bluuebunny/crossref_metadata_2025 huggingface dataset:
Botox injection into the lower esophageal sphincter induces hiatal paralysis and gastroesophageal reflux
Authors: Kumar Dushyant , Zifan Ali , Mittal Ravinder K.
Published: October 2019

Background: Endoscopic intrasphincteric injection of Botox (ISIB) is used routinely for the treatment of achalasia esophagus and other spastic motor disorders. Studies show that the ISIB reduces the smooth muscle lower esophageal sphincter (LES) pressure. The esophageal hiatus, formed by the right crus of diaphragm, surrounds the cranial half of the LES and works like an external LES. We studied the effects of ISIB on the LES and hiatal contraction and gastroesophageal reflux (GER). Fourteen patients treated with ISIB were studied. Esophageal manometry-impedance recordings were performed before and after the ISIB. Hiatal contraction was assessed during tidal inspiration, forced inspiration, Müller’s maneuver, and straight leg raise. In 6 subjects, the manometry were repeated 6–12 mo after the ISIB. The esophagogastric junction (EGJ) pressure was measured at end expiration (LES pressure) and at the peak of maneuvers (hiatal contraction). Transdiaphragmatic pressure (pdi; force of diaphragmatic contraction) was measured at the peak of forced inspiration. GER was measured from the impedance recordings. The EGJ pressure at end expiration (LES pressure) decreased significantly after the Botox injection. The peak EGJ pressure at tidal inspiration, forced inspiration, Müller’s maneuver, and straight leg raise was also dramatically reduced by the ISIB. There was no effect of Botox on the pdi during forced inspiration. Seven of 10 subjects demonstrated GER during maneuvers following the ISIB. Six to 12 mo after ISIB, the LES and hiatal contraction pressure returned to the pre-ISIB levels. ISIB, in addition to decreasing LES pressure, paralyzes the esophageal hiatus (crural diaphragm) and induces GER.

NEW & NOTEWORTHY The sphincter mechanism at the lower end of the esophagus comprises smooth muscle lower esophageal sphincter (LES) and skeletal muscle crural diaphragm (hiatus). Current thinking is that the endoscopic intrasphincteric injection of Botox (ISIB), used routinely for the treatment of achalasia esophagus, reduces LES pressure. Our study shows that ISIB, even though injected into the LES, diffuses into the hiatus and causes its paralysis. These findings emphasize the importance of esophageal hiatus as an important component of the antireflux barrier and that the ISIB is refluxogenic.
Era of Genomic Medicine: A Narrative Review on CRISPR Technology as a Potential Therapeutic Tool for Human Diseases
Authors: Kotagama Odatha W. , Jayasinghe Chanika D. , Abeysinghe Thelma
Published: October 2019

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) provides acquired immunity in microorganisms against exogenous DNA that may hinder the survival of the organism. Pioneering work by Doudna and Charpentier in 2012 resulted in the creation of the CRISPR/Cas9 genome editing tool on the basis of this concept. The aim of this was to create a rapid, efficient, and versatile genome-editing tool to facilitate genetic manipulation. The mechanism relies on two components: the RNA guide which acts as a sentinel and a Cas protein complex which functions as a highly precise molecular knife. The guide RNA can be modified to match a DNA sequence of interest in the cell and accordingly be used to rectify mutations that may otherwise cause disease. Within a few years following the development of the CRISPR/Cas9 tool, its usage has become ubiquitous. Its influence extends into many fields of biological sciences from biotechnology and biochemistry to molecular biology and biomedical sciences. The following review aims at shedding some light on to the applications of the CRISPR/Cas9 tool in the field of biomedical sciences, particularly gene therapy. An insight with relation to a few of the many diseases that are being tackled with the aid of the CRISPR/Cas9 mechanism and the trends, successes, and challenges of this application as a gene therapy are discussed in this review.
Association of Daily Dietary Intake and Inflammation Induced by Marathon Race
Authors: Passos Bharbara N. , Lima Mirthes C. , Sierra Ana P. R. , Oliveira Rodrigo A. , Maciel Jaqueline F. S. , Manoel Richelieau , Rogante Julliane I. , Pesquero João B. , Cury-Boaventura Maria F.
Published: October 2019

Daily food intake is crucial to maintain health and determine endogenous fuel to practice endurance exercise. We investigated the association between quantity of macronutrient and micronutrient daily intake and inflammation induced by long-distance exercise. Methods. Forty-four Brazilian male amateurs’ marathon finishers from 30 to 55 years old participated in this study. Blood samples were collected 1 day before, immediately after, and 1 day and 3 days after São Paulo International Marathon. The serum levels of IL-6, IL-1β, IL-10, IL-8, IL-12p70, and TNF-α were measured to evaluate inflammation. Dietary intake was determined using a prospective method of three food records in the week before marathon race. Results. Marathon race promoted an elevation on IL-6, IL-8, IL-1-β, and IL-10 immediately after the race. The energy intake (EI), carbohydrate, fiber, folic acid, vitamin E, vitamin D, calcium, magnesium, and potassium intakes was below recommended. Immediately after the marathon race, we observed a negative correlation between IL-8 and daily EI, carbohydrate, fiber, fat, iron, calcium, potassium, and sodium intakes, and higher levels of IL-8 on runners with <3 g/kg/day of carbohydrate intake compared to runners with >5 g/kg/day. We demonstrated a positive correlation between daily carbohydrate intake and IL-10 and a negative correlation between TNF-α and % of energy intake recommended, carbohydrate and fiber intakes. Finally, runners with adequate EI had lower levels of IL-1β and TNF-α compared with low EI immediately after the race. Conclusion. Nutrition strategies to promote balanced diet in amateur runners seem to be as important as immunonutrition sports market. Daily food intake, mainly EI, electrolyte and carbohydrate intakes, may modulate exacerbated inflammation after endurance exercise.
When the Uterus Competes for Perfusion: Management of a Pregnant Patient with Bypass Graft Occlusion
Authors: McGriff Sarah , Percer Paige , Sosa Iberia , Mendez-Figueroa Hector , Mills Joseph L. , Gandhi Manisha
Published: October 2019

