bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative stress and macrophages: driving forces behind exacerbations of asthma and chronic obstructive pulmonary disease?
Authors: de Groot Linsey E. S. , van der Veen T. Anienke , Martinez Fernando O. , Hamann Jörg , Lutter René , Melgert Barbro N.
Published: December 2018

Oxidative stress is a common feature of obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD). Lung macrophages are key innate immune cells that can generate oxidants and are known to display aberrant polarization patterns and defective phagocytic responses in these diseases. Whether these characteristics are linked in one way or another and whether they contribute to the onset and severity of exacerbations in asthma and COPD remain poorly understood. Insight into oxidative stress, macrophages, and their interactions may be important in fully understanding acute worsening of lung disease. This review therefore highlights the current state of the art regarding the role of oxidative stress and macrophages in exacerbations of asthma and COPD. It shows that oxidative stress can attenuate macrophage function, which may result in impaired responses toward exacerbating triggers and may contribute to exaggerated inflammation in the airways.
Reflex response to airway occlusion in human inspiratory muscles when recruited for breathing and posture
Authors: Luu Billy L. , McBain Rachel A. , Taylor Janet L. , Gandevia Simon C. , Butler Jane E.
Published: December 2018

Briefly occluding the airway during inspiration produces a short-latency reflex inhibition in human inspiratory muscles. This occlusion reflex seems specific to respiratory muscles; however, it is not known whether the reflex inhibition has a uniform effect across a motoneuron pool when a muscle is recruited concurrently for breathing and posture. In this study, participants were seated and breathed through a mouthpiece that occluded inspiratory airflow for 250 ms at a volume threshold of 0.2 liters. The reflex response was measured in the scalene and sternocleidomastoid muscles during 1) a control condition with the head supported in space and the muscles recruited for breathing only, 2) a postural condition with the head unsupported and the neck flexors recruited for both breathing and to maintain head posture, and 3) a large-breath condition with the head supported and the volume threshold raised to between 0.8 and 1.0 liters to increase inspiratory muscle activity. When normalized to its preocclusion mean, the reflex response in the scalene muscles was not significantly different between the large-breath and control conditions, whereas concomitant recruitment of these muscles for posture control reduced the reflex response by half compared with the control condition. A reflex response occurred in sternocleidomastoid when it contracted phasically as an accessory muscle for inspiration during the large-breath condition. These results indicate that the occlusion reflex does not produce a uniform effect across the motoneuron pool and that afferent inputs for this reflex most likely act via intersegmental networks of premotoneurons rather than at a motoneuronal level.

NEW & NOTEWORTHY In this study, we investigated the effect of nonrespiratory activity on the reflex response to brief sudden airway occlusions in human inspiratory muscles. We show that the reflex inhibition in the scalene muscles was not uniform across the motoneuron pool when the muscle was recruited concurrently for breathing and postural control. The reflex had a larger effect on respiratory-driven motoneurons than those recruited to maintain head posture.
Survey of Torus Palatinus in Patients with End-Stage Renal Disease Undergoing Hemodialysis
Authors: Tai Shao-Yu , Hsu Chia-Lin , Tsai Aileen I. , Chang Chih-Chun , Wang I-Kuan , Weng Cheng-Hao , Huang Wen-Hung , Hsu Ching-Wei , Chang Pei-Ching , Yen Tzung-Hai
Published: December 2018

Introduction.This study attempted to survey the oral findings of hemodialysis patients and analyze the prevalence and predictors for torus palatinus(TP) in this patient population.Methods.A total of 322 hemodialysis patients were recruited. Patients were organized into two groups, based on the presence (n=93) or absence (n=229) of TP. Demographic, laboratory, and dialysis-related data were obtained for analysis.Results.The prevalence of TP was 28.9% in this study. Patients with TP were younger in age [57.8±10.0 (37.4-86.9) versus 62.4±12.3 (25.0-87.8) years old;P=0.001] and predominantly female (60.2% versus 38.0%;P<0.001), compared to patients without TP. All TPs (100.0%) were symmetrical and located along the midpalatal suture. Most TPs were flat-shaped (55.9%) and near premolars (78.5%). The blood tests revealed higher blood concentrations of phosphate (5.4±1.1 versus 4.9±1.1 mg/dL;P=0.001) and lower blood concentrations of bicarbonate (20.9±2.4 versus 22.0±2.3 mmol/L;P<0.001) in patients with TP. Multivariate regression modeling showed that younger age [odds ratio (OR) 0.968; 95% confidence interval (CI) 0.939–0.982;P<0.001], female gender (OR 2.305; 95% CI 1.374–3.867;P=0.002), higher blood concentration of phosphate (OR 1.411; 95% CI 1.110–1.794;P=0.005), and lower blood concentration of bicarbonate (OR 0.868; 95% CI 0.791–0.994;P=0.040) were significant predictors for TP.Conclusion.The prevalence of TP is 28.9%, and the majority of patients suffering TP are female. Younger age, female gender, elevated blood concentration of phosphate, and lower blood concentration of bicarbonate are predictors for TP.
Enhancing the Efficiency of a Decision Support System through the Clustering of Complex Rule‐Based Knowledge Bases and Modification of the Inference Algorithm
Authors: Nowak-Brzezińska Agnieszka
Published: December 2018

