitarsis (Macquart), Hemigymnochaeta bequaerti Curran, H. laticeps Zumpt, Isomyia darwini (Curran), I. deserti (Karsch), I. natalensis (Villeneuve), I. tristis (Bigot), Neocordylobia roubaudi Villeneuve, Perisiella anchora (Wiedemann), Phumosia nanoides Zumpt, Pseudorhyncomyia braunsi (Villeneuve), Rhyncomya bicolor (Macquart), R. cassotis (Walker), R. discrepans Villeneuve, R. hessei Zumpt, R. messoria Villeneuve, R. minutalis Villeneuve, R. io Peris, R. peraequa Villeneuve, R. soyauxi Karsch, R. trispina Villeneuve, R. tristis Séguy, R. zumpti Peris, Stegosoma vinculatum Loew, Stomorhina chapini Curran, S. rugosa (Bigot), Tricyclea claripennis Séguy, T. flavida (Malloch), and T. martini (Zumpt). Records of species from other southern African countries, based on 190 specimens housed in the Namibian National Insect Collection, are provided as an Appendix. Cosmina gracilis Curran and Rhyncomya dasyops Bezzi are new to Angola; Auchmeromyia bequaerti Roubaud and Bengalia cuthbertsoni Zumpt are new to Botswana; B. floccosa (van der Wulp), B. peuhi (Brauer and Bergenstamm) and Hemigymnochaeta unicolor (Bigot) are new to Zambia; and Cosmina gracilis Curran and Tricyclea martini (Zumpt) are new to Zimbabwe.