Background. Peripheral arterial disease (PAD) in pregnancy has serious implications and requires multidisciplinary management. This becomes even more complicated in the setting of active disease and history of prior vascular grafts. Case. A woman presented with increasing left lower extremity pain at 18 weeks of gestation with a complex history of PAD and a previous bifurcated aorta-left femoral, -right iliac bypass. CT angiogram demonstrated known occluded bypass graft. A multidisciplinary team of providers developed guidelines for potential surgical intervention based upon clinical symptoms. Conclusion. Pelvic PAD can worsen in pregnancy in the setting of the enlarging uterus, which can potentially deplete perfusion of existing collateral vessels. Symptomatic approach to worsening disease provided an effective management strategy in this case.
Blowhole Detection Based on Bidirectional Enhancement and Omnidirectional Analysis for X‐Ray Inspection of Castings
Authors: Zhao Xinyue , Liang Jingjing , He Zaixing , Zhang Shuyou
Published: October 2019

Small blurred blowholes are difficult to detect, especially those in castings having a complex structure. In this paper, we propose a blowhole detection method based on bidirectional enhancement and omnidirectional analysis for X‐ray inspection of castings. After obtaining the X‐ray images of a casting from the X‐ray inspection equipment, there are two main processes to detect the blowholes. First, in the extraction process for the potential defect region, we propose a method based on bidirectional enhancement that highlights the blurred defects and models the nondefective structure. Second, in the precise defect identification process, we propose a method to distinguish real defects by 3D model fitting‐based omnidirectional analysis. The experimental results indicate that the proposed method has a higher performance in blowhole detection than comparable methods.
Investigation on the Influence of Water-Shale Interaction on Stress Sensitivity of Organic-Rich Shale
Authors: Liu Xiangjun , Zhuang Yan , Liang Lixi , Xiong Jian
Published: October 2019

Shale reservoirs are characterized by low permeability and natural fractures. In the process of reservoir development, the working fluid enters the reservoir. This may result in the formation of new fractures or expansion of natural fractures. When shale reservoirs are exploited, the fluid pressure in the fracture or pore is reduced. This destroys the stress balance of the reservoir, produces stress sensitivity damage, and reduces the reservoir permeability. Organic-rich shale from the Yanchang Formation, Chang 7 Member of the Ordos Basin, was selected for core flow experiment with helium. The effects of the type of brine, salinity, and soaking time on the stress sensitivity of an organic-rich shale reservoir were investigated. The acoustic characteristics were also investigated to study the effect of interactions between water and shale on stress sensitivity. The experimental results demonstrate that the interactions of water and shale increase the permeability of shale and reduce its stress sensitivity. Furthermore, when the permeability of the shale is excessively low, the stress sensitivity is high. In the acoustic studies, a higher attenuation coefficient of the acoustic wave corresponds to a larger variation in the shale structure and thus a larger permeability of the shale and smaller stress sensitivity coefficient. Whereas there is no apparent effect of the salt water type on the stress sensitivity, higher salinity levels cause higher stress sensitivity. After reacting with 15000 mg/L brine, the stress sensitivity coefficient of shale did not decrease significantly compared with that before action, all of which were above 0.97. However, after reacting with distilled water or 5000 mg/L brine, the stress sensitivity coefficient of shale decreased significantly, and all of them decreased to less than 0.9. Longer water exposures, corresponding to an increased duration of water-shale interactions, result in higher impacts on the stress sensitivity of shale. After 6 hours of shale-brine interaction, the stress sensitivity coefficient of shale is as high as 0.93, while after 48 hours of shale-brine interaction, the stress sensitivity coefficient of shale is reduced to 0.88. This study provides a highly effective reference with regard to the influence of the working fluid on the reservoir during drilling operations and the study of reservoir characteristics after fracturing.
The Superficial Venous System of the Forelimb of the Anubis Baboon (Papio anubis): The Distribution of Perforating Veins and Venous Valves
Authors: Haładaj Robert , Barszcz Karolina , Polguj Michał , Topol Mirosław
Published: October 2019

The superficial veins of the forelimb show high variability, both in man and in other primates, regarding the number of main venous trunks, their course, as well as the origin and location of openings. The distinction between two venous systems–the superficial and deep was made based on the relation of specific venous channels to the deep fascia; both groups of veins anastomose to each other through perforators piercing the deep fascia. In our work, we paid special attention to the organization of the venous system within the forelimb of the Anubis baboon (Papio anubis), as well as communications between the superficial and deep venous system. The main aim of the study was a detailed examination of the location of venous valves and perforating veins in forelimb of Anubis baboon. In the Anubis baboon, we observed the absence of the basilic vein. The main vessel within the forelimb, in the superficial venous system, was a well-developed cephalic vein. In all the cases, the cephalic vein opened into the external jugular vein. Also, in all of the examined specimens, there was an additional anastomosis connecting the cephalic and external jugular vein, i.e., persistent jugulocephalic vein located anterior to the clavicle. The venous vessels in the Anubis baboon were arranged in two main layers: superficial and deep, with both systems being connected by perforators located at the level of the carpus and cubital fossa. The number of venous valves within the cephalic vein was greater on the forearm the same as the mean intervalvular distance.
Functional Hydrogels and Their Application in Drug Delivery, Biosensors, and Tissue Engineering
Authors: Wang Ke , Hao Yuting , Wang Yingna , Chen Jinyuan , Mao Lianzhi , Deng Yudi , Chen Junlin , Yuan Sijie , Zhang Tiantian , Ren Jiaoyan , Liao Wenzhen
Published: October 2019