Decision support systems founded on rule‐based knowledge representation should be equipped with rule management mechanisms. Effective exploration of new knowledge in every domain of human life requires new algorithms of knowledge organization and a thorough search of the created data structures. In this work, the author introduces an optimization of both the knowledge base structure and the inference algorithm. Hence, a new, hierarchically organized knowledge base structure is proposed as it draws on the cluster analysis method and a new forward‐chaining inference algorithm which searches only the so‐called representatives of rule clusters. Making use of the similarity approach, the algorithm tries to discover new facts (new knowledge) from rules and facts already known. The author defines and analyses four various representative generation methods for rule clusters. Experimental results contain the analysis of the impact of the proposed methods on the efficiency of a decision support system with such knowledge representation. In order to do this, four representative generation methods and various types of clustering parameters (similarity measure, clustering methods, etc.) were examined. As can be seen, the proposed modification of both the structure of knowledge base and the inference algorithm has yielded satisfactory results.
Patients with Achilles Tendon Rupture Have a Degenerated Contralateral Achilles Tendon: An Elastography Study
Authors: Li Qianru , Zhang Qi , Cai Yehua , Hua Yinghui
Published: December 2018

Purpose. To evaluate differences of Achilles tendon (AT) hardness and morphology between asymptomatic tendons in patients with acute AT ruptures on the contralateral side and asymptomatic tendons in healthy people by using computer-assisted quantification on axial-strain sonoelastography (ASE). Methods. The study consisted of 33 asymptomatic tendons in 33 patients (study group) and 34 tendons in 19 healthy volunteers (control group). All the tendons were examined by both ASE and conventional ultrasound. Computer-assisted quantification on ASE was applied to extract hardness variables, including the mean (Hmean), 20th percentile (H20), median (H50) and skewness (Hsk) of the hardness within tendon, and the ratio of the mean hardness within tendon to that outside tendon (Hratio) and three morphological variables: the thickness (THK), cross-sectional area, and eccentricity (ECC) of tendons. Results. The Hmean, Hsk, H20, H50, and Hratio in the proximal third of the tendon body in study group were significantly smaller than those in control group (Hmean: 0.43±0.09 vs 0.50±0.07, p=0.001; Hsk: -0.53±0.51 vs -1.09±0.51, p<0.001; H20: 0.31±0.10 vs 0.40±0.10, p=0.001; H50: 0.45±0.10 vs 0.53±0.08, p<0.001; Hratio: 1.01±0.25 vs 1.20±0.23, p=0.003). The THK and cross-sectional area of tendons in the study group were larger than those in the control group (p<0.05). Conclusions. As a quantitative objective method, the computer-assisted ASE reveals that the asymptomatic ATs contralateral to acute rupture are softer than those of healthy control group at the proximal third and the asymptomatic tendons in people with rupture history are thicker, larger, and rounder than those of normal volunteers especially at the middle and distal thirds of AT body.
Side Population: Its Use in the Study of Cellular Heterogeneity and as a Potential Enrichment Tool for Rare Cell Populations
Authors: Wolmarans Elize , Nel Sulette , Durandt Chrisna , Mellet Juanita , Pepper Michael S.
Published: December 2018

There is still much to learn about the cells used for cell- and gene-based therapies in the clinical setting. Stem cells are found in virtually all tissues in the human body. As a result, cells isolated from these tissues are a heterogeneous population consisting of various subpopulations including stem cells. Several strategies have been used to isolate and define the subpopulations that constitute these heterogeneous populations, one of which is the side population (SP) assay. SP cells are identified by their ability to efflux a fluorescent dye at a rate that is greater than the main cell population. This elevated rate of dye efflux has been attributed to the expression of members of the ATP-binding cassette (ABC) transporter protein family. SP cells have been identified in various tissues. In this review, we discuss the research to date on SP cells, focussing on SP cells identified in haematopoietic stem cells, adipose-derived stromal cells, and dental pulp.
Injectable Bulking Agent to Treat Postprostatectomy Urinary Incontinence: A Safety and Effectiveness Pilot Study
Authors: van Uhm Janneke I. M. , Vermeer Marloes , Elzevier Henk W. , Noordzij Joop W. , Koldewijn Evert L. , Cornel Erik B.
Published: December 2018

Objectives. To evaluate the safety and effectiveness of the injectable bulking agent Opsys® (Promedon, Cordoba, Argentina) for treating minimal postprostatectomy stress urinary incontinence (SUI). Patients and Methods. Single-centre, pilot study on ten male patients with SUI, < 30 g urine loss/ 24 h, more than 1 year after radical prostatectomy. Patients were treated by endoscopic transurethral injections of bulking agent in the presphincteric zone of the urethral submucosa. The results were evaluated using a pad weight test to quantify the differences in urine loss at 1, 3, and 6 months after intervention. Subsequently, the results of treatment were also evaluated by International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Incontinence Impact Questionnaire (IIQ-7), Urogenital Distress Inventory Short Form (UDI-6-SF), and the Patient Global Impression of Improvement (PGI-I) at 1, 3, and 6 months after intervention. Results. The primary outcome was the absolute result of the 24-hour pad weight test after treatment. Treatment success was defined as <3 g urine loss/24 h, improvement as ≥50% decrease in urine loss/ 24h, failure as <50% decrease in urine loss/24 h, or worsening of urine loss. Success was demonstrated in one, improvement in one, and failure in eight patients one month after treatment. One patient improved and 9 failed 3 and 6 months after treatment. The median 24-hour pad weight test was higher at all three moments of follow-up (1, 3, and 6 months after treatment). The median 24-hour pad weight test was before treatment 17.3g (6.4-20.9) and 1, 3, and 6 months after treatment, respectively, 40.3g (5.9-130.6) p= 0.038, 38.3g (18.3-202.1) p= 0.014, 55.0g (16.5-314.6) p= 0.028. The ICIQ-SF was significantly higher at 3 and 6 months, respectively 15.0 (12.0-18.5) p= 0.007 and 16.0 (12.5-17.5) p=0.012 versus 10.0 (9.0-12.0) before injection. No significant differences were found between IIQ-7, UDI-6-SF, and PGI-I before and after injection. Complications occurred in four patients: two patients reported spontaneously resolved haematuria and two patients reported urinary frequency. All complications were classified as Clavien–Dindo 1. Conclusion. Injection therapy with Opsys® bulking agent is not an effective treatment option for male SUI after radical prostatectomy. It is not a safe treatment option, due to worsening urine loss after treatment.
miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma
Authors: Wu Gang , Li Zhixi , Wang Youyu , Ju Xueming , Huang Rui
Published: December 2018

Hepatocellular carcinoma (HCC) is the most common type of malignancy of the liver and has been reported as the third most frequent cause of cancer associated death worldwide. Accumulating evidence showed that the expression of miR-34a was abnormal in HCC patients; however, the role of miR-34a in HCC is not clear. In this study, we have observed low expression of the miR-34a in both HCC tissues and hepatoma cell line as compared to normal control. Further to investigate the role of miR-34a in HCC development, HepG2 cells were transfected with miR-34a mimic. Following transfection, miR-34a expression was significantly increased, which further repressed proliferation of HepG2 cells. Bioinformatics, Luciferase Reporter, RT-qPCR, and western blotting assays indicated that special AT-rich sequence-binding protein-2 (SATB2) is a direct target of miR-34a in HCC cells. There was a negative correlation between the expression levels of SATB2 and miR-34a. Investigation into the molecular mechanism indicated that miR-34a regulated cell proliferation through inhibiting SATB2. Therefore, the results of the present study may improve understanding regarding the role of miR-34a in regulating cell proliferation and contribute to the development of novel therapy of HCC.
Molecular Cytogenetics of Pisum sativum L. Grown under Spaceflight-Related Stress
Authors: Yurkevich Olga Yu. , Samatadze Tatiana E. , Levinskikh Margarita A. , Zoshchuk Svyatoslav A. , Signalova Olga B. , Surzhikov Sergei A. , Sychev Vladimir N. , Amosova Alexandra V. , Muravenko Olga V.
Published: December 2018

The ontogenesis and reproduction of plants cultivated aboard a spacecraft occur inside the unique closed ecological system wherein plants are subjected to serious abiotic stresses. For the first time, a comparative molecular cytogenetic analysis of Pisum sativum L. (Fabaceae) grown on board the RS ISS during the Expedition-14 and Expedition-16 and also plants of their succeeding (F1 and F2) generations cultivated on Earth was performed in order to reveal possible structural chromosome changes in the pea genome. The karyotypes of these plants were studied by multicolour fluorescence in situ hybridization (FISH) with five different repeated DNA sequences (45S rDNA, 5S rDNA, PisTR-B/1, microsatellite motifs (AG)12, and (GAA)9) as probes. A chromosome aberration was revealed in one F1 plant. Significant changes in distribution of the examined repeated DNAs in karyotypes of the “space grown” pea plants as well as in F1 and F2 plants cultivated on Earth were not observed if compared with control plants. Additional oligo-(GAA)9 sites were detected on chromosomes 6 and 7 in karyotypes of F1 and F2 plants. The detected changes might be related to intraspecific genomic polymorphism or plant cell adaptive responses to spaceflight-related stress factors. Our findings suggest that, despite gradual total trace contamination of the atmosphere on board the ISS associated with the extension of the space station operating life, exposure to the space environment did not induce serious chromosome reorganizations in genomes of the “space grown” pea plants and generations of these plants cultivated on Earth.
Gastrointestinal Dysfunctions Are Associated withIL-10Variants in Parkinson’s Disease
Authors: Shu Li , Liang Dongxiao , Pan Hongxu , Xu Qian , Yan Xinxiang , Tang Beisha , Sun Qiying
Published: December 2018

Inflammation has been demonstrated to be involved in Parkinson’s disease (PD) pathogenesis. There were evidences that the disturbance of the protective function ofIL-10gene contributed to PD. In our study, haplotype analyses were conducted ofIL-10rs1800871 and rs1800872 on 371 PD patients. Because the two SNPs exposed significant linkage disequilibrium demonstrated by Haploview software, we included 177 carriers of both rs1800871 and rs1800872 and 190 noncarriers in clinical phenotype analyses. As to nonmotor symptoms, the score of the gastrointestinal dysfunction domain in Nonmotor Symptom Scale (NMSS) was lower in the carrier group of both SNPs than in the noncarrier group in PD patients (SC: −0.198,p:0.023). Other nonmotor symptoms reflected by relevant rating scales showed negative results. As to comorbidity, no significant statistical significance was observed between the two SNPs and Charlson Comorbidity Index (CCI). In conclusion, we found less severe gastrointestinal dysfunctions of bothIL-10rs1800871 and rs1800872 carriers than noncarriers in PD.
Potent Oral Hypoglycemic Agents for Microvascular Complication: Sodium-Glucose Cotransporter 2 Inhibitors for Diabetic Retinopathy
Authors: Cho Eun Hyung , Park Se-Jun , Han Seongwook , Song Ji Hun , Lee Kihwang , Chung Yoo-Ri
Published: December 2018

The purpose of this study was to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the progression of diabetic retinopathy (DR) in patients with type 2 diabetes. The medical records of 21 type 2 diabetic patients who used a SGLT2i and 71 patients with sulfonylurea (control) were reviewed retrospectively. The severity of DR was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Fewer patients who used a SGLT2i than control patients with sulfonylurea showed progression of DR based on ETDRS scale (44% versus 14%, P=0.014). Moreover, treatment with a SGLT2i was associated with a significantly lower risk of DR progression (P=0.021), and this effect remained significant after adjusting for the age, duration of diabetes, initial DR grade, and HbA1c level by propensity score matching (P=0.013). Treatment of type 2 diabetic patients with a SGLT2i slowed the progression of DR compared to sulfonylurea, which is independent of its effect on glycemic control. This study provides a foundation for further evaluation of the effect of SGLT2i on the progression of DR.
Sore Throat, Fever, Septic Emboli, and Acute Respiratory Distress Syndrome: A Case of Lemierre Syndrome
Authors: Jafri Farrukh N. , Shulman Jodi , Gómez-Márquez José C. , Lazarus Matthew , Ginsburg David M.
Published: December 2018