Hydrogel is a new class of functional polymer materials with a promising potential in the biomedical field. The purpose of this article is to review recent advancements in several types of biomedical hydrogels, including conductive hydrogels, injectable hydrogels, double network hydrogels, responsive hydrogels, nanocomposite hydrogels, and sliding hydrogels. In comparison with traditional hydrogels, these advanced hydrogels exhibit significant advantages in structure, mechanical properties, and applications. The article focuses on different methods used to prepare advanced biomedical hydrogels and their diversified applications as drug delivery systems, wound dressings, biosensors, contact lenses, and tissue replacement. These advances are rapidly overcoming current limitations of hydrogels, and we anticipate that further research will lead to the development of advanced hydrogels with ubiquitous roles in biomedicine and tissue replacement and regeneration.
Deformation and Failure Characteristics of Soil-Rock Mixture considering Material Composition and Random Structure
Authors: Wang Shengnian , Ji Tingting , Xue Qinpei , Shen Zhifu , Zhang Qiang
Published: October 2019

The soil-rock mixture is a cohesive-frictional geomaterial subjected to impacts of composition and structure seriously. When it suffers from gravity or other kinds of loadings, the loss of its bearing capacity always appears a progressive failure. In this study, the ultimate criterion of the frictional material changing from the deformation stage to the failure stage is analyzed first and then the deformation and failure characteristics of the soil-rock mixture with different compositions and structures are discussed by the discrete element method. The results indicate that the deformation and failure of the soil-rock mixture under axial pressure appear a significant phenomenon of detouring around rock blocks. The bond failure zones and the ultimate shear strain increase with the increase of rock block proportion. The distribution of the bond failure zones always has a good uniformity with the inclination of rock block inclinations. The increase of cementation degree between particles expands the distribution of the bond failure zones but minifies the ultimate shear strain.
Investigation of Damage Diagnosis of Retaining Wall Structures Based on the Hilbert Damage Feature Vector Spectrum
Authors: Xu Qian
Published: October 2019

To diagnose damages within the retaining wall structure, the Hilbert marginal energy spectrum was acquired via the Hilbert–Huang transformation of virtual impulse response functions of responses to the retaining wall under ambient excitations. Based on the Hilbert marginal energy spectrum, the Hilbert damage feature vector spectrum was created. On the basis of the damage feature vector spectrum, a damage identification index was proposed. Based on the damage feature vector spectrum and damage index, the damage state of the retaining wall was detected by the damage feature vector spectrum, damage locations of the wall were diagnosed by the damage index trend surface, and the damage intensity of the wall was identified by the quantitative relationship between the damage index and damage intensity. Based on this, a damage diagnosis method for retaining wall structures was proposed. To verify the feasibility and validity of the damage diagnosis method, both model tests and field tests on a pile plate retaining wall are performed under ambient excitations. Test results show that the damage state of the wall can be detected sensitively, damage locations can be diagnosed validly, and damage intensity can be identified quantitatively via this damage diagnosis method.
Use of Blood Lipid Indicators as a Screening Tool of Insulin Resistance among Individuals in Low-Income Country Sides of China: A Multiethnic Region Study
Authors: Yan Yi-Zhong , Fan Jia-Ning , Liu Jia-Ming , Hu Yun-hua , Ma Jiao-Long , He Jia , Guo Heng , Zhang Xiang-hui , Wang Xin-ping , Li Shu-gang , Guo Shu-Xia
Published: October 2019

Objective. This study is aimed at evaluating the diagnostic value of blood lipid indicators (BLIs) for insulin resistance (IR) among major ethnic groups in Xinjiang, China, to identify the most valuable indicators and appropriate cut-off points for each ethnic group and to lay the foundation for the early detection, diagnosis, and treatment of metabolic diseases in remote rural areas. Methods. Overall, 418 Uygurs, 331 Kazakhs, and 220 Hans were randomly included in our study. The homeostasis model assessment was the gold standard for identifying IR. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value, and the nomogram was utilized to analyze the predictive value. The size of the area under the curve (AUC) reflected the accuracy of screening and prediction. Results. Differences in races were observed in terms of IR and BLIs, and the Kazakhs had the highest IR level at 5.27 mmol/L. The correlation between IR and BLIs differed among the three races. For the Kazakhs and Hans, all BLIs, except total cholesterol (TC), were correlated to IR. However, for the Uygurs, only the triglyceride (TG) level, TG/high-density lipoprotein cholesterol (HDL-C) ratio, and TC/HDL-C ratio were associated with IR. After further adjustment of confounding factors, these indicators were still correlated to IR. BLIs that independently correlated to IR in the three nationalities had a certain diagnostic value for IR. In terms of the AUC size, the TG level was the highest in Uygurs, the TG/HDL-C ratio was the highest for Kazakhs and Hans, and the corresponding best cut-off points for IR were 1.515, 1.230, and 1.495 mmol/L, respectively. In addition, for each race, when the indicators with a certain diagnostic value were combined, the diagnostic value for IR was higher. Conclusion. BLIs had a certain diagnostic value for IR and could be used as a screening tool for IR among Uygurs, Kazakhs, and Hans in Xinjiang. These findings are extremely important for the prevention and treatment of IR and metabolic diseases in remote rural areas.
Faults Detection Using Sliding Mode Observer and Its Application on Elevating Servo Systems
Authors: Tian Lingfei , Qian Linfang , Li Miao , Fu Jiawei
Published: October 2019

The elevating servo system (ESS) of vehicle-mounted howitzer (VMH) is a typical closed-loop electrohydraulic position servo system, and the faults of its actuator and sensor seriously affect the safety and reliability of the system. In practice, model uncertainty, nonlinearities, unknown disturbance, and output noise present enormous challenges to conduct fault detection of the system. In the current paper, an online fault detection scheme using the sliding mode technology is proposed. Not only the derivation method of state equation and some common fault expressions but also a new design of sliding mode observer with the ability to eliminate the influences of the above factors on detection results is given. The observer’s parameter matrices are obtained by the linear matrix inequality. To promote the fault detection capability, a statistical-based dynamic threshold is developed to detect actuator faults and sensor faults simultaneously. Finally, experimental studies are implemented on a test rig for validating the system model, and the results of four experiments show the effectiveness of proposed methods.
Prognostic Nutritional Index and Neutrophil-to-Lymphocyte Ratio Are Respectively Associated with Prognosis of Gastric Cancer with Liver Metatasis Undergoing and without Hepatectomy
Authors: Gao Jialiang , Wang Yimin , Li Fengke , Zhu Ziyu , Han Bangling , Wang Rui , Xie Rui , Xue Yingwei
Published: October 2019

Background. To clarify the efficacy of hepatectomy for gastric cancer liver metastasis (GCLM) and to investigate the association between prognostic nutrition index (PNI) or neutrophil-to-lymphocyte ratio (NLR) and prognosis of GCLM undergoing or without hepatectomy. Methods. We retrospectively studied 374 patients with GCLM. The ROC curve was used to determine the optimal cut-off of PNI and NLR. Patients were divided into groups based on whether hepatectomy was performed, and survival analysis was conducted before and after grouping. The overall survival (OS) time and 1, 3, 5-year survival rates were also compared. Results. Multivariate analysis of all GCLM patients revealed that hepatectomy (p=0.001) was an independent prognosis factor. And there were statistical differences in OS and 1, 3, 5-year survival rates (p=0.001 of all) between hepatectomy group and nonhepatectomy group. Multivariate analysis of GCLM undergoing hepatectomy showed that PNI was an independent prognosis factor (p=0.001). And there were statistical differences in OS and 1, 3, 5‐year survival rates (p=0.001p=0.005, p=0.001 and p=0.020, respectively) between high PNI group and low PNI group. Multivariate analysis of GCLM without hepatectomy showed that NLR was an independent prognosis factor (p=0.001). And there were statistical differences in OS and 1, 3, 5-year survival rates (p=0.001p=0.008p=0.031 and p=0.026, respectively) between low NLR group and high NLR group. Conclusions. GCLM has a better prognosis with hepatectomy. High preoperative PNI is a benign prognostic predictor for patients undergoing hepatectomy. And high preoperative NLR is an adverse prognostic factor for patients without hepatectomy.
Rethinking the Water Leak Incident of Tunnel LUO09 to Prepare for a Challenging Future
Authors: Cheng Wen-Chieh , Li Ge , Zhou Annan , Xu Jian
Published: October 2019

Incident often occurs while deepening excavation pit and/or tunnelling underground pipelines although serious attention from practitioners, engineers, and scientists has received. Prevention and mitigation of incident have thus been deemed to be the key in developing sustainable infrastructure in urban areas. This study analyses and discusses an extensive water leak incident taken place throughout the parallel tunnels LUO09 construction in the soft alluvial deposits in Kaohsiung, Taiwan. Dumping sand bags and quick‐set cement intervened the incident but in vain. The water leak incident is initiated by the piping. The existing vehicle underpass causes the jet‐grout columns installed not exactly in the plumb. Their overlapping is estimated to be less than the design value of 60 cm, and some seepage‐prone weak zones are thus developed. The measured hydraulic gradient being equal to 12.1 and existence of seepage‐prone weak zones are deemed as the main cause initiating the water leak incident. The pinhole test results highlight not only the nonplastic nature of the Kaohsiung silt but also its vulnerability to piping under large hydraulic gradients. Some bullet points that indicate what engineers should do or avoid are learned and summarised.
Short Term Outcome of Adjunct Foam Sclerotherapy for Varicose Veins in Patients Subjected to RFA at Dhulikhel Hospital, Nepal
Authors: Karmacharya R. M. , Shrestha B. , Singh A. , Chandi N. , Bhandari N.
Published: October 2019

Background. Varicose veins are dilated, tortuous, superficial veins usually seen on lower limbs. Various surgical modalities are available for varicose veins including open surgery (Trendelenburg operation), Endovenous Laser Ablation (EVLA), Radiofrequency Ablation (RFA) and Sclerotherapy. The aim of this study is to look for the outcome of adjunct sclerotherapy for varicose veins done as an adjunct with Radio Frequency Ablation. Objective. To know the possible outcome regarding benefits and complications of adjunct sclerotherapy with Radio Frequency Ablation. Methodology. We combined Radio Frequency Ablation of varicose veins with necessary phlebectomy and perforator ligation and performed adjunct sclerotherapy for residual significant varicosities with polidocanol (2%) mixed with 2 ml NS and 2 cc of air (Tessari method) to patients undergoing varicose vein surgery in between 2016 and 2017. Records on complications were enquired immediately following surgery and on 1st follow up done within 3–5 days of the procedure. Results. Among 256 limbs subjected to varicose veins surgery 51 limbs were given adjunct sclerotherapy. Among them, five limbs had perivenous spillage with some localized swelling while there was allergic reaction in one patient as immediate postprocedural complication. Nine limbs had painful thrombosed veins during early follow-up. Conclusions. Adjunct sclerotherapy showed complication rate of roughly one tenth and one fifth of the treated cases in immediate and early postoperative follow-up.
The Triglyceride and Glucose Index Is a Predictor of Incident Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
Authors: Kitae Aya , Hashimoto Yoshitaka , Hamaguchi Masahide , Obora Akihiro , Kojima Takao , Fukui Michiaki
Published: October 2019