Lemierre’s syndrome is an acute oropharyngeal infection with a secondary septic thrombophlebitis of the internal jugular vein (IVJ) that was first reported in literature in 1936. It involves the progression of disease from a focal suppurative peritonsillar infection to a local septic thrombophlebitis with hematogenous progression to and distant septic emboli. It is a rare and potentially fatal syndrome requiring prompt diagnosis and management. We present the case progression of an 18-year-old male who presented to our hospital with resolved sore throat, fever, and chest discomfort who experienced a sharp clinical decline. His case, physical exam, laboratory abnormalities, and radiologic studies highlight important facets of this rare but important syndrome.
A Systematic Review of Continuum Modeling of Skeletal Muscles: Current Trends, Limitations, and Recommendations
Authors: Dao Tien Tuan , Tho Marie-Christine Ho Ba
Published: December 2018

Finite elasticity theory has been commonly used to model skeletal muscle. A very large range of heterogeneous constitutive laws has been proposed. In this review, the most widely used continuum models of skeletal muscles were synthetized and discussed. Trends and limitations of these laws were highlighted to propose new recommendations for future researches. A systematic review process was performed using two reliable search engines as PubMed and ScienceDirect. 40 representative studies (13 passive muscle materials and 27 active muscle materials) were included into this review. Note that exclusion criteria include tendon models, analytical models, 1D geometrical models, supplement papers, and indexed conference papers. Trends of current skeletal muscle modeling relate to 3D accurate muscle representation, parameter identification in passive muscle modeling, and the integration of coupled biophysical phenomena. Parameter identification for active materials, assumed fiber distribution, data assumption, and model validation are current drawbacks. New recommendations deal with the incorporation of multimodal data derived from medical imaging, the integration of more biophysical phenomena, and model reproducibility. Accounting for data uncertainty in skeletal muscle modeling will be also a challenging issue. This review provides, for the first time, a holistic view of current continuum models of skeletal muscles to identify potential gaps of current models according to the physiology of skeletal muscle. This opens new avenues for improving skeletal muscle modeling in the framework of in silico medicine.
Enthalpies of Combustion and Formation of Histidine Stereoisomers
Authors: Neacsu A. , Gheorghe D. , Contineanu I. , Sofronia A. M. , Teodorescu F. , Perişanu S.
Published: December 2018

The combustion energy of histidine enantiomers (L and D) and of their racemic mixture was measured experimentally. The following values for the enthalpies of formation corresponding to the crystalline state were derived (L = −451.7, D = −448.7, DL = −451.5 kJ·mol−1), and information concerning their stability was obtained by correlating the values of the above thermochemical quantity with the structure of the molecules by using the group additivity scheme. The samples were characterized using a simultaneous thermogravimetry (TG) coupled with differential scanning calorimetry (DSC) techniques in the temperature range between ambient and beyond melting-decomposition, and the corresponding parameters were calculated. The high values of the decomposition temperatures highlight the stability of the compounds. The decomposition reactions are discussed in terms of DSC and TG data, obtained by us and other researchers.
Bilateral Proximal Tibia Stress Fractures through Persistent Physes
Authors: Carroll John J. , Kelly Sean P. , Foster James N. , Mathis Derek A. , Alderete Joseph F.
Published: December 2018

Introduction. Fatigue fractures are stress fractures resulting from repetitive trauma in areas of stress concentration. Prior case reports and studies have described stress fractures through persistent physes about the olecranon and distal fibula, as evidenced by hyaline cartilage on histologic analysis. However, there have been no documented proximal tibia stress fractures through persistent physes. Case Presentation. A 29-year-old military male basic trainee with varus alignment about his knees suffered bilateral medial tibial plateau stress fractures several weeks into military basic training. He underwent radiographic and laboratory evaluation of his stress fractures and eventual operative fixation of his bilateral tibial plateau fractures. Intraoperative specimens obtained from the fracture sites distal to the articular surface demonstrated abnormal fibrous appearing tissue. Histology demonstrated the presence of hyaline cartilage. Discussion. A 29-year-old military male basic trainee had bilateral proximal tibia stress fractures through persistent physes confirmed with biopsies demonstrating hyaline cartilage. Our belief is that the patient’s persistent physes placed him at a greater risk for stress fractures and these may benefit from fixation in soldiers and athletes.
A Case of a 5-Year-Old Boy with a Blauth Type IIIB Hypoplastic Thumb Reconstructed with a Nonvascularized, Hemilongitudinal Metatarsal Transfer
Authors: Nakada Mika , Tada Kaoru , Nakajima Tadahiro , Matsuta Masashi , Tsuchiya Hiroyuki
Published: December 2018

The treatment methods used for Blauth type IIIB hypoplastic thumbs are controversial. We performed a nonvascularized, hemilongitudinal metatarsal bone transfer on a 5-year-old boy with a type IIIB hypoplastic thumb. Despite the child’s age, the growth of the thumb was confirmed and the thumb had stabilized. Moreover, growth disorder of the donor toe was not observed. This method is relatively easy to perform. And donor toe deformation can be prevented, because of the preservation of more than half of the metatarsal bone. In our case, the patient was 5 years of age; nevertheless, the epiphyseal line was opened and the grafted metatarsal bone grew. This method is useful in terms of its simplicity and prevention of postoperative complications.
Variable Pore Structure and Gas Permeability of Coal Cores after Microwave Irradiation
Authors: Hong Yi-du , Lin Bai-quan , Xiang Hua , Zhu Chuan-jie , Wang Zheng , Nie Wen
Published: December 2018

The experimental work in this paper investigated the effect of microwave energy on pore structure and gas permeability of coal cores. Fifteen coal samples were irradiated under the condition of 2.45 GHz with 6 kW. The effect of microwave irradiation on the pore structure of coal samples was evaluated by nuclear magnetic resonance (NMR). The water saturation degree has little influence on transverse relaxation time (T2) distribution before the microwave treatment. By contrast, water saturation degree obviously affects the T2 distribution after the microwave energy treatment. Coal permeability increased after microwave energy treatment. But fractal dimension decreased after microwave energy treatment. The results show that microwave energy has a potential for degassing coal seams.
Suspected Reaction with Cephalosporin May Be a Predictive Factor for β-Lactam Allergy in Children
Authors: Eser Simsek Isil , Tuba Cogurlu Mujde , Aydogan Metin
Published: December 2018

Background: Most children diagnosed with β-lactam allergy based only on history are not truly allergic, and mislabeling leads to use of less effective and more costly alternative broader-spectrum antibiotics, significantly increasing drug resistance. Objective: To determine the frequency and risk factors of confirmed allergy in patients with β-lactam allergy reported by parents or their doctors and evaluate cross-reactivity between β-lactams in children with confirmed allergy. Method: Sixty-seven children with suspected β-lactam allergy were evaluated via history, sIgE measurements, skin tests, and drug provocation tests over a period of 5 years. Results: β-Lactam allergy was confirmed in 10 (14.9%) patients. Six patients had a positive intradermal test result to one or more of the penicillin skin test materials or ceftriaxone, 4 patients with negative skin test results had positive test results with suspected drugs. Age, gender, time interval between evaluation and the initial reaction, personal history of atopy, parental history of drug allergy, reaction type, and multiple drug allergy history were not significantly different between allergic and tolerant patients. For culprit drugs, there was a significant different between the 2 groups; the rate of confirmed diagnosis was significantly higher for cephalosporins such as ceftriaxone, cefuroxime, and cefprozil (p = 0.03). Three patients with allergy to penicillin tolerated cefuroxime; in 4 patients with selective allergy to ceftriaxone tolerated cephalosporins with a dissimilar side chain (cefadroxil, cefuroxime, cefaclor, and cefdinir). Conclusion: Our study indicates that most patients with a suspected β-lactam allergy tolerated this drug. An appropriate diagnostic allergy workup may prevent the use of less effective and more expensive alternatives.
Deep Brain Stimulation Surgery without Sedation
Authors: Zech Nina , Seemann Milena , Seyfried Timo F. , Lange Max , Schlaier Juergen , Hansen Ernil
Published: December 2018

Background: Sedatives and opioids used during deep brain stimulation (DBS) surgery interfere with optimal target localization and add to side effects and risks, and thus should be minimized. Objective: To retrospectively test the actual need for sedatives and opioids when cranial nerve blocks and specific therapeutic communication are applied. Methods: In a case series, 64 consecutive patients treated with a strong rapport, constant contact, non-verbal communication and hypnotic suggestions, such as dissociation to a “safe place,” reframing of disturbing noises and self-confirmation, were compared to 22 preceding patients under standard general anaesthesia or conscious sedation. Results: With introduction of the protocol the need for sedation dropped from 100% in the control group to 5%, and from a mean dose of 444 mg to 40 mg in 3 patients. Remifentanil originally used in 100% of the patients in an average dose of 813 µg was reduced in the study group to 104 µg in 31% of patients. There were no haemodynamic reactions indicative of stress during incision, trepanation, electrode insertion and closure. Conclusion: With adequate therapeutic communication, patients do not require sedation and no or only low-dose opioid treatment during DBS surgery, leaving patients fully awake and competent during surgery and testing.
Fracture Cascade in Patients with End-Stage Renal Disease: Complications and Outcome
Authors: Samy Tarek M. , Khalil Tarek M. , Abouelsoud Maged , Abdelrahman Amr , Elghonimy Mohamed B.
Published: December 2018

We report a 68-year-old end-stage renal disease female patient on dialysis for 15 years. She sustained consecutive fractures starting with left-sided femoral neck fracture, followed 16 months later by a right-sided one. On her recovery from her right hip injury she sustained a stress type subtrochanteric fracture at the entry site of the fixation implants and an ipsilateral humeral shaft fracture. Cementless total hip replacement was done for the left femoral neck, and osteosynthesis was done for her undisplaced right femoral neck fracture. Revision fixation was done for her right subtrochanteric fracture with a long Gamma nail that was statically locked. The humeral fracture was fixed with an interlocking nail in a closed manner. This case highlights the fact that sequential hip fractures is an ominous event which is likely to be followed by a quick cascade of bone injuries with trivial trauma and a high rate of unexpected complications. Our treatment approach is explained here, stressing the unexpected complications and challenges met.
Análise de uma Arquitetura da Informação associada a Multimodalidade na capacitação de profissionais de alto desempenho
Authors: Orlandi Tomás Roberto , Duque Claudio Gottschalg
Published: December 2018

A capacitação permanente de profissionais, em qualquer área do conhecimento, é um desafio a ser alcançado nos dias de hoje. Com profissionais de alto desempenho não é diferente, eles devem dominar uma ampla gama de disciplinas que vão desde relacionamentos humanos ao domínio da gestão de riscos empresariais. A pesquisa mostra uma análise da aplicação prática dos conceitos de arquitetura da informação, espaços informacionais e multimodalidade como proposta de atendimento a essas demandas de capacitação desses profissionais. A metodologia empregada foi da pesquisa aplicada, utilizando questionários direcionados para levantamento dos dados. Os resultados iniciais obtidos demonstram uma boa aceitação do modelo e dos conceitos empregados pelo grupo de profissionais de alto desempenho pesquisado, com avaliações concentradas na sua maioria entre boas e ótimas. A multimodalidade aplicada na capacitação profissional pode auxiliar, significativamente, o alcance das necessidades de informação do educando, para que ele possa desempenhar suas atividades técnicas e gerenciais cotidianas.
Abstract 010: Dual Loss of RGS2 and 5 Exacerbates the Progression of Cardiac Hypertrophy in Mice Chronically Treated With Isoproterenol
Authors: Dahlen Shelby A , Mohanty Ipsita , Djameh Ursula , Edwards Alethia , Koch Jennifer , Osei Owusu Patrick
Published: December 2018