Background. The triglyceride and glucose index (TyG), defined as the product of triglycerides (TG) and fasting plasma glucose (FPG), is reported as a surrogate index for insulin resistance. Although a cross-sectional study revealed the association between the TyG-index and the prevalence of nonalcoholic fatty liver disease (NAFLD), few studies have investigated the association between the TyG-index and incident NAFLD. Here we investigated whether the TyG-index can be used to predict incident NAFLD. Methods. This historical cohort study included 16,093 apparently healthy Japanese individuals. The TyG-index was calculated by the established formula: TyG = Ln [TG (mg/dl) ×  FPG (mg/dl)/2]. Fatty liver was diagnosed based on the subjects’ abdominal ultrasonography results. We divided the subjects into tertiles according to the levels of TyG-index. Hazard ratios (HRs) of the TyG-index for incident NAFLD were calculated by a Cox proportional hazards regression model. Results. During the observation period, 27.4% of the men and 11.0% of the women developed NAFLD. The highest TyG-index tertile (men, 8.48 ≤ TyG and women, 7.97 ≤ TyG) (adjusted HR 1.67, 95% CI 1.44–1.94, p<0.001 in the men and 2.06, 1.59–2.70, p<0.001 in the women) and the middle TyG-index tertile (men, 8.00 < TyG ≤ 8.48 and women, 7.53 <TyG ≤7.97) (1.33, 1.15–1.54, p<0.001 in the men and 1.52, 1.16–2.01, p<0.001 in the women) presented a significantly higher risk of incident NAFLD compared to the lowest TyG-index tertile (men, TyG < 8.00 and women, TyG < 7.53). Conclusions. Our findings demonstrate that the TyG-index is significantly associated with incident NAFLD.
Negative Surface Energies of Nickel Ferrite Nanoparticles under Hydrothermal Conditions
Authors: Rák Zs. , Brenner D. W.
Published: October 2019

The formation of nickel ferrite (NiFe2O4) nanoparticles under hydrothermal conditions has been modeled using a method that combines results of first-principle calculations, elements of aqueous thermochemistry, and experimental free energies of formation. The calculations predict negative formation energies for the (111) surfaces and positive free energies for the formation of bulk nickel ferrite. Based on classical nucleation theory, the combination of the negative surface and positive bulk energies yields thermodynamically stable nickel ferrite nanoparticles with sizes between 30 and 150 nm in the temperature range of 300 to 400 K under alkaline conditions. The surface and bulk energetics as well as the stability of the nickel ferrite nanoparticle as a function of temperature and pH are discussed.
Dynamic Changes of Th1 Cytokines and the Clinical Significance of the IFN-γ/TNF-α Ratio in Acute Brucellosis
Authors: Xu Guang , Zhang Peng , Dang Rongjing , Jiang Yanfang , Wang Feng , Wang Bin , Yang Mingyuan
Published: October 2019

Background. T-helper type 1 (Th1) cells and Th1-produced cytokines play essential roles in the immune response to foreign pathogens, such as Brucella spp. The aim of this study was to evaluate the dynamic changes of Th1 cells and Th1-produced cytokines in patients with acute brucellosis and their impact on clinical decision-making. Methods. Fifty-one individuals with acute brucellosis and 17 healthy subjects were enrolled in this study. The brucellosis patients were diagnosed based on clinical symptoms, laboratory tests, and clinical examination. The levels of serum gamma-interferon (IFN-γ) and tumor necrosis factor-alpha (TNF-α), along with the percentage of Th1 cells, were determined by flow cytometry bead arrays (CBA). Results. The frequency of Th1 cells, along with the levels of IFN-γ and TNF-α, was negatively correlated with the clinical parameters. The mean serum levels of IFN-γ and TNF-α and the frequency of Th1 cells were significantly higher in the brucellosis patients in comparison with the healthy subjects (p<0.05). Besides, the cytokine levels were not significantly different between the positive and negative blood culture groups. IFN-γ levels significantly decreased from 6 months to 12 months post treatment (p<0.05). However, the IFN-γ levels remained higher than those of the healthy subjects by 12 months post treatment (p<0.05). The IFN-γ/TNF-α ratio was significantly higher in severe cases than in nonsevere cases (p<0.05). Conclusions. The IFN-γ levels secreted by Th1 cells remain significantly higher than those of healthy subjects more than 12 months after treatment with antibiotics. This finding is different from similar studies. The IFN-γ/TNF-α ratio may be a feasible parameter for assessing clinical severity, yet further longitudinal studies of the immunization and inflammatory reaction of brucellosis are needed in larger patient populations.
Andrographolide Protects against HG-Induced Inflammation, Apoptosis, Migration, and Impairment of Angiogenesis via PI3K/AKT-eNOS Signalling in HUVECs
Authors: Duan Ming-Xia , Zhou Heng , Wu Qing-Qing , Liu Chen , Xiao Yang , Deng Wei , Tang Qi-Zhu
Published: October 2019