This study determined the effect of chronic isoproterenol (ISO) treatment on cardiac structure and function in male mice without or with dual loss of regulator of G protein signaling (RGS) 2 and 5. RGS2 and 5 act as GTPase-activating proteins (GAPs) that preferentially terminate signaling via G
q/11
- and G
i/o
class G proteins, by accelerating GTP hydrolysis. Deletion of either RGS2 or 5 increases susceptibility to cardiovascular disease. However, the effects of dual absence of the two RGS proteins on normal physiology and disease are unknown. Using mice concurrently lacking RGS2 and 5 (
Rgs2/5
dbKO) and wild type (WT) cohort, we determined how the dual absence of both RGS proteins affects cardiac response to chronic β-adrenergic receptor stimulation. WT and
Rgs2/5
dbKO mice were infused with saline or 30 μg/g/day of ISO for 3 or 14 days. At baseline,
Rgs2/5
dbKO mice showed cardiac hypertrophy (WT: 9.06 ± 0.34 vs. dbKO: 10.16 ± 0.32 mg/mm tibia length;
p
<0.05) and left ventricular chamber dilation by echocardiography, without tissue fibrosis. ISO infusion for 3 days caused and augmented cardiac hypertrophy in WT (SAL: 9.65 ± 0.38 vs. ISO: 11.68 ± 0.45 mg/mm tibia length;
p
<0.05) and
Rgs2/5
dbKO (SAL: 9.97 ± 0.43 vs. ISO: 12.57 ± 0.69 mg/mm tibia length;
p
<0.01) mice, respectively, as well as interstitial fibrosis and increased expression of hypertrophic and heart failure gene markers, including
Nppa
,
Serca
,
Mybpc3
and
Tnni3
. Sub-chronic ISO infusion also caused a greater decrease in percent fractional shortening by day 3, in
Rgs2/5
dbKO relative to WT mice (WT: -4.22 ± 4.15 vs. dbKO: -7.69 ± 3.86 %;
p
<0.05). In WT mice, cardiac hypertrophy and left ventricular dilation were lower after 14-day compared to 3-day ISO infusion, but similar to saline-treated control levels (ΔSAL to 3d-ISO: 21.04 ± 0.82 vs. ΔSAL to 14d-ISO: 15.05 ± 0.66 %;
p
<0.05). This was accompanied by a robust increase in
Rgs5
but not
Rgs2
mRNA expression in WT mice. In contrast,
Rgs2/5
dbKO mice continued to show abnormal cardiac structure and function after 14-day ISO infusion. Together, these data suggest that increased expression of RGS5 compensates for the lack of change in RGS2 expression and/or function and protects against transition from ISO-induced cardiac hypertrophy to heart failure.
Abstract 014: Betamethasone: A Novel Therapeutic Intervention for Preeclampsia
Authors: Scroggins Sabrina M , Santillan Donna A , Sandgren Jeremy A , Pierce Gary L , Sigmund Curt D , Grobe Justin L , Santillan Mark K
Published: December 2018

The early pathogenesis of preeclampsia (PE) involves a systemic inflammatory immune response. Recent data demonstrate that increased circulating arginine vasopressin (AVP) in humans is predictive of PE and that infusion of AVP in mouse dams phenocopies the pregnancy-specific cardiovascular and immune alterations observed in human PE. Specifically, AVP suppresses anti-inflammatory cytokines and cells. Betamethasone (BMTZ), commonly given to women at risk for preterm birth, is both an AVP and immune response modulator. We hypothesize that early treatment with BMTZ will prevent the development of AVP-induced PE. C57BL/6J dams were infused with AVP (24 ng/hour) or saline throughout gestation via osmotic minipump. AVP dams received a single subcutaneous injection of BMTZ (100ug) early post-placentation (gestational day (GD) 7). Blood pressure was measured throughout pregnancy. Total protein was measured on 24 hour urine collected on GD 17. Maternal and fetal tissues were collected on GD 18. Cytokine concentrations were determined via commercially available ELISAs and normalized to total protein. BMTZ reversed the hypertension (ANOVA n=11, p=0.007) and proteinuria (ANOVA n=11, p=0.025) induced by AVP. BMTZ reversed the AVP-induced decreases in the maternal and fetal anti-inflammatory responses. In maternal kidney, both anti-inflammatory IL-4 (AVP: 0.034, n=10 vs BTMZ: 0.092, n=5 ug/g, p<0.05) and TGFb (AVP: 4.3, n=10 vs BTMZ: 9.2, n=5 ug/g, p<0.05) were increased in BMTZ-treated dams. Decreases in fetal kidney IL-4 (AVP: 0.013, n=5 vs BTMZ: 0.043, n=5 ug/g, p<0.05), IL-10 (AVP: 1.2, n=5 vs BTMZ: 2.1, n=5 ug/g, p=0.05), and TGFb (AVP: 1.8, n=5 vs BMTZ: 2.9, n=5 ug/g, p<0.05) were reversed with BMTZ treatment. Lastly, placental concentrations of IL-4 (AVP: 0.002, n=5 vs BTMZ: 0.005, n=5 ug/g, p<0.05) and TGFb (AVP: 0.090, n=5 vs BTMZ: 1.4, n=5 ug/g, p<0.05) were also improved following BMTZ in AVP-infused dams. Supportive of our hypothesis, early BMTZ treatment prevented hypertension and reduced proteinuria in AVP-infused dams. BMTZ also reversed AVP-induced inhibition of anti-inflammatory responses, creating a more tolerogenic milieu. These data support the concept for the potential use of BMTZ in early gestation as a novel preventative agent for PE.
Abstract 015: Reduced Placental Expression of Regulator of G Protein Signaling-2 (RGS2) in Preeclampsia: Association, Consequence, and Cause
Authors: Perschbacher Katherine J , Deng Guorui , Sandgren Jeremy A , Santillan Donna A , Devor Eric J , Pierce Gary L , Fisher Rory A , Gibson-Corley Katherine N , Santillan Mark K , Grobe Justin L
Published: December 2018