Andrographolide (Andr) is a major component isolated from the plant Andrographis paniculata. Inflammation, apoptosis, and impaired angiogenesis are implicated in the pathogenesis of high glucose (HG)-induced injury of vascular endotheliocytes. Our study is aimed at evaluating the effect of Andr on HG-induced HUVEC injury and the underlying mechanism. HUVECs were exposed to HG levels (33 mM) and treated with Andr (0, 12.5, 25, and 50 μM). Western blot analysis, real-time PCR, immunofluorescence staining, the scratch test, and the tube formation assay were performed to assess the effects of Andr. We discovered that Andr inhibited the inflammatory response (IL-1β, IL-6, and TNFα), decreased the apoptosis ratio and cell migration, and promoted tube formation in response to HG stimulation. Andr ameliorated the levels of phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT), and phosphorylated eNOS (p-eNOS). The expression of vascular endothelial growth factor (VEGF) protein, a vital factor in angiogenesis, was improved by Andr treatment under HG stimulation. LY294002 is a blocker of PI3K, MK-2206 2HCI (MK-2206) is a highly selective AKT inhibitor, and L-NAME is a suppressor of eNOS, all of which significantly reduce Andr-mediated protective effects in vitro. Hence, Andr may be involved in regulating HG-induced injury by activating PI3K/AKT-eNOS signalling in HUVECs.
Preparation of Nitrogen-Doped Mesoporous TiO2/RGO Composites and Its Application to Visible Light-Assisted Photocatalytic Degradation
Authors: Wen Xin , Zhao Siqin , Asuha S.
Published: October 2019

A series of nitrogen-doped mesoporous TiO2 nanomaterials and nitrogen-doped mesoporous TiO2/reduced graphene oxide (RGO) composites were successfully prepared by hydrothermal method using triammonium citrate as the nitrogen source. The effects of nitrogen and graphene oxide (GO) dopping on the photocatalytic properties of the TiO2 were investigated to optimize preparation conditions. The results showed that all prepared samples were mainly composed of the anatase phase and possessed a mesoporous structure. The use of the triammonium citrate not only significantly increased the specific surface area of the synthesized samples but also caused the partial reduction of GO to RGO, leading to further increase of the specific surface area and the improvement of quantum efficiency of the photogenerated electrons. All synthesized samples showed superior photocatalytic performance for methyl orange solution. Among them, the NMT/RGO-1.8-10 was found to be the best; the degradation rate of methyl orange solution on the sample reached 100% in 30 minutes under visible light irradiation.
Fluid Inclusion and H–O–S–Pb Isotope Geochemistry of the Yuka Orogenic Gold Deposit, Northern Qaidam, China
Authors: Cai Pengjie , Xu Rongke , Zheng Youye , Yin Yueming , Chen Xin , Fan Xianbin , Ma Chao
Published: October 2019

The Yuka gold deposit, located in the western part of northern Qaidam, contains Au orebodies hosted in early Paleozoic metamorphic basic volcaniclastic rocks. The Yuka mineralization can be divided into three stages: early quartz-pyrite (stage-I), middle quartz-gold-polymetallic sulfide (stage-II), and late quartz-carbonate (stage-III). Gold deposition is primarily contained within stage-II. Three types of fluid inclusions were identified in the vein mineral assemblages using petrography and laser Raman spectroscopy: H2O-CO2-NaCl (C-type), H2O-NaCl (W-type), and pure CO2 (PC-type). Stage-I fluids record medium temperatures (205.2°C to 285.5°C) and H2O-CO2-NaCl±CH4 fluids with variable salinities (0.6–8.5 wt.% NaCl equiv.). Stage-II fluids evolved towards a more H2O-rich composition within a H2O-CO2-NaCl±CH4 hydrothermal system at medium temperatures (193.1°C to 271.1°C), with variable salinities (0.4–11.7 wt.% NaCl equiv.). Stage-III fluids are almost pure H2O and characterized by low temperatures (188.1°C to 248.5°C) and salinities (0.4–16.1 wt.% NaCl equiv.). These data indicate that ore-forming fluids are characterized by low to medium homogenization temperatures and low salinity and are evolved from a CO2-rich metamorphogenic fluid to a CO2-poor fluid due to inputs of meteoric waters, which is similar to orogenic-type gold deposits. The average δ18OW of quartz varies from 3.3‰ in stage-I to 2.1‰ in stage-II and to 1.4‰ in stage-III, with the δD values ranging from −41.6‰ to −58.5‰, suggesting that ore-forming fluids formed from metamorphic fluids mixed with meteoric waters. Auriferous pyrite δ34S ranges from 0.5 to 7.4‰ with a mean value of 4.43‰, suggesting that fluids were partially derived from Paleozoic rocks via fluid-wall rock interactions. Auriferous pyrites have 206Pb/204Pb of 18.238–18.600 (average of 18.313), 207Pb/204Pb of 15.590–15.618 (average of 15.604), and 208Pb/204Pb of 38.039–38.775 (average of 38.1697) and stem from the upper crust. Basing on geological characteristics of the ore deposit as well as new data from the ore-forming fluids, and H-O-S-Pb isotopes, the Yuka gold deposit is best described as an orogenic-type gold deposit.
Blockade of IL-17A/IL-17R Pathway Protected Mice from Sepsis-Associated Encephalopathy by Inhibition of Microglia Activation
Authors: Ye Bo , Tao Tianzhu , Zhao Andong , Wen Liyuan , He Xiaofei , Liu Yi , Fu Qiang , Mi Weidong , Lou Jingsheng
Published: October 2019

Sepsis-associated encephalopathy (SAE) is a poorly understood condition that leads to long-term cognitive impairment and increased mortality in survivors. Recent research revealed that IL-17A/IL-17R might serve as a checkpoint in microglia-mediated neuroinflammation. The present study was designed to determine the specific role of IL-17A-mediated microglia activation in the development of SAE. A mouse model of SAE was induced by cecal ligation and puncture (CLP), and behavior performance was evaluated by the inhibitory avoidance test and the open field test. Cytokine expression and microglia activation in brain tissue were determined at 6 h, 12 h, 24 h, 48 h, and day 7 post surgery. Further, septic mice were intracerebral ventricle- (i.c.v.-) injected with recombinant IL-17A, anti-IL-17A ab, anti-IL-17R ab, or isotype controls to evaluate the potential effects of IL-17A/IL-17R blockade in the prevention of SAE. Septic peritonitis induced significant impairment of learning memory and exploratory activity, which was associated with a higher expression of IL-17A, IL-1β, and TNF-α in the brain homogenate. Fluorescence intensity of Iba-1 and IL-17R in the hippocampus was significantly increased following CLP. Treatment with recombinant IL-17A enhanced the neuroinflammation and microglia activation in CLP mice. On the contrary, neutralizing anti-IL-17A or anti-IL-17R antibodies mitigated the CNS inflammation and microglia activation, thus alleviating the cognitive dysfunction. Furthermore, as compared to the sham control, microglia cultured from CLP mice produced significantly higher levels of cytokines and expressed with higher fluorescence intensity of Iba-1 in response to IL-17A or LPS. Pretreatment with anti-IL-17R ab suppressed the Iba-1 expression and cytokine production in microglia stimulated by IL-17A. In conclusion, blockade of the IL-17A/IL-17R pathway inhibited microglia activation and neuroinflammation, thereby partially reversing sepsis-induced cognitive impairment. The present study suggested that the IL-17A/IL-17R signaling pathway had an important, nonredundant role in the development of SAE.
Effect of Nebivolol and Olmesartan on 24-Hour Brachial and Aortic Blood Pressure in the Acute Stage of Ischemic Stroke
Authors: Georgianou Eleni , Georgianos Panagiotis I. , Petidis Konstantinos , Markakis Konstantinos , Zografou Ioanna , Karagiannis Asterios
Published: October 2019

Background. Elevated blood pressure (BP) in the acute phase of ischemic stroke is associated with heightened risk of early disability and death. However, whether BP-lowering in this setting is beneficial and the exact levels at which BP should be targeted remain unclear. This study aimed to evaluate the effect of nebivolol, olmesartan, and no-treatment on 24-hour BP in patients with hypertension during the acute poststroke period. Methods. In a single-blind fashion, 60 patients with acute ischemic stroke and clinic systolic BP (SBP) 160–220 mmHg were randomized to nebivolol (5 mg/day), olmesartan (20 mg/day), or no-treatment between Day 4 and Day 7 of stroke onset. BP-lowering efficacy was assessed through 24-hour BP monitoring using the Mobil-O-Graph device (IEM, Germany). Results. Between baseline and Day 7, significant reductions in 24-hour brachial SBP were noted with nebivolol and olmesartan, but not with no-treatment. Change from baseline (CFB) in 24-hour brachial SBP was not different between nebivolol and olmesartan groups (between-group difference: −3.4 mmHg; 95% confidence interval (CI): −11.2, 4.3), whereas nebivolol was superior to no-treatment in lowering 24-hour brachial SBP (between-group difference: −7.8 mmHg; 95% CI: −7.8 mmHg; 95% CI: −15.6, −0.1). Similarly, nebivolol and olmesartan equally lowered 24-hour aortic SBP (between-group difference: −1.9 mmHg; 95% CI: −10.1, 6.2). Nebivolol and olmesartan provoked similar reductions in 24-hour heart rate-adjusted augmentation index and pulse wave velocity. Conclusion. This study suggests that during the acute phase of ischemic stroke, nebivolol is equally effective with olmesartan in improving 24-hour aortic pressure and arterial stiffness indices. ClinicalTrials.gov identifier number: NCT03655964.
Inactivating NF1 Mutations Are Enriched in Advanced Breast Cancer and Contribute to Endocrine Therapy Resistance
Authors: Pearson Alex , Proszek Paula , Pascual Javier , Fribbens Charlotte , Shamsher Monee K. , Kingston Belinda , O'Leary Ben , Herrera-Abreu Maria T. , Cutts Rosalind J. , Garcia-Murillas Isaac , Bye Hannah , Walker Brian A. , Gonzalez De Castro David , Yuan Lina , Jamal Sabri , Hubank Mike , Lopez-Knowles Elena , Schuster Eugene F. , Dowsett Mitch , Osin Peter , Nerurkar Ashutosh , Parton Marina , Okines Alicia F.C. , Johnston Stephen R.D. , Ring Alistair , Turner Nicholas C.
Published: October 2019

Purpose:

Advanced breast cancer (ABC) has not been subjected to the same degree of molecular scrutiny as early primary cancer. Breast cancer evolves with time and under the selective pressure of treatment, with the potential to acquire mutations with resistance to treatment and disease progression. To identify potentially targetable mutations in advanced breast cancer, we performed prospective molecular characterization of a cohort of patients with ABC.

Experimental Design:

Biopsies from patients with advanced breast cancer were sequenced with a 41 genes targeted panel in the ABC Biopsy (ABC-Bio) study. Blood samples were collected at disease progression for circulating tumor DNA (ctDNA) analysis, along with matched primary tumor to assess for acquisition in ABC in a subset of patients.

Results:

We sequenced 210 ABC samples, demonstrating enrichment compared with primary disease for potentially targetable mutations in HER2 (in 6.19% of samples), AKT1 (7.14%), and NF1 (8.10%). Of these enriched mutations, we show that NF1 mutations were frequently acquired in ABC, not present in the original primary disease. In ER-positive cancer cell line models, loss of NF1 resulted in endocrine therapy resistance, through both ER-dependent and -independent mechanisms. NF1 loss promoted ER-independent cyclin D1 expression, which could be therapeutically targeted with CDK4/6 inhibitors in vitro. Patients with NF1 mutations detected in baseline circulating tumor DNA had a good outcome on the CDK4/6 inhibitor palbociclib and fulvestrant.