To date, the early-gestational mechanisms driving the pathogenesis of preeclampsia (PreE) remain largely unclear. However, altered G protein signaling has been implicated in PreE, including alterations in GPCR agonists such as vasopressin, endothelin, and angiotensin. Regulator of G protein Signaling 2 (RGS2) is an endogenous terminator of Gαq signaling, and mutations in the
Rgs2
gene are linked to hypertension and increased risk of developing PreE. Therefore, we hypothesized reduced placental RGS2 may increase the risk of developing PreE by disinhibiting Gαq signaling.
In silico
reanalysis of a publicly-available microarray dataset (GSE75010) revealed a significant reduction in
Rgs2
mRNA in placentas from PreE pregnancies compared to controls (Con n=35, PreE n=49, p<0.05). We confirmed this reduction in
Rgs2
mRNA by qPCR using human placental tissue samples (PreE 19% of Con, n=11 vs 9, p<0.05). To examine if reduced feto-placental RGS2 was sufficient to induce PreE phenotypes, wildtype C57BL/6J female mice were mated with
Rgs2
-deficient (
Rgs2
-KO) sires or wildtype littermate sires. Dams mated with
Rgs2
-KO sires developed diastolic hypertension (Con 92 ± 2 vs
Rgs2
-KO 98.2 ± 2 [24 hr avg mmHg]; p<0.05 vs pregnant control and pre-pregnancy
Rgs2
-KO) and increased proteinuria compared to dams mated with littermate sires (18.2 ± 2.2, n=7 vs 28.4 ± 2.8, n=10 mg/day, p<0.05). Preliminary histological analysis of placentas from dams mated with an
Rgs2
-KO sire suggest decreased spiral artery number and diameter (SA Number: Con 7.7 ± 0.2 vs
Rgs2
-KO 5.6 ± 0.4, SA Diameter: Con 128 ± 3 vs
Rgs2
-KO 86 ± 12). Previous studies have outlined a CRE element in the
Rgs2
promoter that is critical for transcriptional regulation of
Rgs2
. Thus, we hypothesized loss of cAMP/CREB regulation may lead to reduced RGS2 in human PreE. Indeed, reduced phosphorylated CREB (p-CREB) binding was observed in PreE placentas (Con 0.146 ± 0.024 vs PreE 0.070 ± 0.021 p<0.05). However, loss of p-CREB was not due to decreases in cAMP levels (Con 1.69 ± 0.35 vs PreE 2.18 ± 0.18 nM). These data support a role for reduced placental RGS2 in the pathogenesis of PreE, and demonstrate that changes in p-CREB regulation may explain the loss of RGS2 expression in placental trophoblasts.
Abstract 024: Genetically Inducing Renal Lymphangiogenesis Prevents Angiotensin II-Induced Hypertension in Mice
Authors: Balasubbramanian Dakshnapriya , Lopez-Gelston Catalina A , Lopez Alexandra H , Iskander Geina , Tate Winter , Luera Emily M , Konatham Sunitha , Rutkowski Joseph M , Mitchell Brett M
Published: December 2018

Angiotensin II (AII)-dependent hypertension (AIIHTN) is associated with renal immune cell infiltration and inflammation. Lymphatic vessels drain interstitial fluid and traffic immune cells to draining lymph nodes; however, the role of renal lymphatics in AIIHTN is unknown. Our hypotheses were that: 1) renal lymphatic vessel density is increased in mice with AIIHTN, and 2) that further augmenting renal lymphatic vessels will prevent AIIHTN. Male and female mice were infused with AII (490 ng/kg/min) or saline for 2 or 3 weeks by subdermal osmotic mini pumps. Male and female mice with AIIHTN had markedly increased renal lymphatic vessel density compared to controls. AIIHTN males had significantly increased renal gene expression of the lymphatic vessel markers
Lyve1, Pdpn,
and
Vegfr3,
while
Pdpn
and the lymphangiogenic signal
Vegfc
were increased significantly in AIIHTN females. Kidneys of AIIHTN males had significantly increased F4/80+ macrophages at 2 weeks and F4/80+ macrophages and CD3e+ T cells at 3 weeks as determined by flow cytometry. Unlike in males, renal CD11c+ dendritic cells were increased significantly in females. Renal mRNA levels of the pro-inflammatory cyto/chemokines
Tnfa
,
Il1b
,
Mcp1
, and
Cxcl13
were elevated significantly in males at 2 and 3 weeks and in females at 3 weeks. To determine whether augmenting renal lymphatic vessels prior to AII infusion could prevent AIIHTN, we used transgenic mice that overexpress the lymphangiogenic signal VEGF-D only in the kidney under the control of doxycycline (KidVD+ mice) and thus exhibit renal-specific lymphangiogenesis. Doxycycline initiated 1 week prior to 3-week AII infusion prevented AIIHTN in KidVD+ mice while KidVD- mice still developed AIIHTN (Males SBP: 122±2 vs. 161±3 mmHg; p<0.05; Females SBP: 114±1 vs. 131±4 mmHg; p<0.05). KidVD+ AIIHTN mice had significantly decreased renal levels of CD11c+ dendritic cells and CD8+ T cells. Renal gene expression of
Tnfa
and
Il1b
were normalized in all KidVD+ mice. These data demonstrate that renal lymphatic vessel density is increased in AIIHTN and that genetically inducing renal lymphangiogenesis prior to AII infusion can prevent AIIHTN by reducing renal immune cells and inflammation.
Abstract 025: Cellular Mechanisms of Blood-Brain Barrier Disruption in Ang II-Induced Hypertension
Authors: Santisteban Monica M , Faraco Giuseppe , Lane Diane , Racchumi Gianfranco , Segarra Steven , Schaeffer Samantha , Cipollini Virginia , Anrather Josef , Iadecola Costantino
Published: December 2018

The blood-brain barrier (BBB) is critically important for brain health by regulating molecular exchanges between blood and brain. Hypertension (HTN) induces breakdown of the BBB which may contribute to its deleterious effect on the brain, but the cellular bases of the BBB opening remain to be established. We used a model of angiotensin II (AngII) HTN (600ng/kg/min x 2 weeks; n>5/group) to investigate the mechanisms of the BBB opening. BBB permeability was assessed spectrophotometrically in C57BL/6J mice using 3000 MW FITC-dextran as a tracer. HTN increased BBB permeability in Ang II HTN (29.8 ± 0.9 vs 18.1 ± 0.5 ng/g in control, p<0.01), an effect partially ameliorated by the angiotensin type 1 receptor (AT1R) antagonist losartan in the drinking water (22.9 ± 0.6 ng/g) but not by hydralazine + hydrochlorothiazide (27.4 ± 0.7 ng/g), suggesting involvement of AT1R and not elevated blood pressure. Next, we sought to identify the mechanisms of the breakdown of the BBB in HTN. First, we used electron microscopy to examine the ultrastructure of endothelial tight junctions (TJ) and assess vesicular transport, key components of the BBB. HTN reduced the length (-25%) and complexity (-11%) of TJ, and increased the number of endothelial vesicles (2.22 vs 1.42 vesicles/endothelial area, p<0.05). The TJ remodeling was associated with a reduction in occludin (-17%, p<0.01) and claudin-5 (-30%, p<0.05) mRNA in microvascular preparations. Additionally, the expression of Mfsd2a, a lipid transporter that also suppresses vesicular transcytosis, was markedly attenuated (-43%, p<0.01). Taken together, these data suggest a strong effect of Ang II on cerebral endothelial cells to induce BBB opening. Since perivascular macrophages (PVM) mediate cerebral endothelial dysfunction in HTN (J Clin Invest 2016;126:4674), we tested their involvement in the BBB opening. PVM depletion with icv clodronate or deletion of AT1 receptors in PVM partially attenuated the BBB opening in Ang II HTN (p<0.05). Thus, we conclude that AT1R in cerebral endothelial cells and PVM mediate the BBB opening by targeting both paracellular and vesicular transport. Such increase in BBB permeability to circulating agents may contribute to the cerebrovascular and cognitive dysfunction associated with HTN.
Abstract 028: Susceptibility to Strokes in Spontaneously Hypertensive Rats Due to a Mutation in
Stim1
Authors: Dhande Isha S , Kneedler Sterling C , Zhu Yaming , Hicks M J , Wenderfer Scott E , Braun Michael C , Doris Peter A
Published: December 2018

Stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) develop cerebrovascular disease as a result of naturally occurring genetic variation. We recently identified a novel truncating mutation in the SHR-A3 line affecting the C-terminus of STIM1, a protein involved in the store-operated Ca
2+
entry (SOCE) pathway. The SHR-B2 line, which is also hypertensive but resists end organ injury, expresses the ‘wild type’
Stim1
. Here, we test whether the emergence of cerebrovascular disease in SHR-A3 is prevented by gene rescue of
Stim1
. We created a
Stim1
congenic line (SHR-A3(
Stim1
-B2)), in which the functional
Stim1
allele was transferred from the SHR-B2 line into the stroke-prone SHR-A3 genome. SHR-A3 and SHR-A3(
Stim1
-B2) rats were salt loaded (1% NaCl in drinking water) for 8 weeks starting at 20 weeks of age to induce strokes. Baseline BP measured by telemetry before salt loading was not different between SHR-A3 and SHR-A3(
Stim1
-B2) rats (199.5±6.49 vs 196.26±2.431 mmHg, ns). Salt loading resulted in a progressive increase in BP in SHR-A3 rats, but was blunted in SHR-A3(
Stim1
-B2) rats. Compared to SHR-A3 rats,
Stim1
-rescue congenic rats had improved survival (% survival: 100 (9 of 9) vs 22.2% (2 of 9) at the end of 8 weeks) and lower neurological deficit scores (2.45±0.412 vs 1±0.00, p<0.01). Salt loading resulted in significant cerebral edema in SHR-A3 rats but not in the SHR-A3(
Stim1
-B2) rats (% brain wt/body wt: 0.805±0.045 vs 0.617±0.009, p<0.01). Gross morphology of the brain revealed microbleeds and hemorrhages in 5 of 9 SHR-A3 rats. These lesions were absent in SHR-A3(
Stim1
-B2) rats.
Stim1
gene rescue in the congenic line was also associated with decreased susceptibility to renal injury assessed histologically at 40 weeks of age (glomerular injury: 1.915±0.086 vs 1.355±0.071, p<0.001; tubulointerstitial injury: 3.2±0.102 vs 1.69±0.112, p<0.001). Our findings identify
Stim1
as a major candidate gene that promotes susceptibility to strokes as well as renal injury in spontaneously hypertensive rats.