Conclusions:

Our research identifies multiple therapeutic opportunities for advanced breast cancer and identifies the previously underappreciated acquisition of NF1 mutations.
Hemodynamics and Prognostic Impact of Concomitant Mitral Stenosis in Patients Undergoing Surgical or Transcatheter Aortic Valve Replacement for Aortic Stenosis
Authors: Kato Nahoko , Padang Ratnasari , Pislaru Cristina , Miranda William R. , Hoshina Mizuho , Shibayama Kentaro , Watanabe Hiroyuki , Scott Christopher G. , Greason Kevin L. , Pislaru Sorin V. , Nkomo Vuyisile T. , Pellikka Patricia A.
Published: October 2019

Background:

Mitral stenosis frequently coexists in patients with severe aortic stenosis. Mitral stenosis severity evaluation is challenging in the setting of combined aortic stenosis and mitral stenosis because of hemodynamic interactions between the 2 valve lesions. The impact of aortic valve replacement (AVR) for severe aortic stenosis on mitral stenosis is unknown. This study aimed to assess the effect of AVR on mitral stenosis hemodynamics and the clinical outcomes of patients with severe aortic stenosis with and without mitral stenosis.

Methods:

We retrospectively investigated patients who underwent surgical AVR or transcatheter AVR for severe aortic stenosis from 2008 to 2015. Mean transmitral gradient by Doppler echocardiography ≥4 mm Hg was identified as mitral stenosis; patients were then stratified according to mitral valve area (MVA, by continuity equation) as >2.0 cm
2
or ≤2.0 cm
2
. MVA before and after AVR in patients with mitral stenosis were evaluated. Clinical outcomes of patients with and without mitral stenosis were compared using 1:2 matching for age, sex, left ventricular ejection fraction, method of AVR (surgical AVR versus transcatheter AVR) and year of AVR.

Results:

Of 190 patients with severe aortic stenosis and mitral stenosis (age 76±9 years, 42% men), 184 were matched with 362 with severe aortic stenosis without mitral stenosis. Among all mitral stenosis patients, the mean MVA increased after AVR by 0.26±0.59 cm
2
(from 2.00±0.50 to 2.26±0.62 cm
2
,
P
<0.01). MVA increased in 105 (55%) and remained unchanged in 34 (18%). Indexed stroke volume ≤45 mL/m
2
(odds ratio [OR] 2.40; 95% CI, 1.15–5.01;
P
=0.020) and transcatheter AVR (OR, 2.36; 95% CI, 1.17–4.77;
P
=0.017) were independently associated with increase in MVA. Of 107 with significant mitral stenosis (MVA ≤2.0 cm
2
), MVA increased to >2.0 cm
2
after AVR in 52 (49%, pseudo mitral stenosis) and remained ≤2.0 cm
2
in 55 (51%, true mitral stenosis). During follow-up of median 2.9 (0.7–4.9) years, true mitral stenosis was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.88; 95% CI, 1.20–2.94;
P
<0.01).

Conclusions:

MVA improved after AVR in nearly half of patients with severe aortic stenosis and mitral stenosis. MVA remained ≤2.0 cm
2
(true mitral stenosis) in nearly half of patients with severe aortic stenosis and significant mitral stenosis; this was associated with worse survival among patients undergoing AVR for severe aortic stenosis.
Diagnostic Accuracy of Unattended Automated Office Blood Pressure Measurement in Screening for Hypertension in Kenya
Authors: Etyang Anthony O. , Sigilai Antipa , Odipo Emily , Oyando Robinson , Ong’ayo Gerald , Muthami Lawrence , Munge Kenneth , Kirui Fredrick , Mbui Jane , Bukania Zipporah , Mwai Judy , Obala Andrew , Barasa Edwine
Published: October 2019

Despite increasing adoption of unattended automated office blood pressure (uAOBP) measurement for determining clinic blood pressure (BP), its diagnostic performance in screening for hypertension in low-income settings has not been determined. We determined the validity of uAOBP in screening for hypertension, using 24-hour ambulatory BP monitoring as the reference standard. We studied a random population sample of 982 Kenyan adults; mean age, 42 years; 60% women; 2% with diabetes mellitus; none taking antihypertensive medications. We calculated sensitivity using 3 different screen positivity cutoffs (≥130/80, ≥135/85, and ≥140/90 mm Hg) and other measures of validity/agreement. Mean 24-hour ambulatory BP monitoring systolic BP was similar to mean uAOBP systolic BP (mean difference, 0.6 mm Hg; 95% CI, −0.6 to 1.9), but the 95% limits of agreement were wide (−39 to 40 mm Hg). Overall discriminatory accuracy of uAOBP was the same (area under receiver operating characteristic curves, 0.66–0.68; 95% CI range, 0.64–0.71) irrespective of uAOBP cutoffs used. Sensitivity of uAOBP displayed an inverse association (
P
<0.001) with the cutoff selected, progressively decreasing from 67% (95% CI, 62–72) when using a cutoff of ≥130/80 mm Hg to 55% (95% CI, 49–60) at ≥135/85 mm Hg to 44% (95% CI, 39–49) at ≥140/90 mm Hg. Diagnostic performance was significantly better (
P
<0.001) in overweight and obese individuals (body mass index, >25 kg/m
2
). No differences in results were present in other subanalyses. uAOBP misclassifies significant proportions of individuals undergoing screening for hypertension in Kenya. Additional studies on how to improve screening strategies in this setting are needed.